Adoption of Optimal Small (6-9 mm) Colorectal Polyp Resection Technique Over Time.

BACKGROUND: Cold snare polypectomy (CSP) is the preferred resection technique for small (6-9 mm) polyps due to lower rate of incomplete resection compared to cold forceps polypectomy (CFP) and improved safety profile over hot snare polypectomy (HSP). AIMS: To describe resection techniques for small (6-9 mm) polyps and determine factors associated with sub-optimal technique. METHODS: This was retrospective cohort study of colonoscopies performed by gastroenterological and surgical endoscopists from 2012 to 2019 where at least one 6-9 mm polyp was removed. Patient, provider, and procedure characteristics were collected. Univariate and multivariate regression analyses were performed to determine factors associated with sub-optimal technique. RESULTS: In total, 773 colonoscopies where 1,360 6-9 mm polyps removed by 21 endoscopists were included. CSP was used for 1,122 (82.5%), CFP for 61 (4.5%), and HSP for 177 (13.0%). Surgeon specialty was associated with CFP use (aOR 7.81; 95% CI 3.02-20.16). Polyp location in left colon (aOR 1.65; 95% CI 1.17-2.33) and pedunculated morphology (aOR 12.76; 95% CI 7.24-22.50) were associated with HSP. There was a significant increase in overall CSP use from 30.4% in 2012 to 96.8% in 2019. CONCLUSIONS: 82.5% of all 6-9 mm polyps removed from 2012 to 2019 were removed using a cold snare with significant increase in CSP from 2012 to 2019. Differences in how optimal technique was adopted over time based on specialty highlight the need for standardized practice guidelines and quality monitoring.

Adding efficiency to proficiency: a study of trainee polypectomy efficiency metrics.

BACKGROUND: Although validated colonoscopy assessment tools exist, they do not measure efficiency. This study aimed to assess content validity of polypectomy efficiency (PE) and neoplastic polypectomy efficiency (NPE) as colonoscopy efficiency indices. METHODS: Data from a randomized controlled trial evaluating polypectomy among gastroenterology trainees were utilized. PE and NPE were defined as number of polyps (or neoplastic polyps) removed/withdrawal time × 100. Content validity was assessed by determining the association between efficiency indices and polypectomy times. RESULTS: 20 trainees performed 601 colonoscopies. There was a strong association between PE/NPE and actual polypectomy times: as polypectomy time increased by 1 minute, the PE decreased by 0.48 (P = 0.001) and NPE decreased by 0.24 (P = 0.03). CONCLUSIONS: The study proposed and provided content validity for PE and NPE as colonoscopy efficiency indices.

Biological activity of truncated C-terminus human heat shock protein 72.

Heat shock protein 72 (Hsp72), a canonical intracellular molecular chaperone, may also function as an extracellular danger signal for the innate immune system. To further delineate the biological role of Hsp72 in the innate immune system, we generated two truncated versions of the full length human Hsp72 (N-terminus Hsp72, amino acids 1-430; and C-terminus Hsp72 amino acids 420-641) and directly compared their ability to activate cells from the macrophage/monocyte lineage. In RAW 264.7 macrophages transfected with a NF-κB-dependent luciferase reporter plasmid, C-terminus Hsp72 was a more potent inducer of NF-κB activity than N-terminus Hsp72, and this effect did not seem to be secondary to endotoxin contamination. C-terminus Hsp72-mediated activation of the NF-κB pathway was corroborated by increased activation of IκB kinase, degradation of IκBα, and increased NF-κB-DNA binding. C-terminus Hsp72 was a more potent inducer of tumor necrosis factor-α (TNFα) expression in RAW 264.7 macrophages and in primary murine peritoneal macrophages from wild-type mice. C-terminus Hsp72 did not induce TNFα expression in primary murine peritoneal macrophages from Toll-like receptor (TLR4) mutant mice, indicating a role for TLR4. In human THP-1 mononuclear cells, C-terminus Hsp72 induced tolerance to subsequent LPS stimulation, whereas N-terminus Hsp72 did not induce tolerance. Finally, control experiments using equimolar amounts of N-terminus or C-terminus Hsp72 demonstrated a higher biological potency for C-terminus Hsp72. These data demonstrate that the ability of human Hsp72 to serve as an activator for cells of the macrophage/monocyte lineage primarily lies in the C-terminus region spanning amino acids 420-641.

Apicomplexan UCHL3 retains dual specificity for ubiquitin and Nedd8 throughout evolution.

Post-translational modification of proteins by ubiquitin or ubiquitin-like polypeptides such as Nedd8 controls cellular functions including protein degradation, the cell cycle and transcription. Here we have used an activity-based chemical probe that covalently labels ubiquitin hydrolases. We identify four such enzymes from Toxoplasma gondii by mass spectrometry. The homologue of mammalian UCHL3 was cloned from both T. gondii and Plasmodium falciparum and we show that both enzymes possess deubiquitinating as well as deNeddylating activity. A phylogenetic analysis of the UCHL3 amino acid sequences from several eukaryotes suggests that dual specificity for ubiquitin and Nedd8 was present in the ancestral eukaryotic UCHL3 and has been conserved throughout evolution. Finally, the structural characterization of UCHL3 from T. gondii shows a unique insertion at the surface of this enzyme, which may be involved in novel interactions with other proteins. The characterization of these apicomplexan UCHL3s adds to our understanding of the ubiquitin and Nedd8 pathways in these parasites.