Introduction

Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis (UC).1 The PICaSSO Histological Remission Index (PHRI) is a new simple index for UC disease assessment based only on the detection of neutrophils.2 We evaluate PHRI’s correlation with endoscopy and its prognostic value compared to other established indices.

Aims & Methods

Consecutive patients with UC underwent colonoscopy at 2 referral centers (Birmingham, UK and Milan, Italy) and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI] and Robarts [RHI]) and endoscopy (Mayo Endoscopic Score [MES]; Ulcerative Colitis Severity Endoscopic Index of Severity [UCEIS], and PICaSSO score) was calculated as Spearman coefficients.
Cutoffs for remission were: MES = 0, UCEIS ≤ 1, PICaSSO ≤ 3, PHRI = 0, NHI ≤ 1, RHI ≤ 3 with no neutrophils in the lamina propria or epithelium.
Negative clinical outcomes were defined as: UC-related hospitalization, colectomy, use of steroids, increase in dose in UC therapy or medication change due to uncontrolled inflammation.
The diagnostic performance of endoscopy was assessed with ROC curves and outcome stratification with Kaplan-Meier curves and Cox proportional hazard model.

Results

192 patients with UC were enrolled, representing all grades of endoscopic severity. The correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI (Table 1). In particular, PHRI’s correlation with MES, UCEIS, and PICaSSO was 0.75, 0.72, and 0.69, respectively.

Table 1. Spearman correlation coefficients

Endoscopic score	Robarts	Nancy	PHRI
MES	0.779	0.730	0.745
UCEIS	0.769	0.725	0.718
PICaSSO	0.736	0.694	0.694

Analyzing the diagnostic performance of endoscopy scores to detect histological remission according to the different definitions we found no difference among endoscopy scores. Instead, all endoscopy measures captured with greater precision PHRI and NHI remission, as compared with RHI remission (p<0.005 for PHRI vs RHI, and NHI vs RHI). The areas under the ROC curve for PHRI were 0.91 (95% CI 0.864 – 0.947), 0.91 (95% CI 0.866 – 0.947), and 0.88 (0.828 – 0.926) for MES, UCEIS, and PICaSSO, respectively; for NHI 0.89 (95% CI 0.837 - 0.934), 0.89 (95% CI 0.842 - 0.938) and 0.87 (95% CI 0.814 - 0.921); and for RHI 0.63 (95% CI 0.553 - 0.711), 0.66 (95% CI 0.582 - 0.736), and 0.67 (95% CI 0.591 - 0.744).
We then stratified the risk of suffering any negative disease outcome, a proxy for flare, in the two years following endoscopy, in patients in remission and in activity according to the different histological definitions. The hazard ratios were statistically similar and numerically higher for PHRI (2.87 for PHRI, 2.75 for RHI, and 2.71 for NHI, respectively) proving that a neutrophil-only assessment predicts risk of flare at least as well as established scores.

Conclusion

PHRI correlates with endoscopy and stratifies the risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.

References

1. Magro F, Doherty G, Peyrin-Biroulet L, et al. ECCO Position Paper: Harmonization of the Approach to Ulcerative Colitis Histopathology. J Crohns Colitis 2020;14:1503-1511.
2. Gui X, Bazarova A, Del Amor R, et al. PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system. Gut 2022;71:889-898.

Disclosure

OMN has served as a speaker for Janssen, Ferring, Takeda, Pfizer, Fresenius Kabi
FF ha received consulting fees from Janssen; speaker’s fees from Pfizer and Janssen
SD has served as a speaker, consultant and advisory board member for Schering Plough, Abbott (AbbVie) Laboratories, Merck and Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Vifor and Johnson and Johnson.
AA has received consulting fees from: AbbVie, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; speaker’s fees from: AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda; research support from: MSD, Takeda, Pfizer, Biogen.
SG has served as consultant, Steering committee member, Advisory Board Member and Drug Monitoring committee member for Janssen, Pfizer, Takeda, Abbvie, BMS, Gilead, Galapagos, Celltrion, Eli Lilly, Ferring.
MI has received research grants and equipment loans from Pentax USA, Olympus, and Fujifilm; is partially funded by NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham.

The remaining authors declare no conflict of interest.

Introduction

Upper gastrointestinal bleeding (UGIB) poses a significant threat in patients presenting to the emergency department, particularly in those with associated hemodynamic instability. Despite major advancements in medical and endoscopic therapeutic options, mortality rates have not shown a substantial decline over the years. This study aimed to assess clinical practice patterns in order to gain a clearer understanding of the pre-endoscopic assessment for patients with acute UGIB.

Aims & Methods

This study was an international online survey based on a prospective two-phase data collection approach, conducted between April 2023 and November 2023. The survey targeted practicing physicians actively involved in managing patients with UGIB. Data collection and management were performed through Research Electronic Data Capture (REDCap), an electronic data collection tool. The survey comprised four key domains: demographics and clinical practice, definitions of hemodynamic instability, pre-endoscopic assessment, and optimal timing of endoscopy, encompassing a total of 33 questions. The primary analysis provided a descriptive assessment of responses reported as proportions. Secondary analyses explored differences in responses based on years of clinical experience, practice setting, and the estimated annual number of UGIB cases encountered

Results

A total of 533 clinicians from 50 countries completed our survey. Among respondents, 54.6% work in university-based hospitals, and 67.7% reported managing over 100 UGIB patients annually. Regarding clinical experience, 55.7% have less than 10 years, with 44.3% with over 10 years of experience. Only 47.1% of respondents reported that their hospitals implement a triage system for UGIB patients. Additionally, 39.6% indicated that they do not use any risk stratification scores at the time of patient presentation. For initial fluid resuscitation, 0.9% saline (40.9%) and balanced crystalloid fluids (39.5%) were almost equally preferred. The rate of fluid resuscitation was reported to depend on the patient’s hemodynamic status by 40.2% of respondents. Most respondents indicated that hemodynamically unstable patients are primarily managed in the emergency department or intensive care unit. A total of 34.3% of respondents indicated that they do not routinely use prokinetics prior to endoscopy in UGIB patients, while 27.6% reported not commonly using them even in cases involving severe bleeding or known gastric emptying disorders. Proton pump inhibitors are administered prior to upper GI endoscopy in all cases by 70.4% of respondents, while vasoconstricting agents are used by 61% in cases of suspected variceal bleeding.

Conclusion

Our survey found considerable variability among respondents regarding the pre-endoscopic management of patients presenting with upper gastrointestinal hemorrhage. The overall adherence to international guidelines was low, which can potentially result in a significant negative impact on patient outcomes.

Introduction

Intragastric balloon (IGB) is a minimally invasive intervention used for obese patients who do not achieve adequate weight loss with standard medical therapy (SMT), which includes lifestyle interventions with or without pharmacological treatment. It is also an option for individuals who do not meet the criteria for bariatric surgery or choose not to undergo it. Despite its growing use, there is little data on the short and long-term effectiveness of IGB compared to SMT in randomized controlled trials (RCTs).

Aims & Methods

This systematic review and meta-analysis aimed to compare the efficacy of IGB therapy for at least six months versus SMT in the treatment of obesity, assessing outcomes at 6, 9, and 12 months. A comprehensive literature search was conducted in the MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome was the percentage of excess weight loss (%EWL), while secondary outcomes included absolute weight loss (AWL), percentage of total weight loss (%TWL), and body mass index reduction (BMIR). We calculated mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes. Meta-regression was performed using baseline body mass index (BMI) as a covariate, and subgroup analyses were conducted based on IGB type, baseline BMI, and pharmacological therapy in the SMT group.

Results

A total of 15 RCTs, including 1,961 patients, were included. Compared to SMT, IGB therapy resulted in significantly greater %EWL at 6 months (MD 16.80%; 95% CI [9.22%; 24.38%]), 9 months (MD 14.36%; 95% CI [7.67%; 21.04%]), and 12 months (MD 13.10%; 95% CI [10.43%; 15.77%]). IGB was also superior in AWL, %TWL, and BMIR across all time points (Table 1). Subgroup analyses revealed that results remained consistent regardless of pharmacological therapy use in the SMT group (p=0.77). The Orbera balloon showed superior %TWL at 6 months (p<0.01) and AWL at 6 months (test for subgroup differences with p=0.01), while the Spatz3 balloon demonstrated better %TWL at 9 months (p<0.01). Studies with a baseline BMI >40 kg/m² had significantly greater %TWL at 6 months (p=0.04) and AWL at 6 months (p<0.01) than those with BMI ≤40 kg/m². Meta-regression analysis indicated that higher baseline BMI was associated with greater AWL and BMIR at 6 months.

Conclusion

IGB therapy was significantly more effective than SMT, even when pharmacological therapy was included, leading to superior weight loss outcomes at 6, 9, and 12 months.

Table 1. Summary of findings.

Outcome	Single-arm analysis, mean (95% CI)		Two-arm analysis, Mean difference (95%CI)
	IGB group	SMT group
%EWL 6 months	30.37 (23.25, 37.48)	13.07 (8.17, 17.98)	16.80 (9.22, 24.38)
%EWL 9 months	28.31 (7.93, 48.68)	12.09 (-0.82, 25.01)	14.36 (7.67, 21.04)
%EWL 12 months	34.51 (32.40, 36.62)	20.62 (16.61, 24.62)	13.10 (10.43, 15.77)
%TBWL 9 months	13.11 (9.80, 16.41)	3.78 (2.72, 4.83)	7.66 (3.34, 11.98)
%TBWL 12 months	9.70 (6.13, 13.27)	4.63 (1.84, 7.42)	5.33 (4.16, 6.50)
AWL 9 months, kg	13.14 (8.82, 17.45)	4.37 (2.91, 5.83)	8.65 (4.93, 12.37)
AWL 12 months, kg	10.175 (4.61, 15.73)	5.38 (1.97, 8.78)	4.87 (1.87, 7.88)
BMI loss 12 months, kg/m²	4.85 (2.01, 7.69)	2.61 (1.24, 3.98)	2.27 (0.80, 3.74)

AWL, absolute weight loss; BMI, body mass index; CI, confidence interval; IGB, intragastric balloon; MD, mean difference; RCTs, randomized controlled trials; SMT, standard medical treatment; %EWL, percentage of excess weight loss; %TBWL, percentage of total body weight loss.

References

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Introduction

Precisely matched biomarkers that map both disease activity and disease progression in patients with inflammatory bowel disease (IBD) are essential for individual characterization of this disease and the development of personalized therapy. Biomarkers can also help to establish and confirm the diagnosis of IBD, define risk profiles, and predict the response to drug therapy.

Aims & Methods

The aim of this work was to characterize metabolomic and lipidomic serum profiles of IBD patients to identify metabolic signatures that are unique to the disease and thus can be used as minimally invasive biomarkers. In addition, the determination of lipid subclasses should be used for risk assessment of the cardiovascular risk profile of IBD patients. Serum samples were collected from 55 patients with Crohn's disease (CD), 34 patients with ulcerative colitis (UC), and 40 healthy controls (HC) and analyzed by proton magnetic resonance spectroscopy (1H-NMR). The median age was 40 years in patients with CD and 44 years in UC. In CD, 56% were women and 44 % were men. In UC, the cohort studied consisted of 59 % men and 41 % women. Patients and HC were classified using partial least squares discriminant analysis (PLS-DA) and univariate analysis methods. Disease activity was assessed using the Gastrointestinal Symptom Rating Scale (GSRS), endoscopic activity, and faecal calprotectin.

Results

Serum metabolome differed significantly between CD, UC, and HC. Differences in serum levels of pyruvic acid, histidine, and the branched-chain amino acids leucine and valine were detected. The size of low-density lipoprotein (LDL) particles shifted from large to small, dense particles in patients with CD. A similar trend was observed in UC. Cholesterol and phospholipid composition of very low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) particles were altered in CD compared with HC. Of note, serum levels of apolipoprotein (Apo) A1 and A2 were decreased in CD and UC patients with higher faecal calprotectin levels. GSRS correlated negatively with the expression of ApoA2.

Conclusion

We demonstrate that metabolic profiling from the serum of IBD patients is a promising approach to identify novel biomarkers. Metabolomic assessment of serum samples facilitated the diagnosis of CD and UC. Metabolomic and lipidomic differences compared to non-IBD patients were caused by changes in amino acid and lipoprotein content. Of clinical relevance, disease activity in IBD patients was associated with decreased levels of the atheroprotective apolipoproteins A1 and A2.