Background: Immunocompromised patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection often have prolonged viral shedding, and some are clinically suspected of reinfection with different SARSCoV-2 variants. However, data on this issue are limited. This study investigated the SARS-CoV-2 variants in serially collected respiratory samples from immunocompromised patients with prolonged viral shedding for over 12 weeks or relapsed viral shedding after at least 2 weeks of viral clearance. Materials and Methods: From February 2022 to September 2023, we prospectively enrolled immunocompromised patients with coronavirus disease 2019 who had hematologic malignancies or had undergone transplantation and were admitted to a tertiary hospital. Weekly saliva or nasopharyngeal swabs were collected from enrolled patients for at least 12 weeks after diagnosis. Genomic RNA polymerase chain reaction (PCR) was performed on samples, and those testing positive underwent viral culture to isolate the live virus. Spike gene full sequencing via Sanger sequencing and real-time reverse transcription-PCR for detecting mutation genes were conducted to identify SARSCoV-2 variants. Results: Among 116 enrolled patients, 20 with prolonged or relapsed viral shedding were screened to identify the variants. Of these 20 patients, 7 (35%) exhibited evidence of re-infection; one of 8 patients with prolonged viral shedding and 6 of 12 with relapsed viral shedding were reinfected with SARS-CoV-2. Conclusion Our data suggest that approximately one-third of immunocompromised patients with persistent or relapsed viral shedding had reinfection with different variants of SARS-CoV-2.

Background: Immunocompromised patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection often have prolonged viral shedding, and some are clinically suspected of reinfection with different SARSCoV-2 variants. However, data on this issue are limited. This study investigated the SARS-CoV-2 variants in serially collected respiratory samples from immunocompromised patients with prolonged viral shedding for over 12 weeks or relapsed viral shedding after at least 2 weeks of viral clearance. Materials and Methods: From February 2022 to September 2023, we prospectively enrolled immunocompromised patients with coronavirus disease 2019 who had hematologic malignancies or had undergone transplantation and were admitted to a tertiary hospital. Weekly saliva or nasopharyngeal swabs were collected from enrolled patients for at least 12 weeks after diagnosis. Genomic RNA polymerase chain reaction (PCR) was performed on samples, and those testing positive underwent viral culture to isolate the live virus. Spike gene full sequencing via Sanger sequencing and real-time reverse transcription-PCR for detecting mutation genes were conducted to identify SARSCoV-2 variants. Results: Among 116 enrolled patients, 20 with prolonged or relapsed viral shedding were screened to identify the variants. Of these 20 patients, 7 (35%) exhibited evidence of re-infection; one of 8 patients with prolonged viral shedding and 6 of 12 with relapsed viral shedding were reinfected with SARS-CoV-2. Conclusion Our data suggest that approximately one-third of immunocompromised patients with persistent or relapsed viral shedding had reinfection with different variants of SARS-CoV-2.

Background: Immunocompromised patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection often have prolonged viral shedding, and some are clinically suspected of reinfection with different SARSCoV-2 variants. However, data on this issue are limited. This study investigated the SARS-CoV-2 variants in serially collected respiratory samples from immunocompromised patients with prolonged viral shedding for over 12 weeks or relapsed viral shedding after at least 2 weeks of viral clearance. Materials and Methods: From February 2022 to September 2023, we prospectively enrolled immunocompromised patients with coronavirus disease 2019 who had hematologic malignancies or had undergone transplantation and were admitted to a tertiary hospital. Weekly saliva or nasopharyngeal swabs were collected from enrolled patients for at least 12 weeks after diagnosis. Genomic RNA polymerase chain reaction (PCR) was performed on samples, and those testing positive underwent viral culture to isolate the live virus. Spike gene full sequencing via Sanger sequencing and real-time reverse transcription-PCR for detecting mutation genes were conducted to identify SARSCoV-2 variants. Results: Among 116 enrolled patients, 20 with prolonged or relapsed viral shedding were screened to identify the variants. Of these 20 patients, 7 (35%) exhibited evidence of re-infection; one of 8 patients with prolonged viral shedding and 6 of 12 with relapsed viral shedding were reinfected with SARS-CoV-2. Conclusion Our data suggest that approximately one-third of immunocompromised patients with persistent or relapsed viral shedding had reinfection with different variants of SARS-CoV-2.

Background: Genetic alterations play a pivotal role in multiple myeloma (MM) development and therapeutic resistance. Traditionally, the genetic profiling of MM requires invasive bone marrow (BM) procedures; however, these procedures are associated with patient discomfort and cannot fully capture the spatial and temporal heterogeneity of the disease.Therefore, we investigated the clinical implications of liquid biopsy using targeted deep sequencing. Methods: We analyzed the genetic profiles of circulating tumor DNA (ctDNA) by targeted deep sequencing from 102 patients, including those with monoclonal gammopathy of undetermined significance (MGUS, N = 7), smoldering MM (N = 6), and symptomatic MM (N = 89). Results: The number of ctDNA mutations increased with disease progression from MGUS to MM, with averages of 1.0 mutations in MGUS, 1.8 mutations in smoldering MM, and 1.9 mutations in MM, respectively. Shared mutations between BM and ctDNA were more prevalent in MM (68.9%) than in MGUS (25.0%). RAS/RAF and TP53 mutations were significantly enriched in MM ctDNA. Specific mutations were associated with clinical features in patients with MM: hypercalcemia and TET2 (P = 0.006), renal insufficiency and NRAS (P = 0.012), paramedullary myeloma and TP53(P = 0.02), and extramedullary myeloma and NRAS (P = 0.007). TET2 mutations significantly affected 2-yr progression-free survival (hazard ratio = 7.11, P = 0.003). Serial ctDNA profiling accurately predicted treatment response in patients with MM. Conclusions Our findings highlight the potential of liquid biopsy for understanding MM progression and prognosis utilizing a minimally invasive approach, paving the way for its integration into personalized treatment strategies and real-time disease monitoring.

Objective: To determine the normative values of the Korean version of the Modified Barthel Index (K-MBI) score for typically developing children in Korea and assess its suitability for use in children. Methods: Rehabilitation physicians and occupational therapists with children were invited through an online platform to participate in a survey assessing their children’s performance of activity of daily living (ADL) using the K-MBI. The questionnaire encompassed queries on sociodemographic information of children and the assessment criteria outlined in the K-MBI. The standardized K-MBI scores by age were estimated using the nonlinear least squares method. Results: The analysis incorporated responses from a total of 206 individuals. K-MBI total scores showed a rapid increase over the first 8 years of life, with 99% of children achieving a score of 90 or higher by age 8. Mobility scores exhibited a swift increase during early childhood, surpassing 90% of the maximum score at 3 years of age and nearing 100% at 7 years of age. In contrast, self-care scores demonstrated a more gradual advancement, achieving approximately 100% of the maximum score by the age of 10 years. Conclusion Age-specific normative values for K-MBI scores of typically developing children were established, which can be used as a reference in clinical care. While the K-MBI captured the overall trajectory of children’s ADL development, it did not discern subtle differences across various developmental stages. There is a need for the development of more refined assessment tools tailored specifically to children.

Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety. We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles. Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration’s marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported. Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs’ efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.

Background: The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood.Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC. Methods: We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023. Blood samples were collected at three time-points: within one month of diagnosis (acute phase) and at 1 month, and 3 months post-diagnosis. Following a recent well-designed definition of PASC, PASC patients were defined as those with a questionnaire-based PASC score ≥ 12 persisting for at least 4 weeks after the initial COVID-19 diagnosis. Results: Of 57 eligible COVID-19 patients, 29 (51%) had PASC, and 28 (49%) did not. The PASC group had significantly higher nucleocapsid protein (NP) antigenemia 3 months after COVID-19 diagnosis (P = 0.022). Furthermore, several cytokines, including IL-2, IL-17A, VEGF, RANTES, sCD40L, IP-10, I-TAC, and granzyme A, were markedly elevated in the PASC group 1 and/or 3 month(s) after COVID-19 diagnosis. In contrast, the median values of several serological markers, including thyroid markers, autoimmune indicators, and stress-related hormones, were within the normal range. Conclusion Levels of NP antigen and of various cytokines involved in immune responses become significantly elevated over time after COVID-19 diagnosis in PASC patients compared to non-PASC patients. This suggests that PASC is associated with prolonged immune dysregulation resulting from heightened antigenic stimulation.

Objectives: Estimating the number of deaths caused by smoking is crucial for developing and evaluating tobacco control and smoking cessation policies. This study aimed to determine smoking-attributable mortality (SAM) in Korea in 2020. Methods: Four large-scale cohorts from Korea were analyzed. A Cox proportional-hazards model was used to determine the hazard ratios (HRs) of smoking-related death. By conducting a meta-analysis of these HRs, the pooled HRs of smoking-related death for 41 diseases were estimated. Population-attributable fractions (PAFs) were calculated based on the smoking prevalence for 1995 in conjunction with the pooled HRs. Subsequently, SAM was derived using the PAF and the number of deaths recorded for each disease in 2020. Results: The pooled HR for all-cause mortality attributable to smoking was 1.73 for current men smokers (95% confidence interval [CI], 1.53 to 1.95) and 1.63 for current women smokers (95% CI, 1.37 to 1.94). Smoking accounted for 33.2% of all-cause deaths in men and 4.6% in women. Additionally, it was a factor in 71.8% of men lung cancer deaths and 11.9% of women lung cancer deaths. In 2020, smoking was responsible for 53 930 men deaths and 6283 women deaths, totaling 60 213 deaths. Conclusions Cigarette smoking was responsible for a significant number of deaths in Korea in 2020. Monitoring the impact and societal burden of smoking is essential for effective tobacco control and harm prevention policies.

Objectives: The aim of this study was to evaluate brain activity in youth during chewing gum and wood stick using functional magnetic resonance imaging (fMRI). Methods: Two participants chewed wax gums and wood stick on the rhythm of 1 Hz during MRI scanning. The task paradigm was a block design and each chewing-rest procedure was repeated five times for 30s. Results: The brain regions activated during chewing gum and wood stick were the precentral gyrus, postcentral gyrus, supplementary motor area, thalamus cerebellum. The medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), hippocampus, and precuneus were additionally activated by mastication of the wood stick. Brain activation induced by chewing wood stick was higher than chewing gum. Conclusions Our results suggest that mastication contribute to cognitive improvement through brain activity, this effect is stronger during chewing wood than gum. Therefore, eating harder foods may improve cognitive function more effectively.