Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Purpose: In Korea, the Act on Hospice and Palliative Care and Decisions on Life-Sustaining Treatment (LST) was implemented on February 4, 2018. We aimed to investigate relevant factors and clinical changes associated with LST decisions after law enforcement. Materials and Methods: This single-center retrospective study included patients who completed LST documents using legal forms at Asan Medical Center from February 5, 2018, to June 30, 2020. Results: 5,896 patients completed LST documents, of which 2,704 (45.8%) signed the documents in person, while family members of 3,192 (54%) wrote the documents on behalf of the patients. Comparing first year and following year of implementation of the act, the self-documentation rate increased (43.9% to 47.2%, p=0.014). Moreover, the number of LST decisions made during or after intensive care unit admission decreased (37.8% vs. 35.2%, p=0.045), and the completion rate of LST documents during chemotherapy increased (6.6% vs. 8.9%, p=0.001). In multivariate analysis, age < 65 (odds ratio [OR], 1.724; 95% confidence interval [CI], 1.538 to 1.933; p < 0.001), unmarried status (OR, 1.309; 95% CI, 1.097 to 1.561; p=0.003), palliative care consultation (OR, 1.538; 95% CI, 1.340 to 1.765; p < 0.001), malignancy (OR, 1.864; 95% CI, 1.628 to 2.133; p < 0.001), and changes in timing on the first year versus following year (OR, 1.124; 95% CI, 1.003 to 1.260; p=0.045) were related to a higher self-documentation rate. Conclusion Age < 65 years, unmarried status, malignancy, and referral to a palliative care team were associated with patients making LST decisions themselves. Furthermore, the subject and timing of LST decisions have changed with the LST act.

Purpose: Several types of dermal fillers have been recently introduced and used for penile augmentation (PA). However, few studies have compared outcomes after the injection of different fillers. This study aimed to compare the clinical outcomes of hyaluronic acid (HLA), polylactic acid (PLA), and polymethyl methacrylate (PMA) filler injections, which are the most commonly used for aesthetic purposes. Materials and Methods: This prospective study was conducted for 24 weeks after a filler injection by a surgeon between March 2017 and December 2021. Healthy adult men complaining of small penis were enrolled. Penile girth, satisfaction, and injection-associated adverse events (AEs) were assessed at baseline and 4, 12, and 24 weeks after injection. Results: Of the 301 men who received filler injections, 125, 134, and 42 received HLA, PLA, and PMA fillers, respectively. The augmentation effect was in the order of PMA, HLA, and PLA, respectively, at 24 weeks (PMA vs. HLA, p<0.001; HLA vs. PLA, p=0.006). Satisfaction levels increased significantly at 24 weeks in all groups (each with p<0.001). However, the increase in satisfaction levels was smaller in the PMA group (PMA vs. HLA or PLA, p<0.05, for both penile appearance and sexual life). No serious or systemic AEs were recorded. Filler injection-associated local AEs in the HLA, PLA, and PMA groups occurred in 9 (7.2%), 16 (11.9%), and 6 (14.3%) men, respectively. There was no significant difference in AEs among the groups (p=0.299). Conclusions The augmentative effect was greater in the PMA group than in the HLA and PLA groups, whereas the increase in satisfaction levels was smaller in the PMA group. Our study demonstrated the clinical course of different types of fillers and suggests that the filler type should be selected after detailed counseling considering individual characteristics and preferences.

Purpose: Several types of dermal fillers have been recently introduced and used for penile augmentation (PA). However, few studies have compared outcomes after the injection of different fillers. This study aimed to compare the clinical outcomes of hyaluronic acid (HLA), polylactic acid (PLA), and polymethyl methacrylate (PMA) filler injections, which are the most commonly used for aesthetic purposes. Materials and Methods: This prospective study was conducted for 24 weeks after a filler injection by a surgeon between March 2017 and December 2021. Healthy adult men complaining of small penis were enrolled. Penile girth, satisfaction, and injection-associated adverse events (AEs) were assessed at baseline and 4, 12, and 24 weeks after injection. Results: Of the 301 men who received filler injections, 125, 134, and 42 received HLA, PLA, and PMA fillers, respectively. The augmentation effect was in the order of PMA, HLA, and PLA, respectively, at 24 weeks (PMA vs. HLA, p<0.001; HLA vs. PLA, p=0.006). Satisfaction levels increased significantly at 24 weeks in all groups (each with p<0.001). However, the increase in satisfaction levels was smaller in the PMA group (PMA vs. HLA or PLA, p<0.05, for both penile appearance and sexual life). No serious or systemic AEs were recorded. Filler injection-associated local AEs in the HLA, PLA, and PMA groups occurred in 9 (7.2%), 16 (11.9%), and 6 (14.3%) men, respectively. There was no significant difference in AEs among the groups (p=0.299). Conclusions The augmentative effect was greater in the PMA group than in the HLA and PLA groups, whereas the increase in satisfaction levels was smaller in the PMA group. Our study demonstrated the clinical course of different types of fillers and suggests that the filler type should be selected after detailed counseling considering individual characteristics and preferences.

Digital therapeutics (DTx) are emerging as a transformative innovation in healthcare offering evidence-based digital interventions for the treatment, management, and prevention of various diseases and disorders. In Korea, DTx have gained significant attention as potential solutions to the increasing burden of chronic diseases and mental health conditions. However, the Korean DTx market faces several challenges that hinder its widespread adoption and integration into the national healthcare system. This study provides a comprehensive analysis of the current state of the DTx market in Korea, identifies the key challenges impeding its growth, and proposes strategies for overcoming these obstacles. This study utilized a literature review and market analysis approach to examine the latest research, industry reports, and regulatory documents related to DTx. The analysis focused on three primary areas: (1) the current regulatory landscape, (2) technological advancements and challenges, and (3) economic and commercial factors influencing DTx adoption in Korea. A comparative analysis of global regulatory practices was also conducted to identify best practices. The findings revealed that while Korea has made significant strides in supporting DTx development, the market remains in its early stages. The key challenges include underdeveloped regulatory frameworks, issues with data quality and security, and a lack of established reimbursement pathways. We recommend developing tailored regulatory frameworks for DTx, enhancing policy support for small and medium-sized enterprises involved in DTx development, and increasing investments in technological infrastructure. By addressing these challenges, Korea could position itself as a leader in the global DTx market, delivering innovative and effective treatments to enhance patient care and outcomes.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background: Group B Streptococcus (GBS) is one of the leading causes of neonatal earlyonset sepsis, resulting in high mortality and significant comorbidity. Intrapartum penicillin prophylaxis is recommended for pregnant women with GBS colonization to prevent vertical transmission. For pregnant women at high risk of anaphylaxis to penicillin, clindamycin is recommended only if the susceptibility of GBS isolates has been identified. We retrospectively examined the GBS detection rate and clindamycin resistance among Korean women of reproductive age over the last 20 years. Methods: Microbiologic studies using vaginal, vaginal–rectal or vaginal–perianal swabs from female patients 15–49 years of age during 2003–2022 were reviewed. Annual GBS detection rates and clindamycin resistance rates were calculated. The study period was divided into two periods (period 1, 2003–2015; period 2, 2016–2022) based on the introduction of universal culture-based GBS screening in our center in 2016. GBS detection rates and clindamycin resistance rates were compared between the periods using χ2 tests. Results: A total of 14,571 women were tested 16,879 times and GBS was isolated in 1,054 tests (6.2%), with 423 clindamycin-resistant isolates (40.1%). The GBS detection rate increased from 3.4% (301/8,869) in period 1 to 9.4% (2,753/8,010) in period 2 (P < 0.001). Even during period 1, the GBS detection rate was higher in 2009–2015 compared to 2003–2008 (P < 0.001). Clindamycin resistance rates have remained at similar levels since 2009, which were 39.5% (199/301) in period 1 and 40.2% (303/753) in period 2 (P = 0.833). Conclusion This study demonstrated that GBS detection rates in Korean women of reproductive age significantly increased almost three times during the twenty years of the study period, with a persistently high clindamycin resistance rate of up to 40%.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.

Background: Group B Streptococcus (GBS) is one of the leading causes of neonatal earlyonset sepsis, resulting in high mortality and significant comorbidity. Intrapartum penicillin prophylaxis is recommended for pregnant women with GBS colonization to prevent vertical transmission. For pregnant women at high risk of anaphylaxis to penicillin, clindamycin is recommended only if the susceptibility of GBS isolates has been identified. We retrospectively examined the GBS detection rate and clindamycin resistance among Korean women of reproductive age over the last 20 years. Methods: Microbiologic studies using vaginal, vaginal–rectal or vaginal–perianal swabs from female patients 15–49 years of age during 2003–2022 were reviewed. Annual GBS detection rates and clindamycin resistance rates were calculated. The study period was divided into two periods (period 1, 2003–2015; period 2, 2016–2022) based on the introduction of universal culture-based GBS screening in our center in 2016. GBS detection rates and clindamycin resistance rates were compared between the periods using χ2 tests. Results: A total of 14,571 women were tested 16,879 times and GBS was isolated in 1,054 tests (6.2%), with 423 clindamycin-resistant isolates (40.1%). The GBS detection rate increased from 3.4% (301/8,869) in period 1 to 9.4% (2,753/8,010) in period 2 (P < 0.001). Even during period 1, the GBS detection rate was higher in 2009–2015 compared to 2003–2008 (P < 0.001). Clindamycin resistance rates have remained at similar levels since 2009, which were 39.5% (199/301) in period 1 and 40.2% (303/753) in period 2 (P = 0.833). Conclusion This study demonstrated that GBS detection rates in Korean women of reproductive age significantly increased almost three times during the twenty years of the study period, with a persistently high clindamycin resistance rate of up to 40%.

Background: Immunocompromised (IC) pediatric patients are at increased risk of severe acute respiratory syndrome coronavirus 2 infection, but the viral kinetics and seroimmunologic response in pediatric IC patients are not fully understood. Methods: From April to June 2022, a prospective cohort study was conducted. IC pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) were enrolled. Serial saliva swab and serum specimens were subjected to reverse transcription polymerase chain reaction assays with mutation sequencing, viral culture, anti-spike-protein, anti-nucleocapsid antibody assays, plaque reduction neutralization test (PRNT) and multiplex cytokine assays. Results: Eleven IC children were evaluated. Their COVID-19 symptoms resolved promptly (median, 2.5 days; interquartile range, 2.0–4.3). Saliva swab specimens contained lower viral loads than nasopharyngeal swabs (P = 0.008). All cases were BA.2 infection, and 45.5% tested negative within 14 days by saliva swab from symptom onset. Eight (72.7%) showed a time-dependent increase in BA.2 PRNT titers, followed by rapid waning. Multiplex cytokine assays revealed that monocyte/macrophage activation and Th 1 responses were comparable to those of non-IC adults. Activation of interleukin (IL)-1Ra and IL-6 was brief, and IL-17A was suppressed. Activated interferon (IFN)-γ and IL-18/IL-1F4 signals were observed. Conclusion IC pediatric patients rapidly recovered from COVID-19 with low viral loads.Antibody response was limited, but cytokine analysis suggested an enhanced IFN-γ- and IL-18-mediated immune response without excessive activation of inflammatory cascades. To validate our observation, immune cell-based functional studies need to be conducted among IC and non-IC children.