Introduction

Pancreatic exocrine insufficiency (PEI) is defined as a reduction of pancreatic exocrine activity in the intestine at a level that prevents normal digestion(1). PEI leads to malnutrition-related complications and a reduced quality of life. Faecal pancreatic elastase is an ideal biomarker to assess pancreatic function in patients experiencing PEI. Due to its high stability, faecal pancreatic elastase is concentrated during intestinal passage, thus reflecting the total overall pancreatic secretion.

Aims & Methods

The aim of this work was to evaluate the clinical performance of a particle-enhanced turbidimetric immunoassay (PETIA) that allows automated quantification of pancreatic elastase in faecal extracts on clinical chemistry analyzers. Hundred and eighty-nine samples from 76 controls and 113 diagnosed patients were used to compare the turbidimetric immunoassay and a reference ELISA assay performance. For both assays, sensitivity and specificity were determined using a cutoff of 200 μg/g. Moreover, for samples within the measuring range for both assays, a kappa value and the overall agreement were assessed.

Results

A better clinical performance was obtained by the turbidimetric immunoassay compared to the reference ELISA assay. The turbidimetric immunoassay revealed a sensitivity and specificity of 78% and 74%, respectively, while the reference ELISA assay revealed a sensitivity and specificity of 74% and 68%, respectively. The hundred and twelve samples used to perform a method comparison showed a relative bias at the cutoff (200 μg/g) of -5.72% and an overall analytical agreement between the turbidimetric immunoassay and the reference ELISA assay of 85.7%. Cohen’s kappa agreement showed a substantial agreement of 0.70.

Conclusion

The turbidimetric immunoassay showed good diagnostic performance and a strong agreement with the reference ELISA assay. The particle-enhanced turbidimetric immunoassay is an accurate, non-invasive, automated test and an ideal assay for large-scale determination of pancreatic elastase levels in fecal extracts.

References

(1) Philips ME, et al. BMJ Open Gastro 2021; 8: e000643

Disclosure

“All authors are employees of BÜHLMANN Laboratories AG”

Introduction

Chronic Intestinal Pseudo-Obstruction (CIPO) is a rare disease characterized by a severe impairment of intestinal propulsive activity resulting in a clinical picture mimicking a mechanical intestinal obstruction despite the absence of any physical obstruction. Velusetrag (VEL) is a highly selective oral 5-hydroxytryptamine type 4 receptor (5-HT4R) agonist that enhances peristalsis, stimulates intestinal secretion and inhibits gastrointestinal visceral sensitivity via acetylcholine and calcitonin gene-related peptide released from motor and sensory neurons, respectively. This phase II, multicenter, double-blind, placebo-controlled, 2 treatments, 4 periods, multi-crossover (N-of-1) trial investigates the efficacy and safety of VEL in CIPO patients.

Aims & Methods

Seventeen patients with idiopathic or secondary (to primary neurodegenerative disorders) CIPO with at least 30% of their daily caloric intake from oral nutrition were treated for 4 periods of 4 weeks each with either VEL 15 mg once daily or placebo (PLA), with a washout period of 2 weeks between treatment periods. Each cycle with two periods assigned to either VEL or PLA is considered as a pair of observations. Analysis was performed on the evaluable pairs (i.e., evaluation available both for VEL and PLA within cycle). Each subject could be evaluated twice, once for each cycle, thus, each subject could contribute to 0, 1 or 2 observations for each treatment. The present analysis was performed on 15 patients, assessed as responders or naïve to 5-HT4R agonists. The number of pseudo-obstructive episodes and stool type (Bristol stool scale) were assessed during the entire study.

Results

A 50% reduction in the number of pseudo-obstructive episodes in VEL (n=4) vs PLA (n=8) was detected in 30 evaluable pairs of observations. During VEL treatment, pseudo-obstructive episodes occurred once in 2 patients and twice in 1 patient; during PLA treatment 7 patients experienced 1 episode and 1 during wash-out period after PLA. Complete normalization of constipation was observed only with VEL. In 23 evaluable pairs, all 4 observations with constipation on VEL at pre-treatment had normal stools at end of treatment (from Bristol stool type 1-2 to 3-4); additionally, observations with normal stools increased from 3 (pre-treatment) to 6 (end of treatment). In contrast, all 3 observations with constipation on PLA at pre-treatment remained constipated at end of treatment and other 2 observations with diarrhea at pre-treatment shifted to constipation at the end of treatment (Tab. 1). These results did not reach statistical significance due to limited sample size. The number of subjects with treatment emergent adverse events was similar between VEL and PLA. No cardiovascular adverse reactions or serious treatment emergent adverse events were observed in both treatment groups.

Conclusion

​​​​​​​​A VEL prokinetic effect was confirmed by a decreased number of pseudo-obstructive episodes and a normalization of constipation, two main clinical features of CIPO. VEL was also well-tolerated and safe, with no serious drug-related adverse event reported.

Disclosure

Publications management support was provided by PharmaGenesis London, London, UK, and was funded by Alfasigma S.p.A.

This study was sponsored by Alfasigma S.p.A.

Stanghellini V is a member of advisory boards and/or is a speaker for Alfasigma, Bayer, GE Healthcare and Vibrant Pharma; and receives research support from Alfasigma.

Tack J and Malagelada C have relevant financial relationship(s) to disclose: Alfasigma S.p.A.; consultancy and honoraria.

Grimaldi M, Giovannini R, Gentile E, Scuderi V, Manzoni S, Pasquali E, Costantini C, Barone M and Pellacani A have relevant financial relationship(s) to disclose: Alfasigma S.p.A.; employees.

All other authors declare that they have no relevant conflicts of interest to disclose.

Introduction

Therapeutic monitoring of infliximab (INF) correlates with improved therapeutic outcomes in inflammatory bowel diseases (IBD).

Aims & Methods

The aim of this cross-sectional study was to assess the relationship between serum INF trough levels (TLs) and positive therapeutic outcomes in patients with ulcerative colitis (UC) and Crohn’s disease (CD) in a Greek population. The relationship between adverse events (AEs) and the existence of anti-infliximab antibodies (ADAs) was also investigated. Consecutive adult patients with IBD treated with intravenous INF at maintenance phase in a Greek tertiary centre were included. Investigated therapeutic outcomes included sustained clinical remission (CR), steroid-free clinical remission (SFCR), biomarker remission (CRP <5mg/L, BR) and combined (steroid-free clinical and biochemical) remission (SFCBR). Infliximab TLs and ADAs were assessed using ELISA-based assays.

Results

A total of 77 patients were enrolled (62.3% male, mean age 44 years), 48 (62.3%) with CD, 26 (33.8%) with UC and 3 (3.9%) with unclassified colitis. The mean disease duration was 11.7±8.4 years, while the mean duration of INF infusion was 5.1±4.6 years. Forty-seven (61%) patients had undergone treatment escalation, with a further dose escalation in 7 (9.1%) patients. Concomitant combined therapy was given in 13 (16.8%) patients, 4 (5.2%) of them were receiving azathioprine and 9 (11.7%) corticosteroids. Mean INF-TLs were 7.2±4.9 μg/mL and only correlated with treatment escalation (9.7 vs 3.6 μg/mL, p<0.001). Sixty-eight (88.3%) patients had CR, 62 (80.5%) had SFCR, 48 (62.3%) had BR and 43 (55.8%) had SFCBR. Compared to non-responders, mean INF-TLs were numerically higher, although not significantly different, in CR (7.5 vs 5.5 μg/mL, p=0.254), SFCR (7.3 vs 6.9 μg/mL, p=0.761), BR (7.4 vs 6.9 μg/mL, p=0.707) or SFCBR (7.7 vs 6.6 μg/mL, p=0.349).
In a subgroup analysis, among patients without treatment escalation, 27 (90%) had CR, 25 (83.3%) had SFCR, 22 (73.3%) had BR and 19 (63.3%) had SFCBR. Mean INF-TLs were significantly increased among patients with BR (4.2 vs 0.8 μg/mL, p=0.020) and SFCBR (4.3 vs 1.5 μg/mL, p=0.035). In ROC analysis, TLs could significantly predict (p=0.016) with a good accuracy (AUC 0.768, 95% Cl: 0.584=0.952) patients with SFCBR, with an optimal TL cut-off at 3.4 μg/mL. Among patients with treatment escalation, 41 (87.2%) had CR, 37 (78.7%) had SFCR, 26 (55.3%) had BR and 24 (51.1%) had SFCBR. In ROC analysis, TLs could significantly predict (p=0.018) with a fair accuracy (AUC 0.653, 95% CI: 0.527=0.755) patients with SFCBR, with an optimal TL cut-off at 11 μg/mL.
Twenty patients had TLs <1 μg/mL, of whom 10 had positive ADAs. Among them, 9 showed combined remission, 4 of whom had positive ADAs. Among 21 (27.3%) patients with reported AEs, 8 (10.4%) had an allergic reaction, which was attributed to INF. Allergic reactions had a tendency of correlation with ADA existence, as 4/5 patients with allergic reaction and TLs <1 μg/mL had positive ADAs, while 4/10 patients with positive ADAs reported allergic reaction, compared to 1/10 patients with negative antibodies (p=0.152).

Conclusion

Infliximab TLs correlate with treatment escalation. Higher TLs appear to result in favourable therapeutic outcomes. It is suggested that patients undergoing treatment escalation could benefit from higher INF-TLs in the achievement of favourable outcomes.

Introduction

Serum endomysial antibody (EMA) detection is still an important verification tool with high positive predictive value for coeliac disease (CeD) in patients positive with anti-transglutaminase antibody IgA (TGA) result or in seronegative cases with small intestinal villous atrophy. Moreover, EMA positivity is part of the non-invasive diagnostic criteria of CeD in children and adolescents with TGA+ results above 10 times of the upper limit of normal (>10xULN). EMA detections on the classical substrates, monkey oesophagus or human umbilical cord are less sensitive than TGA and both the preparation of the tissue slides and the reading are time-consuming and need expertise. Moreover, it is getting difficult to get commercial slides for the testing. Human umbilical cord vein-derived endothelial cells (HUVECs) produce in cell culture a regular extracellular matrix (ECM) resembling endomysial network with similar exposure of celiac-relevant transglutaminase epitopes as in tissue sections.

Aims & Methods

The aim of this study was to evaluate the diagnostic performance of EMA testing on HUVEC-ECM. Ninety new patients consecutively referred to our center between May –September 2023 in reason of positive coeliac antibody results in outside laboratories or by various rapid tests were prospectively tested for EMA-IgA on HUVEC-ECM prepared on 18-well plastic slides. Results were compared with those of our hospital’s TGA-IgA ELISA and EMA-IgA performed in 1:2.5 dilutions on a composite substrate containing monkey oesophagus, human umbilical cord and gut wall tissues.

Results

TGA-IgA, EMA-IgA on tissues and EMA-IgA on HUVEC-ECM were positive in 73, 62 and 67 samples with 94.4%, 92.9% and 95.7% accuracies for the final CeD diagnosis (non-invasive + biopsy-based), respectively. In 17 samples all three antibodies were negative; most of these patients had only TGA-IgG or DGP earlier.

Conclusion

The easily available novel HUVEC-ECM substrate provided high sensitivity and specifcity for EMA-IgA detection and also may improve the evaluation of coeliac autoimmunity when TGA is low positive or borderline.

Introduction

Laparoscopic cholecystectomy is well known as a gold standard of treatment for gallstone disease. It has been implied that cholecystectomy is an independent risk factor for metabolic syndrome. Nevertheless, evidence on metabolic outcomes of cholecystectomy is based chiefly on population-based retrospective research and remains inconclusive.

Aims & Methods

The study aims to assess the risk of metabolic syndrome after laparoscopic cholecystectomy prospectively and evaluate the change in serum lipid levels associated with gallbladder removal. The study included individuals undergoing laparoscopic cholecystectomy due to gallstones. The exclusion criteria covered all previous metabolic disorders and influencing drugs. The changes in all metabolic syndrome criteria were evaluated before and three months after the laparoscopic cholecystectomy. The blood evaluation contained serum glucose, total serum cholesterol (TC), low-density (LDL) and high-density lipoprotein cholesterol (HDL), and triglyceride levels (TG). The medical examination evaluated blood pressure (BP), heart rate (HR), weight, and waist circumference. The study was approved by the local ethics committee and was registered on ClinicalTrails.gov. (NCT05557669).

Results

85 participants were enrolled. There were no statistically significant differences postoperatively in weight, body mass index, BP, HR, serum glucose, and TG. Although, there was a remarkable decrease in both TC and LDL levels. HDL increased notably. The prevalence of the MetS changed insignificantly after surgery. The notably lower percentage of individuals after surgery fulfilled the fasting plasma glucose criterion, but other criteria changed unremarkably. The relative risk of developing MetS after laparoscopic cholecystectomy was 0,87 (0.64-1.19; CI 95%).

Table 1. Relative risk (CI 95%) of developing different metabolic syndrome criteria after laparoscopic cholecystectomy.

Conclusion

In contrast to retrospective studies, the prospective evaluation indicated no evidence of increased risk of metabolic syndrome after laparoscopic cholecystectomy. However, further investigation regarding the metabolic consequences of this procedure is required.

References

Latenstein CSS, Alferink LJM, Darwish Murad S, et al. The Association Between Cholecystectomy, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease: A Population-Based Study. Clin Transl Gastroenterol. 2020 Apr;11(4):e00170. PMID: 32352682;
Yue, W., Sun, X. & Du, T. Cholecystectomy versus central obesity or insulin resistance in relation to the risk of nonalcoholic fatty liver disease: the third US National Health and Nutrition Examination Survey. BMC Endocr Disord 19, 95 (2019).
Chen Y, Wu S, Tian Y. Cholecystectomy as a risk factor of metabolic syndrome: from epidemiologic clues to biochemical mechanisms. Lab Invest. 2018 Jan;98(1):7-14. PMID: 28892095.
Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of bile acids and bile acid receptors in metabolic regulation. . Physiol Rev. 2009 Jan;89(1):147-91. PMID: 19126757.
Garruti G, Wang DQ, Di Ciaula A, Portincasa P. Cholecystectomy: a way forward and back to metabolic syndrome? Lab Invest. 2018 Jan;98(1):4-6. PMCID: PMC8114797.
Lyu J, Lin Q, Fang Z, Xu Z, Liu Z. Complex impacts of gallstone disease on metabolic syndrome and nonalcoholic fatty liver disease. Front Endocrinol (Lausanne). 2022 Nov 23;13:1032557. PMID: 36506064;