Background: Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods: In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results: Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Background/Aims: Although endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) and fine needle biopsy (FNB) are widely used for tissue acquisition of pancreatic solid mass, the optimal strategy of this procedure has not been established yet. The aim of this nationwide study was to investigate the current practice patterns of EUS-FNA/FNB for pancreatic solid mass in Korea. Methods: The Policy-Quality Management of the Korean Pancreatobiliary Association (KPBA) developed a questionnaire containing 22 questions. An electronic survey consisting of the questionnaire was distributed by e-mail to members registered to the KPBA. Results: A total of 101 respondents completed the survey. Eighty respondents (79.2%) performed preoperative EUS-FNA/FNB for operable pancreatic solid mass. Acquire needles (60.4%) were used the most, followed by ProCore needles (47.5%). In terms of need size, most respondents (>80%) preferred 22-gauge needles regardless of the location of the mass. Negative suction with a 10-mL syringe (71.3%) as sampling technique was followed by stylet slow-pull (41.6%). More than three needle passes for EUS-FNA/FNB was performed by most respondents (>80%). The frequency of requiring repeated procedure was significantly higher in respondents with a low individual volume (<5 per month, p=0.001). Prophylactic antibiotics were routinely used in 39 respondents (38.6%); rapid on-site pathologic evaluation was used in 6.1%. Conclusions According to this survey, practices of EUS-FNA/FNB for pancreatic solid mass varied substantially, some of which differed considerably from the recommendations present in existing guidelines. These results suggest that the development of evidence-based quality guidelines fitting Korean clinical practice is needed to establish the optimal strategy for this procedure.

Purpose: This prospective, single-center, open-label, therapeutic confirmatory, randomized clinical trial aimed to assess the alleviation of anal pain by applying structured anal skin care including skin protectants in rectal cancer patients with low anterior resection syndrome (LARS) combined with anal pain. Methods: From December 2017 to May 2020, 42 patients with LARS (scores of ≥21) and anal pain (visual analogue scale [VAS] score of ≥3) were randomly assigned and observed for 4 weeks. The conventional treatment consisted of dietary management, sitz baths, prohibition of anal scrubbing, loperamide, and dioctahedral smectite. In the anal care group, cleanser, barrier cream, and barrier spray were applied to the anal skin after defecation following the conventional treatment. The primary outcome was analgesic effect on anal pain after 2 weeks of structured treatment (anal care group) or conventional (control group). The cutoff for analgesic effect was a decrease in the anal pain score (VAS score of ≥2 or ≥30% reduction). Results: As a primary outcome, the analgesic effect was significantly higher in the anal care group (P = 0.034). The incontinence-associated dermatitis skin condition score was significantly improved in the anal care group than control group after 4 weeks (P = 0.023). There were no significant differences in LARS scores and quality of life scores between 2 groups. Conclusion Structured anal skin care has a significant analgesic effect in reducing anal pain and improving anal skin conditions in patients with LARS after rectal cancer surgery.

Objective: It has been reported that emergency physicians experience high levels of depression and psychological burnout due to night shifts and tend to consider early retirement. This study intended to check working hours and intensity, individual health, satisfaction, and overall welfare, given the increase in the numbers of emergency physicians. Methods: The study used the results of the ‘2020 Korean Emergency Physician Survey (KEPS)’ conducted from January 15 to February 26, 2021, which targeted 2,138 emergency physicians registered with the Korean Society of Emergency Medicine. The survey was conducted online through the web and mobile application. Results: One thousand three hundred seven out of the 2,167 emergency physicians (60.3%) registered at the society responded. The average age of the respondents was 42.6 years, and there were 1,148 male emergency physicians and 158 female emergency physicians. The average professional experience was 8.2 years, with 325 professors, 122 commissioned doctors, 648 public servants of which 90 had military service, and 45 medical practitioners. Conclusion In conclusion, the number of working hours of emergency physicians showed a decreasing trend compared to 2010 and 2015. However, emergency physicians often expected early retirement. This suggests that, while the absolute working hours are decreasing, the actual working intensity has not decreased. For the proper development of the emergency medical system, it is necessary to establish a stable working environment for emergency physicians. A systematic study is needed on the working hours and work intensity of emergency physicians.

Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson’s disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

Background: Metabolic syndrome is a nationwide health problem, which is associated with the development of cardiovascular diseases, diabetes, and chronic renal failure. The prevalence of metabolic syndrome in Korea significantly increased from 1998 to 2007. After that, the prevalence was stable in female but still increasing in male. The objective of this study was to evaluate how the prevalence and risk factors for metabolic syndrome changed in Korean adults through the last decade. Methods: Data from the Korea National Health and Nutrition Examination Survey 2008 to 2017 was used. National Cholesterol Education Program Adult Treatment Panel III were used to define metabolic syndrome. We compared how each metabolic syndrome component and the risk factors changed through the years. Results: A total of 51,177 (30,092 female and 21,085 male) people were included in this study. The prevalence of metabolic syndrome in male increased from 24.5% in 2008 to 28.1% in 2017, whereas that in female was stable at 20.5% in 2008 from 18.7% in 2017. Waist circumference measurements and fasting glucose levels increased through the decade in male, whereas only fasting glucose levels increased in female. Conclusion Since the last decade, the prevalence of metabolic syndrome in Korean adults has increased in male but remained stable in female. Lifestyle intervention in male, namely ceasing smoking and drinking could prevent increasing metabolic syndrome prevalence in Korean adults.

Background: Several studies have shown that elevated serum uric acid levels are associated with cardiovascular disease. High sensitivity C-reactive protein (hs-CRP) has been shown to be a measure of the severity and prognosis of cardiovascular disease. The aim of this study was to investigate the association of hs-CRP with hyperuricemia. Methods: From March 2016 to November 2017, a total of 26,987 patients who received a health check-up at a Soonchunhyang University Cheonan Hospital, Korea, were enrolled. Foreigners, patients who had hs-CRP score greater than 10 or white blood cell score greater than 10,000, those who did not respond sincerely, those who had previously been diagnosed with gout and cerebrovascular disease, and females were excluded. Data were collected from 2,808 patients. Results: The subjects were divided into four sections by 25th percentile, 50th percentile, 75th percentile, and 100th percentile based on the distribution of hs-CRP. Serum hs-CRP levels were 1.85 (1.34–2.56), 2.59 (1.90–3.54), and 3.64 (2.70–4.93) respectively in the second, third, and fourth quartiles based on the first quartile. The odds ratios were 1.46 (1.05–2.03), 1.76 (1.27–2.45), and 2.27 (1.64–3.14) after adjusting the disturbance variables of age, body mass index, smoking status, and regular exercise. Conclusion In this study, we evaluated the relationship between serum hs-CRP and hyperuricemia, which are the risk factors for cardiovascular disease, and found statistically significant correlations. These results were still significant after adjusting for age, smoking, exercise, and body mass index.

Background/Aims: The quick Sepsis-related Organ Failure Assessment (qSOFA) is a newly developed risk stratification tool, which has been presented along with a new sepsis definition, to classify infected patients outside of the intensive care unit (ICU). We evaluated the clinical usefulness of qSOFA for predicting adverse outcomes in sepsis patients with liver cirrhosis. Methods: We performed a retrospective cohort study to assess the utility of qSOFA in sepsis patients with liver cirrhosis for whom medical emergency teams (METs) were activated in general wards at an academic tertiary care hospital between March 2008 and December 2015. qSOFA, Systemic inflammatory response syndrome (SIRS), modified early warning score (MEWS), and sequential (sepsis- related) organ failure assessment (SOFA) scores were calculated according to data at MET activation. Results: Of 188 patients, 69 (36.7%) had a qSOFA score of 0 or 1 point and 119 (63.3%) had ≥ 2 points. The areas under the receiver operating characteristic curve (AUROC) for ICU transfer on the SOFA (AUROC, 0.691; 95% confidence interval [CI], 0.615 to 0.767) or MEWS (AUROC, 0.663; 95% CI, 0.586 to 0.739) were significantly higher compared to those for qSOFA (AUROC, 0.589; 95% CI, 0.507 to 0.671) or SIRS (AUROC, 0.533; 95% CI, 0.451 to 0.616). Conclusions Our findings suggest that qSOFA score may have limited utility in predicting adverse outcomes in sepsis patients with liver cirrhosis at MET activation. Either MEWS or another screening tool is needed for detecting early sepsis in these patients.

Purpose: This preliminary in-vitro study was designed to evaluate the risk factors of compression injury from use of a circular stapler for end-to-end anastomosis. Methods: Transparent collagen plates were prepared in dry and wet conditions. Physical properties of collagen plates and porcine colon tissue were examined using a rheometer. Adjustable and fixed-type circular staplers were applied on the collagen plates and the gap distance and compressive pressure were measured during anvil approximation. Tissue injury was evaluated using a compression injury scale. Compression properties were accessed to optimal or overcompression based on gap distance. Results: Unacceptable injuries were rarely observed on the dry collagens, regardless of compression device. In the adjustable compression, the compressibility ratio was similar between dry and wet collagen. Overcompression and unacceptable injury increased on the wet collagens. In the fixed compression, the compressibility ratio increased significantly and unacceptable injuries were observed in more than 50% of wet collagens. Peak pressure was significantly higher in the fixed-compression types than those of adjustable type. On bivariate correlation analysis, fixed-compression type and wet collagens were respectively associated with overcompression. On multivariate analysis, edematous collagen condition was the most important risk factor and proximal anvil side, fixed compression type, and overcompression were also independent risk factors for unacceptable compression injury. Conclusion In the edematous tissue condition, unintentional overcompression could be increased and result in tissue injury on the compression line of the circular stapler.

A human cell-based liver model capable of long-term expansion and mature hepatic function is a fundamental requirement for pre-clinical drug development. We previously established self-renewing and functionally mature human pluripotent stem cell-derived liver organoids as an alternate to primary human hepatocytes. In this study, we tested long-term prolonged culture of organoids to increase their maturity. Organoid growing at the edge of Matrigel started to deteriorate two weeks after culturing, and the expression levels of the functional mature hepatocyte marker ALB were decreased at four weeks of culture. Replating the organoids weekly at a 1：2 ratio in fresh Matrigel, resulted in healthier morphology with a thicker layer compared to organoids maintained on the same Matrigel and significantly increased ALB expression until three weeks, although, it decreased sharply at four weeks. The levels of the fetal hepatocyte marker AFP were considerably increased in long-term cultures of organoids. Therefore, we performed serial passaging of organoids, whereby they were mechanically split weekly at a 1：3∼1：5 ratio in fresh Matrigel. The organoids expanded so far over passage 55, or 1 year, without growth retardation and maintained a normal karyotype after long-term cryopreservation. Differentiation potentials were maintained or increased after long-term passaging, while AFP expression considerably decreased after passaging. Therefore, these data demonstrate that organoids can be exponentially expanded by serial passaging, while maintaining long-term functional maturation potential. Thus, hepatic organoids can be a practical and renewable cell source for human cell-based and personalized 3D liver models.