Introduction

Intestinal methanogen overgrowth (IMO) is characterized by colonization of methanogenic species in the gastrointestinal tract and elevated breath methane levels, which are associated with constipation. It can be diagnosed with a simple, non-invasive hydrogen and methane breath test (HMBT). We wanted to determine if IMO is associated with any other symptoms, medications or medical conditions.

Aims & Methods

A large questionnaire-based study was conducted in over 1000 patients of which 731 patients underwent a lactulose HMBT. The 26-item questionnaire included questions about medical history and symptoms, and we used this to identify positive predictors for IMO. Patients were considered positive for IMO if any of the breath samples provided had a concentration of ≥10 ppm methane. Samples were analysed using gas chromatography and statistical significance of associations and predictors were calculated using chi square and logistic regression, respectively.

Results

232 patients were positive for IMO on HMBT. There was a positive association for constipation (P < 0.001) and negative association for diarrhoea (P = 0.002). Excessive methane was associated with stools that appear fatty/greasy and/or tend float (P < 0.001) where 75% of patients with IMO reported this. 22 patients in this cohort had inflammatory bowel disease (IBD) of which 91% tested negative for methane (P = 0.020).

Conclusion

This large questionnaire study has provided further evidence that excessive breath methane production is associated with constipation and inversely associated with diarrhoea and IBD. We have also shown that excess methane may also lead to fatty/greasy stools that can float. HMBT plays an important role to identify IMO in patients with constipation.

Introduction

Irritable bowel syndrome (IBS) is a multifactorial disorder characterized by recurrent abdominal pain associated with defecation or a change in bowel habits. The pathophysiology of IBS involves alterations in the epithelial barrier, but data on the intestinal vascular barrier are lacking.

Aims & Methods

The aims of this study were to investigate the morpho-functional integrity of the vascular barrier and to correlate barrier dysfunction with IBS symptoms. Forty-eight healthy subjects (AC) and 144 patients with IBS (61 IBS-D, 51 IBS-C and 32 IBS-M) were enrolled in the study. Rome IV criteria, Bowel disease questionnaire, Short Form 12, Hospital Anxiety Depression Scale were used to phenotype patients. Immunohistochemistry, western blot and electron microscopy were used to characterize the vascular barrier. Vascular permeability was evaluated by assessing two markers: plasmalemma vesicle–associated protein-1 (PV1) and vascular endothelial cadherin (VEC). A translational model based on HUVEC was used to evaluate permeability changes induced by mediators spontaneously released by mucosal biopsies, and to highlight the underlying molecular mechanisms. Correlation analyses between experimental and clinical data were performed.

Results

Mucosal vessel density was significantly increased by 1.5 fold in the colonic mucosa of IBS patients compared to AC (P<0.01). PV1 expression was increased (P<0.01) while VEC expression was decreased in the colonic mucosa of IBS patients compared to AC (P<0.05). Compared to AC, IBS mucosal mediators increased permeability in the HUVEC monolayer through the activation of protease-activated receptor (PAR)-2 and histone deacetylase (HDAC)11, resulting in VEC downregulation. PV1 expression significantly correlated with anxiety and depression scores and health-related quality of life reported by IBS patients.

Conclusion

The vascular barrier is impaired in IBS and contributes to clinical manifestations

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

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;

Introduction

Mediastinal lesions develop from structures located in the mediastinal compartments and the paravertebral areas. The diagnosis of these lesions is primarily based on imaging studies such as computed tomography and magnetic resonance imaging, which confirm the presence of the lesions and suspected metastatic disease

Aims & Methods

This study aims to assess the factors that determine the diagnostic accuracy and yield of endoscopic ultrasound (EUS) in diagnosing mediastinal lesions. This multicenter study involved a list of centres providing EUS services across ten countries all over the globe. The appropriate information was collected regarding EUS-FNA and EUS-FNB procedures, including nature of the lesion, needle types, needle passes, and complications of the techniques. The frequency/percentage conveyed data on the qualitative variables. The p-values were obtained using the Chi-square two-tailed exact test. The significance of the analysis was defined as p<0.05. All the syntheses were performed using the Statistical Package for the Social Sciences (SPSS version 27; SPSS Inc., Chicago, IL).

Results

A total of 439 participants were involved in this study, 255 (58.1%) males and 184 (41.9%) females, with a mean age of 55.7314.93 years. The average accuracy from the valid matched cases between EUS, cytopathy, and final diagnosis (300 out of 331) was 90.63%. EUS-FNA and EUS-FNB diagnostic yield was influenced by needle types, needle size, number of needle passes, and lesion size. Needles with smaller diameters (22G) offered greater diagnostic yield than needles with larger diameters (19G). However, the diagnostic matching accuracy of EUS in relation to needle sizes was statistically insignificant (p= 0.774). A minimal number of needle passes (between 2 and 4) showed a higher diagnostic yield than a higher number of needle passes (>5) with more diagnostic matching accuracy (p = 0.009). EUS-FNB accounted for a 0.5% complication incidence rate each for fever, pain, thoracic pain, and hemorrhage. Patients undergoing EUS-FNA, EUS-FNB, or both procedural examinations had no significant complications (p = 0.085) Table 1.

Table 1: Incidence rate of complications associated with EUS examination techniques

Conclusion

The diagnostic yield of EUS procedures is affected by needle types, number of needle passes, lesion size, and needle size. Besides, EUS-FNA and EUS-FNB are infrequently associated with serious complications, these techniques are safe and offer higher diagnostic yield when utilised responsibly by endosonographers.

References

1- Gadour E, Awad A, Hassan Z, Shrwani KJ, Miutescu B, Okasha HH. Diagnostic and therapeutic role of endoscopic ultrasound in liver diseases: A systematic review and meta-analysis. World J Gastroenterol. 2024 Feb 21;30(7):742-758. doi: 10.3748/wjg.v30.i7.742. PMID: 38515947; PMCID: PMC10950627.
2- Okasha HH, El-Meligui A, Pawlak KM, Żorniak M, Atalla H, Abou-Elmagd A, Abou-Elenen S, El-Husseiny R, Alzamzamy A. Practical approach to linear EUS examination of the mediastinum. Endosc Ultrasound. 2021 Nov-Dec;10(6):406-413. doi: 10.4103/EUS-D-21-00019. PMID: 34854401; PMCID: PMC8785678.