Underwater cap-suction pseudopolyp formation for endoscopic mucosal resection: a simple technique for treating flat, appendiceal orifice or ileocecal valve colorectal lesions.

BACKGROUND: We aimed to evaluate the safety and technical success of an easy-to-use technique that applies underwater cap suction pseudopolyp formation to facilitate the resection of flat lesions or those at the appendiceal orifice or ileocecal valve. METHODS: We retrospectively analyzed a register of consecutive cap suction underwater endoscopic mucosal resection (CAP-UEMR) procedures performed at two centers between September 2020 and December 2021. Procedures were performed using a cone-shaped cap, extending 7 mm from the endoscope tip, to suction the lesion while submerged underwater, followed by underwater snare resection. Our primary end point was technical success, defined as macroscopic complete resection. RESULTS: We treated 83 lesions (median size 20 mm; interquartile range [IQR] 15-30 mm) with CAP-UEMR: 64 depressed or flat lesions (18 previously manipulated, 9 with difficult access), 11 from the appendix, and 8 from the ileocecal valve. Technical success was 100 %. There were seven intraprocedural bleedings and two delayed bleedings, all managed endoscopically. No perforations or other complications occurred. Among the 64 lesions with follow-up colonoscopy, only one recurrence was detected, which was treated endoscopically. CONCLUSIONS: CAP-UEMR was a safe and effective technique for removing nonpolypoid colorectal lesions, including those arising from the appendiceal orifice or ileocecal valve.

Induced Heteroresistance in Carbapenem-Resistant Acinetobacter baumannii (CRAB) via Exposure to Human Pleural Fluid (HPF) and Its Impact on Cefiderocol Susceptibility.

Infections caused by Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates, such as hospital-acquired pneumonia (HAP), bacteremia, and skin and soft tissue infections, among others, are particularly challenging to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S. Food and Drug Administration (FDA) in 2019 and prescribed for the treatment of CRAB infections. Despite the initial positive treatment outcomes with this antimicrobial, recent studies reported a higher-than-average all-cause mortality rate in patients treated with cefiderocol compared to the best available therapy. The cause(s) behind these outcomes remains unconfirmed. A plausible hypothesis is heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population that is seemingly isogenic. Recent results have demonstrated that the addition of human fluids to CRAB cultures leads to cefiderocol heteroresistance. Here, we describe the molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations to better understand the nature of the less-than-expected successful outcomes after cefiderocol treatment. Isolation of heteroresistant variants of the CRAB strain AMA40 was carried out in cultures supplemented with cefiderocol and human pleural fluid (HPF). Two AMA40 variants, AMA40 IHC1 and IHC2, were resistant to cefiderocol. To identify mutations and gene expression changes associated with cefiderocol heteroresistance, we subjected these variants to whole genome sequencing and global transcriptional analysis. We then assessed the impact of these mutations on the pharmacodynamic activity of cefiderocol via susceptibility testing, EDTA and boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Heteroresistant variants AMA40 IHC1 and AMA40 IHC2 have 53 chromosomal mutations, of which 40 are common to both strains. None of the mutations occurred in genes associated with high affinity iron-uptake systems or ß-lactam resistance. However, transcriptional analyses demonstrated significant modifications in levels of expression of genes associated with iron-uptake systems or ß-lactam resistance. The blaNDM-1 and blaADC-2, as well as various iron-uptake system genes, were expressed at higher levels than the parental strain. On the other hand, the carO and ompA genes' expression was reduced. One of the mutations common to both heteroresistant strains was mapped within ppiA, a gene associated with iron homeostasis in other species. Static time-kill assays demonstrated that supplementing cation-adjusted Mueller-Hinton broth with human serum albumin (HAS), the main protein component of HPF, considerably reduced cefiderocol killing activity for all three strains tested. Notably, collateral resistance to amikacin was observed in both variants. We conclude that exposing CRAB to fluids with high HSA concentrations facilitates the rise of heteroresistance associated with point mutations and transcriptional upregulation of genes coding for ß-lactamases and biofilm formation. The findings from this study hold significant implications for understanding the emergence of CRAB resistance mechanisms against cefiderocol treatment. This understanding is vital for the development of treatment guidelines that can effectively address the challenges posed by CRAB infections.

Appropriateness of routine pre-endoscopic SARS-CoV-2 screening with RT-PCR in asymptomatic individuals and its impact on delayed diagnosis.

AIMS: Endoscopy units are considered to be at an increased risk of infection by SARS-CoV-2. Our aim is to assess the correlation between pre-endoscopic screening with reverse-transcription-polymerase-chain-reaction (RT-PCR) in asymptomatic individuals scheduled for elective endoscopy and the epidemiological data published by the local Health Administration. PATIENTS AND METHODS: Observational retrospective study collecting the results of our screening strategy spanning June/2020-June/2021, the effective potential growth (EPG), an index measuring the outbreak risk, and the 7 and 14-day cumulative incidence (CI). Indication, delay and the findings of the endoscopic examinations were registered for RT-PCR positive patients. RESULTS: A total of 5808 tests were performed, yielding 125 positive results (2.15%). All positive tests occurred in weeks of high/very high risk (EPG>100) with the highest monthly rate being 9.36%, recorded in January/2021. A significant correlation (rho=0.796; p<0.001) between weekly positive rates and EPG was observed, and a significantly lower weekly number of positive tests was recorded when EPG<100. Planning the screening strategy one week ahead according to EPG>100 would have avoided up to 826 tests with only one positive result to account for. One hundred and thirteen individuals tested positive and 89 endoscopies were delayed. The most common findings were colon polyps, colorectal cancer and gastric metaplasia. Oncological diagnosis was delayed 50±3 days. CONCLUSIONS: No positive RT-PCR test were registered out of high-risk periods. Epidemiological administrative data in the preceding two weeks showed a significant correlation with screening results and could be useful to plan pre-endoscopic screening and avoid unnecessary tests.

Comparative study of electrical and rheological properties of different solutions used in endoscopic mucosal resection.

BACKGROUND AND AIM: The study of electrical and rheological properties of solutions to carry out endoscopic resection procedures could determinate the best candidate. An ex vivo study with porcine stomachs was conducted to analyze electrical resistivity (R) and rheological properties (temperature, viscosity, height and lasting of the cushion) of different substances used in these techniques. METHODS: Tested solutions were: 0.9% saline (S), platelet-rich plasma (PRP), Gliceol (GC), hyaluronic acid 2% (HA), Pluronic-F127 20% (PL), saline with 10% glucose (GS), Gelaspan (GP), Covergel-BiBio (TB) and PRP with TB (PRP+TB). Measurements of electrical and rheological properties were done at 0, 15, 30, 45 and 60 min after submucosal injection. RESULTS: Solutions showed a wide variability of transepithelial R after submucosal injection. Substances able to maintain the highest R 60 min postinjection were TB (7 × 104 Ω), HA (7 × 104 Ω) and PL (7 × 104 Ω). Protective solutions against deep thermal injury (Tª lower than 60°C) were PL (47.6°C), TB (55°C) and HA (56.63°C). Shortest time to carry out resections were observed with GC (17.66″), PRP (20.3″) and GS (23.45″). Solutions with less cushion decrease (<25%) after 60 min were TB (11.74%), PL (18.63%) and PRP (22.12%). CONCLUSIONS: Covergel-BiBio, PL and HA were the best solutions with long-term protective effects (transepithelial R, lower thermal injury and less cushion decrease). Solutions with quicker resection time were GC, PRP and GS.

Endoscopic shielding technique with a newly developed hydrogel to prevent thermal injury in two experimental models.

BACKGROUND AND AIM: A newly developed hydrogel, applied through the endoscope as an endoscopic shielding technique (EndoSTech), is aimed to prevent deep thermal injury and to accelerate the healing process of colonic induced ulcers after therapeutic endoscopy. METHODS: Lesions were performed in rats (n = 24) and pigs (n = 8). Rats were randomized to receive EndoSTech (eight rats each) with: saline (control), hyaluronic acid and product. In pigs, three ulcer sites were produced in each pig: endoscopic mucosal resection (EMR)-ulcer with prior saline injection (A; EMR-saline), EMR-saline plus EndoSTech with product (B; EMR-saline-P), and EMR with prior injection of product plus EndoSTech-P (C; EMR-P-P). At the end of the 14-day study, the same lesions were performed again in healthy mucosa to assess acute injury. Animals were sacrificed after 7 (rats) and 14 (pigs) days. Ulcers were macroscopically and histopathologically evaluated. Thermal injury (necrosis) was assessed with a 1-4 scale. RESULTS: In rats, treatment with product improved mucosal healing comparing with saline and hyaluronic acid (70% vs 30.3% and 47.2%; P = 0.003), avoiding mortality (0% vs 50% and 25%; P = 0.038), and perforation (0% vs 100% and 33.3%; P = 0.02); respectively. In pigs, submucosal injection of product induced a marked trend towards a less deep thermal injury (C = 2.25-0.46 vs A and B = 2.75-0.46; P = 0.127). Mucosal healing rate was higher with product (B = 90.2-3.9%, C = 91.3-5.5% vs A = 73.1-12.6%; P = 0.002). CONCLUSIONS: This new hydrogel demonstrates strong healing properties in preclinical models. In addition, submucosal injection of this product is able to avoid high thermal load of the gastrointestinal wall.