Introduction

Despite advancements in treatment strategies, cardiovascular diseases continue to be a leading cause of death worldwide and persist as a major public health concern. Therefore, it is important to seek new potential therapeutic targets. The gut microbiome is suggested to play a role in the development of coronary artery disease (CAD). Studies have shown different microbiome compositions in patients with CAD (Gao, Kwun), however, it is not yet completely understood whether these dysbiosis signatures are causative for CAD or are a consequence of the disease.

Aims & Methods

In this study, we aimed to investigate whether dysbiosis signatures of CAD are already present in individuals at risk. We conducted a cross-sectional study using shotgun metagenomic sequencing to analyze 411 fecal samples from individuals with low (n=130), intermediate (n=130), and high (n=125) cardiovascular risk, as well as those with ST-elevation myocardial infarction (STEMI) (n=26). Cardiovascular risk was calculated by using the Framingham score. We analyzed alpha and beta diversity in the gut microbiome, as well as the differential abundance of species and functional pathways among the groups.

Results

We identified 8 species and 49 pathways to be differently abundant among the different groups. These findings included an increase of Collinsella stercoris abundance with increasing cardiovascular risk (STEMI vs risk groups; coefficient = 1.75, FDR = 0.005), and reduced abundance of Bacteroides vulgatus and Bacteroides uniformis in the STEMI group compared to the risk groups (respectively; coefficient = -2.28, FDR = 0.013 and coefficient = -1.35, FDR = 0.019). Differential abundance analysis of the pathways identified four upregulated pathways linked to starch biosynthesis and phenolic compound degradation in the STEMI group compared to groups with lower risk. All other differently abundant pathways were decreased in the STEMI group in contrast to other groups. These pathways were associated with many processes such as nucleotide biosynthesis, fatty acid and lipid biosynthesis, and carbohydrate biosynthesis. We did not find significant trends in Shannon diversity and beta diversity.

Conclusion

Our study revealed that specific species and pathways were differently abundant in STEMI patients compared to groups with varying cardiovascular risk. These species are promising candidates for further investigation to improve our understanding of their role in CAD. Our study underscores the need for experimental studies, using culturomics and intervention trials, to gain further insights into the directional and causal relationships of specific gut microbial species in CAD.

References

Gao, J., Yan, K. T., Wang, J. X., Dou, J., Wang, J., Ren, M., Ma, J., Zhang, X., & Liu, Y. (2020). Gut microbial taxa as potential predictive biomarkers for acute coronary syndrome and post-STEMI cardiovascular events. Scientific reports, 10(1), 2639.
Kwun JS, Kang SH, Lee HJ, Park HK, Lee WJ, Yoon CH, Suh JW, Cho YS, Youn TJ, Chae IH. Comparison of thrombus, gut, and oral microbiomes in Korean patients with ST-elevation myocardial infarction: a case-control study. Exp Mol Med. 2020 Dec;52(12):2069-2079.

Introduction

By definition, indeterminate biliary strictures are those that cannot be diagnosed with routine imaging modalities, including ultrasound, CT scan, and MRI. In such cases, single-operator cholangioscopy (SOC) has emerged as a useful tool for diagnostic and therapeutic interventions, which enables visualization of the bile duct and allows for targeted biopsies of suspicious lesions. The use of SOC has been shown to improve diagnostic accuracy, decrease the need for additional procedures, and guide therapeutic interventions. Nevertheless, pooled sensitivity for diagnosis of SOC-guided biopsies in the diagnosis of malignant biliary strictures is limited with approximately 60%. So far, there is no evidence on which biopsy technique is best and how many biopsy samples need to be taken to improve diagnostic accuracy.

Aims & Methods

Aim: To evaluate the best sampling technique comparing two versions of the SpyBite forceps to optimize diagnostic yield for the differentiation of indeterminate biliary stricture.
Patients and methods: Patients with an indeterminate biliary stricture with an independent indication to perform an ERCP with SOC and bile duct sampling were recruited to participate in this prospective, randomized, multicenter study. Patients were equally randomized into the following study arms: (i) single biopsy (SB); (ii) multiple biopsies with suction technique (MB); (iii) bite-on-bite biopsies (BB). At least 6 biopsies had to be obtained in each group. Furthermore, the best sampling technique was transferred into phase 2 of the study comparing conventional forceps (Spybite) vs. larger forceps (Spybite max.). Final diagnosis was defined as prove of malignancy, histology of surgical resectate or 6 months follow-up without signs of malignancy. Adequacy of the samples was rated according to a 6 point rating scale (cytological samples rate 0-2; histological samples rates 3-5). Sensitivity/specificity of samples were defined as primary endpoint.

Results

A total of 60 patients (20pt. per group, mean age 67y, 48% female) were included in the first study phase. In the SB, MB and BB group a mean of 6.4, 6.7 and 6.5 samples was taken, respectively. Of note, in the MB group a significant difference of the number of samples being evaluated (∆=3.5; -47.8%) was observed indicating a loss of samples during suction. Resulting sensitivity/specificity of the obtained samples was: SB 76/89%; MB 61/85%; BB 79/92%, with a significant lower level in the MB group compared to SB and BB (p=0.01). In the 2^nd study phase 20 patients were included per group. Usage of the larger forceps significantly increased sensitivity to 85% (p=0.01) with a specificity of 95% applying the BB technique. Conventional forceps obtained cytological samples in 48.3% and histological samples in 51.7%, whereas larger forceps resulted in 8.3% cytological samples (p=0.0001) and histological samples in 91.7% (p=0.001).

Conclusion

Based on the results of this study, the bite-on-bite biopsy technique using larger forceps (Spybite max.) appears to be the best sampling technique for optimizing diagnostic yield in the differentiation of indeterminate biliary stricture.

Disclosure

Mark Ellrichmann, Arne Kandulski, Markus Dollhopf, Arno Dormann, Alexander Dechene, Torsten Beyna, Christian Gerges received lectures fees from Boston Scientific

Introduction

The American Society for Gastrointestinal Endoscopy (ASGE) grading system for endoscopic retrograde cholangiopancreatography (ERCP) has been shown to predict success and adverse events rates. We compared ERCP outcomes and adverse events between complex and non-complex procedures using the ASGE-grading system. Our study also sought to assess the impact of the ASGE-grading system on ERCP outcomes with and without trainee involvement.

Aims & Methods

We conducted a retrospective study of 1392 patients who underwent ERCP procedures in a single large tertiary insititution between January 2019 and July 2023. Clinical data were prospectively collected during routine ERCP procedures. Demographics, cholangioscopy, procedure and fluoroscopy time, adverse events, and technical success rates were compared between complex (ASGE Grade ≥3) and non-complex (ASGE Grade <3) ERCP procedures as well as with and without trainee involvement. Categorical variables were compared using Pearson’s chi-square test and continuous variables using a standard t-test. Multivariate regressions were performed to adjust for sex, age, clinical setting, and native papilla.

Results

Approximately 83.3% of ERCPs were ASGE Grade <3 and 16.7% were ASGE Grade ≥3. The mean patient age was 62 years, 53% were male. The ampulla was native in 45.3% of ASGE Grade <3 vs. 34.1% of ASGE Grade ≥3 (P=0.002). Cholangioscopy was needed in 1% of ASGE Grade <3 vs. 58.6% of ASGE Grade ≥3 (aOR: 72.2, P <0.001). Procedure and fluroscopy time were longer by 25.4 mins (aOR: 1.04, P < 0.001) and 5 mins (aOR: 1.24, P < 0.001) respectively for ASGE Grade ≥3 . Adverse events (aOR: 0.44, P= 0.274) and technical success (aOR: 1.00, P= 0.983) were similar in both groups. No significant difference was noted between trainees and attending endoscopist in the odds of ERCP adverse events or technical success for ASGE Grade <3 or ASGE Grade ≥3 respectively.

Conclusion

ERCPs with ASGE Grade ≥3 is associated with increased procedure and fluoroscopy time, and displayed increased odds of requiring cholangioscopy. ERCP technical success and adverse events did not significantly differ with trainee participation regardless of procedural complexity.

Table. ERCP outcomes for complex (ASGE Grade ≥ 3) vs. non-complex procedures (ASGE Grade <3). N=1392.

References

References
1. Sahar, N., La Selva, D., Gluck, M., Gan, S. I., Irani, S., Larsen, M., Ross, A. S., & Kozarek, R. A. (2019). The ASGE grading system for ERCP can predict success and complication rates in a tertiary referral hospital. Surgical endoscopy, 33(2), 448–453
2. Zhou, F., Zhan, X., Song, C., Li, G., Hong, J., Chen, Y., & Zhou, X. (2022). The assessment of the ASGE-grading system of ERCP: a large-sample retrospective study. Surgical endoscopy, 36(9), 6480–6487

Introduction

Acute pancreatitis (AP) is one of the most common and widely increasing gastrointestinal diseases leading to hospitalization without specifically available therapy [1]. It is mainly caused by gallstones, possibly by increasing the pressure in pancreatic duct with refluxing of bile acids (BAs) or changing of serum BA concentration due to bile duct obstruction [2]. So far, few existing reports only mentioned total BA measurements without considering their hydrophilic potential. Our data from experimental work showed that systemic BAs can modulate severity of AP depending on their hydrophobicity and the involvement of cholecystokinin [3]. As a further translational step, we aimed to investigate the role of systemic BAs profiles and analysed their association with the etiology and severity of AP in human.

Aims & Methods

Serum from AP patients and a healthy control group was collected and stored at -80⁰C. A profile of 20 different BAs was quantified by liquid chromatography tandem mass spectrometry-based assay using the AbsoluteIDQBAs kit according to the manufacturer’s instruction. The workflow was managed by MetIDQ and the data was analyzed by Oracle database XE software. Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated for each patient at the first and third day of hospitalization and were compared by subtraction of the values (Δ APACHE II). Diagnosis criteria and severity of pancreatitis were assessed according to the Revised Atlanta classification and the APACHE II score.

Results

There were 214 AP patients with mean age of 60±16 (range 26-87) years and 50.4 % were female. Biliary origin was diagnosed in 133 (62.1%) patients and non-biliary pancreatitis (mainly alcoholic AP) in 81 (37.9 %) cases. In non-biliary AP, profiles of both hydrophobic and hydrophilic BAs did not differ from controls. In biliary AP, significantly elevated levels were detected for hydrophobic BAs but not hydrophilic one. The total concentrations of hydrophobic BAs were 33.86±4.51 μM in biliary AP and 8.068±1.98 μM in non-biliary AP (p < 0.0001). Cut-off values were 0.30 μM and 3.78 μM for hydrophilic and hydrophobic BAs, respectively. The total amount of hydrophilic BAs was not different between the groups of deteriorated (Δ APACHE II >0) and ameliorated or stable AP (Δ APACHE II ≤ 0). Conversely, total hydrophobic BAs concentrations were significantly higher in the worsened AP (55.8±12.3 μM) group than in those who recovered or at least did not deteriorate (5.9±0.6 μM). However, ursodeoxycholic acid (UDCA), a hydrophilic BA, was significantly decreased in severe disease and showed a reduced trend in moderately severe AP.
Hydrophobic BAs had more predictive potential with an area under the curve (AUC) of 0.762, a sensitivity of 83.75% and a specificity of 60% at the cut-off value 11.84 μM, whereas hydrophilic BAs were only of limited use for the prediction of AP deterioration, as AUC was 0.57 with a sensitivity of 65% and a specificity of 44% at the cut-off 0.7 μM. Additionally, UDCA concentrations of less than 19 nM can be used to distinguish biliary AP from non-biliary AP with an AUC of 0.723, sensitivity 75%, and specificity 65%. For detection of deterioration, UDCA alone with cut-off concentration 18 nM showed a value with an AUC of 0.68, sensitivity 76%, and specificity 61%.

Conclusion

In patients, the sum of hydrophobic but not total hydrophilic BAs associated with the etiology and severity of AP. Serum levels of UDCA, a particular type of hydrophilic BAs, inversely associated with the severity of AP, which suggests a protective role.

References

[1]. Iannuzzi, J.P.; King, J.A.; Leong, J.H.; Quan, J.; Windsor, J.W.; Tanyingoh, D.; Coward, S.; Forbes, N.; Heitman, S.J.; Shaheen, A.A.; et al. Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis. Gastroenterology 2022, 162, 122-134, doi:10.1053/j.gastro.2021.09.043
[2]. Lerch, M.M.; Aghdassi, A.A. The role of bile acids in gallstone-induced pancreatitis. Gastroenterology 2010, 138, 429-433, doi:10.1053/j.gastro.2009.12.012
[3]. Tran, Q.T.; Sendler, M.; Wiese, M.L.; Doller, J.; Zierke, L.; Gischke, M.; Glaubitz, J.; Tran, V.H.; Lalk, M.; Bornscheuer, U.T.; Weiss F.U; Lerch, M.M and Aghdassi A.A. Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis. International journal of molecular sciences 2022, 23, 13592. doi: 10.3390/ijms232113592

Disclosure

The authors declared no Conflict of Interest.

Introduction

Tofacitinib is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC). The recommended induction scheme is 10 mg twice daily (BID) for at least 8 weeks followed by a maintenance dose of 5 mg BID. However, some patients require 10mg bid, for 16 weeks at the induction phase. Our study aimed to assess the demographics and disease characteristics of such patients and their outcome at 24 weeks.

Aims & Methods

This was a multicenter, retrospective, observational study which included patients with moderate to severe UC, who received induction therapy with Tofacitinib 10mg bid for a 16-week period. Data were collected between July 2018 and November 2022. The primary objective was disease outcome, defined as clinical remission and/or the need of steroids. Secondary outcomes were treatment withdrawal, treatment de-escalation and adverse events.

Results

In total 31 patients, are currently enrolled in our study, from 10 IBD centres [males: 51.6%, mean age at study entry: 40.0 years, median disease duration: 7 years]. Patient demographic and clinical characteristics at baseline are shown in table 1. Four patients (12.9%) discontinued treatment before week 24, due to inadequate response. De-escalation of dosing to 5mg bid tofacitinib was attempted in 13 of 27 patients (48.1%) and was successful in 7 patients (53.8%) who maintained clinical response until week 24 of the study. Of the other 6 out of 13 patients, 6 patients received again the higher dose (10 mg bid) and regained response and only one patient discontinued treatment. Overall, 85.7% (6/7) of the patients who received tofacitinib 5mg bid and 66.7% (14/21) who received 10mg bid at 24 weeks, had received more than one biologic prior to tofacitinib (P=0.34). At week 24, the partial Mayo score was available in 26 patients; 13 patients were in steroid-free clinical remission (pMayo <2). Twelve patients had mild active disease (pMayo 2-4) and 9 of them had stopped steroids. No major adverse events were observed during the entire observation period.

Conclusion

In a real-world setting, a 24-week treatment with tofacitinib 10mg BID is safe and the majority of patients achieve clinical remission and manage to stop steroids. De-escalation at 5mg bid is successful in more than half of them. We prospectively follow up our cohort to investigate whether these preliminary results will be confirmed for a longer period.