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.

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.

Circulating tumor DNA (ctDNA) has emerged as a promising tool for various clinical applications, including early diagnosis, therapeutic target identification, treatment response monitoring, prognosis evaluation, and minimal residual disease detection. Consequently, ctDNA assays have been incorporated into clinical practice. In this review, we offer an indepth exploration of the clinical implementation of ctDNA assays. Notably, we examined existing evidence related to pre-analytical procedures, analytical components in current technologies, and result interpretation and reporting processes. The primary objective of this guidelines is to provide recommendations for the clinical utilization of ctDNA assays.

This retrospective study analyzed medical records of 1,392 people living with HIV (PLWH) diagnosed with latent tuberculosis infection (LTBI) at two provincial central hospitals from 2011 to 2022. LTBI was diagnosed in 152 patients (10.9%) patients aged ≥18 years. Among the 113 patients who initiated treatment, 96 (85.0%) completed isoniazid therapy, while 17 (15.0%) discontinued due to patient refusal, liver function test abnormalities, and other reasons.During a mean follow-up period of 55.0±31.0 months, two cases of active tuberculosis were reported in both thetreatment non-completion group (3.6%) and the completion group (2.1%). This study provides recent real-world insights into LTBI treatment among PLWH in Korea.

Background: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. Materials and Methods: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. Results: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization ( P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12–4.11) and male gender (OR, 2.62; 95% CI, 1.26– 5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24–0.79) was associated with better outcomes. Conclusion Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.

Background: A dual regimen with dolutegravir plus cobicistat-boosted darunavir (DTG+DRV/c) is a promising alternative for patients with human immunodeficiency virus (HIV) with resistance or intolerance to nucleoside reverse transcriptase inhibitors, especially those with a history of treatment failure. Materials and Methods: We included all treatment-experienced patients with HIV who switched to the DTG+DRV/c regimen at a tertiary university hospital. We assessed the regimen's effectiveness, safety, and tolerability through serial laboratory data and clinical findings. The primary endpoint was the proportion of patients with plasma HIV-RNA levels <50 copies/mL at week 144 post-switch. The secondary endpoints were safety and tolerability assessments. Results: Our retrospective analysis involved 40 patients. The leading reasons for switching to DTG+DRV/c were treatment failure in 17 patients (42.5%), simplification after multiple previous regimens in 15 (37.5%), and adverse drug reactions in 8 (20.0%). Among the 17 patients in the treatment failure group, we observed enhanced viral suppression and improved CD4+ T-cell counts after initiating the dual regimen. In the non-treatment failure group (23 patients), viral suppression and CD4+ T-cell levels were consistently maintained. No significant alterations in renal function, liver function, glucose levels, or lipid profiles were observed post-switch. High tolerability was observed, with 34/40 patients (85.0%) responding well to the regimen. However, six patients discontinued treatment before reaching the 144-week mark. Conclusion Our findings confirm that DTG+DRV/c is an effective and well-tolerated switch therapy regimen for treatment-experienced patients with HIV, with sustained benefits observed for up to 144 weeks of follow-up. This regimen showed adaptability across different patient groups and demonstrated virological and immunological improvements, particularly in patients with a history of treatment failure.

Background: A healthcare system’s collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. Methods: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. Results: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. Conclusion In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.