Background/Aims: Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods: This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results: This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups. Conclusions In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.

Background/aims: Opinions differ regarding vibration-controlled transient elastography and magnetic resonance elastography (VCTE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of VCTE and MRE for diagnosing AF. Methods: Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating VCTE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for VCTE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. Results: A total of 19,199 patients from 63 studies using VCTE showed diagnostic AUC of 0.83 (95% confidence interval: 0.80–0.86), 0.83 (0.80–0.86), 0.87 (0.84–0.90), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89 (0.86–0.92), 0.92 (0.89–0.94), 0.89 (0.86–0.92), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. The diagnostic AUC for AF using VCTE was highest at 0.90 with a cut-off of 7.1–7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62–3.8 kPa. Conclusions VCTE (7.1–7.9 kPa) and MRE (3.62–3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

Background: While polystyrene microplastics (PS-MPs) are emerging as potentially significant health threats, linked to cancer and reproductive dysfunction, their precise effects on human health remain largely unknown. We aimed to investigate the underlying mechanisms promoting microplastic-induced damage in the reproductive system. Methods: Thirty C57BL/6 male mice were randomly allocated into six equal-sized groups.Mice were exposed to fluorescent PS-MPs (5 µm, < 18%, green) at a dose of 1 and 3 mg/dL via oral gavage for 28 and 56 days, respectively (control, 0 mg/dL). The presence of antibodies and inflammatory and oxidative stress markers were evaluated using western blotting. Sperm analysis was also performed. Mouse testis Sertoli TM4 cells were divided into two groups:control (medium only) and PS-MPs (medium containing, 1,000 μg/mL) groups and cultured in vitro for 1, 24, 48, or 72 hours. The cells were cultured in a Ham’s F12: Dulbecco's Modified Eagle Medium medium with 0.25% fetal bovine serum at 37°C with humidified atmosphere of 5% carbon dioxide in the air. Protein analyses for interleukin (IL)-6, IL-10, NADPH-oxidase (NOX)-2, NOX-4, hypoxia-inducible transcription factor (HIF)-2α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were performed using western blotting. Results: The testes were evaluated after 28 and 56 days of exposure. Varying sizes of PS-MPs were detected in the testes (ranging from 5.870 to 7.768 µm). Significant differences in sperm concentration, motility, and the proportion of normal sperm were observed between the two groups. An increase in TGF-β, HIF-2α, and NOX-4 levels was observed using western blot analysis. However, no dose-dependent correlations were observed between the two groups.In vitro evaluation of the PS-MPs group displayed PS-MP penetration of the lumen of Sertoli cells after 1 hour. Further PS-MP aggregation within Sertoli cells was observed at 24, 48, and 72 hours. A significant increase in inflammatory protein expressions (IL-10, TGF-β, MCP-1, IL-6, TNF-α, and HIF-2α) was observed through western blotting, although oxidative agents did not show a significant increase. Conclusion PS-MPs induced reproductive dysfunction in male mice provide new insights into PS-MPs-associated toxicity in mammals.

Background: There are inconsistent reports regarding the association between general anesthesia and adverse neurodevelopmental and behavioral disorders in children. Methods: This nationwide administrative cohort study included children born in Korea between 2008 and 2009, and followed until December 31, 2017. The cohort included 93,717 participants who received general anesthesia with endotracheal intubation (ETI) who were matched to unexposed subjects in a 1:1 ratio. General anesthesia was defined by National Health Insurance Service treatment codes with intratracheal anesthesia, and the index date was the first event of general anesthesia. The primary outcome was attention deficit hyperactive disorder (ADHD), which was defined as at least a principal diagnosis of 10th revision of the International Classification of Diseases code F90.X after the age of 72 months.Neurodevelopment, which was assessed using a developmental screening test (Korean-Ages and Stages Questionnaire [K-ASQ]), was a secondary outcome. The K-ASQ is performed annually from 1 to 6 years of age and consists of 5 domains. The association between general anesthesia and ADHD was estimated using a Cox hazard model, and its association with neurodevelopment was estimated using a generalized estimation equation, with control for multiple risk factors beyond 1 year after the index date. Results: The median age at the index date was 3.8 (95% confidence interval [CI], 1.7–5.8) years, and there were 57,625 (61.5%) men. During a mean follow-up period of 5 years, the incidence rate of ADHD was 42.6 and 27.7 per 10,000 person-years (PY) in the exposed and unexposed groups, respectively (absolute rate difference 14.9 [95% CI, 12.5–17.3] per 10,000 PY). Compared to the unexposed group, the exposed group had an increased risk of ADHD (adjusted hazard ratio, 1.41 [95% CI, 1.30–1.52]). In addition, a longer duration of anesthesia with ETI and more general anesthesia procedures with ETI were associated with greater risk of ADHD. General anesthesia with ETI was also associated with poorer results in the K-ASQ. Conclusion Administration of general anesthesia with ETI to children is associated with an increased risk of ADHD and poor results in a neurodevelopmental screening test.

Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and KMbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5~12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors.Recommendations 13~16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

Purpose: This study aims to investigate how medical schools in Korea managed their academic affairs and student support in response to the coronavirus disease 2019 (COVID-19) pandemic and their plans for the post-COVID-19 era. Methods: An online survey was conducted, and a link to a questionnaire was distributed to all the administrators of the 40 medical schools in Korea. The final analysis data involved responses from 33 medical schools and 1,342 students. Frequency analysis, cross-tabulation analysis, Fisher’s exact test, and one-way analysis of variance were applied for statistical analysis. Results: Regarding instruction methods, most medical schools in Korea transitioned from in-person learning to video-on-demand learning (51.5%) and real-time online learning (42.4%). Among the school leaders, 36.4% planned to continue offering online classes combined with in-person classes beyond the end of the pandemic. Among the students, the online class concentration and participation score was 3.0 points or lower, but the class understanding score was 3.6 points, above a moderate level. Conclusion Students cited the shorter times needed to attend school and being able to take classes repeatedly as advantages of online classes, and over one-third of medical schools intended to continue with a hybrid of in-person and online learning even after the COVID-19 pandemic restrictions end.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5–12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13–16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.