Temporary Ureter Occlusion with Simultaneous Urinary Diversion via a Single-Access Route Using a 4-French Balloon Catheter and a Pigtail Nephrostomy Drainage Catheter.

Background and Objectives: This study evaluated the efficacy and safety of temporary ureteral occlusion combined with urinary diversion using a single-access route created by inserting a balloon catheter through a pigtail nephrostomy drainage catheter. With this approach, we aimed to offer an alternative for patients with ureteral leaks who are suboptimal surgical candidates. Materials and Methods: This retrospective study included nine patients (eight of which were bilateral cases and one was unilateral, totaling seventeen cases) who underwent the surgery between September 2023 and March 2024. The method involved gaining percutaneous access to the pelvicalyceal system, inserting a 4-French Fogarty balloon catheter through a pigtail nephrostomy catheter, and inflating the balloon at the proximal or mid-ureter. Results: All 17 cases achieved technical successful with no major complications. The procedure effectively relieved symptoms associated with urinary leakage in most patients. However, the significant deflation of the balloon catheter occurred in five cases (29.4%), with three (17.6%) experiencing complete deflation. In these five cases, the final balloon size was 5.81 mm (range: 0-8.9 mm), confirming a 25.0% decrease in size from pre- to post-procedure. Ureteral occlusion was 28.3 d long on average (range: 8-57 d). All patients experienced symptom relief during temporary ureteral occlusion. Except for two patients lost to follow-up, three patients showed symptom improvement with only PCN and four patients underwent surgical closure of the fistula tract before or after balloon catheter removal. Conclusions: This study confirms that this approach is safe and effective.

Quarantining: a mentally distressful but physically comfortable experience in South Korea.

OBJECTIVE: Quarantine is the first response to the COVID-19 pandemic. Restricting daily life can cause several problems. This study aimed to measure the impact of the COVID-19 quarantine on health-related quality of life (HRQoL) by comparing to the pre-pandemic. METHODS: HRQoL during COVID-19 quarantine was surveyed online using EQ-5D index and matched to that of the pre-pandemic-extracted from nationwide representative data of the Korea Community Health Survey- with propensity scores. A beta regression for the EQ-5D scores and a logistic analysis for individual dimensions of the EQ-5D index were performed to measure the impact of the COVID-19 quarantine on health utility. RESULTS: The overall scores of the EQ-5D index were significantly higher in the group under quarantine during the COVID-19 pandemic (0.971 SD 0.064) than those before the pandemic (0.964 SD 0.079, Diff. 0.007 SD 0.101, p = 0.043). The beta regression for the overall scores of EQ-5D revealed that quarantining during the COVID-19 pandemic increased by 52.7% compared to normal life before the outbreak(p = 0.045). Specifically, "Depression/Anxiety" deteriorated significantly during quarantining (OR = 0.62, 95% CI:0.48-0.80). However, "Pain/Discomfort" and "Mobility" significantly improved (OR = 5.37, 95% CI:3.71-7.78 and OR = 2.05, 95% CI:1.11-3.80, respectively). CONCLUSION: Although the world is facing a challenging moment that it has never been through before, mandatory quarantine has served as an experience that provided mental distress but physical comfort in the Korean context.

Aging and direct medical costs of osteoporotic fractures.

INTRODUCTION: This study estimated the direct medical costs of osteoporotic fractures from a large claims database in Korea. MATERIALS AND METHODS: We compared the medical costs of hip, vertebral, and wrist fractures between two age groups (50-64 years vs 65 years and older). We used a generalized linear model to investigate the drivers of osteoporotic fracture medical costs. RESULTS: Hip fractures had the highest costs, regardless of age, followed by vertebral and wrist. The cost of hip fracture was USD 7285 for those aged 65 years and over and USD 6589 for those aged 50-64 years. The length of hospital days was higher in hip fracture patients, regardless of age, followed by vertebral and wrist. As the number of hospitalizations increased, the medical cost increased by 33.0% (p < 0.0001). Patients older than 65 years who were hospitalized for a fracture had a longer total length of hospital stay, compared to patients aged 50-64, regardlessness of the site of the fracture. The cost of treating fractures among those 65 years and older increased by 31.8% compared to those 50-64 years old (p < 0.0001). The direct medical costs increased by 8.6% as the number of fractures increased (p = 0.041). CONCLUSIONS: We identified that osteoporotic fracture-related medical costs and hospitalization days increased with age. Interventions are effective in reducing fracture risk the potential to yield substantial cost savings.

Bisphosphonates Use and Risk of Subtrochanteric and Diaphyseal Femur Fractures in Korea: Results from the National Claim Registry.

Although Asian with bisphosphonate has been considered to have higher risk of subtrochanteric and diaphyseal femur (ST/DF) fractures, the occurrence of those fractures has been still unclear in Asia. The purpose of this study was to investigate the incidence rate of ST/DF fractures among bisphosphonate users from nationwide database in South Korea. Using national health insurance claim database, we only included the bisphosphonate users who took bisphosphonate for the first time in 2008 and evaluated the incidence rate of ST/DF fracture from 2008 to 2013. Non-user controls were matched to bisphosphonate users by propensity score matching with age and gender. Cox regression models were used to calculate hazard ratios of ST/DF fracture with and without adjustment for comorbidity. A total of 682 ST/DF fractures were observed among 348,311 bisphosphonate users. The incidence rate of ST/DF fracture among bisphosphonate users (37.75/100,000 person years, 95% CI 35.02-40.70) was higher compared with non-users (24.41/100,000 person years, 95% CI 22.31-26.71). The risk of ST/DF fracture was greater in bisphosphonate users compared with non-users (hazard ratio 1.541, 1.370-1.734; p < 0.001). The incidence rate of ST/DF fracture after bisphosphonate use could be determined in Korean patients, which can provide basal information for further studies on risk and benefit of continuing bisphosphonate.

Application of high-surface-area graphitized carbon black with primary secondary amine as an alternative quick, easy, cheap, effective, rugged, and safe cleanup material for pesticide multi-residue analysis in spinach.

A multi-residue method has been developed and validated to determine 46 pesticides in spinach using liquid chromatography tandem mass spectrometry. The method is based on modified quick, easy, cheap, effective, rugged, and safe sample preparation, where high-surface-area graphitized carbon black was used first as sorbent material in the dispersive solid-phase extraction. The method was compared with the quick, easy, cheap, effective, rugged, and safe method. The morphology, surface area, pore size, and pore volume of the sorbent was determined. The results obtained show that the sorbent consists of high surface area (233 m2 /g) and large pore volume (1.5 cm3 /g). The calibration curve correlation coefficient (R2 ) of the method was at least 0.99. The average recoveries ranged from 74 to 116%, and limits of detection and quantification from 0.0001 to 0.002 mg/kg and from 0.0002 to 0.005 mg/kg, respectively. Using the method, the pesticides exhibited low matrix effect (< 20%), except for nicosulfuron (29.86%), methomyl (26.77%), and flufenoxuron (24.65%). The method showed better potential to remove pigments than the quick, easy, cheap, effective, rugged, and safe method. It is demonstrated that the proposed method could be useful alternative for sample preparation of spinach and other matrices in future.

Improving extraction and post-purification concentration of membrane proteins.

Membrane proteins (MPs), despite being critically important drug targets for the pharmaceutical industry, are difficult to study due to challenges in obtaining high yields of functional protein. Most current extraction efforts use specialized non-ionic detergents to solubilize and stabilize MPs, with MPs being concentrated by ultrafiltration (UF). However, many detergents are retained during the UF step, which can destabilize MPs and/or interfere with their characterization. Here, we studied the influence of detergent selection on the extraction and UF-based concentration of biomedically-relevant MPs, the light-driven sodium and chloride transporters, KR2 and halorhodopsin (pHR) which are also model proteins for more complex mammalian rhodopsins. We also designed a flat-bottomed centrifugal filter that can concentrate MPs with enhanced removal of free detergents by promoting concentration polarization (CP). We tested the performance of this new filter using four commonly employed MP detergents, octyl-ß-D maltoside (OM), decyl-ß-D maltoside (DM), dodecyl-ß-D maltoside (DDM) and octyl-ß-D glucoside (OG), over a range of detergent and salt concentrations. Detergent passage is significantly higher for the flat-bottomed filter achieving up to 2-fold greater sieving of detergent in DM-solubilized pHR system due to the high degree of CP. We observe more efficient, up to 5-fold higher extraction of KR2 in the presence of a longer 12-carbon alkyl chain detergent, DDM compared to a shorter 8-carbon detergent, OM. Assuming complete binding and elution of the extracted protein, DDM-based extraction of KR2 could lead to a potential 7-fold improvement in purification yields compared to conventional methods which yield ∼1 mg MP per liter of cell culture. However, the longer chain detergents like DDM form larger micelles that are difficult to remove by UF. Thus, there exists a trade-off between choosing a detergent that will enable efficient extraction of MP while showing easier removal during subsequent UF. The extraction efficiency and UF-based separation of detergent micelles provide insights for other applications involving detergent-mediated separation/extraction.

Compensation for matrix effects in GC analysis of pesticides by using cucumber extract.

Matrix effects (MEs) can adversely affect quantification in pesticide residue analysis using GC. Analyte protectants (APs) can effectively interact with and mask active sites in the GC system, and are added individually or in combination to sample extracts and calibration solutions to minimize errors related to MEs. Unfortunately, APs cannot sufficiently compensate for MEs in all cases. Plant extracts, containing a broad range of natural compounds with AP properties, can also be used for this purpose. In this study, the applicability of cucumber extract as a natural AP mixture was investigated both alone and in combination with traditional APs. Extracts of two selected difficult matrices (onion and garlic) were prepared according to the citrate-buffered QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure. ME values of 40 representative GC-amenable pesticides were compared when calibrating against standards in pure solvent and in cucumber extract, with and without the addition of APs. Using a GC system with a contaminated inlet liner, the use of a cucumber-based calibration solution decreased MEs remarkably. The combination of APs with cucumber raw extract further decreased MEs, resulting in more than 85% of the tested pesticides showing ≤ 10% ME in onion and ≤ 20% ME in garlic. These results demonstrate that the preparation of calibration standards based on cucumber extracts (with or without the addition of APs) is a very useful and practical approach to compensate for MEs in pesticide residue analysis using QuEChERS and GC-MS/MS. The use of various internal standards is furthermore critically discussed.

Identification and characterization of matrix components in spinach during QuEChERS sample preparation for pesticide residue analysis by LC-ESI-MS/MS, GC-MS and UPLC-DAD.

In this article matrix components in spinach were investigated in detail. The samples were prepared using two QuEChERS (quick, easy, cheap, effective, rugged and safe) methods, AOAC and CEN. Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS), gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography-diode array detector (UPLC-DAD), were applied for component identification. The strategies of identification by LC-ESI-MS/MS include accurate mass spectra of the parent ion, comparison with previous literature data and investigation of the mass spectral decomposition pattern. Overall, fourteen components were identified by LC-ESI-MS/MS in each methods of AOAC and CEN, which were phytosteroids, flavonoids, fatty acids and fatty acid amides. Fifty components using AOAC method and fifty-seven components using CEN method were identified in GC-MS by comparing mass data with the National Institute of Standards and Technology (NIST, U.S.) database. The results indicate that the major components of the matrix are terpenoids, fatty acids and fatty acid esters. Moreover, three pigments (neoxanthin, violaxanthin and lutein) in the AOAC method and eight pigments (neoxanthin, violaxanthin, zeaxanthin, lutein, chlorophyll a, chlorophyll b, pheophytin a and beta-carotene) in the CEN method that gave a characteristics peak at 440 nm were identified by the UPLC-DAD. According to the sample preparation condition using different amounts of graphitized carbon black (GCB) in this study, the AOAC method had higher matrix component removal efficiency than the CEN method. A better understanding of matrix components would increase the current knowledge for improvement of existing QuEChERS methodology, as well as contribute to new method developments.

Do newly marketed generic medicines expand markets using descriptive time series analysis and mixed logit models? Korea as an exemplar and its implications.

BACKGROUND: There have been concerns in Korea that the availability of cheaper generics can appreciably increase prescribed volumes thereby negating their beneficial effects on overall pharmaceutical expenditure. Consequently, this study aimed to explore market changes after newly entered generics including market expansion and substitution effects, and to examine factors contributing to the prescribing of newly entered generics using atorvastatin as an exemplar. This is because previous studies have shown market expansion had occurred following generic atorvastatin. METHODS: Explore market expansion effects by extracting all statins users from July 2008 to June 2010 from the nationally representative dataset of 2008, combined with the National Health Insurance Claims data, with atorvastatin's patent expiring in July 2008. The data consisted of medical visit episodes of patients who had been prescribed statins at least once during the observational period. Patients who had been prescribed any statin before the observation period were classified as the previously treated group and those who had not as the newly treated group. Descriptive time series analysis was conducted and the mixed logit model applied to understand factors contributing to generic atorvastatin prescriptions. RESULTS: Market expansion was observed after generic atorvastatin availability with an appreciable increase in number of newly treated patients, whereas substitution effect was found among previously treated patients. Newly treated patients tended to get significantly lower daily doses (p < 0.0001). According to the mixed logistic analysis, newly treated patients were more likely to be prescribed generic atorvastatin (OR = 2.58; 95% CI, 2.05-3.26) than their counterparts. Clinicians and secondary hospitals were also key drivers of generic atorvastatin (ORs were 10.41 and 9.81, respectively). CONCLUSIONS: Newly marketed generic statins in Korea resulted in an expanding market by substantially increasing the number of new patients with clinics and hospitals appreciably using newly marketed generics. However lower doses of statins were prescribed. Policy makers do recognize that generic availability can save costs so should be encouraged. However, this is a concern when generic availability appreciably expands the market, potentially increasing the financial burden. This needs to be addressed. Additionally in Korea, the quality of prescribing should be monitored, especially focusing on clinics and secondary hospitals.

CONSTITUTIVE PHOTOMORPHOGENIC 10 (COP10) Contributes to Floral Repression under Non-Inductive Short Days in Arabidopsis.

In Arabidopsis, CONSTITUTIVE PHOTOMORPHOGENIC/DE-ETIOLATED/FUSCA (COP/DET/FUS) genes act in repression of photomorphogenesis in darkness, and recent reports revealed that some of these genes, such as COP1 and DET1, also have important roles in controlling flowering time and circadian rhythm. The COP/DET/FUS protein COP10 interacts with DET1 and DNA DAMAGE-BINDING PROTEIN 1 (DDB1) to form a CDD complex and represses photomorphogenesis in darkness. The cop10-4 mutants flower normally in inductive long days (LD) but early in non-inductive short days (SD) compared with wild type (WT); however, the role of COP10 remains unknown. Here, we investigate the role of COP10 in SD-dependent floral repression. Reverse transcription-quantitative PCR revealed that in SD, expression of the LD-dependent floral inducers GI, FKF1, and FT significantly increased in cop10-4 mutants, compared with WT. This suggests that COP10 mainly regulates FT expression in a CO-independent manner. We also show that COP10 interacts with GI in vitro and in vivo, suggesting that COP10 could also affect GI function at the posttranslational level. Moreover, FLC expression was repressed drastically in cop10-4 mutants and COP10 interacts with MULTICOPY SUPPRESSOR OF IRA1 4 (MSI4)/FVE (MSI4/FVE), which epigenetically inhibits FLC expression. These data suggest that COP10 contributes to delaying flowering in the photoperiod and autonomous pathways by downregulating FT expression under SD.

Clinical Outcomes and Safety of Transcatheter Arterial Embolization in Patients with Traumatic or Spontaneous Psoas and Retroperitoneal Hemorrhage.

Background: We aimed to assess the effectiveness and safety of transcatheter arterial embolization (TAE) in the management of spontaneous or traumatic psoas and/or retroperitoneal hemorrhage. Methods: This single-center retrospective study enrolled 36 patients who underwent TAE for the treatment of psoas and/or retroperitoneal hemorrhage between May 2016 and February 2024. Results: The patients' mean age was 61.3 years. The spontaneous group (SG, 47.1%) showed higher rates of anticoagulation therapy use compared with the trauma group (TG, 15.8%) (p = 0.042). The TG (94.7%) demonstrated higher survival rates compared with the SG (64.7%; p = 0.023). Clinical failure was significantly associated with the liver cirrhosis (p = 0.001), prothrombin time (p = 0.004), and international normalized ratio (p = 0.007) in SG and pRBC transfusion (p = 0.008) in TG. Liver cirrhosis (OR (95% CI): 55.055 (2.439-1242.650), p = 0.012) was the only identified independent risk factor for primary clinical failure in the multivariate logistic regression analysis. Conclusions: TAE was a safe and effective treatment for psoas and/or retroperitoneal hemorrhage, regardless of the cause of bleeding. However, liver cirrhosis or the need for massive transfusion due to hemorrhage increased the risk of clinical failure and mortality, necessitating aggressive monitoring and treatment.

Use of bio-information and communication technology shortens time to peak at a lower height of the epidemic curve: An alternative to flattening for countries with early COVID-19 outbreaks.

INTRODUCTION: The traditional approach to epidemic control has been to slow down the rate of infection while building up healthcare capacity, resulting in a flattened epidemic curve. Advancements in bio-information-communication technology (BICT) have enabled the preemptive isolation of infected cases through efficient testing and contact tracing. This study aimed to conceptualize the BICT-enabled epidemic control (BICTEC) and to document its relationships with epidemic curve shaping and epidemic mitigation performance. METHODS: Daily COVID-19 incidences were collected from outbreak to Aug. 12, 2020, for nine countries reporting the first outbreak on or before Feb. 1, 2020. Key epidemic curve determinants-peak height (PH), time to peak (TTP), and area under the curve (AUC)-were estimated for each country, and their relationships were analyzed to test if epidemic curves peak quickly at a shorter height. CFR (Case Fatality Rate) and CI (Cumulative Incidence) were compared across the countries to identify relationships between epidemic curve shapes and epidemic mitigation performance. RESULTS: China and South Korea had the quickest TTPs (40.70 and 45.37 days since outbreak, respectively) and the shortest PHs (2.95 and 4.65 cases per day, respectively). Sweden, known for its laissez-faire approach, had the longest TTP (120.36) and the highest PH (279.74). Quicker TTPs were correlated with shorter PHs (ρ = 0·896, p = 0·0026) and lower AUCs (0.790, p = 0.0028), indicating that epidemic curves do not follow a flattened trajectory. During the study period, countries with quicker TTPs tended to have lower CIs (ρ = .855, P = .006) and CFRs (ρ = 0.684, P = .061). For example, South Korea, with the second-quickest TTP, reported the second lowest CI and the lowest CFR. CONCLUSIONS: Countries that experienced early COVID-19 outbreaks demonstrated the epidemic curves that quickly peak at a shorter height, indicating a departure from the traditional flattened trajectory. South Korea's BICTEC was found to be at least as effective as most lockdowns in reducing CI and CFR.

Evaluating Image Quality and Radiation Dose in Low-Dose Thoraco-Abdominal CT Angiography with a Tin Filter for Patients with Aortic Disease.

Background: We aimed to compared radiation exposure and image quality between tin-filter-based and standard dose thoraco-abdominal computed tomography angiography (TACTA) protocols, aiming to address a gap in the existing literature. Methods: In this retrospective study, ninety consecutive patients undergoing TACTA were included. Of these, 45 followed a routine standard-dose protocol (ST100kV), and 45 underwent a low-dose protocol with a tin filter (TF100kV). Radiation metrics were compared. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and figure of merit (FOM) were calculated for the thoracic and abdominal aorta and right common iliac artery. Two independent readers assessed the image noise, image contrast, sharpness, and subjective image quality. Results: The mean dose for the TF100kV group was significantly lower (DLP 128.25 ± 18.18 mGy*cm vs. 662.75 ± 181.29, p < 0.001; CTDIvol 1.83 ± 0.25 mGy vs. 9.28 ± 2.17, p = 0.001), with an effective dose close to 2.3 mSv (2.31 ± 0.33 mSv; p < 0.001). The TF100kV group demonstrated greater dose efficiency (FOM, thoracic aorta: 36.70 ± 22.77 vs. 13.96 ± 13.18 mSv-1, p < 0.001) compared to the ST100kV group. Conclusions: Dedicated low-dose TACTA using a tin filter can significantly reduce the radiation dose while maintaining sufficient diagnostic image quality.

Is the Availability of Biosimilar Adalimumab Associated with Budget Savings? A Difference-in-Difference Analysis of 14 Countries.

OBJECTIVE: The aim was to assess the influence of the presence of biosimilar adalimumab on adalimumab budget savings in 14 high- and upper-middle-income countries. METHODS: This study analyzed Multinational Integrated Data Analysis System (MIDAS)-IQVIA data from the fourth quarter (Q4) of 2018 to the Q4 of 2019, comparing adalimumab expenditure (in United States dollars) and consumption (in standard units [SU]) across 14 countries (Australia, Austria, Brazil, Canada, France, Germany, Italy, Japan, Korea, Singapore, South Africa, Spain, Sweden, and Taiwan). The countries were divided into two groups based on the availability of adalimumab biosimilars during the study period. A difference-in-difference design was employed to analyze the groups, focusing on changes from Q4 2018 to Q4 2019. Additionally, changes in adalimumab expenditure were decomposed into price, quantity, and drug mix during the study period. RESULTS: Among countries with adalimumab biosimilars, there was a significant decrease in expenditure (- $371.0 per gross domestic product per capita; p = 0.03) over four quarters, while the consumption significantly increased (1.0 SU per 1000 population; p = 0.02). This was consistent with visual observations and differed from countries without adalimumab biosimilar. Sensitivity analysis with a narrowed list of countries (12 high-income countries) showed a consistent trend. Adalimumab expenditure decreased by 14% during the study period in countries where adalimumab biosimilars were available, mainly due to the price changes (Pt = 0.85; - 15%) and the drug-mix effect (εt  = 0.88; - 12%). Yet, adalimumab expenditure (Et = 1.04; +4%) changed in a quantity-dependent manner (Qt = 1.06; +6%) in countries where adalimumab biosimilars were absent. CONCLUSION: The availability of biosimilars was associated with a decrease in adalimumab expenditure without compromising the consumption of adalimumab.

Migration of double-J ureteral stent in patients with ureteroileal anastomosis stricture undergoing radical cystectomy and orthotopic neobladder: Analysis risk factors of stent migration.

The objective was to evaluate the incidence and degree of double-J ureteral stent (DJUS) migration. Additionally, we aimed to investigate the risk factors associated with stent migration in the orthotopic neobladder group. In this retrospective study, 61 consecutive patients were included; 35 patients (45 DJUS placements) underwent radical cystectomy with orthotopic neobladder and 26 patients (35 DJUS placements) underwent urinary bladder without cystectomy between July 2021 and March 2023. All the patients were treated with a DJUS for ureteric strictures. The technical success rate was 100% in each group. The DJUS migration was significantly higher in the orthotopic neobladder group, with 22 of 45 cases (48.9%), compared to the urinary bladder group, which had 4 of 35 cases (11.4%) (P ≤ .001). Among the patients in the orthotopic neobladder group who experienced DJUS migration, stent dysfunction occurred in 18 cases (81.8%), which was statistically significant (P = .003). Multivariate logistic regression analysis revealed that only the size of the DJUS was significantly and positively associated with migration (odds ratio:10.214, P = .010). DJUS migration can easily occur in patients undergoing radical cystectomy and orthotopic neobladder, and smaller stent sizes are associated with a higher incidence of migration.

Impact of tissue penetration and albumin binding on design of T cell targeted bispecific agents.

Bispecific agents are a rapidly growing class of cancer therapeutics, and immune targeted bispecific agents have the potential to expand functionality well beyond monoclonal antibody agents. Humabodies⁎ are fully human single domain antibodies that can be linked in a modular fashion to form multispecific therapeutics. However, the effect of heterogeneous delivery on the efficacy of crosslinking bispecific agents is currently unclear. In this work, we utilize a PSMA-CD137 Humabody with an albumin binding half-life extension (HLE) domain to determine the impact of tissue penetration on T cell activating bispecific agents. Using heterotypic spheroids, we demonstrate that increased tissue penetration results in higher T cell activation at sub-saturating concentrations. Next, we tested the effect of two different albumin binding moieties on tissue distribution using albumin-specific HLE domains with varying affinities for albumin and a non-specific lipophilic dye. The results show that a specific binding mechanism to albumin does not influence tissue penetration, but a non-specific mechanism reduced both spheroid uptake and distribution in the presence of albumin. These results highlight the potential importance of tissue penetration on bispecific agent efficacy and describe how the design parameters including albumin-binding domains can be selected to maximize the efficacy of bispecific agents.

Angioinvasive Mucormycosis Mimicking Mass and Pulmonary Thromboembolism in a Patient with Myelodysplastic Syndrome: A Case Report.

Mucormycosis encompasses a range of fungal infections that can impact various organs. Although pulmonary mucormycosis is relatively rare, it poses a significant threat, particularly to individuals with compromised immune systems. Pulmonary mucormycosis presents with various radiological manifestations. Notably, the involvement of the angioinvasive pulmonary artery in pulmonary mucormycosis cases has seldom been documented. In this report, we showcase the radiological characteristics of angioinvasive mucormycosis, which can mimic pulmonary thromboembolism or a pulmonary artery tumor, in a patient diagnosed with myelodysplastic syndrome.

In vivo Auto-tuning of Antibody-Drug Conjugate Delivery for Effective Immunotherapy using High-Avidity, Low-Affinity Antibodies.

Antibody-drug conjugates (ADCs) have experienced a surge in clinical approvals in the past five years. Despite this success, a major limitation to ADC efficacy in solid tumors is poor tumor penetration, which leaves many cancer cells untargeted. Increasing antibody doses or co-administering ADC with an unconjugated antibody can improve tumor penetration and increase efficacy when target receptor expression is high. However, it can also reduce efficacy in low-expression tumors where ADC delivery is limited by cellular uptake. This creates an intrinsic problem because many patients express different levels of target between tumors and even within the same tumor. Here, we generated High-Avidity, Low-Affinity (HALA) antibodies that can automatically tune the cellular ADC delivery to match the local expression level. Using HER2 ADCs as a model, HALA antibodies were identified with the desired HER2 expression-dependent competitive binding with ADCs in vitro. Multi-scale distribution of trastuzumab emtansine and trastuzumab deruxtecan co-administered with the HALA antibody were analyzed in vivo, revealing that the HALA antibody increased ADC tumor penetration in high-expression systems with minimal reduction in ADC uptake in low-expression tumors. This translated to greater ADC efficacy in immunodeficient mouse models across a range of HER2 expression levels. Furthermore, Fc-enhanced HALA antibodies showed improved Fc-effector function at both high and low expression levels and elicited a strong response in an immunocompetent mouse model. These results demonstrate that HALA antibodies can expand treatment ranges beyond high expression targets and leverage strong immune responses.

Who persistently consumes dietary supplements? A multifaceted analysis using South Korea's nationally representative health and nutrition examination survey data.

Objective: This study aimed to identify multifaceted factors affecting intake of dietary supplements among Koreans. Methods: Korean National Health and Nutrition Examination Survey (KNHANES) data from 2018 to 2020 were obtained, pertaining to functional food intake, health related behaviors and morbidities. A total of 12,031 participants representing the Korean adult population were identified into two groups: 1 year more consumer group (N = 4,345) vs. non-consumer group (N = 7,686). A logistic regression analysis was performed to analyze the predictors of dietary supplement consumptions. Results: Sociodemographic variables were associated with dietary supplement use. Participants who were female (odds ratio [OR] = 1.85; 95% CI, 1.59-2.15), older (OR = 1.06; 95% CI, 1.04-1.08), married (OR = 6.39; 95% CI, 3.44-11.85), highly educated, and high income earners consumed significantly more dietary supplements. Non-smoking (OR = 1.27; 95% CI, 1.06-1.53) and performing aerobic exercise (OR = 1.28; 95% CI, 1.13-1.46) predict dietary supplement consumption. Self-rated health status and health-related quality of life increased the likelihood of dietary supplement intake by 1.86 (OR = 1.86; 95% CI, 1.04-3.32) and 7.77 times (OR = 7.77; 95% CI, 1.66-33.40), respectively. The number of chronic diseases, cancer, or stroke was not significantly associated with intake. Those with obesity tended to less consume dietary supplements (OR = 0.85; 95% CI, 0.74-0.97). Hypertension (OR = 3.14; 95% CI, 1.36-7.21), osteoporosis (OR = 1.47; 95% CI, 1.11-1.95), and asthma (OR = 0.44; 95% CI, 0.27-0.73) were significantly associated with the intake. Conclusion: Considering that healthy behaviors and subjective health led to the consumption of dietary supplements, whereas current disease or catastrophic experience did not, the intake of dietary supplements should be included in health promotion in Korea.

Introduction of managed entry agreements in Korea: Problem, policy, and politics.

Objectives: This study aimed to understand Managed Entry Agreements (MEAs) in Korea through the framework of three streams of the policy window model and its practical management and impact on pricing and reimbursement scheme. Methods: An extensive literature review based on Kingdon's model was conducted. We also performed descriptive analyses of MEA implementation using data on medicines listed in Korea and compared its MEA scheme with four different countries. Results: As per problem streams, patients with rare disease or cancers have considerable difficulties in affording their medicines and this has challenged the drug benefit system and raised an issue of patient's access. Policy streams highlighted that MEAs were introduced as a benefit enhancement plan for four major diseases since January 2014. MEAs have also been strengthened as a bypass mechanism to expand the insurance coverage especially for new premium-priced medicines under Moon Care (Listing all non-listed services). In descriptive analysis of MEAs, a total of 48 medicines were contracted as MEAs from January 2014 to December 2020, accounting for 73.4% of listed medicines for cancer or rare diseases and 97.9% of the cases were finance-based contracts. Meanwhile, outcome-based contracts such as CED accounted for only 2.1%. The application of MEAs differs across countries, resulting in a kappa coefficient of 0.00-0.14 (United Kingdom 0.03, Italy 0.00, Australia 0.14), indicating a lack of consistency compared to South Korea. Conclusion: MEAs, which were introduced as a bypass mechanism, have now superseded the standard process for anticancer agents or orphan drugs. Further studies are needed to evaluate the impact of the confidential agreements and effectiveness of new high-priced medicines with limited clinical data at launch.