Background: Rare cases of Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) have been reported following the coronavirus disease 2019 (COVID-19) vaccination; however, the association between COVID-19 vaccination and the risk of developing KD/MIS-C has not yet been established. Methods: We conducted a self-controlled case series analysis using a large-linked database that connects the COVID-19 immunization registry with nationwide claims data. We identified individuals aged < 18 years who received their initial COVID-19 vaccination and had a KD/MIS-C diagnosis with a prescription for intravenous immunoglobulin or corticosteroids between October 18, 2021, and April 15, 2023. The observation period was set as 240 days from the date of the COVID-19 vaccination. The risk window was 60 days after vaccination, with the remaining observation period serving as the control window. The incidence rate ratios (IRRs) and 95% confidence intervals (CIs) in the risk versus control windows were estimated using the conditional Poisson regression model. We further analyzed the vaccine doses and types for secondary analysis. We also performed subgroup analyses stratified by sex, age, comorbidities, and other conditions and sensitivity analyses by varying the length of the risk window and outcome definition. Results: Among 2,369,490 individuals who received the COVID-19 vaccination, 12 cases of KD/MIS-C were identified, which included five and seven patients in the risk and control windows, respectively. There was no increased risk of KD/MIS-C within the 60-day period of vaccination (IRR, 0.53; 95% CI, 0.17–1.60). Secondary subgroup and sensitivity analyses showed no significant increase in the risk of KD/MIS-C after COVID-19 vaccination, which is consistent with the results of the main analysis. Conclusion The results of this nationwide study suggest that the risk of developing KD/MIS-C did not increase after COVID-19 vaccination. However, owing to the lack of a sufficient number of cases, future studies utilizing multinational long-term follow-up databases should be conducted. Considering the increasing incidence of KD/MIS-C and the limited understanding of its precise biological mechanisms, additional research on KD/MIS-C is warranted.

Background: Rare cases of Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) have been reported following the coronavirus disease 2019 (COVID-19) vaccination; however, the association between COVID-19 vaccination and the risk of developing KD/MIS-C has not yet been established. Methods: We conducted a self-controlled case series analysis using a large-linked database that connects the COVID-19 immunization registry with nationwide claims data. We identified individuals aged < 18 years who received their initial COVID-19 vaccination and had a KD/MIS-C diagnosis with a prescription for intravenous immunoglobulin or corticosteroids between October 18, 2021, and April 15, 2023. The observation period was set as 240 days from the date of the COVID-19 vaccination. The risk window was 60 days after vaccination, with the remaining observation period serving as the control window. The incidence rate ratios (IRRs) and 95% confidence intervals (CIs) in the risk versus control windows were estimated using the conditional Poisson regression model. We further analyzed the vaccine doses and types for secondary analysis. We also performed subgroup analyses stratified by sex, age, comorbidities, and other conditions and sensitivity analyses by varying the length of the risk window and outcome definition. Results: Among 2,369,490 individuals who received the COVID-19 vaccination, 12 cases of KD/MIS-C were identified, which included five and seven patients in the risk and control windows, respectively. There was no increased risk of KD/MIS-C within the 60-day period of vaccination (IRR, 0.53; 95% CI, 0.17–1.60). Secondary subgroup and sensitivity analyses showed no significant increase in the risk of KD/MIS-C after COVID-19 vaccination, which is consistent with the results of the main analysis. Conclusion The results of this nationwide study suggest that the risk of developing KD/MIS-C did not increase after COVID-19 vaccination. However, owing to the lack of a sufficient number of cases, future studies utilizing multinational long-term follow-up databases should be conducted. Considering the increasing incidence of KD/MIS-C and the limited understanding of its precise biological mechanisms, additional research on KD/MIS-C is warranted.

Background: Rare cases of Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) have been reported following the coronavirus disease 2019 (COVID-19) vaccination; however, the association between COVID-19 vaccination and the risk of developing KD/MIS-C has not yet been established. Methods: We conducted a self-controlled case series analysis using a large-linked database that connects the COVID-19 immunization registry with nationwide claims data. We identified individuals aged < 18 years who received their initial COVID-19 vaccination and had a KD/MIS-C diagnosis with a prescription for intravenous immunoglobulin or corticosteroids between October 18, 2021, and April 15, 2023. The observation period was set as 240 days from the date of the COVID-19 vaccination. The risk window was 60 days after vaccination, with the remaining observation period serving as the control window. The incidence rate ratios (IRRs) and 95% confidence intervals (CIs) in the risk versus control windows were estimated using the conditional Poisson regression model. We further analyzed the vaccine doses and types for secondary analysis. We also performed subgroup analyses stratified by sex, age, comorbidities, and other conditions and sensitivity analyses by varying the length of the risk window and outcome definition. Results: Among 2,369,490 individuals who received the COVID-19 vaccination, 12 cases of KD/MIS-C were identified, which included five and seven patients in the risk and control windows, respectively. There was no increased risk of KD/MIS-C within the 60-day period of vaccination (IRR, 0.53; 95% CI, 0.17–1.60). Secondary subgroup and sensitivity analyses showed no significant increase in the risk of KD/MIS-C after COVID-19 vaccination, which is consistent with the results of the main analysis. Conclusion The results of this nationwide study suggest that the risk of developing KD/MIS-C did not increase after COVID-19 vaccination. However, owing to the lack of a sufficient number of cases, future studies utilizing multinational long-term follow-up databases should be conducted. Considering the increasing incidence of KD/MIS-C and the limited understanding of its precise biological mechanisms, additional research on KD/MIS-C is warranted.

Background: Rare cases of Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) have been reported following the coronavirus disease 2019 (COVID-19) vaccination; however, the association between COVID-19 vaccination and the risk of developing KD/MIS-C has not yet been established. Methods: We conducted a self-controlled case series analysis using a large-linked database that connects the COVID-19 immunization registry with nationwide claims data. We identified individuals aged < 18 years who received their initial COVID-19 vaccination and had a KD/MIS-C diagnosis with a prescription for intravenous immunoglobulin or corticosteroids between October 18, 2021, and April 15, 2023. The observation period was set as 240 days from the date of the COVID-19 vaccination. The risk window was 60 days after vaccination, with the remaining observation period serving as the control window. The incidence rate ratios (IRRs) and 95% confidence intervals (CIs) in the risk versus control windows were estimated using the conditional Poisson regression model. We further analyzed the vaccine doses and types for secondary analysis. We also performed subgroup analyses stratified by sex, age, comorbidities, and other conditions and sensitivity analyses by varying the length of the risk window and outcome definition. Results: Among 2,369,490 individuals who received the COVID-19 vaccination, 12 cases of KD/MIS-C were identified, which included five and seven patients in the risk and control windows, respectively. There was no increased risk of KD/MIS-C within the 60-day period of vaccination (IRR, 0.53; 95% CI, 0.17–1.60). Secondary subgroup and sensitivity analyses showed no significant increase in the risk of KD/MIS-C after COVID-19 vaccination, which is consistent with the results of the main analysis. Conclusion The results of this nationwide study suggest that the risk of developing KD/MIS-C did not increase after COVID-19 vaccination. However, owing to the lack of a sufficient number of cases, future studies utilizing multinational long-term follow-up databases should be conducted. Considering the increasing incidence of KD/MIS-C and the limited understanding of its precise biological mechanisms, additional research on KD/MIS-C is warranted.

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 life expectancy of people living with human immunodeficiency virus (PLWH) has significantly improved with advancements in antiretroviral therapy (ART). However, aging PLWH face a growing burden of noncommunicable diseases (NCDs), polypharmacy, and drug-drug interactions (DDIs), which pose challenges in their management. This study investigates the prevalence of NCDs, polypharmacy, and DDIs among PLWH aged ≥50 years in Korea and their impact on quality of life (QOL). Materials and Methods: A cross-sectional study was conducted among 243 PLWH aged ≥50 years receiving ART for at least three months at three university hospitals in Korea between January and July 2022. Data were collected through electronic medical records and personal interviews, assessing demographics, comorbidities, polypharmacy, ART adherence, and QOL using the Korean version of WHOQOL-HIV BREF scale. Potential DDIs were analyzed using the University of Liverpool HIV Drug Interaction Database, and potentially inappropriate medications (PIMs) were identified using the 2023 American Geriatrics Society Beers Criteria. We classified participants into three age groups:50–<65 years, 65–<75 years, and ≥75 years. Results: The prevalence of comorbidities was 71.6%, with older participants (≥75 years) showing a significantly higher burden, including bone diseases, osteoarthritis, and dementia (P<0.001). Polypharmacy was observed in 28.4% of participants and increased with age, with 53.3% of those aged ≥75 years taking ≥10 pills daily.Polypharmacy was associated with poorer QOL (71.6 vs. 76.6, P=0.010). Amber-flag DDIs were found in 81 participants (33.3%), most commonly involving metformin and divalent cations. No red-flag DDIs were identified.PIMs were observed in 6.6% of participants aged ≥65 years. Conclusion Aging PLWH in Korea face significant challenges from comorbidities, polypharmacy, and DDIs, which negatively impact QOL. Integrated, age-specific, and multidisciplinary care strategies are urgently needed to improve outcomes and ensure the well-being of older PLWH.

Background: The life expectancy of people living with human immunodeficiency virus (PLWH) has significantly improved with advancements in antiretroviral therapy (ART). However, aging PLWH face a growing burden of noncommunicable diseases (NCDs), polypharmacy, and drug-drug interactions (DDIs), which pose challenges in their management. This study investigates the prevalence of NCDs, polypharmacy, and DDIs among PLWH aged ≥50 years in Korea and their impact on quality of life (QOL). Materials and Methods: A cross-sectional study was conducted among 243 PLWH aged ≥50 years receiving ART for at least three months at three university hospitals in Korea between January and July 2022. Data were collected through electronic medical records and personal interviews, assessing demographics, comorbidities, polypharmacy, ART adherence, and QOL using the Korean version of WHOQOL-HIV BREF scale. Potential DDIs were analyzed using the University of Liverpool HIV Drug Interaction Database, and potentially inappropriate medications (PIMs) were identified using the 2023 American Geriatrics Society Beers Criteria. We classified participants into three age groups:50–<65 years, 65–<75 years, and ≥75 years. Results: The prevalence of comorbidities was 71.6%, with older participants (≥75 years) showing a significantly higher burden, including bone diseases, osteoarthritis, and dementia (P<0.001). Polypharmacy was observed in 28.4% of participants and increased with age, with 53.3% of those aged ≥75 years taking ≥10 pills daily.Polypharmacy was associated with poorer QOL (71.6 vs. 76.6, P=0.010). Amber-flag DDIs were found in 81 participants (33.3%), most commonly involving metformin and divalent cations. No red-flag DDIs were identified.PIMs were observed in 6.6% of participants aged ≥65 years. Conclusion Aging PLWH in Korea face significant challenges from comorbidities, polypharmacy, and DDIs, which negatively impact QOL. Integrated, age-specific, and multidisciplinary care strategies are urgently needed to improve outcomes and ensure the well-being of older PLWH.