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.

Double-lumen endotracheal tubes (DLT) are essential for one-lung ventilation during thoracic surgery. Bronchoscopy is crucial for correct placement of a DLT to avoid complications such as hypoxemia. This study evaluated the effectiveness of the triple-cuffed DLT (tcDLT) in the supine and lateral positions for correct placement without bronchoscopic guidance. Methods: This prospective observational study included 167 patients scheduled for elective thoracic surgery requiring one-lung ventilation. The incidence of successful placement of left-sided tcDLTs was compared between the supine and lateral decubitus positions under bronchoscopic surveillance. Successful tcDLT placement was defined as the placement of the proximal end of the bronchial cuff within 5 mm of the carina. Results: Among 153 patients who completed the study, the successful tcDLT placement rate in the lateral position (70.6%) was significantly higher than that in the supine position (50.3%). The rate of difference was 20.3% (95% confidence interval [CI], 10.6–29.9%). The extended successful placement rate, including slightly deeper placements, showed no significant differences between the positions (88.9%; 95% CI, 83.9–93.9% in supine, 86.3%; 95% CI, 80.8–91.7% in lateral). Conclusions: tcDLT facilitates correct tube placement in both the supine and lateral positions, with a higher lateral success rate. This finding supports the idea that tcDLTs offer a reliable alternative for lung separation when bronchoscopy is not feasible.

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.

Advances in surgical techniques, perioperative management, and immunosuppressive therapies (ISs) have significantly improved the clinical outcomes of liver transplantation (LT). However, these advancements have also highlighted the importance of addressing non-hepatic complications, particularly cardiovascular events (CVEs), in the management of LT patients. Key risk factors for CVEs in post-LT patients include metabolic conditions such as diabetes mellitus (DM), hypertension (HTN), and dyslipidemia. The continued need for ISs contributes to the development of these metabolic complications, making their management crucial for optimizing patient outcomes. This review aims to summarize current strategies for managing metabolic complications, including DM, HTN, and dyslipidemia, in post-LT patients.

Rotator cuff tears are common shoulder injuries that often necessitate surgical intervention, particularly when nonoperative treatments fail. Arthroscopic rotator cuff repair is the current gold standard; however, challenges, such as high retear rates, especially in large tears, persist. Traditional techniques, such as single-row and double-row repairs, have limitations in fully restoring the anatomical footprint and ensuring optimal healing. This review examines the novel double pulley-triple row technique, which aims to overcome these limitations by enhancing the footprint contact area, load distribution, and tendon healing. By evaluating the double pulley-triple row method in comparison to established techniques, this study explores the potential advantages, limitations, and future directions of rotator cuff repair.

Background: The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus. Methods: Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis. Results: During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration. Conclusion Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.

Background: Given the association between nonalcoholic fatty liver disease and metabolic risks, a new term, metabolic dysfunction- associated steatotic liver disease (MASLD) has been proposed. We aimed to explore the association between MASLD and all-cause, cause-specific mortalities. Methods: We included individuals with steatotic liver disease (SLD) from the Korean National Health Insurance Service. Moreover, SLD was defined as a fatty liver index ≥30. Furthermore, MASLD, metabolic alcohol-associated liver disease (MetALD), and alcoholic liver disease (ALD) with metabolic dysfunction (MD) were categorized based on alcohol consumption and MD. We also analyzed all-cause, liver-, cancer-, hepatocellular carcinoma (HCC)- and cardiovascular (CV)-related mortalities. Results: This retrospective nationwide cohort study included 1,298,993 individuals aged 40 to 79 years for a mean follow-up duration of 9.04 years. The prevalence of MASLD, MetALD, and ALD with MD was 33.11%, 3.93%, and 1.00%, respectively. Relative to the “no SLD” group, multivariable analysis identified that MASLD (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.26 to 1.31), MetALD (aHR, 1.38; 95% CI, 1.32 to 1.44), and ALD with MD group (aHR, 1.80; 95% CI, 1.68 to 1.93) have a significantly higher risk of all-cause mortality. Furthermore, MASLD, MetALD, ALD with MD groups showed higher liver-, cancer- and HCC-related mortality than “no SLD” group. While all-cause specific mortalities increase from MASLD to MetALD to ALD with MD, the MetALD group shows a lower risk of CV-related mortality compared to MASLD. However, ALD with MD group still have a higher risk of CV-related mortality compared to MASLD. Conclusion SLD is associated with an increased risk of all-cause, liver-, cancer-, HCC-, and CV-related mortalities.

Background: The mortality of sepsis without direct drugs is high. The association between prediabetes, based on a single fasting glucose (FG), or long-term type 2 diabetes mellitus (T2DM) and sepsis remains unclear. Methods: Of the adults aged ≥20 years who were included in the National Health Screening Program (NHSP) in 2009, 40% were randomly sampled. After excluding patients with type 1 diabetes mellitus, with missing information, and who were diagnosed with sepsis during the wash-out (between 2001 and the NHSP) or 1-year lag period, a cohort comprised of 3,863,323 examinees. Body mass index (BMI) measurements, FG tests, and self-reported questionnaires on health-related behaviors were conducted. Individual information was followed up until 2020 and censored upon the first occurrence of sepsis or death. The incidence of sepsis was compared using a multivariable regression adjusted for age, sex, income, BMI, smoking, drinking, physical activity levels, and chronic diseases. Results: The cohort was divided into those with normal FG (n=2,675,476), impaired fasting glucose (IFG) (n=890,402, 23.0%), T2DM <5 years (n=212,391, 5.5%), or T2DM for ≥5 years (n=85,054, 2.2%). The groups with IFG (adjusted hazard ratio [aHR], 1.03; 95% confidence interval [CI], 1.01 to 1.05), T2DM <5 years (aHR, 1.43; 95% CI, 1.40 to 1.47), and T2DM for ≥5 years (aHR, 1.82; 95% CI, 1.77 to 1.87) exhibited significantly higher incidence of sepsis (P<0.001), with the greatest risk in patients with T2DM aged <40 years (aHR, 1.96; 95% CI, 1.71 to 2.25). Conclusion Patients with long-standing and young-onset T2DM show a substantially high risk of sepsis, emphasizing the need for infection prevention and vaccination.

Background: We aimed to investigate the predictive values of plasma C-peptide levels and the continuous glucose monitoring (CGM)-defined coefficient of variation (CV) in risk prediction for hypoglycemia in Korean people with diabetes with normal and impaired kidney function. Methods: We analyzed data from 1,185 participants diagnosed with type 1 and type 2 diabetes who underwent blinded professional CGM between January 2009 and May 2021 at outpatient clinics. We explored correlations among CGM-defined CV, plasma C-peptide levels, and time below range at <70 and 54 mg/dL across different kidney function categories. Results: In patients with chronic kidney disease (CKD) stages 1–2 (n=934), 89.3% who had a random plasma C-peptide level higher than 600 pmol/L exhibited a CV of ≤36%. Among those in CKD stage 3 (n=161) with a random plasma C-peptide level exceeding 600 pmol/L, 66.7% showed a CV of ≤36%. In stages 4–5 of CKD (n=90), the correlation between random C-peptide levels and CV was not significant (r=–0.05, P=0.640), including cases with a CV greater than 36% despite very high random plasma C-peptide levels. Random plasma C-peptide levels and CGM-assessed CV significantly predicted hypoglycemia in CKD stages 1–2 and 1–5, respectively. Conclusion The established C-peptide criteria in Western populations are applicable to Korean people with diabetes for hypoglycemic risk prediction, unless kidney function is impaired equivalent to CKD stage 3–5. The CGM-defined CV is informative for hypoglycemic risk prediction regardless of kidney function.