Detection of Clarithromycin resistance in Helicobacter pylori using MmaxSure™ H. pylori & ClaR Assay.

Introduction Clarithromycin resistance is a crucial factor in the eradication of Helicobacter pylori. This study aimed to evaluate the performance of MmaxSure™ H. pylori & ClaR Assay (MmaxSure™) in the diagnosis and detection of clarithromycin resistance in H. pylori. Methods Subjects who underwent esophagogastroduodenoscopy between April 2020 and October 2022 were enrolled. The diagnostic performance of MmaxSure™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with rapid urease test and culture. Secondary gene sequencing analysis was performed in discordant cases of PCR tests. Results A total of 156 gastric biopsy samples were analyzed. In H. pylori detection, MmaxSure™ showed a 95.9% sensitivity (95%CI 90.6-98.6), a 42.7% specificity (95%CI 26.3-60.7), and a Kappa value of 0.457. For the detection of A2143G mutation samples, MmaxSure™ showed a 91.2% sensitivity (95%CI: 76.3-98.1), a 93.4% specificity (95%CI: 87.5-97.1), and a Kappa value of 0.804. There was a total of 10 discordant cases compared to gene sequencing in A2143G mutation detection for MmaxSure™. Conclusion In this study, MmaxSure™ showed comparable diagnostic performance to the DPO-PCR in the detection of the H. pylori and A2143G mutation. Further research is needed to confirm the clinical effectiveness of the MmaxSure™ assay in H. pylori eradication.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

Factors influencing occurrence of metachronous gastric cancer after endoscopic resection: a systematic review and meta-analysis.

BACKGROUND/AIMS: Metachronous gastric cancer (MGC) can occur after endoscopic resection for gastric cancer. Further studies on factors other than Helicobacter pylori infection are needed. This systematic review and meta-analysis aimed to evaluate risk factors for metachronous recurrence of endoscopically resected gastric cancer. METHODS: We searched medical literature published by February 2023 and identified patients with MGC after endoscopic resection for gastric cancer. The occurrence of MGC and the presence of intestinal metaplasia (IM), severe atrophic gastritis (AG), and H. pylori infection were quantitatively analyzed. RESULTS: We identified 2,755 patients from nine cohort studies who underwent endoscopic resection for gastric cancer by 2018. Those with severe AG or presence of IM had a significantly higher incidence of MGC than those without (RR 2.00, 95% CI 1.35-2.98, I2 = 52% for severe atrophy on antrum; RR 7.08, 95% CI 3.63-13.80, I2 = 0% for antral IM). Absolute risk difference of MGC occurrence was 7.1% in those with severe AG and 9.2% in those with IM. The difference in incidence rate per 1,000 person-years was 17.5 person-years for those with severe AG and 24.7 person-years for those with IM. However, H. pylori eradication did not significantly affect the occurrence of MGC (RR 1.18, 95% CI 0.88-1.59, I2 = 10%). CONCLUSION: Gastric cancer patients with severe AG or presence of IM had a 2.0-fold or 7.0-fold higher risk of MGC occurrence after endoscopic resection than those without, respectively. They need more stringent follow-up to monitor MGC occurrences (CRD42023410940).

Dense D2C-Net: dense connection network for display-to-camera communications.

In this paper, we introduce a novel Dense D2C-Net, an unobtrusive display-to-camera (D2C) communication scheme that embeds and extracts additional data via visual content through a deep convolutional neural network (DCNN). The encoding process of Dense D2C-Net establishes connections among all layers of the cover image, and fosters feature reuse to maintain the visual quality of the image. The Y channel is employed to embed binary data owing to its resilience against distortion from image compression and its lower sensitivity to color transformations. The encoder structure integrates hybrid layers that combine feature maps from the cover image and input binary data to efficiently hide the embedded data, while the addition of multiple noise layers effectively mitigates distortions caused by the optical wireless channel on the transmitted data. At the decoder, a series of 2D convolutional layers is used for extracting output binary data from the captured image. We conducted experiments in a real-world setting using a smartphone camera and a digital display, demonstrating superior performance from the proposed scheme compared to conventional DCNN-based D2C schemes across varying parameters such as transmission distance, capture angle, display brightness, and camera resolution.

The optimal interval of surveillance gastroscopy after endoscopic resection for gastric neoplasia: a multicenter cohort study.

BACKGROUND/AIMS: Due to the possible metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia. METHODS: Medical records were reviewed retrospectively in patients who underwent endoscopic resection for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into two groups; annual surveillance vs. biannual surveillance. The incidence of metachronous gastric neoplasia was identified, and the risk factors for metachronous gastric neoplasia were investigated. RESULTS: Among the 1,533 patients who underwent endoscopic resection for gastric neoplasia, 677 patients were enrolled in this study (annual surveillance 302, biannual surveillance 375). Metachronous gastric neoplasia was observed in 61 patients (annual surveillance 26/302, biannual surveillance 32/375, P = 0.989), and metachronous gastric adenocarcinoma was observed in 26 patients (annual surveillance 13/302, biannual surveillance 13/375, P = 0.582). All the lesions were removed by endoscopic resection successfully. In a multivariate analysis, severe atrophic gastritis on gastroscopy was an independent risk factor for metachronous gastric adenocarcinoma (odds ratio 3.8, 95% confidence interval 1.4‒10.1; P = 0.008). CONCLUSIONS: Meticulous observation to detect the metachronous gastric neoplasia is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after endoscopic resection for gastric neoplasia. Annual surveillance gastroscopy might be enough after endoscopic resection for gastric neoplasia.

The Impact of Sedation on Cardio-Cerebrovascular Adverse Events after Surveillance Esophagogastroduodenoscopy in Patients with Gastric Cancer: A Nationwide Population-Based Cohort Study.

Background/Aims: The impact of sedation on cardio-cerebrovascular (CCV) adverse events after esophagogastroduodenoscopy (EGD) in patients with gastric cancer (GC) is unclear. We investigated the incidence rate and impact of sedation on CCV adverse events after surveillance EGD in patients with GC. Methods: We performed a nationwide population-based cohort study using the Health Insurance Review and Assessment Service databases from January 1, 2018, to December 31, 2020. Using a propensity score-matched analysis, patients with GC were divided into two groups: sedative agent users and nonusers for surveillance EGD. We compared the occurrence of CCV adverse events within 14 days between the two groups. Results: Of the 103,463 patients with GC, newly diagnosed CCV adverse events occurred in 2.57% of patients within 14 days after surveillance EGD. Sedative agents were used in 41.3% of the patients during EGD. The incidence rates of CCV adverse events with and without sedation were 173.6/10,000 and 315.4/10,000, respectively. Between sedative agent users and nonusers based on propensity score matching (28,008 pairs), there were no significant differences in the occurrence of 14-day CCV, cardiac, cerebral, and other vascular adverse events (2.28% vs 2.22%, p=0.69; 1.44% vs 1.31%, p=0.23; 0.74% vs 0.84%, p=0.20; 0.10% vs 0.07%, p=0.25, respectively). Conclusions: Sedation during surveillance EGD was not associated with CCV adverse events in patients with GC. Therefore, the use of sedative agents may be considered in patients with GC during surveillance EGD without excessive concerns about CCV adverse events.

Photonic structures in radiative cooling.

Radiative cooling is a passive cooling technology without any energy consumption, compared to conventional cooling technologies that require power sources and dump waste heat into the surroundings. For decades, many radiative cooling studies have been introduced but its applications are mostly restricted to nighttime use only. Recently, the emergence of photonic technologies to achieves daytime radiative cooling overcome the performance limitations. For example, broadband and selective emissions in mid-IR and high reflectance in the solar spectral range have already been demonstrated. This review article discusses the fundamentals of thermodynamic heat transfer that motivates radiative cooling. Several photonic structures such as multilayer, periodical, random; derived from nature, and associated design procedures were thoroughly discussed. Photonic integration with new functionality significantly enhances the efficiency of radiative cooling technologies such as colored, transparent, and switchable radiative cooling applications has been developed. The commercial applications such as reducing cooling loads in vehicles, increasing the power generation of solar cells, generating electricity, saving water, and personal thermal regulation are also summarized. Lastly, perspectives on radiative cooling and emerging issues with potential solution strategies are discussed.

Quantitative multiplex real-time polymerase chain reaction assay for the detection of Helicobacter pylori and clarithromycin resistance.

BACKGROUND: Identifying clarithromycin resistance is essential for eradicating Helicobacter pylori (HP). Therefore, we evaluated the performance of Allplex™ H.pylori & ClariR Assay (Allplex™) for diagnosing and detecting clarithromycin resistance in HP. METHODS: Subjects who underwent esophagogastroduodenoscopy between April 2020 and August 2021 at Incheon St. Mary's hospital were enrolled in this study. The diagnostic performances of Allplex™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with sequencing as the gold standard. RESULTS: A total of 142 gastric biopsy samples were analyzed. Gene sequencing revealed 124 HP infections, 42 A2143G mutations, 2 A2142G mutations, one dual mutation, and no A2142C mutation. DPO-PCR showed 96.0% sensitivity and 100.0% specificity for HP detection; the corresponding rates for Allplex™ were 99.2% and 100.0%. DPO-PCR showed 88.3% sensitivity and 82.0% specificity for A2143G mutation, and Allplex™ showed 97.6% and 96.0%. The Cohen's Kappa coefficient for overall test results was 0.56 for DPO-PCR and 0.95 for Allplex™. CONCLUSION: Allplex™ showed comparable diagnostic performance with direct gene sequencing and non-inferior diagnostic performance to DPO-PCR. Further research is required to confirm whether Allplex™ is an effective diagnostic tool for the eradication of HP.

Enhanced nuclear translation is associated with proliferation and progression across multiple cancers.

Recent technological advances have re-invigorated the interest in nuclear translation (NT), but the underlying mechanisms and functional implications of NT remain unknown. Here we show that NT is enhanced in malignant cancer cells and is associated with rapid cell growth. Nuclear ribopuromycylation analyses in a panel of diverse cell lines revealed that NT is scarce in normal immortalized cells, but is ubiquitous and robust in malignant cancer cells. Moreover, NT occurs in the nucleolus and requires normal nucleolar function. Intriguingly, NT is reduced by cellular stresses and anti-tumor agents and positively correlates with cancer cell proliferation and growth. By using a modified puromycin-associated nascent chain proteomics, we further identified numerous oncoproteins that are preferentially translated in the nucleus, such as transforming growth factor-beta 2 (TGFB2) and nucleophosmin 1 (NMP1). Specific overexpression of TGFB2 and NMP1 messenger RNAs in the nucleus can increase their protein levels and promote tumorigenesis. These findings establish a previously unknown link between NT and malignancy and suggest that cancer cells might have adapted a mechanism of NT to support their need for rapid growth, which highlight the potential of NT in tumorigenesis and might also open up new possibilities for therapeutic targeting of cancer-specific cellular functions.

Cold snare polypectomy versus cold endoscopic mucosal resection for small colorectal polyps: a multicenter randomized controlled trial.

BACKGROUND: Cold snare polypectomy (CSP) is recommended for the resection of small colorectal polyps. However, few studies have investigated the efficacy of cold endoscopic mucosal resection (cold EMR) for small polyps. Thus, the aim of this study was to investigate the efficacy and safety of cold EMR compared with CSP for small colorectal polyps. METHODS: This was a multicenter, randomized trial conducted in three tertiary centers from January 2018 to February 2021. Patients with polyps sized 6-10 mm were randomized to CSP or cold EMR group. After polypectomy, two additional biopsies were performed to assess the completeness of resection. The primary outcome was complete polyp resection rate. Secondary outcomes were total procedure time and rate of adverse events such as immediate bleeding, delayed bleeding, and perforation. RESULTS: A total of 444 polyps in 327 patients were assessed and randomly assigned to each group. Of those, 425 polyps were finally analyzed based on pathology results. The complete resection rate was not significantly different between cold EMR and CSP groups (91.9% vs 89.8%, p = 0.24). However, the total procedure time was significantly increased in cold EMR (87.6 s vs. 45.8 s, p < 0.001). The rate of polypectomy adverse events was not significantly different between the two groups. No patient had massive bleeding or perforation. CONCLUSIONS: There was no difference in complete resection rate or adverse events between CSP and cold EMR. However, CSP reduced the total procedure time.

Efficacy of bougie dilation for normal diet in benign esophageal stricture.

OBJECTIVES: Bougination is one of the first-line treatments in benign esophageal stricture (BES). The aim of the study was to identify clinical and endoscopic factors affecting the achievement of a normal diet with only bougie dilation in patients with BES. PATIENTS AND METHODS: Patients treated with only bougination for BES at three hospitals were retrospectively investigated. Data including patient demographics, stricture and procedural characteristics were collected. Clinical success was defined as normal diet without additional procedures for two months after bougination. Clinical success rate and associated factors were assessed. RESULTS: A total of 121 patients with BES were included. The most common cause of BES was post-operative stricture (n = 55). Finally, 43 (36%) patients were able to eat a normal diet with only bougination. Of these patients, 42 (97.7%) achieved clinical success in the first three sessions or less. Among causes of stenosis, corrosive injury had the lowest success rate (9/40, 22.5%). Clinical success rate was significantly higher for those with the length of stricture of less than 2 cm (47.2%), those with pre-procedural dysphagia of semi-solid or soft diet (51.3%) and those with dilation of 13 mm or more (46.1%). However, the duration of symptom, the number of previous endoscopic treatments and the location of stenosis were not related to clinical success. CONCLUSIONS: Normal diet is possible in one-third of BES after bougination alone. Predictable factors for achieving a normal diet were less than four sessions of dilation, short length of stricture, pre-procedural dysphagia status and diameter of dilator.

Effective Eradication Regimen and Duration According to the Clarithromycin Susceptibility of Helicobacter pylori Determined Using Dual Priming Oligonucleotide-Based Multiplex Polymerase Chain Reaction.

Background/Aims: Dual priming oligonucleotide-based multiplex polymerase chain reaction (DPO-PCR) has recently been used for both the detection of Helicobacter pylori and the identification of H. pylori 23S ribosomal RNA point mutations that cause clarithromycin resistance. The aim of this study was to investigate the duration of effective standard triple therapy in a clarithromycin susceptible group and of bismuth-based quadruple therapy in a resistant group based on DPO-PCR. Methods: We retrospectively analyzed the electronic medical records of 184 patients who, between September 2019 and December 2020, received eradication therapy following detection of H. pylori, and the subsequent identification of the clarithromycin susceptibility of their H. pylori using DPO-PCR. Patients were treated with 7- or 14-day standard triple therapy in the clarithromycin susceptible group, whereas 7- or 14-day bismuth-based quadruple therapy in the clarithromycin resistance group. Results: In the clarithromycin susceptible group, per-protocol analyses showed eradication rates of 87.5% (42/48; 95% confidence interval [CI], 77.1% to 95.8%) for 7-day therapy and 87.2% (41/47; 95% CI, 78.7% to 95.7%) for 14-day therapy (p=0.969). The eradication rates in the clarithromycin resistance group were 91.4% (32/35; 95% CI, 80.0% to 100.0%) for 7-day therapy and 90.3% (28/31; 95% CI, 77.4% to 100.0%) for 14-day therapy (p=0.876). There was no significant difference in the eradication rates, patient compliance, or rate of adverse events between the 7- and 14-day therapies for both groups. Conclusions: Compared to the 14-day therapy, 7-day eradication therapy is sufficient after DPO-PCR-based clarithromycin susceptibility testing.

Endoscopist-Driven Sedation Practices in South Korea: Re-evaluation Considering the Nationwide Survey in 2019.

Background/Aims: This study aimed to determine changes in endoscopist-driven sedation practices 5 years after the first nationwide survey in 2014 by the Korean Society of Gastrointestinal Endoscopy (KSGE). Methods: A 59-item survey covering current practices was electronically mailed to all members of the KSGE in 2019. Results: In total, 955 (12.8%) out of 7,486 questionnaires were returned. A total of 738 (77.7%) out of 955 respondents attended dedicated sedation education programs. The American Society of Anesthesiologists class was recorded by 464 (51.2%) out of 907 respondents. The recording rate was higher in respondents who completed sedation education (p=0.014) and worked in general or tertiary hospitals (p<0.001). Compared to that reported in the previous survey, the reported use of propofol was higher in 2019. The respondents had higher satisfaction scores for propofol-based sedation compared with midazolam monotherapy (p<0.001). The rates of oxygen supplementation (p<0.001) and oxygen saturation level monitoring (p<0.001) during sedative endoscopy were higher in 2019 than in the previous survey. A total of 876 (98.4%) out of 890 respondents reported a separate recovery bay, and 615 (70.5%) out of 872 respondents reported that personnel were assigned solely to the recovery bay. Conclusions: Endoscopist-driven sedation and monitoring practices in 2019 were significantly different than those in 2014. The respondents favored propofol-based sedation and utilized oxygen supplementation and monitoring of O2 saturation more frequently in 2019 than in 2014.

New sedatives and analgesic drugs for gastrointestinal endoscopic procedures.

Procedural sedation has become increasingly common in endoscopy. Sedatives and analgesics induce anxiolysis and amnesia. In addition, an appropriate level of sedation is necessary for safe procedures including therapeutic endoscopy. Midazolam and propofol are the most commonly used drugs in sedative endoscopy. In recent years, the need to ascertain the safety and effectiveness of sedation has increased in practice. Therefore, new sedatives and analgesic drugs for optimal sedative endoscopy, have recently emerged. This article reviews the characteristics of sedatives and analgesics, and describes their clinical use in gastrointestinal endoscopy.

Triple Therapy-Based on Tegoprazan, a New Potassium-Competitive Acid Blocker, for First-Line Treatment of Helicobacter pylori Infection: A Randomized, Double-Blind, Phase III, Clinical Trial.

Background/Aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication. Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)- based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases. Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences. Conclusions: TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223).

Biomimetic reconstruction of butterfly wing scale nanostructures for radiative cooling and structural coloration.

A great number of butterfly species in the warmer climate have evolved to exhibit fascinating optical properties on their wing scales which can both regulate the wing temperature and exhibit structural coloring in order to increase their chances of survival. In particular, the Archaeoprepona demophon dorsal wing demonstrates notable radiative cooling performance and iridescent colors based on the nanostructure of the wing scale that can be characterized by the nanoporous matrix with the periodic nanograting structure on the top matrix surface. Inspired by the natural species, we demonstrate a multifunctional biomimetic film that reconstructs the nanostructure of the Archaeoprepona demophon wing scales to replicate the radiative cooling and structural coloring functionalities. We resorted to the SiO2 sacrificial template-based solution process to mimic the random porous structure and laser-interference lithography to reproduce the nanograting architecture of the butterfly wing scale. As a result, the biomimetic structure of the nanograted surface on top of the porous film demonstrated desirable heat transfer and optical properties for outstanding radiative cooling performance and iridescent structural coloring. In this regard, the film is capable of inducing the maximum temperature drop of 8.45 °C, and the color gamut of the biomimetic film can cover 91.8% of the standardized color profile (sRGB).

[Gastrointestinal Disease in the Population Aged 80 Years and above in Korea during Recent Decades: Multi-center Cross-sectional Study].

Background/Aims: Globally, the population aged 80 years or older is growing faster due to the rising life expectancy. Korea has already entered into an advanced aged society, and a post-aged society is expected in 2025. This study evaluated the patterns of gastrointestinal disease in the population aged 80 years or older during the recent decade in Korea. Method: This study retrospectively reviewed the medical records of patients admitted to the gastrointestinal department of Suwon St. Vincent's hospital, Incheon St. Mary's hospital, and Uijeongbu St. Mary's Hospital - general hospitals of Seoul-Gyeonggi province in Korea. It was a repeated cross-sectional study in 2009 and 2019. Results: The number of admitted patients aged 80 years or older increased from 549 (9.0%) in 2009 to 1,073 (14.4%) in 2019 (p<0.01). As for the in-hospital mortality, there was no significant difference (p=0.25). On the other hand, the combined morbidities increased, and the duration of admission also increased (7.2±7.8 days vs. 8.1±8.2 days, p=0.03). The number of upper gastrointestinal hemorrhage and patients who are bleeding associated with drugs users increased (p<0.01). The proportion of lower gastrointestinal disease decreased (p<0.01) because of the decrease in procedure-related admissions (p<0.01). The number of those with pancreaticobiliary tract disease increased markedly (p<0.01), and the rate of cases that could not perform the procedure decreased (p=0.04). Conclusion: The patterns of gastrointestinal disease in the population aged 80 years or older have changed in the recent decade in Korea. Hence, more preparation for this medical environment is needed.

2021 Korean Society of Gastrointestinal Endoscopy Clinical Practice Guidelines for Endoscopic Sedation.

Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Such cardiopulmonary complications are usually temporary, and most patients recover without sequelae. However, these events may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.

Inhibition of the CDK2 and Cyclin A complex leads to autophagic degradation of CDK2 in cancer cells.

Cyclin-dependent kinase 2 (CDK2) complex is significantly over-activated in many cancers. While it makes CDK2 an attractive target for cancer therapy, most inhibitors against CDK2 are ATP competitors that are either nonspecific or highly toxic, and typically fail clinical trials. One alternative approach is to develop non-ATP competitive inhibitors; they disrupt interactions between CDK2 and either its partners or substrates, resulting in specific inhibition of CDK2 activities. In this report, we identify two potential druggable pockets located in the protein-protein interaction interface (PPI) between CDK2 and Cyclin A. To target the potential druggable pockets, we perform a LIVS in silico screening of a library containing 1925 FDA approved drugs. Using this approach, homoharringtonine (HHT) shows high affinity to the PPI and strongly disrupts the interaction between CDK2 and cyclins. Further, we demonstrate that HHT induces autophagic degradation of the CDK2 protein via tripartite motif 21 (Trim21) in cancer cells, which is confirmed in a leukemia mouse model and in human primary leukemia cells. These results thus identify an autophagic degradation mechanism of CDK2 protein and provide a potential avenue towards treating CDK2-dependent cancers.