Changes in gut microbiome can be associated with abrupt seizure exacerbation in epilepsy patients.

OBJECTIVE: Seizures can be triggered by a variety of endogenous or exogenous factors. We hypothesized that alterations in the gut microbiome may be a seizure precipitant and analyzed the composition and characteristics of the gut microbiome in epilepsy patients who experienced an abrupt seizure exacerbation without a clear seizure precipitant. METHODS: We prospectively enrolled 25 adult patients with epilepsy and collected fecal samples on the admission and after seizure recovery for next-generation sequencing analysis. We performed nonparametric paired t-test analysis to evaluate changes in the gut microbiota as seizures worsened and when it recovered and also estimated alpha and beta diversities in each category. RESULTS: A total of 19 patients (13 males) aged between 19 and 78 years (mean 45.2 years) were included in the study. The composition of the gut microbiota underwent a significant change following an abrupt seizure exacerbation. At the phylum level, the relative abundance of Fusobacteria and Synergistetes was decreased in the seizure recovery state compared to the acute seizure exacerbation. A similar trend was observed at the lower hierarchical levels, with a decrease in the relative abundance of Fusobacteria, Tissierellia, and Synergistia at the class level, and that of Synergistales, Tissierellales, and Fusobacteriales at the order level. At the family level, the relative abundance of Fusobacteriaceae and Staphylococcaceae was decreased, whereas that of Leuconostocaceae was increased. No statistical differences were observed in alpha and beta diversity between the pre- and post-acute seizure exacerbation periods. SIGNIFICANCE: Our study suggests that the changes in Fusobacteriaceae and Lecuonostocaceae may be associated with acute seizure exacerbation in epilepsy patients. Given that Fusobacteriaceae are associated with various systemic diseases due to their invasive properties and that Leuconostocaceae are known to produce GABA, our results may suggest a gut microbiome-based treatment option for epilepsy patients.

Characteristic differences between full-term and premature infants with intermittent exotropia.

Strabismus is prevalent among preterm infants of low gestational age and birth weight in Southeast Asian countries, with intermittent exotropia (IXT) being the most common type in South Korea. In this retrospective, cross-sectional study, we investigated the differences between full-term and premature infants with IXT. IXT patients with available childbirth history were divided into two groups: preterm vs. full-term and low birth weight (LBW) vs. normal birth weight (NBW). Parameters related to exotropia including parental heredity, surgical history, and treatment options were investigated. In univariate regression for gestational age, a result of ≥ 100 s in the Titmus test was 1.352 times more frequent in preterm than in full-term infants. When birth weight was considered instead, a result of ≥ 100 s in the Titmus test was 1.412 times more frequent in the LBW compared to the NBW group. In multivariate regression for birth weight, the frequency of a result of ≥ 100 s in the Titmus test for the LBW group was 2.032 times higher than that for the NBW group. It is particularly important to examine stereopsis in preterm and LBW patients affected by IXT to ensure timely surgical planning and avoid potential recurrence after surgery.

Effects of maternal nonylphenol exposure on the proliferation of glial cells in the brain of male offspring mice.

Glial cells play a significant role in maintaining brain homeostasis and normal brain development, and their functions can be impaired by exposure to endocrine disruptors. 4-n-Nonylphenol (NP), a representative endocrine disruptor, is widely used in personal care products and industrial materials. NP accumulates in various organs, including the brain, of living organisms and adversely influences brain health. However, studies on the effects of NP on glial cells are limited. This study aims to investigate the effects of NP on glial cells using primary mixed glial cells and offspring mice exposed to NP during gestation and lactation. In vitro experiments revealed that NP exposure stimulated the astrocytes and microglia proliferation but not oligodendrocytes. NP exposure activated microglia and reduced myelin protein expression in oligodendrocytes. Moreover, maternal NP exposure increased the numbers of microglia and oligodendrocytes in the cerebral cortex of adult offspring. NP exposure caused anxiety- and depressive-like behaviors in adult mice. Collectively, these findings suggest that maternal NP exposure negatively affects the brain development in adult offspring mice.

Simultaneous removal and separate recovery of radioactive Cs+ and I- ions from wastewater using a reusable bifunctional composite, Ni@Pt/K2NiFe(CN)6.

Radioactive Cs+ and I- ions are major components of nuclear wastewater, typically existing as counter ions. Due to their high water solubility and mobility, these ions can spread through contaminated water and soil into ecosystems, necessitating continuous removal and management. In this study, we synthesized a reusable bifunctional Ni@Pt/K2NiFe(CN)6 composite that can simultaneously remove radioactive Cs+ and I- ions and, for the first time, enable their separate recovery in aqueous solutions. In this material, K2NiFe(CN)6 acted as an electrochemically switched ion exchanger, controlling the adsorption/desorption of Cs+, while Pt enabled the spontaneous adsorption and electrochemical desorption of I-, and the magnetic Ni core allowed for efficient adsorbent recovery. The adsorption isotherms of both Cs+ and I- were best fitted using the Langmuir model, and the corresponding adsorption capacities were comparable to those of conventional adsorbents used for the separate removal of Cs+ and I-. Furthermore, the composite demonstrated stability over 100 sorption cycles, maintaining high recovery efficiencies of 97.9 % for Cs+ and 99.7 % for I-, thereby proving its reusability. Thus, the developed composite holds great promise for radioactive wastewater treatment and environmental restoration.

Recurrent and De Novo Focal Segmental Glomerulosclerosis After Kidney Transplantation: Comparison of Clinical Features and Transplant Outcomes.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a notable subtype of glomerulonephritis in kidney transplantation, often resulting in graft failure. Yet, research comparing transplant outcomes between de novo and recurrent FSGS is scarce. This study aims to compare clinical features and transplant outcomes between these two categories. METHODS: This retrospective study enrolled 773 kidney transplant recipients from two centers between January 2008 and October 2021. Patients diagnosed with FSGS through graft kidney biopsy were included. They were categorized into two groups based on the time of FSGS occurrence and results of native kidney biopsy: the recurrent FSGS group and the de novo FSGS group. RESULTS: Of 773 kidney transplant patients, 24 had primary FSGS-causing end-stage renal disease. During a median 65-month follow-up, 5 of these patients developed recurrent FSGS (incidence: 26.3%). Among 749 patients with other kidney diseases causing end-stage renal disease, 9 had de novo FSGS (incidence: 1.2%). In the recurrent FSGS group, 2 out of 5 patients experienced graft failure, with no deaths or acute rejections. Similarly, in the de novo FSGS group, 3 out of 9 patients experienced graft failure, with no deaths or acute rejections. Kaplan-Meier analysis showed slower graft loss in de novo FSGS, resulting in a higher graft survival rate compared to recurrent FSGS (probability of graft survival, 60% vs 33.3%, P = .036). CONCLUSIONS: Graft loss progresses more slowly in de novo FSGS compared to recurrent FSGS, resulting in a higher long-term graft survival rate in de novo FSGS than in recurrent FSGS.

Psychotropic drug prescribing before and during the COVID-19 pandemic among people with depressive and anxiety disorders: a multinational network study.

BACKGROUND: People with mental health conditions were potentially more vulnerable than others to the neuropsychiatric effects of the COVID-19 pandemic and the global efforts taken to contain it. The aim of this multinational study was to examine the changes in psychotropic drug prescribing during the pandemic among people with depressive and anxiety disorders. METHODS: This study included electronic medical records and claims data from nine databases in six countries (France, Germany, Italy, the UK, South Korea, and the USA) of patients with a diagnosis of depressive or anxiety disorders between 2016 and 2021. The outcomes were monthly prevalence rates of antidepressant, antipsychotic, and anxiolytic drug prescribing. The associations between the pandemic and psychotropic drug prescribing were examined with interrupted time series analyses for the total sample and stratified by sex and age group. People with lived experience were not involved in the research and writing process. FINDINGS: Between Jan 1, 2016 and Dec 31, 2020, an average of 16 567 914 patients with depressive disorders (10 820 956 females [65·31%] and 5 746 958 males [34·69%]) and 15 988 451 patients with anxiety disorders (10 688 788 females [66·85%] and 5 299 663 males [33·15%]) were identified annually. Most patients with depressive disorders and anxiety disorders were aged 45-64 years. Ethnicity data were not available. Two distinct trends in prescribing rates were identified. The first pattern shows an initial surge at the start of the pandemic (eg, antipsychotics among patients with depressive disorders in MDCD_US (rate ratio [RR] 1·077, 95% CI 1·055-1·100), followed by a gradual decline towards the counterfactual level (RR 0·990, 95% CI 0·988-0·992). The second pattern, observed in four databases for anxiolytics among patients with depressive disorders and two for antipsychotics among patients with anxiety disorders, shows an immediate increase (eg, antipsychotics among patients with anxiety disorders in IQVIA_UK: RR 1·467, 95% CI 1·282-1·675) without a subsequent change in slope (RR 0·985, 95% CI 0·969-1·003). In MDCD_US and IQVIA_US, the anxiolytic prescribing rate continued to increase among patients younger than 25 years for both disorders. INTERPRETATION: The study reveals persistently elevated rates of psychotropic drug prescriptions beyond the initial phase of the pandemic. These findings underscore the importance of enhanced mental health support and emphasise the need for regular review of psychotropic drug use among this patient group in the post-pandemic era. FUNDING: University Grants Committee, Research Grants Council, The Government of the Hong Kong Special Administrative Region.

Laser-responsive erastin-loaded chondroitin sulfate nanomedicine targeting CD44 and system xc- in liver cancer: A non-ferroptotic approach.

Erastin, a ferroptosis-inducing system xc- inhibitor, faces clinical challenges due to suboptimal physicochemical and pharmacokinetic properties, as well as relatively low potency and off-target toxicity. Addressing these, we developed ECINs, a novel laser-responsive erastin-loaded nanomedicine utilizing indocyanine green (ICG)-grafted chondroitin sulfate A (CSA) derivatives. Our aim was to improve erastin's tumor targeting via CSA-CD44 interactions and enhance its antitumor efficacy through ICG's photothermal and photodynamic effects in the laser-on state while minimizing off-target effects in the laser-off state. ECINs, with their nanoscale size of 186.7 ±â€¯1.1 nm and high erastin encapsulation efficiency of 93.0 ±â€¯0.8 %, showed excellent colloidal stability and sustained drug release up to 120 h. In vitro, ECINs demonstrated a mechanism of cancer cell inhibition via G1-phase cell cycle arrest, indicating a non-ferroptotic action. In vivo biodistribution studies in SK-HEP-1 xenograft mice revealed that ECINs significantly enhanced tumor distribution of erastin (1.9-fold greater than free erastin) while substantially reducing off-target accumulation in the lungs and spleen by 203-fold and 19.1-fold, respectively. Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system xc-.

Sustainable Management of Medical Plastic Waste through Carbon Dioxide-Assisted Pyrolysis.

To address the challenges associated with medical plastic waste and to characterize its heterogeneity, non-recyclability, and potential biohazard risks, this study explored a carbon dioxide (CO2)-assisted pyrolysis process as a sustainable disposal method. Medical plastic waste typically includes polypropylene, polystyrene, and polyvinyl chloride. To experimentally evaluate the functional reactivity of CO2, we employed three pyrolysis setups (one-stage, two-stage, and catalytic processes). The technical advantages of using CO2 over inert gases such as nitrogen (N2) were demonstrated through pyrolysis tests. The results showed that energy production was enhanced under CO2 conditions, with catalytic pyrolysis generating 146% more flammable gases compared to pyrolysis in an N2 environment. The use of CO2 also led to a reduction in the formation of toxic chemicals due to improved thermal cracking. The CO2-assisted pyrolysis process exhibited net negative CO2 emissions when a catalyst was present, as a substantial amount of CO2 was consumed during the process. In conclusion, CO2-assisted pyrolysis of medical plastic waste offers a sustainable management solution that maximizes the utilization of carbon resources.

Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection.

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.

Analysis of the current status of interview evaluations in Korean medical schools and professors' perceptions of the interview evaluations process.

PURPOSE: This study aimed to investigate the overall operational status of medical school admission interview evaluations in South Korea and explore the operational experience of universities conducting interview evaluations. METHODS: This study used a mixed-methods approach, combining quantitative and qualitative methods. Through a nationwide survey and data collection from 39 medical schools, the quantitative analysis explored interview evaluations procedures, the purpose of the interview evaluations, and the competencies expected of medical school freshmen. Concurrently, qualitative data were obtained through focus group discussions with 12 professors from 10 medical schools, providing in-depth insights into the operational experiences and challenges faced during interview evaluations. RESULTS: In the quantitative data, interview evaluations were most prevalent in the "comprehensive school records screening" for rolling admissions (85.5%), but less common in regular admissions (18.6%). Private schools (64.2%) showed a statistically significant higher proportion of interview admissions than public schools (11.1%) in the "high school grades focused admission" (p<0.01). Metropolitan areas (50.0%) conducted interview evaluations more frequently than non-metropolitan areas (11.1%) in the "College Scholastic Ability Test-focused admissions" (p<0.05). In the qualitative data, professors recognize the dominant role of "negative selection" in filtering out unsuitable candidates. Challenges in maintaining a consistent evaluator pool and team-based question development were acknowledged. Strategies, such as seeking student feedback for question improvement and conducting study meetings for interviewer preparation are essential. CONCLUSION: This study illuminates the operation of admissions interview evaluations in South Korea, revealing variations across regions and admissions types. These findings offer insights for enhancing medical school admission processes, guiding future research and policy.

Efficacy and safety of inflator-monitored balloon-occluded retrograde transvenous obliteration for gastric varices.

PURPOSE: To investigate the diagnostic efficacy of inflator-monitored balloon-occluded retrograde transvenous obliteration (ImBRTO) in detecting balloon rupture and to evaluate the efficacy and safety of the ImBRTO in treating gastric varices. METHODS: Between June 2018 and June 2024, 31 consecutive patients (age: 61.7 ± 12.4 years; male 20, female 11) underwent ImBRTO for gastric varices. An occlusion balloon was inflated with an inflation device to monitor for balloon rupture during sclerosing, maintaining the balloon inflation for at least 3 h. RESULTS: The technical success rate was 100%. The incidence of balloon rupture was 6.5% (2/31), both diagnosed by a pressure drop in the inflation device. In one of the two patients, catheter replacement and an additional injection of a sclerosing agent were required due to early balloon rupture (< 3 h). Clinical success and complete elimination of gastric varices were achieved in all cases. No procedure-related complications were observed. There were no cases of recurrent variceal bleeding at the end of the follow-up (median: 5.2 months). CONCLUSION: ImBRTO proves to be an effective and safe technique for treating gastric varices. The real-time monitoring of balloon integrity allows for timely decisions, resulting in excellent clinical outcomes.

Impact of the life-sustaining treatment decision act on organ donation in out-of-hospital cardiac arrests in South Korea: a multi-centre retrospective study.

BACKGROUND: The demand for organ transplants, both globally and in South Korea, substantially exceeds the supply, a situation that might have been aggravated by the enactment of the Life-Sustaining Treatment Decision Act (LSTDA) in February 2018. This legislation may influence emergency medical procedures and the availability of organs from brain-dead donors. This study aimed to assess LSTDA's impact, introduced in February 2018, on organ donation status in out-of-hospital cardiac arrest (OHCA) patients in a metropolitan city and identified related factors. METHODS: We conducted a retrospective analysis of a regional cardiac arrest registry. This study included patients aged 16 or older with cardiac arrest and a cerebral performance category (CPC) score of 5 from January 2015 to December 2022. The exclusion criteria were CPC scores of 1-4, patients under 16 years, and patients declared dead or transferred from emergency departments. Logistic regression analysis was used to analyse factors affecting organ donation. RESULTS: Of the 751 patients included in this study, 47 were organ donors, with a median age of 47 years. Before the LSTDA, there were 30 organ donations, which declined to 17 after its implementation. In the organ donation group, the causes of cardiac arrest included medical (34%), hanging (46.8%), and trauma (19.2%). The adjusted odds ratio for organ donation before the LSTDA implementation was 6.12 (95% CI 3.09-12.12), with non-medical aetiology as associated factors. CONCLUSION: The enactment of the LSTDA in 2018 in South Korea may be linked to reduced organ donations among patients with OHCA, underscoring the need to re-evaluate the medical and legal aspects of organ donation, especially considering end-of-life care decisions.

IDH2 regulates macrophage polarization and tumorigenesis by modulating mitochondrial metabolism in macrophages.

BACKGROUND: Targeting the tumor microenvironment represents an emerging therapeutic strategy for cancer. Macrophages are an essential part of the tumor microenvironment. Macrophage polarization is modulated by mitochondrial metabolism, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and reactive oxygen species content. Isocitrate dehydrogenase 2 (IDH2), an enzyme involved in the TCA cycle, reportedly promotes cancer progression. However, the mechanisms through which IDH2 influences macrophage polarization and modulates tumor growth remain unknown. METHODS: In this study, IDH2-deficient knockout (KO) mice and primary cultured bone marrow-derived macrophages (BMDMs) were used. Both in vivo subcutaneous tumor experiments and in vitro co-culture experiments were performed, and samples were collected for analysis. Western blotting, RNA quantitative analysis, immunohistochemistry, and flow cytometry were employed to confirm changes in mitochondrial function and the resulting polarization of macrophages exposed to the tumor microenvironment. To analyze the effect on tumor cells, subcutaneous tumor size was measured, and growth and metastasis markers were identified. RESULTS: IDH2-deficient macrophages co-cultured with cancer cells were found to possess increased mitochondrial dysfunction and fission than wild-type BMDM. Additionally, the levels of M2-associated markers decreased, whereas M1-associated factor levels increased in IDH2-deficient macrophages. IDH2-deficient macrophages were predominantly M1. Tumor sizes in the IDH2-deficient mouse group were significantly smaller than in the wild-type mouse group. IDH2 deficiency in macrophages was associated with inhibited tumor growth and epithelial-mesenchymal transition. CONCLUSIONS: Our findings suggest that IDH2 deficiency inhibits M2 macrophage polarization and suppresses tumorigenesis. This study underlines the potential contribution of IDH2 expression in macrophages and tumor microenvironment remodeling, which could be useful in clinical cancer research.

Comparative analysis of body composition using torso CT from PET/CT with bioelectrical impedance and muscle strength in healthy adults.

The role of torso computed tomography (CT) in evaluating body composition has been unexplored. This study assessed the potential of low-dose torso CT from positron emission tomography (PET)/CT for analyzing body composition and its relation to muscle strength. We retrospectively recruited 384 healthy Korean adults (231 men, 153 women) who underwent torso 18F-FDG PET/CT, bioelectrical impedance analysis (BIA), and muscle strength tests (handgrip strength [HGS] and knee extension strength [KES]). CT images were segmented into three compartments: torso volumetric, abdominal volumetric, and abdominal areal. Muscle amounts from each compartment were indexed to height (m2). BIA and HGS served as reference standards, with correlation coefficients (r) calculated. Torso muscle volumetric index (TorsoMVI) had the strongest correlations with BIA-derived values (r = 0.80 for men; r = 0.73 for women), surpassing those from the abdominal compartments. TorsoMVI was also correlated significantly with HGS (r = 0.39, p < 0.01) and differentiated between normal and possible sarcopenia in men (n = 225, 5960 ± 785 cm3/m2 vs. n = 6, 5210 ± 487 cm3/m2, p = 0.02). In women, KES correlated more strongly with muscle parameters than HGS. Despite gender-specific variations, torso CT-derived parameters show promise for evaluating body composition and sarcopenia.

Genomic and Conventional Inbreeding Coefficient Estimation Using Different Estimator Models in Korean Duroc, Landrace, and Yorkshire Breeds Using 70K Porcine SNP BeadChip.

The purpose of this study was to estimate the homozygosity distribution and compute genomic and conventional inbreeding coefficients in three genetically diverse pig breed populations. The genomic and pedigree data of Duroc (1586), Landrace (2256), and Yorkshire (3646) were analyzed. We estimated and compared various genomic and pedigree inbreeding coefficients using different models and approaches. A total of 709,384 ROH segments in Duroc, 816,898 in Landrace, and 1,401,781 in Yorkshire, with average lengths of 53.59 Mb, 56.21 Mb, and 53.46 Mb, respectively, were identified. Relatively, the Yorkshire breed had the shortest ROH segments, whereas the Landrace breed had the longest mean ROH segments. Sus scrofa chromosome 1 (SSC1) had the highest chromosomal coverage by ROH across all breeds. Across breeds, an absolute correlation (1.0) was seen between FROH total and FROH1-2Mb, showing that short ROH were the primary contributors to overall FROH values. The overall association between genomic and conventional inbreeding was weak, with values ranging from 0.058 to 0.140. In contrast, total genomic inbreeding (FROH) and ROH classes showed a strong association, ranging from 0.663 to 1.00, across the genotypes. The results of genomic and conventional inbreeding estimates improve our understanding of the genetic diversity among genotypes.

Genomic and metabolomic analysis of Latilactobacillus sakei DCF0720 for black soybean yogurt fermentation.

Lactic acid bacteria are commonly used in plant-based fermentation to reduce off-flavor and improve sensory characteristics. However, there have been few studies on Latilactobacillus sakei for plant-based yogurt fermentation and, particularly, its metabolic features at the genomic level remain unclear. This study aims to analyze the fermentation characteristics of the L. sakei DCF0720 strain and compare genetics and metabolic relations. For this, DCF0720 was used to ferment the black soybean milk and conduct the physicochemical analysis and sensory test. The genomic and metabolic analyses were performed by complete genome sequencing and 500 MHz 1H NMR, respectively. As a result, DCF0720 exhibited enhanced fermentation performance and sensory evaluations at 37 °C compared to 30 °C, which is generally recognized as the optimal growth temperature for most L. sakei strains. It also produced flavor enhancing volatile compounds such as acetoin and hydroxyacetone, possessing all three key genes for acetoin biosynthesis. DCF0720 lacks 2,3-butanediol dehydrogenase, which leads to the inhibition of acetoin production. DCF0720 possesses a complete pathway to utilize primary black soybean carbon sources such as sucrose, raffinose, and stachyose. DCF0720 also possesses genes for the GH28 family, including the key enzymes in the hydrolysis of pectin substances, which means eliminating the main soybean nonstarch polysaccharides. This study demonstrates that DCF0720 is a suitable starter for plant-based yogurt fermentation, providing a better understanding of fermentation conditions with genetic and metabolic features for black soybean yogurt. Various carbon source utilization abilities with depth metabolic pathway analysis provide that DCF0720 can be employed to develop enhanced starter cultures for black soybean yogurt and diverse plant-based yogurts.

Diagnostic Performance of Surgical Indication for Branch-duct or Mixed-type Intraductal Papillary Mucinous Neoplasms of the Revised International Association of Pancreatology (IAP) 2023 Guidelines.

OBJECTIVE: To evaluate the diagnostic performance of surgical indications of the revised International Association of Pancreatology (IAP) 2023 guidelines compared to the IAP 2017 and European 2018 guidelines. SUMMARY BACKGROUND DATA: The revised IAP guidelines for surgical indications for branch duct (BD) intraductal papillary mucinous neoplasms (IPMN) include the presence of at least two worrisome features without mandatory endoscopic ultrasound. METHODS: Among 663 patients who underwent resection for pathologically confirmed IPMN in a tertiary hospital between 2013 and 2023, 556 patients with BD or mixed-type IPMN were retrospectively reviewed. Diagnostic performances of the three guidelines for predicting high-grade dysplasia or IPMN with invasive carcinoma were compared. The primary outcome was the malignancy rate. Clinicopathological and radiological imaging data were analyzed. RESULTS: A total of 540, 451, and 490 patients met the surgical indications of the IAP, 2017, 2023, and European guidelines, respectively. Malignant IPMN was observed in 229 (41.2%) patients (high-grade dysplasia, n=99; invasive carcinoma, n=130). Surgical indication by the IAP 2023 guidelines showed higher specificity (29.1 vs. 4.9%, P<0.001), positive predictive value (48.6 vs. 42.4%, P=0.031), and accuracy (55.5 vs. 44.1%, P<0.001) than the IAP 2017 guidelines. It also had higher specificity than the European guidelines (18.7%, P=0.024). The IAP 2023 guidelines showed a superior AUC of surgical indication (0.623 vs. 0.582 for the European guidelines, P<0.001; and 0.524 for the IAP guidelines, P=0.008). CONCLUSIONS: The IAP 2023 guidelines showed better malignancy prediction than the IAP 2017 and European guidelines, potentially reducing unnecessary surgeries.

High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide Population-Based Matched Cohort Study.

BACKGROUND: Systemic corticosteroids have become the standard of care for severe to critically ill patients with coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids remain uncertain. METHODS: We conducted a nationwide, population-based, matched cohort study of severe to critically ill adult patients with COVID-19 between January 2020 and June 2021 in Korea using the National Health Information Database. Patients using systemic corticosteroids were included and high-dose corticosteroid use was defined as a daily mean prescribed dose of more than 6 mg of dexamethasone. We then employed a proportional hazard regression model to identify prognostic factors for 28-day all-cause mortality and conducted a Fine and Gray regression model to assess risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA). RESULTS: During the study period, 102,304 patients with COVID-19 were screened, 5,754 met the eligibility criteria, and 2,138 were successfully matched. The mean prescribed daily dose was 4.2 mg and 13.4 mg in the standard- and high-dose groups, respectively, and the mean duration of use was not different between the groups. High-dose corticosteroid use independently increased all-cause mortality at 28 days (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.25-1.76) and 90 days (aHR, 1.63; CI, 1.44-1.85) after admission. Subgroup analysis revealed a statistically significant elevation in the risk of mortality among patients using low-flow or high-flow nasal cannulas, with aHRs of 1.41 and 1.46, respectively. No significant impact of high-dose steroids was observed, even in patients who underwent mechanical ventilation at 28 days (aHR, 1.17; CI, 0.79-1.72). As a safety outcome, high-dose corticosteroid use showed an association with the development of CAPA (aHR, 2.97; 95% CI, 0.94-9.43). CONCLUSION: Among severe to critically ill patients with COVID-19, high-dose corticosteroid use was associated with increased 28-day all-cause mortality and showed a trend toward the development of CAPA.

Development of a novel sandwich immunoassay based on targeting recombinant Francisella outer membrane protein A for the diagnosis of tularemia.

Introduction: Tularemia, caused by the bacterium Francisella tularensis, poses health risks to humans and can spread through a variety of routes. It has also been classified as a Tier 1 Select agent by the CDC, highlighting its potential as a bioterrorism agent. Moreover, it is difficult to diagnose in a timely fashion, owing to the non-specific nature of tularemia infections. Rapid, sensitive, and accurate detection methods are required to reduce mortality rates. We aimed to develop antibodies directed against the outer membrane protein A of F. tularensis (FopA) for rapid and accurate diagnosis of tularemia. Methods: We used a baculovirus insect cell expression vector system to produce the FopA antigen and generate anti-FopA antibodies through immunization of BALB/c mice. We then employed hybridoma and phage display technologies to screen for antibodies that could recognize unique epitopes on FopA. Result: Two monoclonal antibodies, 6B12 and 3C1, identified through phage display screening specifically bound to recombinant FopA in a dose-dependent manner. The binding affinity of the anti-FopA 6B12 and 3C1 antibodies was observed to have an equilibrium dissociation constant of 1.76 × 10-10 M and 1.32 × 10-9 M, respectively. These antibodies were used to develop a sandwich ELISA system for the diagnosis of tularemia. This assay was found to be highly specific and sensitive, with detection limits ranging from 0.062 ng/mL in PBS to 0.064 ng/mL in skim milk matrices. Discussion: Our findings demonstrate the feasibility of a novel diagnostic approach for detecting F. tularensis based on targeting FopA, as opposed to existing tests that target the bacterial lipopolysaccharide.