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/Aims: We investigated the clinical practice patterns of Korean endoscopists for the endoscopic resection of colorectal polyps. Methods: From September to November 2021, an online survey was conducted regarding the preferred resection methods for colorectal polyps, and responses were compared with the international guidelines. Results: Among 246 respondents, those with <4 years, 4–9 years, and ≥10 years of experiencein colonoscopy practices accounted for 25.6%, 34.1%, and 40.2% of endoscopists, respectively. The most preferred resection methods for non-pedunculated lesions were cold forceps polypectomy for ≤3 mm lesions (81.7%), cold snare polypectomy for 4–5 mm (61.0%) and 6–9 mm (43.5%) lesions, hot endoscopic mucosal resection (EMR) for 10–19 mm lesions (72.0%), precut EMR for 20–25 mm lesions (22.0%), and endoscopic submucosal dissection (ESD) for ≥26 mm lesions (29.3%). Hot EMR was favored for pedunculated lesions with a head size <20 mm and stalk size <10 mm (75.6%) and for those with a head size ≥20 mm or stalk size ≥10 mm (58.5%). For suspected superficial and deep submucosal lesions measuring 10–19 mm and ≥20 mm, ESD (26.0% and 38.6%) and surgery (36.6% and 46.3%) were preferred, respectively. The adherence rate to the guidelines ranged from 11.2% to 96.9%, depending on the size, shape, and histology of the lesions. Conclusions Adherence to the guidelines for endoscopic resection techniques varied depend-ing on the characteristics of colorectal polyps. Thus, an individualized approach is required to increase adherence to the guidelines.

Background/Aims: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.

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.

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%.