Introduction

The latest ESGE technical review guideline advocates real-time monitoring in the first hour of small bowel capsule endoscopy (SBCE) to ensure entire small bowel visualization. However, a survey demonstrated poor adherence to this statement in clinical practice, and supporting data are scarce.

Aims & Methods

We aimed to evaluate predictive factors of incomplete SBCE and to ascertain the importance and cost-effectiveness of real-time monitoring.
We retrospectively included consecutive patients who ingested SBCE (PillCam SB3) at our tertiary referral center from 2013 to 2020. Clinical and endoscopic characteristics were analyzed. Real-time monitoring was not applied according to local protocol. Prolonged gastric transit time (GTT) was defined when the capsule crossed the pylorus > 2 hours from ingestion, and prolonged small bowel transit time (SBTT) when cecum was reached > 6 hours from pylorus crossing. A logistic regression analysis was done to find significative risk factors associated with incomplete SBCE. Exclusion criteria included: capsule retention, endoscopic delivery of capsule, and major technical issues (i.e., eating within a standard gastric transit time of the capsule or major recording issues).

Results

A total of 859 SBCE were analyzed, with a completion rate of 94.5%. A prolonged GTT and a prolonged SBTT were found in respectively 46 (5.4%) and 152 (17.6%) procedures. At multivariate analysis, one modifiable (prolonged GTT[p=0.02]) and two unmodifiable risk factors (inpatient status [p<0.01] and history of incomplete SBCE [p=0.02]) were associated with a higher rate of incomplete SBCE, with increased odds ratio of 3.0 (CI95%= 1.2-7.4), 2.3 (CI95%= 1.2–4.2), and 3.7 (CI95%= 1.2-11.9), respectively. Pretest probability of SBCE completion rate was 90.5% and 95.7% in patients with and without unmodifiable risk factors (p=0.01).
Considering the rates of prolonged GTT, the number of patients to be monitored with real-time viewer to identify and treat one patient with prolonged GTT is 14.5 in patients with unmodifiable risk factors for incomplete SBCE and 20.3 in patients without risk factors for incomplete SBCE (p=0.27).
Direct cost for 1-hour real-time monitoring and intervention in case of prolonged GTT (i.e., dedicated room, nurse, +/- metoclopramide and IV access) are equal to circa 35 €. If all patients of our cohort would undergo real-time monitoring, the expense would be equal to 30065 €. Given that in our cohort 6 patients had an incomplete SBCE, the cost of RTM to prevent one incomplete SBCE would be equal to 5010 €. If RTM would be limited to patients with unmodifiable risk factors for incomplete SBCE, the total cost would be equal to 6615 €. In this sub-group only 2 patients had an incomplete SBCE, therefore, to prevent one incomplete SBCE, the total expense would be 3307 €.

Conclusion

The inpatient status, a prolonged GTT and a previous incomplete SBCE are risk factors for incomplete SBCE. According to our direct costs analysis, the number needed to treat one prolonged GTT to decrease the rate of incomplete SBCE appears to be cost-effective in patients with unmodifiable risk factors (i.e., inpatient status and history of incomplete SBCE).

Introduction

Nowadays one of the biggest healthcare burdens is the diseases of the gastrointestinal tract (GIT). Taking into consideration, that the human gut harbors more than 10¹⁴ CFU of bacteria, through the years scientists have linked those diseases to bacteria species like: Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli, and Helicobacter pylori. Nevertheless, according to World Health Organisation (WHO), Klebsiella pneumoniae is the priority pathogen with the main bacterial pool in the gastrointestinal tract and is easily transmitted between patients, leading to nosocomial outbreaks. Therefore, scientific research with dependable murine models of Klebsiella pneumoniae infection in GIT is highly required.

Aims & Methods

Within the frames of this study, we aimed to develop a dependable mice model for gastrointestinal tract infection of K. pneumoniae as a method for testing novel antimicrobial therapies. Three different study design settings, overall, six experimental groups, and two bacterial strains (ATCC12657, ATCC43816) were used to test the most effective approach for Klebsiella pneumoniae infection: Control groups (10⁸ CFU: G1 - K. pneumoniae ATCC12657; G4 - K. pneumoniae ATCC43816); antibiotics (penicillin 2000 U/ml, streptomycin 2 mg/ml) pre-treated groups with ampicillin therapy (125 mg/l) (10⁸ CFU: G2 - K. pneumoniae ATCC12657; G3, G5, G6 - K. pneumoniae ATCC43816). Real-time PCR for khe (specific K. pneumoniae gene) and 16S rRNA gene sequencing was performed on DNA extracted from faecal samples of the study animals.

Results

The gastrointestinal K. pneumoniae colonization was detected in the antibiotic pre-treated mice group followed by the introduction of K. pneumoniae in all study groups. The control groups of just K. pneumoniae inoculation for three continuous days resulted in (G1) 2,1 x 10⁸ CFU/50mg and (G4) 6.39 x 10⁸ CFU/50mg (p=0,008). To disrupt the host microbiota, the antibiotic pre-treatment in drinking water (streptomycin and penicillin) for three continuous days and low dose ampicillin afterward, were used in two study groups (G2) 6,67 x 10⁸ CFU/50 mg; (G3) 8,24 x 10⁸ CFU/50 mg (p=0,03). Because of sufficient colonization results using three days of antibiotic pre-treatment, one study group was tested with a singular dose of streptomycin and penicillin before bacterial inoculation ((G5) 6,24 x 10⁸ CFU/50 mg) and another one with additional ampicillin therapy ((G6) 9,01 x 10⁸CFU/50 mg) (p=0,31). Analysis of the gastrointestinal tract colonization with K. pneumoniae proved effective with or without antibiotic pre-treatment. The effectiveness and differences in microbiota using two bacterial species were also confirmed by 16S rRNA gene sequencing. All above-mentioned results are statistically significant considering p<0.05 with ±95% confidence intervals.

Conclusion

Our study demonstrates that colonization of mice intestinal tract by K. pneumoniae can be achieved with or without eradicating resident gut microbiota. Nevertheless, any of the six murine models can be used in further studies of GIT diseases.

References

1. Kaur, Christina Parvinder, et al. “Impact of Klebsiella Pneumoniaein Lower Gastrointestinal Tract Diseases.” Journal of Digestive Diseases, vol. 19, no. 5, 2018, pp.262–271., https://doi.org/10.1111/1751-2980.12595.
2. Zhou, Bolun, et al. “Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract.” Frontiers in Immunology, vol. 11, 2020, https://doi.org/10.3389/fimmu.2020.00575.

Introduction

Per-oral endoscopic myotomy (POEM) has revolutionised achalasia treatment, nevertheless there is still a lack of technical standardization. No clear definition of “long”, “standard” or “short” POEM exists to date. With the exception of type III achalasia, there is evidence that myotomy limited to the lower esophageal sphincter (<6 cm) may be highly effective, time-saving and associated with less post-postoperative gastroesophageal reflux, yet it is common practice to use long myotomy in these patients.

Aims & Methods

We conducted a systematic review with meta-analysis to define current myotomy length standards during POEM. A literature search was performed on MEDLINE-Pubmed, Embase, Scopus, and Cochrane Library (from inception to December 2022). We included prospective, retrospective clinical studies and randomized controlled trials reporting technical details of POEM, in which no definite or comparative myotomy length was intentionally adopted thus representing a “standard” myotomy for the operator. The primary outcome was the pooled mean total myotomy length. Secondary outcomes included clinical success and reflux symptoms. Main exclusion criteria were: patient age < 18 years; studies providing achalasia diagnosis without high-resolution manometry, studies including patients with non-achalasia esophageal motility disorders, studies comparing different myotomy lengths or adopting pre-specified myotomy lengths, studies including type III achalasia patients only. Sub-group analyses were performed to explore heterogeneity across studies and to assess the impact of different subtypes, geography and time trends on the primary outcome.

Results

From initial 7,172 records, after exclusion criteria were applied, a total of 25 articles were included. Of those, 6 provided results on the primary outcome in separate subgroups and were therefore included as separate studies. Overall, 31 studies with a total 3023 patients were evaluated. The pooled mean of total myotomy length was 10.39 cm (95% CI 10.06-10.71; I² 99.3%). The pooled mean of esophageal and gastric myotomy length, provided by 17 studies, was 7.11 cm (95% CI 6.51-7.71; I² 99.8%) and 2.81 cm (95% CI 2.41-3-22; I² 99.8%) respectively. At the subgroup analysis for achalasia subtypes, pooled mean length in non-spastic achalasia (type I and II) was 10.17 cm (95% CI 9.91-10.43; I² 94.2%), while in type III attested at 14.02 cm (95% CI 10.59-17.44; I² 98.9%). Pooled mean myotomy length for studies conducted between 2014-2018 was 10.56 cm (95% CI 9.51-11.61; I² 99.0%) while studies between 2019-2022 showed a mean length of 10.3 cm (95% CI 9.99-10.61; I² 99.6%). No geographical difference was observed: in eastern countries mean length was 10.2 cm (95% CI 9.12-10.92; I² 98.9%), while in western countries was 10.95 cm (95% CI 9.83-12.07; I² 99.5%). At a median follow-up of 29 months, the pooled clinical success rate was 91% (95% CI 88.9%-93.2%; I² 67.2%), while the pooled rate of post-POEM clinical reflux was 26% (95% CI 21.0%-31.3%; I² 89.5%).

Conclusion

Our meta-analysis found that the pooled mean myotomy length during a "standard” POEM is 10.4 cm, remaining over 10 cm in non-spastic (type I and II) achalasia. The high heterogeneity across studies confirms that POEM technique needs further standardization. We found no time trend towards adopting short POEM, despite recent evidence supporting efficacy and safety of this approach.

Introduction

Dysfunctional and leaky gut barrier are characteristics of cirrhosis and associated with disease progression and mortality. Utility of biomarkers, indicating the presence and extent of intestinal barrier dysfunction, remains a controversial issue in the prognosis and risk stratification of decompensated cirrhosis. Villin-1 (VIL1) is an actin-bundling protein, present in the intestinal, renal and biliary brush border. VIL1 is downregulated in response to chronic injury and diverse cellular stressors, including the microbiome, while during acute stress it is redistributed from the brush border to the basolateral membrane, which facilitates its release into the blood.

Aims & Methods

We investigated clinical significance of serum VIL1 levels in patients with cirrhosis and acute decompensation (AD).Patients (n = 86) and healthy controls (HC; n = 50) from the MICROB-PREDICT cohort were tested for serum VIL1 by ELISA. Four patient severity sub-groups were defined according to the PREDICT study (stable AD (SDC), unstable AD (UDC), pre-ACLF and ACLF [acute-on-chronic liver failure]). VIL1 immunohistochemistry (IHC) evaluation of duodenum biopsy was performed in a sub-cohort of the patients (n = 13) and controls (n = 11).

Results

Serum VIL1 levels were decreased in SDC patients (median [IQR]: 6.5 [4.9-10.4] vs 12 [8.4-14.9] ng/mL, p < 0.001) compared to controls and increased in more severe disease. This difference was confirmed in duodenum tissue by IHC. Significantly higher serum VIL1 levels were detected in pre-ACLF patients compared to those who did not develop ACLF (10.7 [7.8-22.9] vs 6.9 [5.0-10.5] ng/mL, p = 0.004), while in ACLF survivors decreased VIL1 levels were observed on day-7 compared to day-0 (9.8 [7.3-14.6] vs 12.7 [9.7-18.1] ng/mL, p = 0.010). High serum VIL1 levels (≥16.17 ng/mL) predicted 90-day mortality (AUROC:0.73, 95%CI: 0.563-0.888, p = 0.013) and in combination with high (≥ 50) CLIF-C AD score the prediction accuracy was excellent (both is high: 75%; all other together: 8% mortality, LogRank p < 0.001). High serum VIL1 level was able to predict mortality both in the presence (20% vs 62% LogRank p = 0.030) and absence (14% vs 40% LogRank p = 0.008) of renal failure.

Conclusion

Besides the six organ failures included in CLIF-SOFA, patients with cirrhosis and AD may also develop intestinal failure, as an additional organ failure. Serum VIL1 level could reliably indicate this organ failure and made the mortality risk stratification performed by CLIF-C OF score more accurate.

Disclosure

The MICROB-PREDICT project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 825694