Rhinoviruses are the most prevalent respiratory viruses across age groups, responsible for a wide spectrum of illnesses ranging from mild upper respiratory symptoms to lower airway involvement. Moreover, rhinovirus infection is also a major driver of asthma exacerbation and development, imposing a substantial disease burden. Rhinoviruses are classified into three species: Rhinovirus A, Rhinovirus B, and Rhinovirus C, each utilizing distinct host cell receptors and exhibiting different clinical patterns. Rhinovirus A and Rhinovirus C are more frequently associated with clinically significant disease outcomes compared to Rhinovirus B. Rhinovirus C binds to cadherin-related family member 3 (CDHR3), and a missense variant in CDHR3 (rs6967330) increases epithelial expression of the receptor, enhancing susceptibility to infection and severe illness, particularly in early life. Rhinovirus infection induces complex immune responses, characterized by impaired interferon signaling, type 2 inflammation, and epithelial barrier disruption. In individuals with asthma, altered interferon responses and T2-high immune profiles are closely linked to rhinovirus-induced exacerbations.In infants with atopic traits, such as eosinophilia, allergen sensitization, or a family history of allergic diseases, rhinovirus infection is strongly associated with subsequent development of asthma. Rhinovirus vaccine is needed to prevent severe respiratory infections and asthma exacerbations, particularly in vulnerable populations. Rhinovirus vaccine development has been challenging due to extensive antigenic diversity and limited cross-protective immunity. Recent progress in high-valency inactivated vaccines has demonstrated the feasibility of eliciting broad neutralizing responses. Prioritizing rhinovirus types linked to greater clinical severity may enable targeted vaccine strategies for high-risk populations, offering a promising approach to reducing the global burden of rhinovirus-associated illnesses.

Purpose: Asthma is characterized by chronic type 2/eosinophilic inflammation in the airway mucosa. This study aimed to explore the clinical value of 2 cutoffs of blood eosinophil counts (≥ 300/μL and ≥ 150/μL) in eosinophilic asthma, with relation to eosinophilderived neurotoxin (EDN), a surrogate marker of eosinophilic activity. Methods: To compare clinical features and eosinophil-related mediators according to 2 cutoffs of peripheral blood eosinophil counts (≥ 300/μL and ≥ 150/μL), 137 adult asthmatics who had maintained antiasthmatic medications, including inhaled corticosteroid and long-acting beta 2 agonist, without biologics, were enrolled. EDN levels in serum, urine and sputum were measured by enzymelinked immunosorbent assay. Results: Patients with asthma and higher blood eosinophil counts ( ≥ 300/μL) had a higher prevalence of severe asthma, chronic rhinosinusitis, partly controlled/uncontrolled status, and higher levels of sputum eosinophils and EDN in serum/sputum than those with lower blood eosinophil counts (< 300/μL). When compared between patients with asthma having higher blood eosinophils ( ≥ 150/μL) and those with lower eosinophils ( < 150/μL), there were no differences in symptom severity, control status or lung function parameters. Conclusion These findings suggest that blood eosinophil count ≥ 300/μL may identify asthma patients at higher risk for severity and heightened eosinophil activity, supporting its utility as a biomarker in a real clinical setting.

Purpose: Treatment responses to Mycoplasma pneumoniae (MP) pneumonia in children exhibit considerable variability. It is essential to identify predictive indicators and elucidate mechanisms associated with treatment responses. This study aimed to characterize the clinical, radiological, laboratory, and cytokine profiles associated with treatment responses in pediatric MP pneumonia. Methods: A retrospective analysis was performed in 85 children hospitalized with MP pneumonia between May 2019 and March 2020.Patients were categorized into the good response group (n=74) or the poor response group (n=11) based on clinical responses to step-wise treatment. Clinical characteristics, radiological findings, laboratory parameters, and serum levels of 27 cytokines obtained at admission were compared between the groups. Results: Compared to the good response group, the poor response group exhibited significantly longer fever duration (11.36 ± 5.33 days vs. 5.77 ± 3.95 days, P = 0.006), more frequent lobar consolidation (63.6% vs. 20.3%, P = 0.043), and higher lactate dehydrogenase levels (1,146±505 IU/L vs. 731±231 IU/L, P=0.008) and MP-specific immunoglobulin M index (6.49±3.01 vs. 3.85±3.28, P=0.014).Among the cytokines assessed, IL-21, IL-22, and IL-31 levels were significantly elevated in the good response group. IL-17A levels were also higher in this group, albeit not statistically significant. Conclusion Early identification of clinical, laboratory, and radiologic markers may facilitate early prediction of treatment response in pediatric MP pneumonia. Elevated IL-21, IL-22, and IL-31 levels in the good response group suggest a potential role for Th17-related cytokine activity in favorable treatment outcomes, warranting further investigation in larger cohorts.

Background: The diagnosis of tuberculous pleural effusion (TPE) often relies on pleural fluid adenosine deaminase (ADA) levels. The diagnostic utility of ADA, however, is influenced by the prevalence of tuberculosis (TB) in local populations. Malignant pleural effusion (MPE) cases can exhibit moderately elevated ADA levels comparable to those seen in TPE. As population aging potentially impacts ADA levels, global TB incidence is decreasing whereas the burden of malignancy is on the rise. Consequently, epidemiological shifts and temporal changes in ADA distribution complicate the differential diagnosis between TPE and MPE when ADA levels are within the 40–70 IU/L range. Nonetheless, data specific to this subset are scarce. Methods: This retrospective study included consecutive patients aged > 18 years with confirmed TPE and MPE, spanning from 2012 to 2023. ADA levels in pleural fluid were categorized into three groups: < 40 IU/L, 40–70 IU/L, and > 70 IU/L. The study examined annual trends in the frequency of new cases and ADA level distributions over time and identified discriminating factors between TPE and MPE in cases with ADA levels of 40–70 IU/L. Results: In total, 297 TPE and 369 MPE cases were included in this study. Over the study period, the frequency of TPE progressively declined, while that of MPE increased. In the most recent four-year period, new TPE and MPE cases with ADA levels of 40–70 IU/L occurred at comparable numbers. Multivariable analysis identified pleural fluid carcinoembryonic antigen (CEA) levels and the number of focal pleural nodules as independent predictors for MPE. Specifically, the presence of either CEA levels > 15.7 ng/mL or more than eight pleural nodules yielded the highest diagnostic accuracy with a sensitivity of 88%, specificity of 100%, and an area under the curve of 0.95. Conclusion The differential diagnosis between TPE and MPE with pleural ADA levels of 40–70 IU/L has become increasingly critical due to evolving epidemiological patterns and ADA distribution changes over time. Pleural fluid CEA levels and the characteristics of pleural nodules may offer valuable guidance in distinguishing between TPE and MPE within this diagnostic gray zone.

Clonorchiasis is a parasitic disease caused by Clonorchis sinensis, a trematode that inhabits the intrahepatic bile ducts of humans and mammals. C. sinensis is one of common foodborne trematodes, prevalent in East Asia including Korea. The International Agency for Research on Cancer reclassified C. sinensis as the Group 1 biological carcinogen of human cholangiocarcinoma (CCA). Evidence supporting the carcinogenicity of C. sinensis includes epidemiological studies showing increased prevalence and odds ratio (OR) of CCA in clonorchiasis patients, the development of CCA in experimental animals, and molecular studies. Approximately 10% of CCA in Korea are believed to be solely caused by clonorchiasis, with an OR of 4.7 for CCA risk among clonorchiasis patients. All hamsters exposed to both of C. sinensis and N-nitrosodimethylamine (NDMA) developed CCA while those exposed to either C. sinensis or NDMA alone did not. In vitro studies using cell models investigated carcinogenetic changes of the intracellular molecules and genes following stimulation with a soluble extract of C. sinensis. The in vitro stimulated cells showed a significant shift to G2/M phage, produced oncogenic molecules, changed expression of oncogenes, increased cell proliferation and suppressed apoptosis. Additionally, the gap-junction proteins between cells, such as connexin (Cx) 43, Cx 26, and Cx 32, were changed significantly, disrupting intercellular homeostasis. These findings suggest that C. sinensis and nitrogen compounds synergistically stimulate the cholangiocytes to become neoplastic. C. sinensis is a biological carcinogen of human CCA, and the World Health Organization guidelines enlist food-borne trematodes as one of target neglected tropical diseases to be eliminated by 2030. The present article reviews and updates perspectives on clonorchiasis, focusing on carcinogenesis.

Background: The Korean National Cancer Screening Program (NCSP) for gastric cancer requires economic evaluation due to the low sensitivity of upper gastrointestinal series (UGIs) and the associated low cancer survival rate. This study aimed to ascertain the most cost-effective strategy for the NCSP. Methods: The hypothetical target population of this study was aged 40 years or older, and no actual participants were involved. Markov simulation models were constructed for 25 strategies, combinations of 1) screening methods (UGIs or endoscopy vs. endoscopy-only), 2) screening intervals (one, two, or three-year), and 3) upper age limit of screening (69, 74, 79 years old, or “no limit”). Costs, utility, and other input parameters were extracted from various databases and previous studies. Cost-utility, sensitivity, and scenario analyses were conducted. Results: The endoscopy-only strategy with a three-year interval with an upper age limit of 69 was the most cost-effective strategy with an incremental cost-utility ratio of KRW 13,354,106 per quality-adjusted life years. According to the probabilistic sensitivity analysis, the uncertainty of the result was significantly small. Scenario analysis is showed that as the screening rate increased, the endoscopy-only strategy saved more costs compared to the current NCSP. Therefore, it is important to maintain a high screening rate when altering the NCSP strategy. Conclusion Endoscopy-only screening was more cost-effective method than UGIs for the NCSP. Furthermore, a three-year interval with an upper-age limit of 69 years was the most cost-effective strategy. Efforts to improve cost-effective screening guidelines will support the efficient use of medical resources. Additionally, maintaining a higher screening rate may maximize the impact of the modification in strategy on cost-effectiveness.

Background: The accuracy of Logical Observation Identifiers Names and Codes (LOINC) mappings is reportedly low, and the LOINC codes used for research purposes in Korea have not been validated for accuracy or usability. Our study aimed to evaluate the discrepancies and similarities in interoperability using existing LOINC mappings in actual patient care settings. Methods: We collected data on local test codes and their corresponding LOINC mappings from seven university hospitals. Our analysis focused on laboratory tests that are frequently requested, excluding clinical microbiology and molecular tests. Codes from nationwide proficiency tests served as intermediary benchmarks for comparison. A research team, comprising clinical pathologists and terminology experts, utilized the LOINC manual to reach a consensus on determining the most suitable LOINC codes. Results: A total of 235 LOINC codes were designated as optimal codes for 162 frequent tests.Among these, 51 test items, including 34 urine tests, required multiple optimal LOINC codes, primarily due to unnoted properties such as whether the test was quantitative or qualitative, or differences in measurement units. We analyzed 962 LOINC codes linked to 162 tests across seven institutions, discovering that 792 (82.3%) of these codes were consistent. Inconsistencies were most common in the analyte component (38 inconsistencies, 33.3%), followed by the method (33 inconsistencies, 28.9%), and properties (13 inconsistencies, 11.4%). Conclusion This study reveals a significant inconsistency rate of over 15% in LOINC mappings utilized for research purposes in university hospitals, underlining the necessity for expert verification to enhance interoperability in real patient care.

Background: Shortage of organ donors in the Republic of Korea has become a major problem. To address this, it has been questioned whether heart transplant (HTx) allocation should be modified to reduce priority of older patients. We aimed to evaluate post-HTx outcomes according to recipient age and specific pre-HTx conditions using a nationwide prospective cohort. Methods: We analyzed clinical characteristics of 628 patients from the Korean Organ Transplant Registry who received HTx from January 2015 to December 2020. Enrolled recipients were divided into three groups according to age. We also included comorbidities including ambulatory status. Non-ambulatory status was defined as pre-HTx support with either extracorporeal membrane oxygenation, continuous renal replacement therapy, or mechanical ventilation. Results: Of the 628 patients, 195 were < 50 years, 322 were 50–64 years and 111 were ≥ 65years at transplant. Four hundred nine (65.1%) were ambulatory and 219 (34.9%) were nonambulatory. Older recipients tended to have more comorbidities, ischemic cardiomyopathy, and received older donors. Post-HTx survival was significantly lower in older recipients (P = 0.025) and recipients with non-ambulatory status (P < 0.001). However, in contrast to non-ambulatory recipients who showed significant survival differences according to the recipient’s age (P = 0.004), ambulatory recipients showed comparable outcomes (P = 0.465). Conclusion Our results do not support use of age alone as an allocation criterion. Transplant candidate age in combination with some comorbidities such as non-ambulatory status may identify patients at a sufficiently elevated risk at which suitability of HTx should be reconsidered.

Background: The health system's capacity to store vaccines in North Korea has been less studied. In this study, we aimed to investigate if the current vaccine cold chain in North Korea can store routine vaccines and if it has the storage capacity to handle pandemic vaccination activities (PVAs) without interrupting the country’s successful routine immunization program. Methods: We used tables extracted from an evaluation report of The Global Alliance for Vaccines and Immunization (GAVI)’ Health Systems Strengthening program in North Korea from 2007 to 2014. We then used the World Health Organization’s Immunization Supply Chain Sizing Tool to estimate gaps and the cost of scaling up cold chain storage. Results: We found that the vaccine cold chain in North Korea has adequate storage capacity for routine vaccines. While we found a deficit of 7,172 L at the central medical warehouse (CMW) and 14,256 L at the provincial medical warehouses (PMWs), the storage at the county warehouses (CoMW) had a surplus. When assessed for PVA, we found an aggregated deficit of 115,574 L (CMW), 113,160 L (PMW), and 25,133 L (CoMW). To fill the gaps, investments of 229,917 USD, and 2,262,211 USD were estimated for routine and PVA vaccination programs, respectively. Conclusion As countries and the international community work to improve systems in preparation for future pandemics, there is a need to scale up the North Korean vaccine cold chain to a pandemic-ready state.

Background: Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Secondary transplantation has been recognized as a potential curative intervention. Methods: This study aimed to investigate the characteristics and outcomes of salvage transplantation by analyzing the patients who underwent a second HCT for GF following the initial allo-HCT between 1998 and 2020. Results: Overall, 23 recipients were identified, including 14 and 9 individuals with primary and secondary GF, respectively. Nine recipients underwent a second transplant from the same donor. Familial mismatched donors predominated in the second HCT (86.9%), with reduced-intensity conditioning as the prevailing approach (60.9%). Neutrophil engraftment occurred in 17 patients (73.9%) following the second HCT at a median of 17 days (range: 9–58 days) post-transplantation. However, secondary GF subsequently occurred in 5 patients, and successful engraftment following salvage transplantation was achieved in 12 (52.2%) patients. In the entire study population, the estimated 5-year probability of overall survival (OS) and treatment-related mortality (TRM) were 30.4% and 58.5%, respectively. Among patients who achieved successful engraftment following a second transplantation, the OS and TRM rates were 41.7% and 33.3%, respectively, indicating a trend toward better OS and significantly lower TRM compared to those with GF. Notably, 17 patients died, with infection being the most common cause (n = 12), irrespective of the engraftment status. Conclusion A successful engraftment following a second allo-HCT reduced the TRM; however, the OS remained suboptimal. The effective control of infectious diseases remains crucial for patients with GF, regardless of the engraftment status following salvage transplantation.