Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

Purpose: Human epidermal growth factor receptor 2 (HER2) is amplified or overexpressed in various malignancies, including breast and gastric cancers, and is associated with poor prognosis. Although HER2-targeted therapies, such as trastuzumab, improve outcomes in HER2-positive tumors, resistance often develops, and HER2-low tumors remain largely untargeted. Trastuzumab deruxtecan (T-DXd; DS-8201a) is a HER2-targeted antibody-drug conjugate with potent activity in HER2-positive and HER2-low tumors. This study evaluates its antitumor mechanisms and efficacy in HER2-positive, HER2-low, and homologous recombination deficiency (HRD)–associated models. Materials and Methods: Effects of T-DXd were assessed in cancer cell lines with diverse HER2 expression and HRD status. In vivo efficacy was evaluated using a xenograft model derived from HER2-low SNU-601 gastric cancer cells. Results: T-DXd reduced HER2 phosphorylation and downstream signaling (AKT, ERK) in HER2-positive cells. It induced DNA damage accumulation, as evidenced by increased γH2AX and p-Chk1 expression, and triggered apoptosis through cleaved poly(ADP-ribose) polymerase and caspase-3 activation, confirmed by annexin V staining. Similar effects were observed in HER2-low cells, with greater sensitivity in HRD cells. In xenografts, T-DXd reduced tumor volume by up to 80% at 4 mg/kg and 10 mg/kg. Histological analyses showed decreased Ki-67 and increased apoptosis. Furthermore, T-DXd induced G2/M cell cycle arrest and nuclear anaplasia, suggesting disruption of chromosomal stability as a potential antitumor mechanism. No significant toxicity, including body weight loss, was observed. Conclusion These findings highlight T-DXd’s effectiveness in HER2-low and HRD tumors, supporting its broader clinical application, including strategies targeting DNA damage repair pathways.

The impact of Streptococcus pneumoniae coinfection on coronavirus disease 2019 (COVID-19) prognosis remains uncertain. We conducted a retrospective analysis of patients hospitalized with COVID-19 who underwent a pneumococcal urinary antigen (PUA) test to assess its clinical utility. Results showed that PUA-positive patients required more oxygen support, high-flow nasal cannula, and dexamethasone compared to PUA-negative patients.Furthermore, the significantly higher incidence of a National Early Warning Score ≥5 in the PUA-positive group (P<0.001) suggests that a positive PUA test is associated with a severe disease course. However, no significant difference in mortality was observed between the two groups, and antibiotics were used in almost all patients (96.2%). While the PUA test may help guide antibiotic use in COVID-19 patients, its interpretation should be approached with caution.

The impact of Streptococcus pneumoniae coinfection on coronavirus disease 2019 (COVID-19) prognosis remains uncertain. We conducted a retrospective analysis of patients hospitalized with COVID-19 who underwent a pneumococcal urinary antigen (PUA) test to assess its clinical utility. Results showed that PUA-positive patients required more oxygen support, high-flow nasal cannula, and dexamethasone compared to PUA-negative patients.Furthermore, the significantly higher incidence of a National Early Warning Score ≥5 in the PUA-positive group (P<0.001) suggests that a positive PUA test is associated with a severe disease course. However, no significant difference in mortality was observed between the two groups, and antibiotics were used in almost all patients (96.2%). While the PUA test may help guide antibiotic use in COVID-19 patients, its interpretation should be approached with caution.

The impact of Streptococcus pneumoniae coinfection on coronavirus disease 2019 (COVID-19) prognosis remains uncertain. We conducted a retrospective analysis of patients hospitalized with COVID-19 who underwent a pneumococcal urinary antigen (PUA) test to assess its clinical utility. Results showed that PUA-positive patients required more oxygen support, high-flow nasal cannula, and dexamethasone compared to PUA-negative patients.Furthermore, the significantly higher incidence of a National Early Warning Score ≥5 in the PUA-positive group (P<0.001) suggests that a positive PUA test is associated with a severe disease course. However, no significant difference in mortality was observed between the two groups, and antibiotics were used in almost all patients (96.2%). While the PUA test may help guide antibiotic use in COVID-19 patients, its interpretation should be approached with caution.

Lomentospora prolificans is a rare opportunistic mold with high intrinsic resistance to most antifungal agents. It causes disseminated infections in immunocompromised patients and localized infections in immunocompetent hosts, often involving the bones, joints, or skin. However, prosthetic joint infections (PJI) due to L. prolificans have not been previously reported.Here, we describe the first case of L. prolificans PJI in an immunocompetent 51-year-old male patients, who had no significant comorbidities other than hypertension. The patient presented with right knee pain and swelling one year after total knee arthroplasty. Cultures of the joint fluid and periprosthetic tissue yielded L. prolificans, as confirmed by matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS) and rRNA gene sequencing. Susceptibility testing showed high minimum inhibitory concentrations for most currently available antifungal agents, including azoles, amphotericin B, echinocandins, and terbinafine. Despite prosthesis removal, multiple surgical debridements, and prolonged antifungal therapy, including voriconazole and terbinafine, the infection persisted over a five-year period.Amputation was discussed as a potential curative measure; however, no consensus has been reached due to its long-term impact. This case highlights the clinical challenges of managing L. prolificans PJI and underscores the need for novel antifungal therapies to treat rare drugresistant fungal infections.

Purpose: Our study aimed to delve beyond a surface-level understanding and explore the various dimensions of the global health curriculum from the perspective of both learners and educators using the Context, Input, Process, and Product (CIPP) model. Methods: From 2020 to 2021, interviews were conducted with a total of 10 individuals, including five students who had taken at least one elective course and at least one elective research course, three teaching assistants (TA), and two faculty members who had taken more than four global health courses in multiple phases in the global health curriculum. Semi-structured interview questions based on the CIPP model were used and qualitative data were analyzed through content analysis. Results: The study identified 12 sub-themes. Students held idealized views of global health careers and sought to bridge the gap through global health classes. They desired early exposure to global health courses, emphasizing both pre-medical and clinical phases. Challenges in adjusting course difficulty and recruiting faculty were identified, along with a preference for interactive teaching methods and offline discussions. The curriculum promoted reflection on medicine’s essence, expanded career perspectives, and emphasized competencies like altruism, communication skills, and crisis management in the evolving global health landscape. Conclusion This study showed that a comprehensive approach is possible from the perspective of learners and educators by identifying strengths, weaknesses, and the value of the curriculum’s goals, plans, implementations, and results through the CIPP model. For optimal curriculum design, a sequential approach from basic to advanced courses is essential, promoting hands-on global health experiences for students.

Background: Polycystic ovary syndrome (PCOS) and endometriosis are widely recognized as significant risk factors affecting the reproductive health of women. The underlying mechanisms impacting fertility may vary, potentially leading to divergent outcomes. We aimed to examine and contrast the prevalence patterns of diseases coexisting with PCOS and endometriosis, using a large-scale nationwide insurance claims data from Asian women of reproductive age. Methods: We analyzed health insurance and examination data of 157,662 Korean women aged 15–45 years, drawn from the Korea National Health Insurance Service-National Sample Cohort database. International Classification of Disease, Tenth Revision codes were mapped to phenome-wide association study codes (phecodes). Subsequently, multivariate logistic regression was performed to assess the comorbidity patterns among patients diagnosed with PCOS and endometriosis and healthy control groups. Results: Our analysis revealed that PCOS was correlated with a wider range of metabolic disorders and symptoms, such as hyperlipidemia, type 2 diabetes, various gastrointestinal (GI) issues, and an array of pregnancy-related complications. Conversely, endometriosis was more prevalent among benign neoplasms of female reproductive and digestive organs, endometrial hyperplasia, and angina pectoris. Notably, infertility and glaucoma demonstrated significant associations with both conditions. Furthermore, a comparison of symptom-related codes in women with endometriosis revealed a predominance of painrelated symptoms, whereas those with PCOS exhibited a broader spectrum, encompassing pain, pruritus, GI problems, cough, fever, menstrual cycle disorders, edema, and dizziness. Conclusion PCOS and endometriosis, which are prevalent gynecological disorders affecting similar age groups of women, rarely co-occur and exhibit unique comorbidity profiles.Tailored healthcare strategies that take into account these distinct patterns have the potential to enhance long-term healthcare outcomes of affected patients. Further research is required to elucidate the underlying mechanisms and contrasting comorbidity profiles between PCOS and endometriosis.

Background: Polycystic ovary syndrome (PCOS) and endometriosis are widely recognized as significant risk factors affecting the reproductive health of women. The underlying mechanisms impacting fertility may vary, potentially leading to divergent outcomes. We aimed to examine and contrast the prevalence patterns of diseases coexisting with PCOS and endometriosis, using a large-scale nationwide insurance claims data from Asian women of reproductive age. Methods: We analyzed health insurance and examination data of 157,662 Korean women aged 15–45 years, drawn from the Korea National Health Insurance Service-National Sample Cohort database. International Classification of Disease, Tenth Revision codes were mapped to phenome-wide association study codes (phecodes). Subsequently, multivariate logistic regression was performed to assess the comorbidity patterns among patients diagnosed with PCOS and endometriosis and healthy control groups. Results: Our analysis revealed that PCOS was correlated with a wider range of metabolic disorders and symptoms, such as hyperlipidemia, type 2 diabetes, various gastrointestinal (GI) issues, and an array of pregnancy-related complications. Conversely, endometriosis was more prevalent among benign neoplasms of female reproductive and digestive organs, endometrial hyperplasia, and angina pectoris. Notably, infertility and glaucoma demonstrated significant associations with both conditions. Furthermore, a comparison of symptom-related codes in women with endometriosis revealed a predominance of painrelated symptoms, whereas those with PCOS exhibited a broader spectrum, encompassing pain, pruritus, GI problems, cough, fever, menstrual cycle disorders, edema, and dizziness. Conclusion PCOS and endometriosis, which are prevalent gynecological disorders affecting similar age groups of women, rarely co-occur and exhibit unique comorbidity profiles.Tailored healthcare strategies that take into account these distinct patterns have the potential to enhance long-term healthcare outcomes of affected patients. Further research is required to elucidate the underlying mechanisms and contrasting comorbidity profiles between PCOS and endometriosis.

Purpose: The partner and localizer of breast cancer 2 (PALB2) mutation is a predisposition to breast cancer development. However, limited clinical data are available for the Korean population. Therefore, this study aimed to compare the characteristics and oncological outcomes of patients with PALB2-mutated and non-mutated PALB2 in Korea. Methods: A total of 1,463 breast cancer (BRCA) 1/2 mutation-negative breast cancer underwent comprehensive multigene sequencing between 2016 and 2019 at Severance Hospital, Seoul, Korea. Clinicopathological data and oncological results of PALB2 mutated patients were prospectively collected and compared with those of the non-mutated group. Results: PALB2 mutations were identified in 1.2% (17/1,463) of the patients. The median age at diagnosis was 46 (30–73) years, and the median tumor size was 1.8 (0.05–3.5) cm. All patients with PALB2 mutations had histologic grades II–III, and a triple-negative subtype was found in 23.5% (4/17); however, there were no significant differences in clinicopathological data between the groups. During the median follow-up time of 38.5 months, locoregional recurrence occurred in 4.2% (44/1,043), distant recurrence was reported in 3.0% (31/1,043), and contralateral breast cancer was diagnosed in 0.8% (9/1,043) of patients, with no significant difference observed between the groups. All-cause mortality was observed in 1.8% (19/1,028) of the non-mutated group and none in the PALB2 mutation group. However, survival analyses demonstrated no significant differences in all-cause mortality (p = 0.524) and recurrence-free survival (p = 0.319). Conclusion Clinicopathological features and oncological outcomes of PALB2 mutated breast cancer were not significantly different from those of non-mutated breast cancer in the Korean population.