Clinical Case Summary

Glucosamine is a natural amino-monosaccharide and a precursor of hyaluronic acid (HA), which is well known to play an important role in wound healing. So far, the most well documented use of oral glucosamine is in osteoarthritis (1-4). Very little is known about its use in wound closure (5). Vitamin C is an antioxidant crucial for collagen production.
We hypothesized that their combined use could accelerate the healing of difficult-to-close surgical/traumatic wounds and we report a case where this treatment was applied successfully on a patient with a non-healing anal wound.
The patients was a 37 year-old woman with no relevant medical history, who underwent surgery for a posterior fissure with hypertonia, which did not heal after a 2-month local treatment with HA, glyceryl trinitrate and mesalazine. The surgery included fissurectomy, anoplasty and the removal of a 8 mm fibroepithelial polyp. No lateral internal sphinterectomy was performed. No intraoperative complications occurred. After four months from the operation, the patient kept experiencing bleeding and soiling. Local treatment with HA did not improve the situation. Oral treatment with glucosamine phosphate 1000 mg tid and vitamin C 500 mg bid was then initiated.
After two weeks of treatment, bleeding and soiling disappeared and the wound had completely healed. Patient continued therapy for another month after the wound closure to consolidate the result.
Glucosamine is a natural, well-absorbed, inexpensive substance with basically no side effects at clinical doses. We suggest that oral glucosamine could accelerate surgical/traumatic anal wounds closure in cases of delayed/difficult healing, especially when combined with vitamin C.
Whether its use can prove beneficial on other conditions as well, such as gastrointestinal ulcers, needs to be investigated.

References

1) McCarty MF. Enhanced synovial production of hyaluronic acid may explain rapid clinical response to high-dose glucosamine in osteoarthritis. Med Hypotheses 1998; 50: 507–10.
2) Dodge GR, Jimenez SA. Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes. Osteoarthritis Cartilage 2003; 11: 424–32.
3) Bassleer C, Rovati L, Franchimont P. Stimulation of proteoglycan production by glucosamine sulfate in chondrocytes isolated from human osteoarthritic articular cartilage in vitro. Osteoarthritis Cartilage 1998; 6: 427–34.
4) McCarty M F. The neglect of glucosamine as a treatment for osteoarthritis – a personal perspective. Med Hypotheses 1994; 42: 323-327.
5) McCarty MF. Glucosamine for Wound Healing. Med Hypotheses (1996) 47, 273-275.

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.

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.

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).

Clinical Case Summary

Placement of self-expandable metal stents (SEMS) is a standard treatment in the palliation of unresectable malignant biliary obstruction, whereas multidisciplinary oncology treatment prolongs patient survival. Consequently, the likelihood of stent-related complications has increased. Distal migration is a rare cause of stent dysfunction and SEMSs are relatively hard to extract after insertion. We present the management of a patient with dislocated SEMS using argon plasma coagulation (APC).
An 88-year-old man with unresectable ampullary cancer and consequential biliary stricture underwent a transpapillary placement of a 6-cm-long, 10-mm diameter uncovered SEMS (uSEMS).
Twelve months later, he presented to our department with vomiting. Given the high index of suspicion for stent dysfunction, a duodenoscopy was performed. Direct endoscopic visualization showed a distal 3-cm-long migration of the uSEMS. The distal end of uSEMS was firmly impacted in the contralateral duodenal wall resulting in reactive tissue ingrowth narrowing both the stent and the duodenal lumen. Significant malignant duodenal obstruction was detected below the dislocated uSEMS.
Subsequently, it was attempted to trim the distal 2 cm of the stent using an axial APC probe (power setting 80W, gas flow 0,8 L/min). The trimmed stent was removed with biopsy forceps. The procedure lasted 20 min, without immediate complications and the patient was discharged within 2 days.
One month after the procedure, the patient was readmitted with recurrent vomiting. Endoscopy revealed duodenal stricture below the papilla of Vater, due to malignant disease progression. Therefore, an 8-cm-long, 20-mm diameter duodenal SEMS placement was performed under simultaneous endoscopic and fluoroscopic control and symptoms were soon relieved.
This case highlights endoscopic APC stent trimming as an efficient procedure, which allows easy, reproducible and well−tolerated management of migrated uSEMS-related complications.

References

Fig. 1. Dislocated uSEMS and reactive tumor ingrowth
Fig. 2. (a) Trimming of the distal end using APC (b) the remaining stent in situ

1. Yokode, M., Matsumori, T., Uza, N., Kuwada, T., Shiokawa, M., Maruno, T., & Seno, H. (2022). Usefulness of a circumferential argon plasma coagulation probe in trimming a dislocated distal biliary metal stent. Endoscopy, 54, E802–E803. https://doi.org/10.1055/a-1816-7903
2. Azevedo, R., Libânio, D., Bastos, P., Dinis Ribeiro, M., & Brandão, C. (2019). Going through the Mesh: Argon Plasma Trimming of a Metal Biliary Stent. GE Portuguese Journal of Gastroenterology, 26(4), 295–297. https://doi.org/10.1159/000493352
3. Ishii, K., Itoi, T., Sofuni, A., Itokawa, F., Tsuchiya, T., Kurihara, T., Tsuji, S., Ikeuchi, N., Umeda, J., Moriyasu, F., & Tsuchida, A. (2011). Endoscopic removal and trimming of distal self-expandable metallic biliary stents. World Journal of Gastroenterology, 17(21), 2652–2657. https://doi.org/10.3748/WJG.V17.I21.2652
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