Purpose: To investigate the outcomes of brolucizumab reinjection after intraocular inflammation (IOI) development. Methods: This retrospective study analyzed patients with brolucizumab injections from April 2021 to January 2024. Patients who developed IOI after brolucizumab were included and categorized into subgroups depending on reinjection, discontinuation, and further IOI development. Results: A total of 472 eyes of 432 patients received brolucizumab injections. Thirty-eight cases developed IOI at least once, and 25 continued brolucizumab. Sixteen cases had no more IOI events, and nine experienced a second or more IOI events. Among the nine cases, three maintained brolucizumab injections despite IOI recurrence. The incidence of IOI was 8.1% based on the number of eyes (38 of 472 eyes) and 2.0% based on the number of brolucizumab injections (50 of 2,468 injections). The incidence of occlusive retinal vasculitis was 0.2% (1 of 472 eyes). The recurrence rate was 23.7% (9 of 38 eyes). The average number of injections between the first brolucizumab injection and the injection date on which IOI first developed was 2.15 times in the no-reinjection group, 3.44 times in the no-IOI-recurrence group, and 2.0 times in the second-IOI-episode group. Time to IOI occurrence in cases with first IOI episode was 18.60 ± 16.73 days, with 15 cases developing IOI within 1 week. Conclusions This study elucidates the real-world incidence of brolucizumab associated IOIs, with a description of information related to reinjections after the IOI episodes. A comprehensive understanding of brolucizumab reinjection is essential for its optimal utilization.

Background: The significance of risk modification in patients with acute coronary syndrome (ACS) is well recognized; however, the optimal timing for adminstering PCSK9 inhibitors remains unclear. Additionally, the lipid-lowering efficacy of evolocumab and alirocumab has not been fully established. This study evaluated the lipid-lowering effects of these two PCSK9 inhibitors. Methods: Patients diagnosed with ACS, including unstable angina, ST-segment elevation myocardial infarction, and non-ST-segment elevation myocardial infarction, who were treated with a PCSK9 inhibitor (evolocumab or alirocumab) during hospitalization for ACS between 2021 and 2023 were retrospectively analyzed. Baseline low-density lipoprotein cholesterol (LDL-C) levels were assessed, and changes in LDL-C levels during the acute and subacute phases after PCSK9 inhibitor administration were compared between the evolocumab and alirocumab groups. Results: Among 80 patients diagnosed with ACS, 36 received evolocumab, while 44 were treated with alirocumab. The mean baseline LDL-C level was 123 mg/dL in the evolocumab group and 128 mg/dL in the alirocumab group (p=0.456). In the subacute phase, the mean follow-up LDL-C levels were 47.05 mg/dL in the evolocumab group and 49.5 mg/dL in the alirocumab group (p=0.585). The mean percentage reduction in LDL-C levels during the subacute phase was 60.41% in the evolocumab group and 58.51% in the alirocumab group (p=0.431). These differences were not statistically significant. Conclusions No significant differences were observed between evolocumab and alirocumab. LDL-C levels exhibited a similar trend, characterized by a rapid decline in the acute phase, followed by a slight rebound in the subacute phase.

Objective: Previous studies have reported an association between cancer-related symptoms and perceived social support (PSS). The objective of this study was to analyze whether Chemotherapy-Induced Peripheral Neuropathy (CIPN), a prevalent side effect of chemotherapy, varies according to PSS level using a validated tool for CIPN at prospective follow-up. Methods: A total of 39 breast cancer patients were evaluated for PSS using the Multidimensional Scale of Perceived Social Support (MSPSS) prior to chemotherapy and were subsequently grouped into one of two categories for each subscale: low-to-moderate PSS and high PSS. CIPN was prospectively evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) at five time points. A linear mixed-effects model with square root transformation was employed to investigate whether the CIPN20 scales varied by PSS level and time point. Results: Statistical analysis of the MSPSS total scale and subscales revealed a significant effect of the friends subscale group and time point on the CIPN20 sensory scale. The sensory scale score of CIPN20 was found to be lower in participants with high PSS from friends in comparison to those with low-to-moderate PSS at 1 month post-chemotherapy (p=0.010). Conclusion This is the first study to prospectively follow the long-term effect of pre-treatment PSS from friends on CIPN. Further studies based on larger samples are required to analyze the effects of PSS on the pathophysiology of CIPN.

Objective: This study aimed to investigate the prevalence and characteristics of impacted teeth (ITs) in orthodontic patients at university dental hospitals in Korea. Methods: This study included 14,774 patients who visited the Department of Orthodontics at 10 university dental hospitals in Korea between 2020 and 2022 and underwent orthodontic diagnosis. The prevalence and characteristics of ITs were investigated using orthodontic diagnostic records, radiographs, and diagnostic casts. Results: The prevalence of ITs, excluding third molar impaction, in Korean orthodontic patients was 13.6% (n = 2,014).The prevalence of ITs in pediatric orthodontic patients was 24.5% (n = 1,614).Of these patients, 68.2% had one IT, 27.5% had two ITs, 24.3% had bilateral IT, and 75.7% had unilateral IT. The most frequent IT was the maxillary canine (50.1%), followed by the mandibular second molar (11.7%), and maxillary second premolar (9.6%). An abnormal eruption path (46.5%) was the most frequent etiology. Orthodontic traction after surgical exposure (70.6%) was the most frequent treatment option. Among the patients with ITs, 29.8% had other dental anomalies, such as tooth agenesis (8.7%), microdontia (8.0%), and supernumerary teeth (5.1%). Furthermore, 50.8% had complications such as cystic lesions (18.3%), transposition (17.7%), and root resorption (14.8%).Among the patients with maxillary canine impaction, 62.2% had labial maxillary canine impaction and 21.1% had palatal maxillary canine impaction. Conclusions The prevalence of ITs in Korean orthodontic patients at university dental hospitals was high, particularly in pediatric orthodontic patients.

Objective: Using finite element method (FEM) analysis of a clear aligner (CA), this study aimed to investigate the effects of varying the edentulous space on canine distal bodily movement during space closure following maxillary first premolar extraction. Methods: FEM analysis was used to simulate distal canine bodily movement following maxillary first premolar extraction using CAs. Four CA designs for edentulous spaces were compared: no-pontic, full-pontic, halfpontic, and beam. Three-dimensional models of the tooth components and CA were created. The target was set at a 0.25-mm distal canine movement. Long-term tooth movement was simulated using an iterative calculation method. Results: All the groups initially showed crown displacement, distal tipping, and distal rotation.Over time, the movement patterns differed in relation to the design. The no-pontic design exhibited the greatest displacement and tipping. The beam design exhibited the largest initial displacement but showed the lowest displacement and tipping thereafter. Full- and half-pontic designs yielded intermediate results. Significant force reduction was observed immediately after CA application, and was followed by a gradual decrease. The mean tooth-movement achievement rate was approximately 76.7%. Conclusions The edentulous space design of the CA substantially affected tooth-movement behavior. An iterative simulation is necessary to evaluate longterm tooth-movement patterns. The beam design demonstrated optimal suitability for bodily movement with minimal tipping. For optimal results, additional setup or overcorrection may be necessary.

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.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Background: s/Aims: Hepatocellular carcinoma (HCC) is a malignant cancer with an increasing incidence worldwide. Although numerous efforts have been made to identify effective therapies for HCC, current strategies have limitations. We present a new approach for targeting L-arginine and argininosuccinate synthetase 1 (ASS1). Methods: ASS1 expression in HCC cell lines and primary hepatocytes was detected using polymerase chain reaction and western blotting. Proliferation, migration, signaling pathways, and nitric oxide production in HCC cell lines were measured using MTS, colony formation, wound healing, Western blot, and Griess assays. Results: ASS1 expression varied among the HCC cell lines, and cisplatin cytotoxicity was ASS1-dependent. L-arginine alone induced apoptosis in HCC cell lines, regardless of ASS1 expression; however, its effect was enhanced in ASS1-expressing HCC cell lines. Cisplatin cytotoxicity also increased, suggesting that L-arginine acts as a sensitizer to cisplatin in HCC cell lines. ASS1 and L-arginine produced nitric oxide and inhibited key proliferation- and survival-related signaling pathways such as PI3K/Akt and MAPK. Additionally, ASS1 and L-arginine reduced the expression of PKM1 and PKM2 in the glycolysis pathway. Conclusions Our study revealed that ASS1 and L-arginine exhibited anticancer effects in HCC and sensitized cisplatin-resistant HCC cells to chemotherapy. The combination of ASS1 and L-arginine significantly enhanced the anticancer effects, even in HCC cell lines with low or absent ASS1 expression. These findings highlight the critical roles of arginine and ASS1 in HCC and suggest that increasing arginine availability could be a promising therapeutic strategy.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background and Objectives: Pediatric chronic rhinosinusitis (CRS) significantly affects children’s quality of life and learning abilities. This study aimed to evaluate the postoperative outcomes in pediatric patients who underwent functional endoscopic sinus surgery (FESS) for CRS. Methods: A retrospective review was conducted on pediatric patients who underwent FESS for CRS at 11 university hospitals. The inclusion criteria were patients under 20 years old with bilateral disease who were operated on between January 2005 and December 2021. The data collected included demographics, clinical history, blood tests, preoperative computed tomography, and preoperative and postoperative symptom control. The Kruskal-Wallis and Fisher exact tests were used to compare the quantitative and qualitative data, respectively. Results: In total, 213 patients were enrolled. The mean age was 13.4±3.0 years, and 145 (68.1%) were male. One hundred sixty-four patients (77.0%) had nasal polyps and 33 patients (15.5%) underwent revision FESS. The preoperative symptoms, in order of prevalence, included nasal obstruction (87.8%), rhinorrhea (71.8%), a sense of postnasal drip (58.2%), hyposmia (44.6%), cough (24.4%), and facial fullness (18.3%). These symptoms were significantly alleviated for up to 3 years after surgery (p<0.001). At the time of the last follow-up, 121 patients (56.8%) were controlled, 80 (37.6%) were partly controlled, and 12 (5.6%) were uncontrolled. Patients in the uncontrolled group had higher Lund-Mackay scores, longer follow-up durations, and more instances of revision surgery compared to those in the controlled and partly controlled groups. When age was categorized into three groups, those aged 16 years or older tended to have lower Lund-Mackay scores and better control. Conclusion FESS significantly improves both the postoperative symptoms and the long-term quality of life in pediatric CRS patients. Better symptom control is associated with older age and a lower disease burden.