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Exposure-crossover observations of air pollution after large-scale fireworks in two Korean megacities, Seoul and Busan: Empirical evidence toward sustainable festivals
No full textFirework burning can significantly contribute to emissions of ambient air pollutants such as particulate matters (PM), which might pose serious public health concerns. Nevertheless, environmental research and public health attention to this matter are limited in many countries, particularly in Korea where firework festivals remain popular in megacities. This study aimed to examine temporal and spatial patterns of ambient air pollution during large-scale firework festivals in two megacities of Korea, focusing on each event held in Seoul (the second highest population in the world, as a metropolitan area) and Busan (the second highest population in Korea) in 2023. We used self-matched exposure-crossover design to compare ambient air pollution trends on exposure-event days (firework festival dates) with those on reference days (one week before and after festival dates) to evaluate a sole contribution of firework display. We analyzed data from air quality monitoring stations and visualized spatiotemporal changes in concentrations of air pollutants (i.e., PM(2.5), PM(10), and SO(2)) during the festival period. Analysis of the Seoul festival revealed significant increases in PM(2.5) and PM(10) concentrations following fireworks, with peaks reaching 320 and 371 mug/m(3). Similar patterns were observed after the Busan festival, with peak concentrations of 241 and 253 mug/m(3) for PM(2.5) and PM(10). These concentrations were 7.4-12.2 times higher than those observed on reference days. Spatiotemporal analysis demonstrated that PM(2.5) and PM(10) emitted from fireworks dispersed in the direction of wind. In contrast to high increases in PM(2.5) and PM(10), SO(2) levels showed light increases after both festivals, with a peak concentration of 4.9 ppb in Seoul and 5.7 ppb in Busan. Considering the estimated attendance of about a million at each festival and the high-density population area around two firework locations, the potential health risk posed by firework-related air pollution is a significant public health concern
Conventional versus Instillation Negative-Pressure Wound Therapy for Severe Soft Tissue Injury in Open Pelvic Fractures: A Retrospective Review
No full textPURPOSE: We investigated the clinical features, current negative-pressure wound therapy (NPWT) management strategies, and outcomes of pelvic-perineal soft tissue infection after open pelvic fractures. MATERIALS AND METHODS: We analyzed the data of patients admitted to our trauma center with pelvic-perineal soft tissue after open pelvic fractures over a 7-year period. We investigated the injury severity score (ISS), medical costs, number of NPWTs, time required to reach definite wound coverage, complications, fracture classifications, transfusion requirements, interventions, length of stay (LOS) in hospital and intensive care unit (ICU), and prognosis. RESULTS: Twenty patients with open pelvic fractures were treated with NPWT, and one patient who underwent NPWT died of pelvic sepsis during ICU treatment. The median LOS in hospital and medical costs were 98 [56-164] days and 106400 [65600-171100] USD, respectively. Patients treated with instillation NPWT (iNPWT, n=10) had a shorter NPWT duration (24 [13-39] vs. 46 [42-91] days, p=0.023), time to definite wound coverage (30 [21-43] vs. 49 [42-93] days, p=0.026), and hospital LOS (56 [43-72] vs. 158 [101-192] days, p=0.001), as well as lower medical costs (67800 [42500-102500] vs. 144200 [110400-236000] USD, p=0.009) compared to those treated with conventional NPWT. CONCLUSION: NPWT is a feasible method for treating pelvic soft tissue infections in patients with open pelvic fractures. iNPWT can reduce the duration of NPWT, hospital LOS, and medical costs
Semantic variant primary progressive aphasia with ANXA11 p.D40G
No full textINTRODUCTION: Pathogenic variants of annexin A11 (ANXA11) have been identified in patients with amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). We explored ANXA11 pathogenic variants in a Korean FTD cohort to investigate the prevalence and the role of ANXA11 variation in FTD. METHODS: We used next-generation sequencing (NGS) to search for pathogenic variants in ANXA11 in two nationwide FTD cohorts in Korea. RESULTS: We identified a pathogenic variant in ANXA11, c.119A > G (p.D40G), in six patients with semantic variant primary progressive aphasia (svPPA), representing 5.5% of the svPPA cohort (6/109), and representing 2.3% of the FTD cohort overall (6/259). Only one patient later developed features suggestive of ALS. DISCUSSION: This study links a rare variant in ANXA11 to a sporadic clinical syndrome in which specific TAR DNA-binding protein-43 (TDP-43) forms an obligate co-fibril with annexin A11. The variant, p.D40G, lies within the N-terminal portion of annexin A11's TDP-43 type C interacting domain, suggesting that genetic variation in that region may promote co-fibrillization. HIGHLIGHTS: The pathogenic variant of annexin A11 (ANXA11I) is linked to frontotemporal dementia (FTD) syndrome. ANXA11 (p.D40G) may be one of the possible genetic causes of semantic variant primary progressive aphasia (svPPA). ANXA11 (p.D40G) may enhance heteromeric amyloid filaments of annexin A11 and TDP-43, promoting frontotemporal lobar degeneration with TAR DNA-binding protein-43 (TDP-43) inclusions (FTLD-TDP) type C
Psychological distress in newly diagnosed patients with gastrointestinal cancer: A scoping review
No full textOBJECTIVE: A cancer diagnosis often triggers significant emotional and psychological challenges, underscoring the importance of addressing psychological distress. While psychological distress in patients with gastrointestinal (GI) cancer has been widely studied, less attention has been focused on those who are newly diagnosed. This scoping review aims to map the existing literature on psychological distress in newly diagnosed patients with GI cancer. METHODS: A scoping review was conducted following the framework outlined by Arksey and O'Malley. The last search was carried out on September 23, 2024, across PubMed, CINAHL, EMBASE, Scopus, and PsychINFO for literature published between January 2013 and September 2024. The search terms included "newly diagnosed," "distress," "patients," and "gastrointestinal cancer." A meta-analysis was conducted using the R package to synthesize the prevalence of psychological distress across studies, with a random-effects model applied to account for heterogeneity. RESULTS: Fifteen studies were included in the analysis, revealing an average prevalence of psychological distress of 28.1% (99% CI: 181.84, 433.39). Psychological distress was most prevalent during the diagnostic phase and gradually decreased over time. Factors such as older age, advanced cancer stage, poor performance status, and a lack of social support contributed to increased psychological distress. Additionally, only 20% of the studies were intervention-based. CONCLUSIONS: Approximately one-third of newly diagnosed patients with GI cancer may experience psychological distress. Early identification and intervention to address this distress before treatment initiation are crucial for improving patient outcomes. SYSTEMATIC REVIEW REGISTRATION: osf.io/n2796
Analysis of Retinal Thickness in Patients With Chronic Diseases Using Standardized Optical Coherence Tomography Data: Database Study Based on the Radiology Common Data Model
No full textBACKGROUND: The Observational Medical Outcome Partners-Common Data Model (OMOP-CDM) is an international standard for harmonizing electronic medical record (EMR) data. However, since it does not standardize unstructured data, such as medical imaging, using this data in multi-institutional collaborative research becomes challenging. To overcome this limitation, extensions such as the Radiology Common Data Model (R-CDM) have emerged to include and standardize these data types. OBJECTIVE: This work aims to demonstrate that by standardizing optical coherence tomography (OCT) data into an R-CDM format, multi-institutional collaborative studies analyzing changes in retinal thickness in patients with long-standing chronic diseases can be performed efficiently. METHODS: We standardized OCT images collected from two tertiary hospitals for research purposes using the R-CDM. As a proof of concept, we conducted a comparative analysis of retinal thickness between patients who have chronic diseases and those who have not. Patients diagnosed or treated for retinal and choroidal diseases, which could affect retinal thickness, were excluded from the analysis. Using the existing OMOP-CDM at each institution, we extracted cohorts of patients with chronic diseases and control groups, performing large-scale 1:2 propensity score matching (PSM). Subsequently, we linked the OMOP-CDM and R-CDM to extract the OCT image data of these cohorts and analyzed central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness using a linear mixed model. RESULTS: OCT data of 261,874 images from Ajou University Medical Center (AUMC) and 475,626 images from Seoul National University Bundang Hospital (SNUBH) were standardized in the R-CDM format. The R-CDM databases established at each institution were linked with the OMOP-CDM database. Following 1:2 PSM, the type 2 diabetes mellitus (T2DM) cohort included 957 patients, and the control cohort had 1603 patients. During the follow-up period, significant reductions in CMT were observed in the T2DM cohorts at AUMC (P=.04) and SNUBH (P=.007), without significant changes in RNFL thickness (AUMC: P=.56; SNUBH: P=.39). Notably, a significant reduction in CMT during the follow-up was observed only at AUMC in the hypertension cohort, compared to the control group (P=.04); no other significant differences in retinal thickness were found in the remaining analyses. CONCLUSIONS: The significance of our study lies in demonstrating the efficiency of multi-institutional collaborative research that simultaneously uses clinical data and medical imaging data by leveraging the OMOP-CDM for standardizing EMR data and the R-CDM for standardizing medical imaging data
How to treat recurrent focal segmental glomerulosclerosis after kidney transplantation in children
No full textFocal segmental glomerulosclerosis (FSGS), a significant cause of kidney failure in children, is a common pathological diagnosis in cases of idiopathic nephrotic syndrome, especially steroid-resistant ones. FSGS has the potential to recur after kidney trans-plantation, often leading to graft loss. However, not all children with FSGS experience recurrence posttransplantation, such as those with genetic or secondary forms, which have minimal risk. Moreover, advancements in management, including intensive plasmapheresis and immunosuppressive therapies like rituximab, have increased remission rates in cases of recurrence. Iden-tifying patients at high risk of recurrence, such as those with an initial treatment response or previous failed transplantation, is crucial. These children require close monitoring of proteinuria and prompt, intensive treatment upon recurrence to improve outcomes
KASL clinical practice guidelines for the management of metabolic dysfunction-associated steatotic liver disease 2025
No full textPalbociclib plus endocrine therapy versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (Young-PEARL): overall survival analysis of a randomised, open-label, phase 2 study
No full textBACKGROUND: The phase 2 randomised Young-PEARL study demonstrated that palbociclib plus exemestane with ovarian function suppression significantly prolonged progression-free survival compared with capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Here, we report results of the protocol-specified secondary endpoint of overall survival. METHODS: Young-PEARL was a multicentre, randomised, open-label, phase 2 study conducted at 14 institutions in South Korea. Premenopausal women aged 19 years or older with histologically confirmed hormone receptor-positive, HER2-negative metastatic breast cancer that recurred or progressed during or after previous tamoxifen treatment, who were aromatase inhibitor naive, and had an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. One previous line of chemotherapy was permitted in the metastatic setting. Eligible patients were randomly assigned (1:1), using block randomisation (block size of two) stratified by previous chemotherapy for metastatic breast cancer and presence of visceral metastasis, to receive either palbociclib (orally, 125 mg per day on a 3-weeks-on, 1-week off schedule) plus exemestane (orally 25 mg daily) with leuprorelin (subcutaneously 3.75 mg on day 1 of each 28-day cycle) or capecitabine (orally, 1250 mg/m(2) twice a day on a 2-weeks-on, 1-week-off schedule) until disease progression or unacceptable toxicity). The primary endpoint was progression-free survival. Overall survival was a secondary endpoint. All analyses were done in the modified intention-to-treat population (ie, included all patients randomly assigned to treatment who had at least one post-baseline CT scan and excluded those who did not receive study medication and who had any major violation of the eligible criteria). Safety was assessed in all patients who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02592746, and is now complete. FINDINGS: Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled. 184 patients were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92), of whom 174 were included in the modified intention-to-treat population (n=90 in the palbociclib plus endocrine therapy group and n=84 in the capecitabine group). All patients were female and ethnicity data were not collected. As of data cutoff (Feb 29, 2024), median follow-up was 54.0 months (IQR 34.1-74.4). Median progression-free survival was 19.5 months (90% CI 14.3-22.2) for palbociclib plus endocrine therapy and 14.0 months (11.7-18.7) for capecitabine (hazard ratio 0.74 [90% CI 0.57-0.98]; one-sided log-rank p=0.036). 52 (58%) of 90 patients in the palbociclib plus endocrine therapy group and 48 (57%) of 84 in the capecitabine group died, with a median overall survival of 54.8 months (95% CI 48.9-77.1) in the palbociclib plus endocrine therapy group versus 57.8 months (46.3-89.2) in the capecitabine group (hazard ratio 1.02 [95% CI 0.69-1.51]; p=0.92). The most common grade 3 or worse adverse event was neutropenia (59 [64%] of 92 in the palbociclib plus endocrine therapy group vs 15 [18%] of 85 in the capecitabine group) . No treatment-related deaths occurred. INTERPRETATION: With extended follow-up, palbociclib plus exemestane with ovarian function suppression continued to show a significant benefit in progression-free survival compared with capecitabine in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who had been previously treated with tamoxifen; however, no improvement in overall survival was seen. Given the progression-free survival benefit, the upfront use of palbociclib plus endocrine therapy is the preferred option for premenopausal women, although a capecitabine-first strategy might be an alternative treatment strategy for maintaining overall survival in resource-limited settings. FUNDING: Pfizer and Ministry of Health & Welfare, South Korea
Integrative transcriptomic and genomic analyses unveil the IFI16 variants and expression as MASLD progression markers
No full textBACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a broad and continuous spectrum of liver diseases ranging from fatty liver to steatohepatitis. The intricate interactions of genetic, epigenetic, and environmental factors in the development and progression of MASLD remain elusive. Here, we aimed to achieve an integrative understanding of the genomic and transcriptomic alterations throughout the progression of MASLD. APPROACH AND RESULTS: RNA-Seq profiling (n = 146) and whole-exome sequencing (n = 132) of MASLD liver tissue samples identified 3 transcriptomic subtypes (G1-G3) of MASLD, which were characterized by stepwise pathological and molecular progression of the disease. Macrophage-driven inflammatory activities were identified as a key feature for differentiating these subtypes. This subtype-discriminating macrophage interplay was significantly associated with both the expression and genetic variation of the dsDNA sensor IFI16 (rs6940, A>T, T779S), establishing it as a fundamental molecular factor in MASLD progression. The in vitro dsDNA-IFI16 binding experiments and structural modeling revealed that the IFI16 variant exhibited increased stability and stronger dsDNA binding affinity compared to the wild-type. Further downstream investigation suggested that the IFI16 variant exacerbated DNA sensing-mediated inflammatory signals through mitochondrial dysfunction-related signaling of the IFI16-PYCARD-CASP1 pathway. CONCLUSIONS: This study unveils a comprehensive understanding of MASLD progression through transcriptomic classification, highlighting the crucial roles of IFI16 variants. Targeting the IFI16-PYCARD-CASP1 pathway may pave the way for the development of novel diagnostics and therapeutics for MASLD
Pan-Variant SARS-CoV-2 Vaccines Induce Protective Immunity by Targeting Conserved Epitopes
No full textThe development of a globally effective COVID-19 vaccine faces significant challenges, particularly in redirecting the B-cell response from immunodominant yet variable regions of viral proteins toward their conserved domains. To address this, an integrated strategy is implemented that combines classical B-cell epitope prediction with protein-antibody cluster docking and antibody titer analysis from 30 vaccinated and convalescent individuals. This approach yields stable immunodominant and immunoprevalent B-cell epitopes capable of eliciting robust antibody responses in BALB/c mice and effectively neutralizing pseudoviruses expressing the Spike protein of SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, Delta, and Omicron. To achieve a broader T-cell-based immune response, promiscuous T-cell epitopes are identified by integrating classical T-cell epitope predictions, differential scanning fluorimetry, and peptide-MHC structural analysis. Unique peptides with conserved MHC-anchoring residues are identified, enabling binding to a spectrum of MHC-I and MHC-II haplotypes. These peptides elicit strong interferon gamma responses in human peripheral blood mononuclear cells and demonstrate cross-species efficacy by activating both CD4+ and CD8+ T-cells in BALB/c mice. Collectively, these findings highlight the significance of innovative vaccine strategies targeting immunodominant/immunoprevalent B-cell and promiscuous T-cell epitopes to drive broad and robust humoral and cellular immune responses against a wide range of SARS-CoV-2 variants