High-level production of keratinocyte growth factor 2 in Escherichia coli.

Recombinant human keratinocyte growth factor 2 (KGF-2), also known as repifermin, is used in various therapeutic applications. However, KGF-2 production has not been optimized for facilitating large-scale production. Therefore, we attempted to attain high-level production of bioactive KGF-2. KGF-2 was fused with 6HFh8 (6HFh8-KGF-2) at the tobacco etch virus protease cleavage site. The 6HFh8-KGF-2 was expressed in Escherichia coli with high expression levels of approximately 33% and 20% of soluble protein in flask culture and 5 L fermentation, respectively. 6HFh8-KGF-2 was purified via nickel affinity chromatography. To maintain a stable form of KGF-2, the conditions of the cleavage reaction were optimized based on the isoelectric point. KGF-2 was purified via ion-exchange chromatography to high purity (>99%) with an optimal purification yield (91%). Circular dichroism spectroscopy demonstrated that purified KGF-2 had a secondary structure and thermal stability similar to that of commercial KGF-2. Bioactivity assays indicated that purified KGF-2 could induce MCF-7 cell proliferation in the same manner as commercial KGF-2. These results demonstrate that bioactive KGF-2 was overexpressed in E. coli and purified to high quality. Our findings indicated that bioactive KGF-2 can be produced in large quantities in E. coli.

Production of a 135-residue long N-truncated human keratinocyte growth factor 1 in Escherichia coli.

BACKGROUND: Palifermin (trade name Kepivance®) is an amino-terminally truncated recombinant human keratinocyte growth factor 1 (KGF-1) with 140 residues that has been produced using Escherichia coli to prevent and treat oral mucositis following radiation or chemotherapy. In this study, an amino-terminally shortened KGF-1 variant with 135 residues was produced and purified in E. coli, and its cell proliferation activity was evaluated. RESULTS: We expressed soluble KGF-1 fused to thioredoxin (TRX) in the cytoplasmic fraction of E. coli to improve its production yield. However, three N-truncated forms (KGF-1 with 140, 138, and 135 residues) were observed after the removal of the TRX protein from the fusion form by cleavage of the human enterokinase light chain C112S (hEKL C112S). The shortest KGF-1 variant, with 135 residues, was expressed by fusion with TRX via the hEKL cleavage site in E. coli and purified at high purity (> 99%). Circular dichroism spectroscopy shows that purified KGF-1135 had a structure similar to that of the KGF-1140 as a random coiled form, and MCF-7 cell proliferation assays demonstrate its biological activity. CONCLUSIONS: We identified variations in N-terminus-truncated KGF-1 and selected the most stable form. Furthermore, by a simple two-step purification, highly purified KGF-1135 was obtained that showed biological activity. These results demonstrate that KGF-1135 may be considered an alternative protein to KGF-1.

Inoculation of ACC deaminase-producing endophytic bacteria down-regulates ethylene-induced pathogenesis-related signaling in red pepper (Capsicum annuum L.) under salt stress.

Pathogenesis-related (PR) signaling plays multiple roles in plant development under abiotic and biotic stress conditions and is regulated by a plethora of plant physiological as well as external factors. Here, our study was conducted to evaluate the role of an ACC deaminase-producing endophytic bacteria in regulating ethylene-induced PR signaling in red pepper plants under salt stress. We also evaluated the efficiency of the bacteria in down-regulating the PR signaling for efficient colonization and persistence in the plant endosphere. We used a characteristic endophyte, Methylobacterium oryzae CBMB20 and its ACC deaminase knockdown mutant (acdS- ). The wild-type M. oryzae CBMB20 was able to decrease ethylene emission by 23% compared to the noninoculated and acdS- M. oryzae CBMB20 inoculated plants under salt stress. The increase in ethylene emission resulted in enhanced hydrogen peroxide concentration, phenylalanine ammonia-lyase activity, ß-1,3 glucanase activity, and expression profiles of WRKY, CaPR1, and CaPTI1 genes that are typical salt stress and PR signaling factors. Furthermore, the inoculation of both the bacterial strains had shown induction of PR signaling under normal conditions during the initial inoculation period. However, wild-type M. oryzae CBMB20 was able to down-regulate the ethylene-induced PR signaling under salt stress and enhance plant growth and stress tolerance. Collectively, ACC deaminase-producing endophytic bacteria down-regulate the salt stress-mediated PR signaling in plants by regulating the stress ethylene emission levels and this suggests a new paradigm in efficient colonization and persistence of ACC deaminase-producing endophytic bacteria for better plant growth and productivity.

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Cell-free protein synthesis system: A new frontier for sustainable biotechnology-based products.

Cell-free protein synthesis (CFPS) system is an innovative technology with a wide range of potential applications that could challenge current thinking and provide solutions to environmental and health issues. CFPS system has been demonstrated to be a successful way of producing biomolecules in a variety of applications, including the biomedical industry. Although there are still obstacles to overcome, its ease of use, versatility, and capacity for integration with other technologies open the door for it to continue serving as a vital instrument in synthetic biology research and industry. In this review, we mainly focus on the cell-free based platform for various product productions. Moreover, the challenges in the bio-therapeutic aspect using cell-free systems and their future prospective for the improvement and sustainability of the cell free systems.

Serrated Polyps and the Risk of Metachronous Colorectal Advanced Neoplasia: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Surveillance recommendations for serrated polyps (SPs) are based on insufficient evidence. We aimed to evaluate the risk of metachronous advanced colorectal neoplasia (ACRN) associated with SPs. METHODS: We searched all relevant studies published through August 2020 that examined the risk of SPs for developing metachronous lesions. We performed meta-analyses of the risk of metachronous ACRN or colorectal cancer (CRC) between patients with SPs (or sessile serrated lesions [SSLs]) alone and those with conventional adenomas alone, and between patients with synchronous SPs (or SSLs) and conventional adenomas and those with conventional adenomas alone. RESULTS: Eleven studies with 1,079,315 patients were included in the meta-analysis. No significant differences in the risks of metachronous ACRN and CRC were found between the SPs alone and conventional adenomas alone groups (odds ratio [OR] [95% confidence interval [CI]]: ACRN, 0.70 [0.27-1.82]; CRC, 0.74 [0.47-1.14]). The risks were similar between SSLs alone and conventional adenomas alone (OR [95% CI]: ACRN, 0.91 [0.23-3.63]; CRC, 1.11 [0.42-2.97]). Significant heterogeneity was identified in these comparisons. Synchronous SPs (or SSLs) and high-risk adenomas (HRAs) had a higher risk of metachronous ACRN than HRAs alone (OR [95% CI]: SPs+HRAs, 1.64 [1.21-2.24]; SSLs+HRAs, 3.10 [1.92-4.99]); however, there was no difference in the risk between synchronous SPs (or SSLs) and low-risk adenomas and low-risk adenomas alone. CONCLUSIONS: The results of this meta-analysis support the current guidelines, which recommend similar surveillance intervals for SSLs and conventional adenomas. Patients with synchronous SPs (or SSLs) and HRAs appear to be at an increased risk of metachronous ACRN, and further studies are needed to determine whether they require more intensive surveillance.

Label-free proteomics approach reveals candidate proteins in rice (Oryza sativa L.) important for ACC deaminase producing bacteria-mediated tolerance against salt stress.

The omics-based studies are important for identifying characteristic proteins in plants to elucidate the mechanism of ACC deaminase producing bacteria-mediated salt tolerance. This study evaluates the changes in the proteome of rice inoculated with ACC deaminase producing bacteria under salt-stress conditions. Salt stress resulted in a significant decrease in photosynthetic pigments, whereas inoculation of Methylobacterium oryzae CBMB20 had significantly increased pigment contents under normal and salt-stress conditions. A total of 76, 51 and 33 differentially abundant proteins (DAPs) were identified in non-inoculated salt-stressed plants, bacteria-inoculated plants under normal and salt stress conditions respectively. The abundances of proteins responsible for ethylene emission and programmed cell death were increased, and that of photosynthesis-related proteins were decreased in non-inoculated plants under salt stress. However, bacteria-inoculated plants had shown higher abundance of antioxidant proteins, RuBisCo and ribosomal proteins that are important for enhancing stress tolerance and improving plant physiological traits. Collectively, salt stress might affect plant physiological traits by impairing photosynthetic machinery and accelerating apoptosis leading to a decline in biomass. However, inoculation of plants with bacteria can assist in enhancing photosynthetic activity, antioxidant activities and ethylene regulation related proteins for attenuating salt-induced apoptosis and sustaining growth and development.

7-day versus 14-day tegoprazan-based triple therapy to treat Helicobacter pylori infection: Real-world evidence.

BACKGROUND AND AIM: Potassium-competitive acid blockers (P-CABs) can be used to eradicate Helicobacter pylori infection. We aimed to evaluate the impact of treatment duration (7 vs 14 days) on successful H. pylori eradication with P-CAB-based triple therapy in Korea, where clarithromycin resistance rate is high. METHODS: We retrospectively reviewed the data of patients who received first-line treatment for H. pylori infection with tegoprazan-based triple therapy (50 mg tegoprazan + 1000 mg amoxicillin + 500 mg clarithromycin twice daily for 1 or 2 weeks). The primary endpoint was the eradication rate in intention-to-treat (ITT) analysis. RESULTS: Of the 948 patients included in the study, 435 and 513 received 7-day and 14-day tegoprazan-based triple therapy, respectively. The eradication rate was higher in the 14-day therapy group than in the 7-day therapy group (ITT, 63.9%; 95% confidence interval [CI], 59.3-68.3%] vs 78.6% [95% CI, 74.9-81.9%], respectively, P < 0.001; per-protocol, 70.5% [95% CI, 65.8-74.8%] vs 85.1% [81.7-88.1%], respectively, P < 0.001). Overall adverse event rates did not differ between the two groups. Although six patients in the 14-day treatment group discontinued the prescribed medications due to adverse events, four of them (67%) discontinued the medication within 4 days. CONCLUSIONS: The 14-day tegoprazan-based triple therapy showed a superior eradication rate and acceptable adverse events compared with the 7-day tegoprazan-based triple therapy. A 14-day treatment regimen may be required when H. pylori infection is treated with tegoprazan-based triple therapy in regions with high clarithromycin resistance.

Risk of post-polypectomy bleeding after endoscopic mucosal resection in patients receiving antiplatelet medication: comparison between the continue and hold groups.

BACKGROUND: Current guidelines recommend continuing aspirin and discontinuing clopidogrel for colon polypectomy, but evidence for endoscopic mucosal resection (EMR) is insufficient. We aimed to assess post-polypectomy bleeding (PPB) in patients receiving antiplatelet agents and underwent EMR for various polyp sizes. METHODS: A single-center, prospective observational study was performed. Patients who underwent at least one EMR for polypectomy and those who received aspirin or clopidogrel were included. We compared PPB between the antiplatelet hold group (stopped antiplatelet therapy at least 5 days before the procedure) and continue group (antiplatelet therapy was maintained or stopped within 5 days before the procedure). RESULTS: Among patients who underwent EMR, 305 took aspirin (hold group 257, continue group 48) and 77 took clopidogrel (hold group 66, continue group 11). The mean number of polyps was four, and the mean size was 8.6 mm. There was no difference in the major PPB rate between the hold and continue groups among aspirin users (2.0% vs. 4.2%, P = 0.30), but it was significantly higher in the continue group than in the hold group among clopidogrel users (18.2% vs. 0%, P = 0.02). In patient- and polyp-based logistic regression analysis of clopidogrel users, the number of EMRs (OR 2.12, 95% CI 1.16-3.88), polyp size (OR 1.26, 95% CI 1.06-1.49), and continuing clopidogrel (OR 9.75, 95% CI 1.99-47.64) were independent risk factors for PPB. CONCLUSION: Continuous administration of antiplatelet agents was significantly associated with higher PPB in clopidogrel users, but not in aspirin users. Endoscopists should consider holding clopidogrel if the EMR includes polypectomy.

Enhanced tolerance of Cupriavidus necator NCIMB 11599 to lignocellulosic derived inhibitors by inserting NAD salvage pathway genes.

Polyhydroxybutyrate (PHB) is a bio-based, biodegradable and biocompatible plastic that has the potential to replace petroleum-based plastics. Lignocellulosic biomass is a promising feedstock for industrial fermentation to produce bioproducts such as polyhydroxybutyrate (PHB). However, the pretreatment processes of lignocellulosic biomass lead to the generation of toxic byproducts, such as furfural, 5-HMF, vanillin, and acetate, which affect microbial growth and productivity. In this study, to reduce furfural toxicity during PHB production from lignocellulosic hydrolysates, we genetically engineered Cupriavidus necator NCIMB 11599, by inserting the nicotine amide salvage pathway genes pncB and nadE to increase the NAD(P)H pool. We found that the expression of pncB was the most effective in improving tolerance to inhibitors, cell growth, PHB production and sugar consumption rate. In addition, the engineered strain harboring pncB showed higher PHB production using lignocellulosic hydrolysates than the wild-type strain. Therefore, the application of NAD salvage pathway genes improves the tolerance of Cupriavidus necator to lignocellulosic-derived inhibitors and should be used to optimize PHB production.

Protein Kinase B2 (PKB2/AKT2) Is Essential for Host Protection in CVB3-Induced Acute Viral Myocarditis.

Protein kinase B2 (AKT2) is involved in various cardiomyocyte signaling processes, including those important for survival and metabolism. Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. The role of AKT2 in CVB3 infection is not yet well understood. We used a cardiac-specific AKT2 knockout (KO) mouse to determine the role of AKT2 in CVB3-mediated myocarditis. CVB3 was injected intraperitoneally into wild-type (WT) and KO mice. The mice's survival rate was recorded: survival in KO mice was significantly decreased compared with WT mice (WT vs. KO: 73.3 vs. 27.1%). Myocardial damage and inflammation were significantly increased in the hearts of KO mice compared with those of WT mice. Moreover, from surface ECG, AKT2 KO mice showed a prolonged atria and ventricle conduction time (PR interval, WT vs. KO: 47.27 ± 1.17 vs. 64.79 ± 7.17 ms). AKT2 deletion induced severe myocarditis and cardiac dysfunction due to CVB3 infection. According to real-time PCR, the mRNA level of IL-1, IL-6, and TNF-α decreased significantly in KO mice compared with WT mice on Days 5 after infection. In addition, innate immune response antiviral effectors, Type I interferon (interferon-α and ß), and p62, were dramatically suppressed in the heart of KO mice. In particular, the adult cardiac myocytes isolated from the heart showed high induction of TLR4 protein in KO mice in comparison with WT. AKT2 deletion suppressed the activation of Type I interferon and p62 transcription in CVB3 infection. In cardiac myocytes, AKT2 is a key signaling molecule for the heart from damage through the activation of innate immunity during acute myocarditis.

Optimization of the surveillance strategy in patients with colorectal adenomas: A combination of clinical parameters and index colonoscopy findings.

BACKGROUND AND AIM: In addition to index colonoscopy findings, demographic parameters including age are associated with the risk of metachronous advanced colorectal neoplasia. Here, we aimed to develop a risk scoring model for predicting advanced colorectal neoplasia (ACRN) during surveillance using a combination of clinical factors and index colonoscopy findings. METHODS: Patients who underwent the removal of one or more adenomas and surveillance colonoscopy were included. A risk scoring model for ACRN was developed using the Cox proportional hazard model. Surveillance interval was determined as a time point exceeding 4% of the cumulative ACRN incidence in each risk group. RESULTS: Of 9591 participants, 4725 and 4866 were randomly allocated to the derivation and validation cohorts, respectively. Age, abdominal obesity, advanced adenoma, and ≥ 3 adenomas at index colonoscopy were identified as risk factors for metachronous ACRN. Based on the regression coefficients, point scores were assigned as follows: age, 1 point (per 1 year); abdominal obesity, 10 points; advanced adenoma, 10 points; and ≥ 3 adenomas, 15 points. Patients were classified into high-risk (≥ 80 points), moderate-risk (50-79 points), and low-risk (30-49 points) groups. In the validation cohort, the high-risk and moderate-risk groups showed a higher risk of ACRN than the low-risk group (hazard ratio [95% confidence interval]: 7.11 [4.10-12.32] and 1.58 [1.09-2.30], respectively). Two-, 4-, and 5-year surveillance intervals were recommended for the high-risk, moderate-risk, and low-risk groups, respectively. CONCLUSIONS: Our proposed model may facilitate effective risk stratification of ACRN during surveillance and the determination of appropriate surveillance intervals.

Structural basis of mRNA recognition and cleavage by toxin MazF and its regulation by antitoxin MazE in Bacillus subtilis.

MazF is an mRNA interferase, which, upon activation during stress conditions, cleaves mRNAs in a sequence-specific manner, resulting in cellular growth arrest. During normal growth conditions, the MazF toxin is inactivated through binding to its cognate antitoxin, MazE. How MazF specifically recognizes its mRNA target and carries out cleavage and how the formation of the MazE-MazF complex inactivates MazF remain unclear. We present crystal structures of MazF in complex with mRNA substrate and antitoxin MazE in Bacillus subtilis. The structure of MazF in complex with uncleavable UUdUACAUAA RNA substrate defines the molecular basis underlying the sequence-specific recognition of UACAU and the role of residues involved in the cleavage through site-specific mutational studies. The structure of the heterohexameric (MazF)2-(MazE)2-(MazF)2 complex in Bacillus subtilis, supplemented by mutational data, demonstrates that the positioning of the C-terminal helical segment of MazE within the RNA-binding channel of the MazF dimer prevents mRNA binding and cleavage by MazF.

Chromosomal features revealed by comparison of genetic maps of Glycine max and Glycine soja.

Recombination is a crucial component of evolution and breeding. New combinations of variation on chromosomes are shaped by recombination. Recombination is also involved in chromosomal rearrangements. However, recombination rates vary tremendously among chromosome segments. Genome-wide genetic maps are one of the best tools to study variation of recombination. Here, we describe high density genetic maps of Glycine max and Glycine soja constructed from four segregating populations. The maps were used to identify chromosomal rearrangements and find the highly predictable pattern of cross-overs on the broad scale in soybean. Markers on these genetic maps were used to evaluate assembly quality of the current soybean reference genome sequence. We find a strong inversion candidate larger than 3 Mb based on patterns of cross-overs. We also identify quantitative trait loci (QTL) that control number of cross-overs. This study provides fundamental insights relevant to practical strategy for breeding programs and for pan-genome researches.

Comparison of Bone Regeneration in Different Forms of Bovine Bone Scaffolds with Recombinant Human Bone Morphogenetic Protein-2.

The aim of this study was to compare the bone regeneration ability of particle and block bones, acting as bone scaffolds, with recombinant human bone morphogenetic protein (rhBMP)-2 and evaluate them as rhBMP-2 carriers. Demineralized bovine bone particles, blocks, and rhBMP-2 were grafted into the subperiosteal space of a rat calvarial bone, and the rats were randomly divided into four groups: particle, block, P (particle)+BMP, and B (block)+BMP groups. The bone volume of the B+BMP group was significantly higher than that of the other groups (p < 0.00), with no significant difference in bone mineral density. The average adipose tissue volume of the B+BMP group was higher than that of the P+BMP group, although the difference was not significant. Adipose tissue formation was observed in the rhBMP-2 application group. Histologically, the particle and B+BMP groups showed higher formation of a new bone. However, adipose tissue and void spaces were also formed, especially in the B+BMP group. Hence, despite the formation of a large central void space, rhBMP-2 could be effectively used with block bone scaffolds and showed excellent new bone formation. Further studies are required to evaluate the changes in adipose tissue.

Relationship between Hallux Valgus and Pes Planus in Adult Patients.

This study aimed to determine whether the degree of pes planus was associated with hallux valgus severity and hallux valgus surgery outcomes. A total of 122 feet were retrospectively analyzed after hallux valgus surgery. The hallux valgus angle, inter-metatarsal angle, lateral talo-first metatarsal angle, calcaneal pitch, and talonavicular coverage angle were measured. The Foot and Ankle Outcome Score and Foot Function Index were evaluated. A significant correlation between radiographic parameters of pes planus and hallux valgus severity, radiographic outcomes, Foot and Ankle Outcome Score, and Foot Function Index were not noted. The hallux valgus angle and inter-metatarsal angle changed significantly after the surgery (p < .001 and p < .001, respectively); however, a significant difference was not noted between the pes planus and non-pes planus groups (p = .279 and p = .632, respectively). A significant interaction between the time points and groups was not observed with respect to the hallux valgus angle (p = .311) and inter-metatarsal angle (p = .417). Multivariable logistic regression revealed that none of the radiographic parameters for pes planus affected hallux valgus recurrence. Pes planus in adult patients is not significantly associated with hallux valgus severity and recurrence, radiographic outcomes, or clinical scores.

Effect of Cotinine-Verified Change in Smoking Status on Risk of Metachronous Colorectal Neoplasia After Polypectomy.

BACKGROUND & AIMS: Previous assessments of colorectal neoplasia (CRN) recurrence after polypectomy used self-report to determine smoking status. We evaluated the association between change in smoking status and metachronous CRN risk after polypectomy using cotinine level in urine to determine tobacco exposure. METHODS: We performed a retrospective study of participants in the Kangbuk Samsung Health Study in Korea who underwent a screening colonoscopy examination and measurement of cotinine in urine samples. Our analysis included 4762 patients who had 1 or more adenomas detected in an index colonoscopy performed between January 2010 and December 2014, and underwent a surveillance colonoscopy, 6 or more months later, until December 2017. RESULTS: Patients were classified into 4 groups based on the change in cotinine-verified smoking status from index to follow-up colonoscopy (mean interval, 3.2 ± 1.3 y), as follows: remained nonsmokers (n = 2962; group 1), smokers changed to nonsmokers (n = 600; group 2), nonsmokers changed to smokers (n = 138; group 3), and remained smokers (n = 1062; group 4). After adjustment for confounding factors, group 4 had a significantly higher risk of metachronous CRN than group 1 (hazard ratio [HR], 1.54; 95% CI, 1.36-1.73) and group 2 (HR, 1.63; 95% CI, 1.39-1.99). Group 4 also had a higher risk of metachronous advanced CRN than group 1 (HR, 2.84; 95% CI, 1.79-4.53) and group 2 (HR, 2.10; 95% CI, 1.13-3.89). Group 3 had a higher risk of metachronous CRN than group 1 (HR, 1.50; 95% CI, 1.14-1.97) and group 2 (HR, 1.62; 95% CI, 1.20-2.20). CONCLUSIONS: In a retrospective study of individuals with at least 1 adenoma, we found that cotinine-verified changes in smoking status between index and follow-up colonoscopy are associated with a risk of metachronous CRN. Helping patients quit smoking is important for effective prevention of colorectal cancer.

Risk of developing metachronous advanced colorectal neoplasia after resection of low-risk diminutive versus small adenomas.

BACKGROUND AND AIMS: Current postpolypectomy guidelines classify 1 to 2 diminutive (1-5 mm) nonadvanced adenomas (NAAs) and 1 to 2 small (6-9 mm) NAAs as low-risk adenomas and recommend the same surveillance interval for both lesions. We compared the risk of metachronous advanced colorectal neoplasia (ACRN) for both groups. METHODS: We studied 8602 patients who underwent removal of ≥1 NAA and follow-up colonoscopic surveillance. Patients were categorized into 4 groups based on size and number of baseline NAAs: group 1, ≤2 diminutive NAAs (n = 6379); group 2, ≤2 small NAAs (n = 1672); group 3, ≥3 diminutive NAAs (n = 293); and group 4, ≥3 small NAAs (n = 258). Size was classified based on the largest NAA. RESULTS: The 5-year cumulative incidence rates of metachronous ACRN in groups 1, 2, 3, and 4 were 2.7%, 5.1%, 10.7%, and 15.1%, respectively. Groups 2, 3, and 4 had a higher risk of metachronous ACRN than group 1. Compared with group 1, the adjusted hazard ratios for metachronous ACRN were 2.06 (95% confidence interval [CI], 1.46-2.91) for group 2, 2.75 (95% CI, 1.53-4.96) for group 3, and 4.49 (95% CI, 2.62-7.70) for group 4. However, the risk of metachronous ACRN was not significantly different between groups 3 and 4 (adjusted hazard ratio, 1.62; 95% CI, .76-3.44). CONCLUSIONS: Among patients with ≤2 NAAs, patients with 1- to 5-mm NAAs had a lower risk of metachronous ACRN than those with 6- to 9-mm NAAs. The guidelines should consider extending surveillance intervals in patients with ≤2 diminutive NAAs.

Skeletal muscle mass and risk of advanced adenoma in surveillance colonoscopy.

BACKGROUND AND AIM: Sarcopenia has been suggested to be associated with chronic inflammation and insulin resistance. This study aimed to evaluate whether low muscle mass is associated with the incidence and recurrence of advanced colorectal adenoma. METHODS: We conducted a cohort study including 14 701 participants who underwent first-time screening colonoscopy between 2003 and 2012 and follow-up colonoscopy until 2017. Skeletal muscle mass was measured using a bioelectrical impedance analyzer and divided by body weight to calculate the skeletal muscle mass index (SMI). RESULTS: During a median 47 (interquartile range, 35-58) months of follow-up, overall and advanced adenoma developed in 2988 (20.3%) and 207 (1.41%) participants, respectively. In multivariate analysis using models adjusted for baseline adenoma risk, lifestyle factors, markers for insulin resistance and chronic inflammation, and metabolic syndrome, decreasing SMI quartiles were associated with increased risk of occurrence of advanced adenoma and overall adenoma. The adjusted hazard ratios (95% confidence intervals) comparing SMI quartiles 3, 2, and 1 to quartile 4 were 1.57 (1.03-2.41), 1.22 (0.78-1.92), and 1.77 (1.13-2.76), respectively, for advanced adenoma (P for trend = 0.049) and 1.05 (0.95-1.17), 1.09 (0.98-1.21), and 1.26 (1.13-1.41), respectively, for overall adenoma (P for trend < 0.001). CONCLUSIONS: In this large cohort with long-term colonoscopy follow-up, low relative muscle mass was associated with increased risk of occurrence of advanced adenoma and overall adenoma at follow-up colonoscopy, independent of metabolic and inflammatory markers. Timely and thorough surveillance colonoscopy may be emphasized in such populations.

Simple proxies for detection of clinically significant serrated polyps and data for their benchmarks.

BACKGROUND AND AIMS: Serrated polyp detection rate (SDR) is a potential quality indicator for preventing colorectal cancer associated with the serrated pathway. Using clinically significant SDR (CSSDR) has been suggested based on clinically significant serrated polyp's ability to be colorectal cancer precursors. Correlations between CSSDR and simpler SDRs, other than proximal SDR, have not yet been studied. We aimed to investigate which simpler SDR indicator is most relevant to CSSDR or adenoma detection rate (ADR) and provide benchmark data. METHODS: We analyzed 26 627 colonoscopies performed by 30 endoscopists. Clinically significant serrated polyps were defined as any sessile serrated adenoma/polyp or traditional serrated adenoma, hyperplastic polyps ≥ 5 mm in the proximal colon, or hyperplastic polyps ≥ 10 mm anywhere in the colon. Correlation of CSSDR and ADR with other simple SDRs, SDR-pathology (sessile serrated adenoma/polyp or traditional serrated adenoma), SDR-size (≥ 10 mm), and SDR-location (proximal location) was analyzed using Pearson's correlation test and Steiger's z-test. RESULTS: The CSSDR was 1.7% to 13.2% (mean = 6.1%). The correlation coefficient of CSSDR/SDR-size was 0.91 (P < 0.01), which was higher than that of CSSDR/SDR-location (0.64, P < 0.01) (0.91 vs 0.61, P < 0.01). The correlation coefficient of ADR/CSSDR and ADR/SDR-location was 0.41 (P < 0.01) and 0.81 (P < 0.01), respectively. For ADR ≥ 25%, endoscopists' median screening CSSDR was 5.4%, while SDR-location and SDR-size were 10.9% and 2.2%, respectively. CONCLUSION: Large SDR could be a simple proxy for CSSDR, in addition to proximal SDR. Large SDR and proximal SDR benchmarks of 2.2% and 10.9% may guide adequate serrated polyp detection with uniform definitions and simpler calculations.