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: Posterior reversible encephalopathy syndrome (PRES) is a rare complication of lung transplantation with poorly understood risk factors and clinical characteristics. This study aimed to examine the occurrence, risk factors, and clinical data of patients who developed PRES following lung transplantation. Methods: A retrospective analysis was conducted on 147 patients who underwent lung transplantation between February 2013 and December 2023. The patients were diagnosed with PRES based on the clinical symptoms and radiological findings. We compared the baseline characteristics and clinical information, including primary lung diseases and immunosuppressive therapy related to lung transplantation operations, between the PRES and non-PRES groups. Results: PRES manifested in 7.5% (n=11) of the patients who underwent lung transplantation, with a median onset of 15 days after operation. Seizures were identified as the predominant clinical manifestation (81.8%, n=9) in the group diagnosed with PRES. All patients diagnosed with PRES recovered fully. Patients with PRES were significantly associated with connective tissue disease-associated interstitial lung disease (45.5% vs. 18.4%, P=0.019, odds ratio=9.808; 95% CI, 1.064–90.386; P=0.044). Nonetheless, no significant variance was observed in the type of immunotherapy, such as the use of calcineurin inhibitors, blood pressure, or acute renal failure subsequent to lung transplantation. Conclusions PRES typically manifests shortly after lung transplantation, with seizures being the predominant initial symptom. The presence of preexisting connective tissue disease as the primary lung disease represents a significant risk factor for PRES following lung transplantation.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and lacks clinical biomarkers. Exosomes are extracellular vesicles that facilitate cell–cell communication by distributing macromolecules, such as small RNAs (smRNAs). We assessed the potential of exosome-derived small RNAs (Ex-smRNAs) as PDAC biomarkers. Methods: Peripheral blood was collected from 51 patients with PDAC and 15 control individuals. Exosomes were isolated using an aqueous two-phase system. Ex-smRNAs were analyzed using smRNA sequencing. smRNA-mediated target gene regulation was verified via The Cancer Genome Atlas analysis and in vitro transfection and wound-healing assays using PDAC organoids. Results: The total Ex-smRNA count was substantially reduced in patients with PDAC compared with that in control individuals. The levels of microRNAs (miRNAs) miR-125a-5p, miR-30e-5p, miR-16-2-3p, miR-98-5p, and the let-7 family were significantly suppressed, whereas that of miR-6731-5p was significantly elevated. Let-7c-5p and miR-98-5p were found to interact with the long non-coding RNA OLMALINC to regulate their common target genes, BACH1 and CCND1, thus controlling PDAC proliferation and migration. The expressions of CARS1-AS1 and miR-142-5p were upregulated in treatment-responsive patients.Multivariable Cox regression analyses, adjusting for potential prognostic factors such as sex, Eastern Cooperative Oncology Group performance status, and tumor size and stage, revealed that CARS1-AS1 (adjusted hazard ratio [HR] 0.33; 95% confidence interval [CI], 0.15–0.73; P = 0.0061) and miR-142-5p (adjusted HR 0.79; 95% CI, 0.61–1.01; P = 0.0581) were associated with improved overall survival. Conclusions We identified potential Ex-smRNA biomarkers involved in PDAC progression and prognosis that reflect key molecular alterations in PDAC and may serve as clinically relevant biomarkers for disease monitoring.

Purpose: The optimal reconstruction method following distal gastrectomy has not been elucidated. Since Billroth-II (B-II) reconstruction is commonly associated with increased bile reflux, Braun jejunojejunostomy has been proposed to reduce this complication. Materials and Methods: We retrospectively analyzed 325 patients with gastric cancer who underwent distal gastrectomy with B-II reconstruction between January 2015 and December 2017, comprising 159 patients without Braun anastomosis and 166 with Braun anastomosis.Outcomes were assessed over three years using annual gastroscopy based on the residual food, gastritis, and bile reflux criteria and the Los Angeles classification for reflux esophagitis. Results: In the first postoperative year, the group with Braun anastomosis showed a significant reduction in bile reflux compared to the group without Braun anastomosis (75.9% vs. 86.2%; P=0.019). Moreover, multivariate analysis identified Braun anastomosis as the sole factor associated with this outcome. Additionally, the group with Braun anastomosis had a lower incidence of heartburn (12.0% vs. 20.1%; P=0.047) and reduced use of prokinetics (P<0.001) and acid reducers (P=0.002) compared to the group without Braun anastomosis.However, these benefits diminished in subsequent years, with no significant differences in residual food, gastritis, or reflux esophagitis between the groups. Both groups showed similar body mass index scores and nutritional outcomes over the 3-year follow-up period. Conclusions Although Braun anastomosis offers short-term benefits in reducing bile reflux after B-II reconstruction, these effects are not sustainable. The routine use of Braun anastomosis should be reconsidered, though either approach remains a viable option depending on the patient’s circumstances.

Background: Barriers to treatment with intravenous thrombolysis (IVT) for patients with acute ischemic stroke (AIS) in South Korea remain incompletely characterized. We analyze a nationwide prospective cohort to determine patient-level features associated with delayed presentation and non-treatment of potential IVT-eligible patients. Methods: We identified consecutive patients with AIS from 01/2011 to 08/2023 from a multicenter and prospective acute stroke registry in Korea. Patients were defined as IVT candidates if they presented within 4.5 hours from the last known well, had no lab evidence of coagulopathy, and had National Institute of Health Stroke Scale (NIHSS) ≥ 4. Multivariable generalized linear mixed regression models were used to investigate the associations between their characteristics and the IVT candidates or the use of IVT among the candidates. Results: Among 84,103 AIS patients, 41.0% were female, with a mean age of 69 ± 13 years and presentation NIHSS of 4 [interquartile range, 1–8]. Out of these patients, 13,757 (16.4%) were eligible for IVT, of whom 8,179 (59.5%) received IVT. Female sex (adjusted risk ratio [RR], 0.90; 95% confidence interval [CI], 0.86–0.94) and lower years of education (adjusted RR, 0.90; 95% CI, 0.84–0.97 for 0–3 years, compared to ≥ 13 years) were associated with a decreased likelihood of presenting as eligible for IVT after AIS; meanwhile, young age (adjusted RR, 1.12; 95% CI, 1.01–1.24 for ≤ 44 years, compared to 75–84 years) was associated with an increased likelihood of being an IVT candidate. Among those who were eligible for IVT, only age was significantly associated with the use of IVT (adjusted RR, 1.09; 95% CI, 1.03–1.16 for age 65–74 and adjusted RR, 0.83; 95% CI, 0.76–0.90 for ≥ 85 years, respectively). Conclusion Most patients with AIS present outside IVT eligibility in South Korea, and only 60% of eligible patients were ultimately treated. We identified increased age, female sex and lower education as key features on which to focus interventions for improving IVT utilization.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.

Background: Tinnitus is a multifactorial condition with no universally accepted assessment guidelines. The Korean Tinnitus Study Group previously established consensus statements on the definition, classification, and diagnostic tests for tinnitus. As a continuation of this effort, this study aims to establish expert consensus on tinnitus assessment and treatment outcome evaluation, specifically tailored to the Korean clinical context. Methods: A modified Delphi method involving 26 otology experts from across Korea was used. A two-round Delphi survey was conducted to evaluate statements related to tinnitus assessment before and after treatment. Statements were rated on a scale of 1 to 9 for the level of agreement. Consensus was defined as ≥ 70% agreement (score of 7–9) and ≤ 15% disagreement (score of 1–3). Statistical measures such as content validity ratio and Kendall’s coefficient of concordance (W) were calculated to assess agreement levels. Results: Of the 46 assessment-related statements, 17 (37%) reached consensus, though overall pre-treatment assessments showed weak agreement (Kendall’s W = 0.319). Key areas of agreement included the use of the visual analogue scale, numeric rating scale, and validated questionnaires for pre-treatment evaluation. Five statements, such as the use of computed tomography, magnetic resonance imaging, and angiography for diagnosing pulsatile tinnitus, achieved over 90% agreement. For treatment outcome measurements, 8 of 12 statements (67%) reached a consensus, with moderate agreement (Kendall’s W = 0.513). Validated questionnaires and psychoacoustic tests were recommended for evaluating treatment effects within 12 weeks. While standardized imaging for pulsatile tinnitus and additional clinical tests were strongly recommended, full consensus was not achieved across all imaging modalities. Conclusion This study provides actionable recommendations for tinnitus assessment and treatment evaluation, emphasizing the use of standardized tools and individualized approaches based on patient needs. These findings offer a practical framework to enhance consistency and effectiveness in tinnitus management within Korean clinical settings.

Background: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Objectives: Statins are essential in the prevention of cardiovascular disease; however, their association with type 2 diabetes mellitus (T2DM) risk is concerning. We examined whether genetic susceptibility to T2DM modifies the association between regular statin use and T2DM risk. Methods: This study included 447 176 individuals from the UK Biobank without baseline diabetes or major cardiovascular disease. Statin use was recorded at baseline, and T2DM incidence was determined using clinical records. Polygenic risk scores (PRS) for T2DM risk were provided by the UK Biobank. Using propensity scores adjusted for age, sex, body mass index, and comorbidities, 14 831 statin users were matched with 37 060 non-users. Cox proportional hazards models were used to estimate the interaction effect of statin use and PRS on T2DM incidence, adjusting for key confounders. Results: In the propensity-matched cohort, 3675 of 51 891 participants developed T2DM over a mean follow-up period of 13.7 years. Within the top 5% of the PRS distribution, per 1000 person-years, the incidence of T2DM was 15.42 for statin users versus 12.18 for non-users. Among the lowest 5%, the incidence was 1.90 for statin users and 1.65 for non-users. Based on the Cox proportional hazards model, regular statin use was associated with a 1.24-fold increased T2DM risk (95% confidence interval [CI], 1.15 to 1.33). Furthermore, PRS exhibited a significant multiplicative interaction with regular statin use (odds ratio, 1.10; 95% CI, 1.02 to 1.19). Conclusions PRS may help identify individuals particularly susceptible to the diabetogenic effects of statins, providing a potential path for personalized cardiovascular disease management.