Clinical Case Summary

A 47-year-old Iranian man with chronic pancreatitis was referred due to abdominal pain. He reported previous heavy alcohol and tobacco consumption with slight pain improvement after abstinence. EUS and MRCP showed main pancreatic duct (MPD) dilation with intraductal stones, the largest with 16mm being impacted in the isthmus. Two prior attempts of endoscopic therapy through conventional ERCP were performed in Iran which were unsuccessful because the impacted stone could not be transposed with the guidewire.
Pancreatoscopy-assisted electrohydraulic lithotripsy (EHL) was proposed. A side-viewing duodenoscope, a 3.6mm cholangioscope (Spyglass™DSII) and Autolith™ EHL System were used during a 3-hour procedure. Deep MPD cannulation was achieved. After 8mm hydrostatic balloon dilation of the papilla and distal MPD the cholangioscope was advanced showing dense, hard and whitish intraductal stones in the pancreatic head and a proximal obstructive large stone impacted in the isthmus. Pancreatoscopy-guided EHL was performed until complete fragmentation of the largest stone, nevertheless being limited by its extreme hardness requiring three different probes. Stone fragments were removed with a Dormia basket and extraction balloon, but some debris persisted. A 5-French 12cm plastic stent was deployed. Sporadic abdominal pain was reported after 3 months.
A second session of EHL was further performed, but stone clearance was not accomplished. In order to avoid long-term pancreatic stent placement, a third session using pancreatoscopy-assisted laser lithotripsy was schedulled 6 months later. A residual 8mm stone was evident in the pancreatic body during pancreatoscopy. Intraductal lithotripsy using holmium laser (AURIGA XL™) with a 365um LightTrail™ fiber allowed complete stone fragmentation. Removal of all fragments was possible with an extraction balloon and saline instillation through a nasopancreatic tube left during 24h. The patient became asymptomatic after the procedure.

References

Images of pancreatoscopy, including electrohydraulic and laser lithotripsy
Fluoroscopic images of the procedures

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, with potential progression to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized obesity treatment, but their role in MASH with fibrosis remains under investigation.

Aims & Methods

This study evaluates the efficacy and safety of GLP-1 RAs in MASH with fibrosis. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) from PubMed, Embase, and Cochrane. Primary outcomes included histologic improvement in fibrosis without worsening MASH, MASH resolution without worsening fibrosis, and improvement in disease activity score. Secondary outcomes included adverse events (AEs), laboratory, and anthropometric data.

Results

Six RCTs (1,000 patients, mean follow-up: 47 weeks) were included. GLP-1 RAs did not significantly improve fibrosis without worsening MASH (RR 1.35; 95% CI 0.91–2.01; p=0.141; I²=53.5%) or disease activity score (RR 1.33; 95% CI 0.93–1.89; p=0.114; I²=64%). However, they significantly increased MASH resolution without worsening fibrosis (RR 3.50; 95% CI 2.44–5.02; p<0.001; I²=0%). No significant differences were observed in serious AEs. GLP-1 RAs improved laboratory, imaging, glycemic, lipidic, blood pressure, and anthropometric parameters.

Conclusion

GLP-1 RAs appear effective and safe in MASH with fibrosis, particularly in resolving MASH without worsening fibrosis.

Introduction

Pain in chronic pancreatitis (CP) varies between patients in pattern, severity, and psychological impact. CP pain assessment has been focused on intensity, missing the complexity. To address the importance of multidimensional pain evaluations, we aimed to identify pain phenotypes based on multidimensional pain assessments and examine their association with clinical factors.

Aims & Methods

We studied 248 patients with painful CP from Asia, Europe, and the USA. A cluster analysis was performed on patients with painful CP, including five pain dimensions from the COMPAT-SF questionnaire (severity, fluctuation, provocative factors, spreading pain, and qualitative descriptors). The resulting clusters were compared based on demographics and clinical data, including patient-reported outcomes and quantitative sensory testing.

Results

		Cluster 1	Cluster 2	Cluster 3	p-value​
Questionnaires	Quality of life	66.3 (22.5)	64.8 (27.7)	51.1 (24.6)	<0.001
	Catastrophizing	10.7 (11.2)	19.1 (12.4)	24.3 (13.0)	<0.001
	Anxiety	5.3 (4.1)	6.2 (4.2)	8.7 (4.5)	<0.001
	Depression	4.3 (4.3)	5.5 (4.6)	7.3 (4.7)	<0.001
	Sleep	5.0 (3.5)	5.9 (3.8)	7.5 (4.5)	<0.001
QST	PPDT sum, kPa	2284 (997)	1811.5 (574.6)	1640.1 (600.4)	<0.001
	PPTT sum, kPa	2909.6 (1247.3)	2227.1 (691.3)	2184.9 (903.2)	<0.001
	Temporal summation, abdomen	1.7 (1.8)	1.9 (1.5)	1.4 (1.8)	0.178
	CPM (%)	2.3 (18.3)	5.1 (23.7)	7.2 (17.7)	0.135

Three distinct pain phenotypes were identified in the cluster analysis. Cluster 1 (n=73) included patients with low-severity pain; Cluster 2 (n=80) was characterized by severe, fluctuating pain; and Cluster 3 (n=95) comprised patients reporting constant, severe pain. Patients in Clusters 1 and 2 reported low scores across the remaining dimensions, whereas Cluster 3 consistently scored higher. Quality of life and sleep were best in Cluster 1, declined in Cluster 2, and were lowest in Cluster 3 (both p<0.001). Scores for anxiety, depression, and catastrophizing increased progressively across clusters (all p<0.001). Sensory testing revealed a pattern of increasing hyperalgesia, with Cluster 3 showing the most pronounced responses (p<0.001).

Conclusion

The COMPAT-SF questionnaire identifies three pain phenotypes in CP. Greater pain severity and persistence correlate with increased hyperalgesia, higher psychological distress, and worse overall well-being.

Introduction

Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide, affecting more than 65% of patients with Type 2 Diabetes Mellitus (T2DM). The aim of our study was to determine the prevalence of MASLD among T2DM patients, with or without coexisting significant fibrosis, to assess its association with diabetic complications, and to identify the factors linked to MASLD in our population.

Aims & Methods

We conducted a retrospective, descriptive, and analytical study including T2DM patients admitted to the Endocrinology Department in 2019. MASLD diagnosis was based on the presence of hepatic steatosis detected by abdominal ultrasound or a Hepatic Steatosis Index (HSI) >36. Fibrosis was assessed using the Fibrosis-4 (FIB-4) index (with a threshold of ≥1.3 or <1.3). Chronic Kidney Disease (CKD) associated with T2DM was defined by an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² and/or dipstick-positive proteinuria (>1+). Diabetic Peripheral Neuropathic Pain (DPNP) was assessed using the Douleur Neuropathique 4 (DN4) questionnaire, and Diabetic Retinopathy was diagnosed via dilated eye examination.

Results

Among the 202 patients included, the median age was 57 years (±12 years) with a marked female predominance (sex ratio = 2.6). Regarding comorbidities, 58.4% of patients had hypertension and 34.2% had dyslipidemia. The median Body Mass Index (BMI) was 27 kg/m² (±5.62), with overweight or obesity present in 61.4% of the cohort. The median duration of diabetes was 10 years (±7.8 years). Impaired renal function (eGFR <60 ml/min/1.73 m²) was found in 9.9% of patients, and proteinuria in 6.9%. Diabetic neuropathy (DN4 score ≥4) was present in 7.9% of patients, while diabetic retinopathy was diagnosed in 37.6% of cases.
The prevalence of MASLD in our cohort was 73.3%. The median FIB-4 score was 0.91 (±0.63), with 25.7% of patients presenting a FIB-4 >1.3. Statistical analysis identified several factors significantly associated with the presence of MASLD: female sex (p=0.004), dyslipidemia (p=0.004), BMI (p<0.001), alanine aminotransferase (ALT) levels (p<0.001), low-density lipoprotein cholesterol (LDL-C) levels (p=0.006), and triglyceride levels (p=0.013). In particular, higher BMI was strongly associated with MASLD (Odds Ratio [OR] = 1.970; 95% Confidence Interval [CI]: 1.580–2.460; p<0.001), as were elevated ALT levels (OR = 1.115; 95% CI: 1.053–1.18; p<0.001).
However, after adjustment, LDL-C levels (p=0.163), triglycerides (p=0.402), dyslipidemia (p=0.329), and sex (p=0.360) were no longer significantly associated with MASLD. Finally, a significantly higher proportion of CKD was observed in patients with MASLD (22.3%) compared to those without MASLD (9.2%, p=0.036), although this association was not maintained in the subgroup with advanced fibrosis (FIB-4 >1.3).

Conclusion

Our study confirmed the high prevalence of MASLD among patients with T2DM. Early screening is therefore essential, particularly in female patients and in those presenting with chronic kidney disease or other associated cardiometabolic risk factors such as obesity and dyslipidemia.

References

Younossi ZM, Golabi P, Price JK, Owrangi S, Gundu-Rao N, Satchi R, Paik JM. The Global Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among Patients With Type 2 Diabetes. Clin Gastroenterol Hepatol. 2024 Oct;22(10):1999-2010.e8. doi: 10.1016/j.cgh.2024.03.006. Epub 2024 Mar 21. PMID: 38521116.

Introduction

Inflammatory bowel disease (IBD) is a complex disease characterized by the dysregulation of host immunity. A key feature is the intestinal activation of T cells with cytotoxic activity and pro-inflammatory cytokine release. Therefore, targeting these pro-inflammatory T cells is a reasonable therapeutic approach. CCR9 is the main activator of gut tropism in the lymphocytes and a promoter of their migration into the lamina propria.
SBR3 is a best-in-class anti-CCR9 monoclonal antibody that effectively depletes CD4⁺ CCR9⁺ T cells in intestinal biopsies and peripheral blood of Crohn’s Disease (CD) and Ulcerative Colitis (UC) patients, which leads to a marked reduction in pro-inflammatory cytokines and restoration of immune homeostasis.
The main objective of this study is to evaluate the translational efficacy of SRB3 in depleting CD4⁺CCR9⁺ T cells in intestinal explants from patients with UC and CD, and to assess its correlation with clinical parameters such as fecal calprotectin levels and current treatments.

Aims & Methods

Intestinal biopsies were collected in routine colonoscopies with inflammatory activity (defined as a Mayo Endoscopic Score <1 in ulcerative colitis and presence of ulcers in CD) from a cohort of IBD patients that included both naïve individuals and those previously treated with biologics, including TNF inhibitors (adalimumab, infliximab) and IL-12/23 antagonists (ustekinumab). Gut explants were cultured and treated ex vivo with SRB3. The frequency of CD4⁺CCR9⁺ T cells and cytokine levels were measured by flow cytometry and multiplex immunoassays. Clinical and demographic parameters from the patient cohort, including smoking habits, type of disease, Montreal Classification, and fecal calprotectin levels (μg/g), were reviewed to evaluate correlations with SRB3 response.

Results

SRB3 efficiently depleted CD4⁺ CCR9⁺ T cells in both naïve patients and those treated with biologic therapies, including anti-TNF agents and IL-12/23 antagonists, indicating robust activity across diverse treatment backgrounds.
Importantly, higher levels of fecal calprotectin showed a statistically significant correlation (p = 0.032) with the extent of CCR9⁺ cell depletion following SRB3 treatment. Given that elevated calprotectin levels are commonly associated with active disease or acute inflammatory flares, this finding suggests that SRB3 is particularly effective in patients with moderate-severe inflammatory activity.

Conclusion

These findings support the broad therapeutic potential of SRB3 in IBD patients, demonstrating efficacy not only in bio-exposed patients but also in those with active disease, where higher calprotectin levels correlate with stronger depletion levels.

Disclosure

Dr. Barreiro and Dr. Conde are both collaborators in a project funded by SunRock Biopharma.