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.

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.

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.

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.

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.

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.

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.

Diffuse Large B-Cell Lymphoma Manifesting as Miliary Nodules in the Lung: A Case Report.

Malignant lymphoma has various pulmonary manifestations on chest CT, including nodules, masses, areas of consolidation, and ground-glass opacity. These presentations can pose a diagnostic challenge, as they mimic other disease patterns. Herein, we report a case of diffuse large B-cell lymphoma (DLBCL) manifesting as miliary nodules in a 67-year-old male initially presenting with dyspnea and fever. Radiologic findings included diffuse, bilateral, multiple tiny nodules consistent with metastasis, miliary tuberculosis, and fungal infection. However, further investigations, including laboratory tests, imaging, and biopsies, led to the diagnosis of DLBCL involving the lungs. Herein we reported a rare case of lymphoma involvement of the lung presenting as miliary nodules. Accurate diagnosis relies on a comprehensive evaluation of the clinical history, physical features, laboratory test results, and imaging findings.

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Primary masses rarely originate from the heart and great vessels, and a malignant peripheral nerve sheath tumor (MPNST) is extremely rare. A 76-year-old male with pleural effusion underwent contrast-enhanced computed tomography, which revealed a hypoattenuating mass involving the right pulmonary vein and left atrium. Ultrasonography showed that the mass originated from the right pulmonary vein. Surgical resection confirmed an MPNST that originated from the pulmonary vein. We report the first Korean case of a primary MPNST originating from the pulmonary vein. We have also described the radiologic findings suggestive of a pulmonary vein mass.

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.

Insidious Onset Multifocal Chest Wall and Spinal Abscess Caused by Previous Candidemia: A Case Report.

Abscess formation due to Candida albicans infection is extremely rare. Radiological diagnosis of an atypical abscess at an uncommon site is challenging. In this study, we present a case of insidious onset multifocal chest wall and spinal abscess after candidemia in a young woman in the intensive care unit due to postpartum bleeding.

Engineered peptide-drug conjugate provides sustained protection of retinal ganglion cells with topical administration in rats.

Effective eye drop delivery systems for treating diseases of the posterior segment have yet to be clinically validated. Further, adherence to eye drop regimens is often problematic due to the difficulty and inconvenience of repetitive dosing. Here, we describe a strategy for topically dosing a peptide-drug conjugate to achieve effective and sustained therapeutic sunitinib concentrations to protect retinal ganglion cells (RGCs) in a rat model of optic nerve injury. We combined two promising delivery technologies, namely, a hypotonic gel-forming eye drop delivery system, and an engineered melanin binding and cell-penetrating peptide that sustains intraocular drug residence time. We found that once daily topical dosing of HR97-SunitiGel provided up to 2 weeks of neuroprotection after the last dose, effectively doubling the therapeutic window observed with SunitiGel. For chronic ocular diseases affecting the posterior segment, the convenience of an eye drop combined with intermittent dosing frequency could result in greater patient adherence, and thus, improved disease management.

Immunoglobulin G4-Related Myocarditis with Eosinophilic Infiltration: A Case Report.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder that can involve any organ system; however, myocarditis is extremely rare. A 52-year-old male with dyspnea and chest discomfort underwent cardiac MRI that revealed edema and nodular, patchy, mesocardial and subendoardial delayed enhancement of left ventricle, suggesting myocarditis. Laboratory findings revealed elevated serum IgG4 and eosinophilia. Cardiac biopsy confirmed eosinophilic myocarditis with IgG4-positive cells. Here, we present an unusual case of IgG4-RD manifesting as eosinophilic myocarditis.

Machine learning-driven multifunctional peptide engineering for sustained ocular drug delivery.

Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We develop a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) is conjugated to brimonidine, an intraocular pressure lowering drug that is prescribed for three times per day topical dosing, intraocular pressure reduction is observed for up to 18 days after a single intracameral injection in rabbits. Further, the cumulative intraocular pressure lowering effect increases ~17-fold compared to free brimonidine injection. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond.

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.

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.

Corrigendum: Pregnancy and Neonatal Outcomes After Exposure to Alprazolam in Pregnancy.

[This corrects the article DOI: 10.3389/fphar.2022.854562.].

Pregnancy and Neonatal Outcomes After Exposure to Alprazolam in Pregnancy.

Alprazolam is a commonly prescribed benzodiazepine for anxiety or panic disorder, even in pregnant women. Information on the safety of alprazolam during pregnancy is insufficient. We aimed to evaluate pregnancy and neonatal outcomes after exposure to alprazolam during pregnancy. A prospective study was conducted on 725 pregnancies from January 2000 to December 2019. Participants were recruited through the Korean Mother-Safe Program, a service providing information on drug-induced teratogenic risk during pregnancy and breastfeeding. Exposed (N = 96) and non-exposed (N = 629) women to alprazolam during pregnancy were selected and followed-up until delivery. Pregnancy outcomes, including spontaneous abortion, still birth, low birth weight (LBW), preterm birth, Apgar score (at 1 and 5 min), and malformations were measured and compared. Multivariable logistic regression was performed to examine the association between alprazolam exposure and outcomes. The mean age was 32.9 (SD 4.0) years in the alprazolam-exposed group and 31.8 (SD 3.8) years in the unexposed group (p = 0.008). The alprazolam exposure group demonstrated a significantly higher likelihood of pregnancy and neonatal outcomes: spontaneous abortion (OR = 2.38; 95% CI 1.20-4.69), LBW (OR = 3.65; 95% CI 1.22-11.00), and Apgar score at 1 min ≤ 7 (OR = 2.19; 95% CI 1.02-4.67). There was no significant difference in congenital abnormalities between the exposure and non-exposure groups. Our findings confirmed that alprazolam exposure during pregnancy was significantly associated with adverse pregnancy and neonatal outcomes, including spontaneous abortion, low birth weight, and Apgar score at 1 min ≤ 7. Alprazolam during pregnancy should be appropriately regulated and monitored.