In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

Background: The growing number of elderly individuals living alone presents a major social issue, encompassing loneliness, isolation, economic and health challenges, and increased risk of suicide. This study aimed to identify factors associated with suicide risk among elderly individuals living alone in Jeju. Methods: A total of 4,742 participants completed questionnaires to assess their sociodemographic characteristics. Depressive symptoms were evaluated using the Short Form Geriatric Depression Scale-Korean version (sGDS-K), with a cutoff score of eight indicating the presence of depressive symptoms. Suicide risk was assessed using the MiniInternational Neuropsychiatric Interview-Plus. Multivariate logistic regression analysis was performed to identify significant correlates of suicide risk. Results: Multivariate logistic regression analysis identified the following factors as significantly associated with suicide risk: poor subjective health status (odds ratio [OR]=1.590, 95% confidence interval [CI]: 1.137-2.224), current drinking (OR=1.511, 95% CI: 1.119-2.042), hypertension (OR=1.419, 95% CI: 1.133-1.778), and sGDS scores ≥8 (OR=4.318, 95% CI: 3.408-5.469). Conclusion This study highlights the importance of intensive mental health services and socioeconomic support in preventing suicide among elderly individuals living alone. Targeted interventions should focus on those who have poor subjective health status, are current drinkers, have hypertension, or exhibit depressive symptoms.

Objective: In South Korea, there is a significant gap in systematic, evidence-based research on intensive case management (ICM) for individuals with severe mental illness (SMI). This study aims to evaluate the effectiveness of ICM through a randomized controlled trial (RCT) comparing ICM with standard case management (non-ICM). Methods: An RCT was conducted to assess the effectiveness of Seoul-intensive case management (S-ICM) vs. non-ICM in individuals with SMI in Seoul. A total of 78 participants were randomly assigned to either the S-ICM group (n=41) or the control group (n=37). Various clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), Montgomery–Åsberg Depression Rating Scale, Health of the Nation Outcome Scale, and Clinical Global Impression-Improvement (CGI-I), along with quality-of-life measures such as the WHO Disability Assessment Schedule, WHO Quality of Life scale, and Multidimensional Scale of Perceived Social Support (MSPSS) were evaluated over a 3-month period. Statistical analyses, including analysis of covariance and logistic regression, were used to determine the effectiveness of S-ICM. Results: The S-ICM group had significantly lower odds of self-harm or suicidal attempts compared to the control group (adjusted odds ratio [aOR]=0.30, 95% confidence interval [CI]: 0.21–1.38). Psychiatric symptoms measured by the BPRS and perceived social support measured by the MSPSS significantly improved in the S-ICM group. The S-ICM group also had significantly higher odds of CGI-I compared to the control group (aOR=8.20, 95% CI: 2.66–25.32). Conclusion This study provides inaugural evidence on the effectiveness of S-ICM services, supporting their standardization and potential nationwide expansion.

Background/Aims: Krebs von den Lungen-6 (KL-6) is associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between the prognosis of COVID-19 and varying KL-6 levels at different time points. We investigated the optimal cutoff values of the initial and peak serum KL-6 levels to predict mortality and evaluated their correlation with mortality. Methods: This retrospective cohort study collected data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between October 2020 and January 2022 at a single tertiary hospital in South Korea. The area under the receiver operating characteristic curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between the initial and peak KL-6 values was assessed by univariate and multivariate logistic regression models. Results: A total of 349 patients were included in this study. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group than in the survivor group. The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL and 660.05 U/mL, respectively. An initial KL-6 level greater than 491.85 U/mL and a peak KL-6 level greater than 660.05 U/mL were significantly associated with 30-day mortality. Conclusions The initial and peak levels of KL-6 were significantly associated with 30-day mortality in hospitalized patients with COVID-19. These findings suggest that serially monitoring blood KL-6 levels could be a valuable prognostic indicator for COVID-19.

Background/Aims: Portal vein thrombosis (PVT) frequently occurs in patients with inflammatory bowel disease (IBD), particularly when influenced by factors such as abdominal infections, IBD flare-ups, or surgical procedures. The implications of PVT range from immediate issues such as intestinal ischemia to long-term concerns including portal hypertension and its complications. However, there is a notable gap in comprehensive studies on PVT in IBD, especially with the increasing incidence of IBD in Asia. This research aimed to evaluate the clinical features and outcomes of PVT in patients with IBD at a leading hospital in South Korea. Methods: This retrospective analysis reviewed adult patients diagnosed with both IBD and PVT from 1989 to 2021 at a renowned South Korean medical center. The study focused on patient characteristics, specifics of PVT, administered treatments, and outcomes, all confirmed through enhanced CT scans. Results: A total of 78 patients met the study’s criteria. Notably, only 20.5% (16/78) were treated with oral anticoagulants; however, a vast majority (96.2%; 75/78) achieved complete radiographic resolution (CRR). When comparing patients receiving anticoagulants to those who did not, a significant preference for anticoagulant use was observed in cases where the main portal vein was affected, as opposed to just the left or right veins (p = 0.006). However, multivariable analysis indicated that neither anticoagulant use nor previous surgeries significantly impacted CRR. Conclusions Patients with IBD and PVT generally had favorable outcomes, regardless of anticoagulant use.

Purpose: Several types of dermal fillers have been recently introduced and used for penile augmentation (PA). However, few studies have compared outcomes after the injection of different fillers. This study aimed to compare the clinical outcomes of hyaluronic acid (HLA), polylactic acid (PLA), and polymethyl methacrylate (PMA) filler injections, which are the most commonly used for aesthetic purposes. Materials and Methods: This prospective study was conducted for 24 weeks after a filler injection by a surgeon between March 2017 and December 2021. Healthy adult men complaining of small penis were enrolled. Penile girth, satisfaction, and injection-associated adverse events (AEs) were assessed at baseline and 4, 12, and 24 weeks after injection. Results: Of the 301 men who received filler injections, 125, 134, and 42 received HLA, PLA, and PMA fillers, respectively. The augmentation effect was in the order of PMA, HLA, and PLA, respectively, at 24 weeks (PMA vs. HLA, p<0.001; HLA vs. PLA, p=0.006). Satisfaction levels increased significantly at 24 weeks in all groups (each with p<0.001). However, the increase in satisfaction levels was smaller in the PMA group (PMA vs. HLA or PLA, p<0.05, for both penile appearance and sexual life). No serious or systemic AEs were recorded. Filler injection-associated local AEs in the HLA, PLA, and PMA groups occurred in 9 (7.2%), 16 (11.9%), and 6 (14.3%) men, respectively. There was no significant difference in AEs among the groups (p=0.299). Conclusions The augmentative effect was greater in the PMA group than in the HLA and PLA groups, whereas the increase in satisfaction levels was smaller in the PMA group. Our study demonstrated the clinical course of different types of fillers and suggests that the filler type should be selected after detailed counseling considering individual characteristics and preferences.

Peyronie’s disease is an acquired condition characterized by penile deformities caused by fibrosis of the penile tunica albuginea, leading to symptoms such as penile pain, erectile dysfunction, and other associated issues. Despite extensive research, the pathophysiology of this condition remains poorly understood, and standardized diagnostic and treatment protocols are lacking. While clinical guidelines from several professional societies exist, they do not consistently account for factors such as patient ethnicity, geography, and socioeconomic status. Thus, the Korean Society for Sexual Medicine and Andrology (KSSMA) aimed to develop recommendations tailored to clinical practice in Korea. These recommendations summarize the latest evidence, including clinical practice guidelines from various international professional societies, and represent the consensus opinion of an expert group within the KSSMA. They encompass all aspects of Peyronie’s disease, including the definition, diagnosis, non-surgical interventions, and surgical treatment options.

Background: Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge. Methods: We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores. Results: We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05). Conclusion This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.

Background/Aims: Globus is often linked with gastroesophageal reflux disease, which influences its treatment strategies. This study aims to investigate clinical characteristics of patients with refractory proton pump inhibitor (PPI) globus to better understand its etiology. Methods: Between 2017 and 2023, 122 out of 592 patients with globus from the Samsung Medical Center outpatient clinic who were unresponsive to 8 weeks of PPI treatment were analyzed. Patients underwent 24-hour esophageal pH monitoring and high-resolution manometry (HRM). They were divided into acid reflux, non-acid reflux, and no reflux groups, with basal impedance (BI) measurements taken at 3, 9, and 15 cm along the esophagus. These values were compared against data of healthy volunteers to identify significant differences across groups. Results: The acid reflux group displayed a median impedance of 1152 Ω at 3 cm, which was significantly lower than the median impedance of the non-acid reflux group (2644 Ω) and the no-reflux group (3083 Ω) (P = 0.015). Most patients in non-acid reflux and no-reflux groups showed higher impedance levels at both 3 cm and 15 cm compared to the first quartile of healthy individuals with significant differences (P = 0.032 and P = 0.029, respectively). Proximal BI was significantly lower than distal BI in both groups: 2278 Ω vs 2644 Ω in the non-acid reflux group (P = 0.035) and 2387 Ω vs 3083 Ω in the no-reflux group (P < 0.001). Conclusions Reduced proximal BI values compared to distal BI values suggest increased permeability in globus patients. Further studies with a larger cohort of refractory PPI patients and healthy volunteers are needed to explore these findings and their implications on globus etiology.