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

Endoscopic retrograde cholangiopancreatography (ERCP) is associated with increased technical difficulty and can potentially contribute to prolonged procedural duration and excess exposure to ionizing radiation.

Aims & Methods

The purpose of the present study was to present descriptive information about fluoroscopy during ERCP from a large reference center and to investigate possible determinants of the radiation dose or fluoroscopy duration during ERCP. We examined a prospectively collected single-center database of adult patients undergoing ERCP between 09/2021 and 12/2023 in a tertiary greek public hospital. Detailed information concerning patient, endoscopist and procedural parameters including ERCP indication, degree of difficulty of ERCP (defined using the Schutz score), types of interventions and fluoroscopy were recorded retrospectively. Non parametric statistical methods were used (Mann–Whitney U-test and Kruskal–Wallis test) for the analysis.

Results

In total, data of 1051 ERCPs were collected at first, while 1028 ERCPs with complete information for fluoroscopy duration and radiation dose were included (mean patient age 72.20 ±14.02years, 49.1% men) in the analysis. The mean procedure time was 34.22 ± 14.9 minutes, carried out by three different endoscopists (n₁=321, 31.4%, n₂=338, 33%, n₃= 363, 35.6%). The majority of ERCPs were performed for treatment of choledocholithiasis (64.5%) and were classified as of intermediate difficulty according to Schutz scoring system [Schutz score 2 (n=523, 53.4%)]. Fluoroscopy was used in 1010 ERCPs (98.2%) and the median fluoroscopy duration was 2.4 minutes (IQR=2.6 min) and the median radiation dose was 1031.6 μGym²(IQR=1237.5 μGym²). ERCPs performed with an indication of biliary tract neoplasm (e.g. cholangiocarcinoma, liver metastases) were associated with prolonged fluoroscopy duration [5.05min (IQR=6.35 min), p=0.008] and increased radiation dose [2372.75 μGym² (IQR=2462.68 μGym²), p=0.003] in comparison to the rest of the indications including choledocholithiasis, pancreatic neoplasm, obstructive jaundice and other indications.ERCP difficulty was also related with increased radiation; ERCPs with Schutz score ≥3 were associated with increased radiation dose and fluoroscopy duration compared with ERCP procedures evaluated as Schutz sore ≤2 [3.3min (IQR=3.9 min) vs. 2.1min (IQR=2.15 min), p<0.001 and 1280.8 μGym² (IQR=1836.8 μGym²) vs. 937.6 μGym² (IQR=820.25 μGym²),p<0.001 respectively]. There was no significant difference of the fluoroscopy duration (p=0.495) and radiation dose (p=0.950) among the three performing endoscopists.

Conclusion

Increased difficulty of ERCP and the indication of biliary tract neoplasm were related to higher radiation dose and prolonged fluoroscopy duration. These factors could be utilized to predict ERCP procedures related to increased radiation exposure and may contribute to adoption of appropriate radiation reduction methods.

Clinical Case Summary

The ubiquitous availability of digital media does not only have advantages. Inexperienced mushroom pickers increasingly frequently use APPs for mushroom identification and consume forest mushrooms with false security. Currently, for example, life-threatening Amanita phalloides poisoning is becoming more frequent.
A 65-year-old patient presented with a latency period of approximately 40 hours after consumption of the mushrooms. Nausea and vomiting, as well as loss of strength and cramps in arms and legs, had already been present for about 24 hours. Laboratory tests revealed coagulation failure and markedly elevated transaminases (INR 2.1, GOT 2590 U/l, GPT 3119 U/l). The Meld Score was 33. Only when asked explicitly the patient reported eating wild mushrooms he had collected. The vomit and mushroom debris were recovered and immediately examined by a mushroom expert. Immediately after admission to our intensive care unit, liver protective therapy with Silibinin and N-Acetylcysteine was initiated.
Analysis by a fungal expert revealed evidence of Amanita phalloides. At an INR of 3.3 with massive diffuse skin hemorrhages and rising transaminases (GOT 4825U/l, GPT 4104U/l), repeated therapeutic plasma exchange (exchange of 1.3 times the plasma volume) was performed to control the complications of liver failure. In the course, transaminases and coagulation parameters stabilized, and liver transplantation was not necessary. The patient is now in excellent general health.
Our patient case shows that early diagnosis, as well as therapy, are crucial to reducing the lethality of tuberous leaf fungus poisoning. Patients are often unaware of the danger, so if they have symptoms, they should be asked explicitly about consuming collected mushrooms. As a bridging therapy for the stabilization and regeneration of liver function, therapeutic plasma exchange is an excellent option.

Disclosure

No conflicts of interests

Introduction

Tradipitant is a novel NK-1 receptor antagonist studied in diabetic and idiopathic gastroparesis for short-term relief of nausea. This report presents the pooled analysis from 2 multicenter, randomized, double-blind, placebo-controlled studies (VP-VLY-686-3301 and VP-VLY-686-2301) assessing the efficacy of tradipitant in relieving symptoms of gastroparesis.

Aims & Methods

N=342 idiopathic and diabetic gastroparesis patients with delayed gastric emptying, moderate to severe nausea were included in the pooled ITT (Intent-to-Treat) population. Subjects were randomized to 85mg tradipitant twice a day (n=175) or placebo (n=167) and endpoints were assessed at Week 4. Nausea was assessed with the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptom improvement was evaluated with the Patient Global Impression of Change (PGI-C) and Overall Patient Benefit (OPB) scales. Sensitivity analyses were performed to control for confounders.

Results

In a pooled analysis of double-blind subjects in the ITT population of Study 1 and Study 2, tradipitant demonstrated a clinically meaningful and statistically significant improvement in average nausea at week 4 (-1.15 for tradipitant v. -0.85 for placebo, p=0.0138). Significant improvement was seen in the number of nausea free days (20.96% improvement for tradipitant v. 12.52% for placebo, p=0.0085). Tradipitant also showed improvement in other gastroparesis symptoms as measured by the GCSI total score (-0.99 for tradipitant v. -0.76 for placebo, p=0.0265). Responder rates for PGI-C were 79.3% on tradipitant versus 69% on placebo at week 4 (p value = 0.036). For the Overall Patient Benefit, more patients improved on tradipitant versus placebo with 85.3% v. 71.2% at week 4 (p= 0.002). Sensitivity analysis adjusting for drug compliance confirmed the PK population (tradipitant blood levels ≥ 140ng/mL) in the pooled data set (n=284). In the pooled PK Population, tradipitant significantly improved average nausea at week 4 with -1.38 for tradipitant v. -0.85 for placebo (p=0.0001).

Conclusion

Pooling the data provided an opportunity to analyze a much larger data set, increase statistical power, and confirm results and subpopulations from the two separate studies. In the pooled analysis, we observed a clinically meaningful and significant effect on change of nausea severity at week 4. Improvements were also seen across core gastroparesis symptoms and overall measures of gastroparesis.

Disclosure

Study was sponsored by Vanda Pharmaceuticals, Inc. Authors are employees of Vanda Pharmaceuticals, Inc.

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.