Introduction

The role of faecal immunochemical testing (FIT) as a biomarker to stratify patients with lower gastrointestinal (GI) symptoms is well established. However, its use in patients with iron deficiency anaemia (IDA) is unclear. The aim of this study was to investigate the role of FIT in predicting small bowel (SB) pathology in patients with IDA.

Aims & Methods

This was a single tertiary centre prospective study. Inclusion criteria was adults (>18 years and < 80 years) with IDA who were referred to secondary care for upper and lower gastrointestinal tract (GI) endoscopy. These patients also had a FIT test done in primary care. All participants had a small bowel capsule endoscopy (SBCE) prior to their endoscopic investigations. Participants with subsequent upper or lower gastrointestinal tract malignancy were excluded from the study as this was considered as the most likely cause of IDA. IDA was defined as a Hb < 131g/L for men and < 110 g/L for women with ferritin< 30ug/L and/ or iron levels < 11umol/L.

Results

In total 79 patients were included in the final analysis with a median age of 67yrs (IQR 52-74); haemoglobin 103(IQR 95- 118) and ferritin 11(IQR 6-11). There were 13 patients on NSAID’s at the time of their investigations. There were 35 (44%) patients with significant findings on SBCE which was classed as contributing to IDA. These findings included angioectasia in n= 21 (26%) of the patients which was the most common finding. The other findings included erosions= 5 (6.3%); inflammatory strictures= 3 (3.8%); active Crohn’s n=1 (1%); visible blood with no clear source n=3 (3.8%); bleeding angioectasia n=1 (1%); and ulcer=1 (1%). A positive FIT (>10) had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 34.29%, 54.55%, 37.5% and 51.08% respectively.

Conclusion

Patients with IDA have a high diagnostic yield on SBCE and should routinely have SBCE as part of the work up for IDA. There is a pressing need for biomarkers to help triage SBCE referrals, however FIT is not a reliable biomarker for the presence of small bowel pathology in patients with IDA.

Introduction

In patients with upper gastrointestinal bleeding (UGIB), the European Society of Gastrointestinal Endoscopy (ESGE) recommends adopting the following definitions regarding the timing of upper GI endoscopy: urgent (6-12h), early (≤24h), and delayed (>24h) (1). There is no consensus definition of emergent endoscopy, but previous publications use the timeline of <6h (2).
Early endoscopy is associated with better outcomes, and guidelines suggest that it should be performed within this time frame (1).
Last ESGE guideline about variceal bleeding (VB) suggests performing urgent endoscopy in this context (3). This is based on a meta-analysis showing lower overall mortality when endoscopy was performed <12h compared to >12h (4). Surprisingly, ESGE concludes that the optimal timing in this setting is controversial due to a lack of high-level evidence. In fact, except for this study, all the others examining this aspect show that performing endoscopy before 12h does not provide benefits (5,6).

Aims & Methods

We aim to compare whether urgent endoscopy (6-12h) provides benefits to VB and explore predictors for mortality.
Methods: Retrospective analysis of a prospective registry of UGIB patients admitted to 'Virgen de las Nieves University Hospital' (2013-2020). VB was defined as that coming from gastric or esophageal varices. Endoscopy timings were defined according to ESGE: emergent (<6h), urgent (6-12h), early (≤24h) and delayed (>24h) (1).
Main outcomes were in-hospital (endoscopy therapy, transfusion, rebleeding, misbalance of chronic condition, hospital stay, and mortality) and delayed-6 months (bleeding, cardiovascular events, mortality). Statistical analysis was performed using SPSS.

Results

1459 UGIB patients were collected, 216 with VB.
Statistical differences in main outcomes are shown in Table 1 (each letter in the subscript denotes column proportions that do not differ significantly from each other). No differences were found for the other outcomes.

Timing (% patients)	<6h (39.7%)	6-12h (28.8%)	12-24h (17.4%)	24h (2.7%)	p
Endoscopy therapy	85.1% a	63.5% b	65.8% b	66.7% b	0.014
Misbalance of chronic condition	48.3% a	30.2% b	23.7% b	50% a	0.026
Rebleeding	22.1% a	7.9% b	7.9% b	16.7% a	0.037
In-hospital mortality	27.4% a	13.6% b	11.1% b	50% a	0.025

We also compared basal characteristics and found differences in MAP(ASH) score≥2 (92.3% vs. 66.7% vs. 77.4% vs. 75%; p=0.003) and GBS≥12 (69% vs. 44.4% vs. 52.6% vs. 83.3%; p= 0.011).
Independent risk factors for in-hospital mortality were MAP(ASH)≥2 (1.26, 95% CI 1.03-1.54), misbalance of chronic condition (OR 9.92, 95% CI 3.56-27.61, p=0.000), and rebleeding (OR 3.95, 95% CI 1.45-10.79, p=0.007). The timing of endoscopy performing was not an independent prognostic factor for mortality.
We also conducted subgroup analysis to assess whether performing endoscopy before 12h provides benefits in other UGIB patients, without finding differences for patients with non-variceal bleeding or in those at higher risk of poor outcomes (GBS≥12, MAP(ASH)≥2, ASA≥3).

Conclusion

Our study highlights, in line with the majority of available ones (5,6), that endoscopy before 12h does not provide a benefit in patients with VB. This necessitates a reconsideration of the ESGE recommendation. Patients with endoscopy performed before 6 or after 24h have poor outcomes. However, multivariate analysis shows that the timing of endoscopy is not an independent prognostic factor for mortality. On the other hand, the decompensation of basal chronic disease and the severity of bleeding (determined by MAP(ASH) and rebleeding) are the determinants of patient outcomes.

References

1. Gralnek IM, Stanley AJ, Morris AJ, Camus M, Lau J, Lanas A, et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021. Endoscopy. 2021 Mar;53(3):300-332.
2. Laursen SB, Leontiadis GI, Stanley AJ, Møller MH, Hansen JM, Schaffalitzky de Muckadell OB. Relationship between timing of endoscopy and mortality in patients with peptic ulcer bleeding: a nationwide cohort study. Gastrointest Endosc. 2017 May;85(5):936-944.e3.
3. Gralnek IM, Camus Duboc M, Garcia-Pagan JC, Fuccio L, Karstensen JG, Hucl T, et al.. Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2022 Nov;54(11):1094-1120.
4. Bai Z, Wang R, Cheng G, Ma D, Ibrahim M, Chawla S, Qi X. Outcomes of early versus delayed endoscopy in cirrhotic patients with acute variceal bleeding: a systematic review with meta-analysis. Eur J Gastroenterol Hepatol. 2021 Dec 1;33(1S Suppl 1):e868-e876.
5. Zhang W, Huang Y, Xiang H, Zhang L, Yuan L, Wang X, et al. Timing of endoscopy for acute variceal bleeding in patients with cirrhosis (CHESS1905): A nationwide cohort study. Hepatol Commun. 2023 May 4;7(5):e0152.

Introduction

Suspected foreign body ingestion and food bolus impaction are common indications for urgent esophagogastroduodenoscopy. Nevertheless, most of the ingested foreign bodies (80 to 90%) pass spontaneously throughout the gastrointestinal tract. In 2022, the Decision-To-Scope (DTS) Score was developed, revealing an excellent accuracy in predicting foreign bodies in the esophagus.

Aims & Methods

Our aim was to prospectively evaluate the diagnostic accuracy of the DTS-Score.
We have prospectively included consecutive patients admitted for suspected foreign body in the upper gastrointestinal tract, for a 6-month period. Previously to endoscopic evaluation, the DTS-score - time since ingestion < 6 hours (+1pt); absence of any meal since the suspected ingestion (+2pts); dysphagia (+3pts); odynophagia (+1pt) and drooling (+4pts) - was applied in each patient. The maximal possible value was 11 points, with a DTS-Score ≥5 being considered to assign a high probability of endoscopic confirmation of the foreign body.

Results

Final sample included 47 patients, from which 26 (55.3%) were females, with a mean age of 60±16 years. From these, most (n=42; 91.5%) were evaluated for accidental ingestion of food-related foreign bodies (fish or chicken bones) or suspected food bolus impaction. A DTS-Score ≥5 was calculated in 11 (23.4%) of the patients, with an esophageal foreign body being confirmed in 12 (25.5%) of them. DTS-score presented an excellent accuracy in predicting the endoscopic confirmation of a foreign body in the esophagus (AUC=0.94; 95%CI 0.85-1.00; p<0.001). The originally defined cut-off (DTS-Score ≥5) presented a specificity of 97.1%, a sensitivity of 83.3%, a positive predictive value of 90.9% and a negative predictive value of 94.4%.

Conclusion

When prospectively applied, the DTS-score demonstrated an excellent acuity in stratifying the probability of endoscopic confirmation of a suspected foreign body in the esophagus. This tool may be included in future clinical algorithms for suspected foreign bodies ingestion.

Introduction

Non-variceal upper gastrointestinal bleeding (NVUGI) represents a significant gastrointestinal disorder with elevated mortality rates (1). Non-steroidal anti-inflammatory drugs (NSAIDs) have been firmly established as a risk factor for NVUGI, yet their precise impact on clinical outcomes remains insufficiently defined (2,3). Conversely, proton pump inhibitors (PPIs) have shown efficacy in reducing the incidence of NVUGI associated with NSAIDs. However, the extent of their influence on the clinical outcomes of NVUGI remains inadequately substantiated. Therefore, it is necessary to study the impact of these drugs on the clinical outcomes of patients with NVUGI.

Aims & Methods

The primary objective of our study is to compare the outcomes of NVUGI patients using NSAIDs with or without PPIs against those who did not use either medication. We conducted a retrospective analysis at a Spanish tertiary hospital, encompassing NVUGI cases from 2013 to 2022. NVUGI was defined as hematemesis or melena accompanied by a two-point decrease in hemoglobin or hemodynamic instability. Key clinical outcomes included the necessity for intervention (endoscopic, radiological, or surgical) and in-hospital mortality. Additionally, we compared baseline characteristics and pertinent clinical results such as rebleeding and delayed cardiovascular events. Statistical analysis was performed using SPSS.

Results

​A total of 1200 cases were included, with 6.6% undergoing concomitant treatment with PPIs and NSAIDs, and 15.7% utilizing NSAIDs alone. Patients who took NSAIDs alone were younger (57 years vs. 66 in both other groups) and had a lower rate of comorbidities. Table 1 presents risk scores and outcome comparisons among the three groups. Statistical differences were observed, revealing lower acute mortality (9.6% vs. 7 vs. 2.8%, p=0.011) and reduced need for intervention (74% vs. 69.6 vs. 57.8%, p<0.001) in the group using NSAIDs alone. In multivariate analysis, MAP(ASH) > 2 (OR: 8, CI: 3-21, p<0.001) and ASA > 2 (OR: 4.4, CI: 1.7-11.4, p:0.002) emerged as independent risk factors for acute mortality, with an elevated MAP(ASH) score (OR: 8.8, CI: 5.9-13, p<0.001) being the sole independent factor explaining the need for intervention.

	Naive	NSAIDs and PPIs	NSAIDs without PPIs	P
ASA 3-4	596 (64,3%)	50 (63,3%)	63 (33,7%)	<0,001
MAPASH>2	448 (59,3%)	39 (65%)	52 (34,4)	<0,001
Need for intervention	691 (74%)	55 (69,6%)	108 (57,8%)	<0,001
Rebleeding	96 (10,3%)	9 (11,4%)	6 (3,2%)	0,008
Acute mortality	86 (9,6%)	5 (7%)	5 (2,8%)	0,011
Mortality at 6 months	77 (8,8%)	7 (9,3%)	7 (3,8%)	0,075
Delayed Cardiovascular event	77 (8,7%)	3 (3,9%)	4 (2,2%)	0,004
Delayed rebleeding	145 (16,4%)	15 (19,5%)	6 (3,3%)	<0,001

Conclusion

Patients abstaining from NSAIDs or those concurrently undergoing PPI therapy exhibited a higher incidence of intervention or acute mortality compared to those solely using NSAIDs. Through multivariate analysis, our study indicates that bleeding severity and baseline comorbidities, expressed by elevated MAP(ASH) scores and ASA classification, are pivotal factors influencing the clinical outcomes of NVUGI. In summary, the use of NSAIDs or PPIs to safeguard against gastrointestinal lesions induced by these drugs did not demonstrate a discernible impact on the short-term outcomes of patients with non-variceal upper gastrointestinal bleeding.

References

1. Lakatos L, Gonczi L, Lontai L, Izbeki F, Patai A, Racz I, et al. Incidence, predictive factors, clinical characteristics and outcome of non-variceal upper gastrointestinal bleeding – a prospective population-based study from hungary. Journal of Gastrointestinal and Liver Diseases. 2021 Sep 1;30(3):327–33.
2. Durak MB, Şimşek C, Yüksel İ. Clinical Outcomes of Older Patients with Non-Variceal Upper Gastrointestinal Bleeding Taking Anti-Thrombotic or Non-Steroidal Anti-Inflammatory Agents. Turkish Journal of Gastroenterology. 2023 Sep 1;34(9):918–24.
3. Åhsberg K, Höglund P, Kim WH, Von Holstein CS. Impact of aspirin, NSAIDs, warfarin, corticosteroids and SSRIs on the site and outcome of non-variceal upper and lower gastrointestinal bleeding. Scand J Gastroenterol. 2010 Dec;45(12):1404–15.

Introduction

Proton pump inhibitors (PPIs) are frequently used in daily clinical practice, but often without a valid indication. Strategies to identify inappropriate PPI use are widely available, although the true challenge is to discontinue PPIs in these patients without developing rebound symptoms. There is therefore a need for a tool to guide patients during this process.

Aims & Methods

We aimed to evaluate the effect of a smartphone app that provides an individualized educational approach as a tool to achieve sustained PPI discontinuation. This multicenter randomized controlled trial included adult patients on daily PPI for at least four weeks without chronic PPI indication from the outpatient clinics of Internal Medicine, Gastroenterology, Rheumatology and Nephrology in two community hospitals and one university hospital in the Netherlands. Patients were excluded in case they could not understand the study (procedures) or in case of a limited life span. Patients were randomly assigned to either the smartphone app providing timely information on PPI discontinuation (intervention group) or usual care which consisted of patients receiving a brochure explaining how to stop PPI and manage symptoms providing all information at once (control group). Primary endpoint was the discontinuation rate at 2-months follow-up, defined as self-declared intake of a maximum of one tablet in the previous 14 days. Patient recruitment has ended and we anticipate final results in August 2023. We now only present preliminary numerical data.

Results

Preliminary follow up results are based on 129 (2-months) and 99 (4-months) of 165 included patients (median age 55 y/o [IQR 46-64 y/o], 61 males [47%]). More patients succeeded to discontinue PPI use at 2-months follow-up in the intervention group: 54/62 (87%) vs. 44/67 (66%). This was also seen after 4-months follow-up: 44/55 (80%) patients in the intervention group vs. 41/61 (67%) patients in the control group.

Conclusion

A smartphone app intervention providing timely guidance in discontinuing inappropriate PPI use seems to be an effective tool to improve the discontinuation rate of inappropriate PPI use compared with a one-time information folder. These preliminary data suggest that patients are able to successfully discontinue inappropriate use of medication without the time-consuming support of a healthcare worker. (Clinical trial registration number: NCT05348252).

Introduction

Copeptin is a stable surrogate biomarker for the activation of the arginine vasopressin (AVP) system [1] as occurs in patients with cirrhosis and clinically significant portal hypertension (CSPH). Specifically, CSPH-induced haemodynamic alterations characterized by reduced peripheral vascular resistance and splanchnic hyperemia cause subsequent AVP system activation [2]. We aimed to evaluate serum copeptin levels (i) in different stages of cirrhosis and (ii) their prognostic value for clinical events in a cohort of stable outpatients with cirrhosis.

Aims & Methods

Stable outpatients with cirrhosis undergoing hepatic venous pressure gradient (HVPG) measurements and available copeptin levels were included; while patients with liver transplantation, malignacy, vascular liver disease, transjugular intrahepatic portosystemic shunt, heart failure and infection were excluded. Patients were stratified into 6 subgroups (S0-S5) for their clinical stage of cirrhosis, with S0-S2 representing compensated cirrhosis (S0: subclinical portal hypertension (PH) with an HVPG of 6-9 mmHg, S1: CSPH without varices, S2: CSPH with varices) and S3-S5 decompensated cirrhosis (S3: history of variceal bleeding, S4: non-bleeding decompensation, S5: further decompensation). Competing risk regression models were used to evaluate the association between copeptin levels and the risk of acute on chronic liver failure (ACLF) and liver-related death (LRD). Liver transplantation was considered as a competing event. Our previously established serum copeptin cut-off at >11.4 pmol/L [3] was used to stratify the patients into a high vs. low AVP system activation group.

Results

In total, 475 patients (S0: n=49, S1: n=53, S2: n=75, S3: n=22, S4: n=156, S5: n=120) with male predominance (72.6%; median age: 57.1 years) were included. Median follow-up time was 26.4 months. Median copeptin levels significantly increased throughout the substages of ACLD (from S0: 7.5 pmol/L to S5: 14.3 pmol/L; p<0.001). Patients with ascites had significantly higher copeptin levels (11.3 pmol/L vs. 7.2 pmol/L in non-ascites patients; p=<0.001).
Serum copeptin correlated significantly with C-reactive protein (ρ=0.281; p<0.001) and interleukin-6 levels (ρ=0.416; p<0.001) in patients with decompensated cirrhosis.
AVP system activation (i.e., Copeptin high >11.4 pmol/L) was found in n=194/475 (40.8%) patients. Patients with high-Copeptin had a significantly higher median MELD-Na (15 vs. low-Copeptin: 12; p<0.001) as well as significantly lower median mean arterial pressure (97 mmHg vs. low-Copeptin: 101 mmHg; p=0.027). The cumulative incidence of ACLF and LRD was significantly higher in patients with high-Copeptin at 1 year (ACLF: 24.1% vs. 4.0%; LRD: 21.9% vs. 4.0%), 2 years (ACLF: 32.0% vs. 7.2%; LRD: 26.7% vs. 6.3%) and 3 years (ACLF: 34.4% vs. 11.6%; LRD: 29.9% vs. 11.2%) of follow-up (p<0.001 for ACLF and LRD).
In competing risk regression adjusted for age, Child Turcotte Pugh score, creatinine, sodium and HVPG, higher levels of copeptin were independently predictive of ACLF (adjusted subdistribution hazard ratio [asHR] per pmol/L: 1.01; 95% confidence interval [95%CI]: 1.00-1.01; p=0.014), as well as LRD (asHR: 1.01; 95%CI: 1.00-1.01; p=0.024).

Conclusion

In ACLD, copeptin levels are upregulated with increasing disease severity suggesting progressive AVP system activation, associated with hemodynamic dysregulation and systemic inflammation. High-Copeptin represents an independent risk factor for ACLF and LRD development.

References

1. Abudeif A, Hashim MS, Ahmed NM, Ahmed AO. Serum copeptin is associated with major complications of liver cirrhosis and spontaneous bacterial peritonitis. Clin Exp Hepatol. 2023;9(1):71-8.

2. Kerbert AJ, Weil D, Verspaget HW, Moréno JP, van Hoek B, Cervoni JP, et al. Copeptin is an independent prognostic factor for transplant-free survival in cirrhosis. Liver Int. 2016;36(4):530-7.

3. Hartl L, Jachs M, Desbalmes C, Schaufler D, Simbrunner B, Paternostro R, et al. The differential activation of cardiovascular hormones across distinct stages of portal hypertension predicts clinical outcomes. Hepatol Int. 2021;15(5):1160-73.