Purpose: Cannabidiol (CBD) is a promising treatment option for pediatric drug-resistant epilepsy (DRE). The aim of this study was to assess the tolerability and safety of CBD in a single-center retrospective cohort based on real-world clinical experience. Methods: This study included 71 pediatric patients (median age, 8.9 years; interquartile range [IQR], 6.2 to 14.0) with Lennox–Gastaut syndrome who received purified CBD (Epidiolex, GW Pharmaceuticals) between March 2019 and July 2024. All patients had previously failed treatment with more than five anti-seizure medications (ASMs). Responder rate (≥50% seizure frequency reduction), retention rate, adverse effects (AEs), and predictors of favorable treatment response were analyzed over a median follow-up of 21.3 months (IQR, 2.8 to 38.5). Results: The initial responder rate during the first 3 months was 45.1%, which increased to 70.8% at 18 months and 63.0% at 24 months. The retention rate at 24 months was 52.4% (33/71). Seven patients (9.9%) achieved seizure freedom beyond 24 months of CBD therapy, and five of these patients were able to reduce their concomitant ASM burden. AEs were observed in 39.4% (28/71) of patients, with the most frequent being somnolence (20 cases) and increased seizure frequency (six cases); 92.9% of AEs occurred within the first 3 months of treatment. No serious AEs requiring treatment discontinuation were identified. Conclusion In this real-world study, CBD demonstrated potential as an adjunctive therapy with manageable AEs. These findings highlight that CBD can reduce seizure frequency while maintaining tolerability in pediatric patients with DRE.

Rectal cancer, which accounts for approximately 40% of colorectal cancers, remains a major clinical concern. Recent advances in diagnostic imaging, surgical techniques, radiotherapy, and systemic treatment have steadily improved rectal cancer outcomes. Considering this, the Korean Rectal Cancer Multidisciplinary (KRCM) Committee has aimed to provide clinicians and policymakers with up-to-date, evidence-based clinical practice guidelines to support optimal decision-making, reflecting current evidence, the Korean healthcare context, and patient values and preferences. The Clinical Practice Guidelines for Rectal Cancer version 2.0 were developed through multidisciplinary collaboration with related academic societies, building upon and updating the KRCM Clinical Practice Guidelines version 1.0 (titled “Multidisciplinary guidelines for the management of rectal cancer”). These consensus guidelines of the KRCM were established based on a comprehensive literature review, evidence synthesis, with recommendation development guided by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and consideration of applicability in real-world clinical practice under the national health insurance system. Each recommendation has been presented with its strength and level of evidence.

Zelkova serrata (Thunb.) Makino is a deciduous tree commonly distributed in East Asia. Several investigations have documented the biological activity of extracts of this species, igniting increased interest in its therapeutic potential. However, the phytochemical constituents accountable for these activities remain largely unexplored. In this study, we focused on the antioxidant potential of the leaves and twigs, utilizing bioactivityguided fractionation combined with LC-QTOF-MS online DPPH screening to systematically identify the active compounds. This approach led to the isolation of eight compounds, three of which (compounds 1, 3, and 7) have not previously been documented in the genus Zelkova. Among the isolates, 4 emerged as the most potent antioxidant, exhibiting significant radical scavenging activity in both DPPH (IC 50 = 13.67 ± 1.21 μM) and ABTS (IC50 = 2.69 ± 0.48 μM) assays, exceeding ascorbic acid (IC 50 = 61.51 ± 10.22 μM) and trolox (IC50 = 8.22 ± 2.16 μM), respectively. Our findings not only enrich the phytochemical profile of Z. serrata but also highlight the effectiveness of LC-MS-DPPH as an effective approach for rapid antioxidant discovery.

Purpose: There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the epidermal growth factor receptor (EGFR) mutation. Materials and Methods: A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue. Results: In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22.0%, 9.8%, and 29.3%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 36.6%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 82.9% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation. Conclusion We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

Purpose: This study evaluates the Korean Cancer Study Group Geriatric Score-7 (KG-7) frailty screening tool’s effectiveness in elderly multiple myeloma (MM) patients to prevent under and overtreatment. Materials and Methods: This prospective pilot cohort study included 100 elderly patients aged 70 and older with newly diagnosed MM who had not undergone transplantation from August 2020 to January 2022. Results: The median age was 77 years, and 73.0% of patients were classified at International Staging System stages 2 or 3. Using a 5-point cutoff on the KG-7 index (non-frail, score ≥ 5; frail, score < 5), 31% were categorized as frail. After a median follow-up of 26.8 months, the 3-year overall survival rate was 73.0%. There was no statistically significant association between any frailty index and the risk of death. However, frail patients defined by the simplified frailty index (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.09 to 5.95; p=0.030) and by KG-7 (HR, 2.43; 95% CI, 1.03 to 5.86; p=0.043) had a significantly higher risk of grade 3-4 non-hematologic toxicity, whereas the International Myeloma Working Group definition did not. Over a 24-month tracking period, vulnerability as measured by KG-7 either improved or deteriorated. Conclusion The pilot study, which had a limited number of participants, did not demonstrate KG-7’s effectiveness in predicting survival; however, it successfully predicted severe non-hematologic toxicities. We plan to conduct larger studies in elderly MM patients to determine whether KG-7 can help tailor their treatment regimens.

Purpose: High-cost novel therapies for multiple myeloma (MM) require evaluation of efficacy and cost-effectiveness. Materials and Methods: This study developed a methodology to assess cost-effectiveness using nationwide data from 11,450 newly diagnosed MM patients. A novel algorithm was applied to identify lines of therapy (LoT). Results: The number of newly diagnosed MM patients increased significantly, from 873 in 2010 to 1,464 in 2019 (p < 0.001). Advancing LoT was associated with shorter time to next treatment (TTNT) and overall survival (OS) (p < 0.001), while all-cause medical costs increased with each LoT (p < 0.001). Bortezomib-melphalan-prednisolone was the most common frontline regimen for transplant-ineligible patients (29.2%), while bortezomib-thalidomide-dexamethasone was most used for transplant-eligible patients (11.3%). Daratumumab monotherapy demonstrated superior second TTNT (7.8 vs. 5.2 months) and OS (8.5 vs. 5.3 months) compared to standard care in heavily treated MM patients, with statistical significance maintained after cost adjustment. For subsequent therapies following daratumumab, a methodology was developed to estimate required medical costs using the incremental cost-effectiveness ratio (ICER): Expected cost ($)=ICER×(Expected life expectancy–0.567)+35,601. Conclusion This study provides a novel cost-effectiveness framework linking treatment efficacy and real-world costs, supporting predictions of societal costs for future MM therapies.

Objective: To analyze the microbiological and clinical characteristics of vulvovaginitis in girls, distinguishing between the premenarcheal and postmenarcheal groups in a tertiary center in South Korea. Methods: This retrospective cohort study included 195 patients under 20 years of age diagnosed with vulvovaginitis at a tertiary hospital between 2014 and 2023. The patients were categorized into premenarcheal (n=95) and postmenarcheal (n=100) groups. Data on initial symptoms, microbial cultures, and treatment methods were analyzed. Results: The most common initial symptom was vaginal discharge, reported in 63.1% of cases. Culture results showed a 51.3% positivity rate for any microorganism, with a prevalence of gram-negative rods (32.8%) and gram-positive cocci (14.4%). The most frequently isolated microorganisms were Escherichia coli (17.9%), Candida albicans (7.7%), and Enterococcus faecalis (6.7%). Gram-negative rods were more common in the premenarcheal group (37.1% vs. 25.0%; p=0.01). No significant differences were observed in the prevalence of gram-positive cocci and Candida species between the two groups (16.8% vs. 12.0%, p=0.22; 6.3% vs. 13.0%, p=0.09; respectively). The susceptibilities of grampositive microorganisms to penicillin, oxacillin, clindamycin, vancomycin, and tetracycline were 58.8%, 58.3%, 94.7%, 100.0%, and 73.7%, respectively. The susceptibilities of gram-negative microorganisms to amoxicillin/clavulanic acid, ciprofloxacin, ceftriaxone, and nitrofurantoin were 89.3%, 85.3%, 76.0%, and 100.0%, respectively. Conclusion This study identified differences in the microbial profiles associated with vulvovaginitis between premenarcheal and postmenarcheal girls. Age-specific and history-based clinical approaches tailored to menarcheal status are warranted to improve the management and outcomes of pediatric and adolescent vulvovaginitis.

Background/Aims: Proprotein-converting enzyme subtilisin-kexin type 9 (PCSK9) inhibitors act more promptly and efficiently than statins and reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). This study aimed to assess the short-term effects of perioperative administration of a single-dose PCSK9 inhibitor in patients with ACS. Methods: This study included 789 consecutive patients undergoing percutaneous coronary intervention (PCI) for ACS. The primary clinical endpoint was the occurrence of major adverse cardiovascular events (MACEs) within one month, including cardiac death, non-fatal myocardial infarction, unanticipated revascularization, stroke, stent thrombosis, and rehospitalization for ischemic causes or heart failure. Results: PCSK9 inhibitors were administered to 201 of 789 patients. MACEs occurred in eight patients (4.0%) in the treated group and 60 patients (10.2%) in the non-treated group for one month (hazard ratio 0.38, 95% confidence interval 0.18 to 0.80, p = 0.010). The benefit of PCSK9 inhibitors in terms of MACEs was greater in the subgroup of patients treated more than 1 hour before PCI than in the subgroup treated less than 1 hour before PCI or treated after PCI and in the non-treated group. Conclusions In patients undergoing PCI for ACS, the risk of MACEs was lower in those treated with perioperative single-dose PCSK9 inhibitors than in those in the untreated group. This benefit was especially noticeable in the subgroups treated > 1 hour before PCI than in those treated less than 1 hour before PCI or after PCI, regardless of the clinical presentation of ACS.

Objective: To quantitatively analyze and compare the forces and moments generated by thermoformed polyethylene terephthalate glycol (PETG) and direct-printed TC-85 clear aligners (CAs), with various margin designs, during premolar rotation. Methods: In total, 132 CAs were fabricated and divided into four groups (n = 33 per group). Group C consisted of thermoformed PETG aligners with a 2 mm gingival margin. Group E comprised direct-printed TC-85 aligners with equi-gingival margin, whereas Group G utilized direct-printed TC-85 aligners with 2 mm gingival margins.Finally, Group T featured direct-printed TC-85 aligners with an additional 1 mm thickness at the mesial embrasure. The forces and moments were measured using a 6-axis force/moment transducer at 2°, 3°, and 4° of rotation. All measurements were conducted at 37°C to simulate intraoral conditions. Forces were measured in the buccolingual, anteroposterior, and vertical directions, while moments were measured in the mesiodistal, buccolingual, and rotational planes. Results: The PETG aligners (Group C) showed significantly increased buccal and posterior force across the rotation angles (P < 0.05), whereas the intrusive force remained consistent. In contrast, the TC-85 aligners maintained consistent forces across all rotation angles.Direct-printed aligners demonstrated significantly lower intrusive forces than PETG aligners (P < 0.001). Group T exhibited reduced unwanted forces while maintaining effective rotational moments. Furthermore, all direct-printed aligners showed more predictable force delivery patterns than thermoformed aligners. Conclusions Direct-printed TC-85 aligners demonstrated superior force consistency and reduced unwanted side effects compared with traditional PETG aligners. Although marginal design modifications did not significantly improve rotational efficiency, they effectively reduced unwanted intrusive forces.

The 5-hydroxytryptamine type3 (5-HT3 ) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission. It has been implicated in various neuropsychiatric disorders. This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT3 receptor-mediated currents in NCB20 neuroblastoma cells. Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism. Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC50 without altering the maximal response (Emax ), suggesting a competitive inhibition. Quetiapine's IC50 varied with 5-HT concentration and treatment condition. The IC50 value of quetiapine was 0.58 μM with 3μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration. Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC50 from 25.23 μM to 0.20 μM.Interaction kinetics experiments revealed an IC50 of 5.17 μM for an open state of the 5-HT3 receptor, suggesting weaker affinity during receptor activation. Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states. Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics. Inhibition of the 5-HT3 receptor by quetiapine was voltage-independent, and quetiapine exhibited no usedependency, further supporting its role as a competitive antagonist. These findings provide insights into inhibitory mechanism of quetiapine on 5-HT3 receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.