Purpose: Although human epidermal growth factor receptor 2 (HER2) positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy. Materials and Methods: The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed. Results: The analysis included 799 female patients. The median age was 51 years (range, 23 to 79 years), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n=238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% confidence interval [CI], 114.0 to 127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1 to 93.3), 97.5% (95% CI, 96.4 to 98.7), and 98.8% (95% CI, 98.0 to 99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease. Conclusion A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.

Purpose: Based on the KEYNOTE-522 study, neoadjuvant pembrolizumab plus chemotherapy has become the standard treatment for early-stage triple-negative breast cancer (TNBC).This study evaluated the real-world efficacy, safety, and predictors of pathologic complete response (pCR) in Korean patients. Methods: We conducted a retrospective cohort study of 174 patients with early-stage TNBC who received the KEYNOTE-522 regimen (neoadjuvant pembrolizumab plus paclitaxel and carboplatin, followed by doxorubicin and cyclophosphamide) at a tertiary cancer center between August 2022 and July 2024. We assessed the primary endpoints, including pCR rate and event-free survival (EFS). We performed univariable and multivariable logistic regression analyses to identify independent predictors of pCR. Results: The median patient age was 50 years (range, 24–74 years). The clinical stages were II and III in 79.3% and 20.1% of patients, respectively, and 10.9% had clinical N3 disease. The overall pCR rate was 62.1%, and the N3 subgroup had a pCR rate of 47.4%. On multivariable analysis, high baseline Ki-67 expression (≥ median, 75%) was significantly associated with pCR (odds ratio, 2.84; 95% confidence interval, 1.45 to 5.66; p = 0.002). At a median followup of 18.4 months, the 12-month EFS rate was 97.4%, with significantly superior outcomes observed in patients who achieved pCR compared with those who did not achieve pCR (100% vs. 93.1%, p = 0.007). The treatment completion rate was 92.0%, and immune-related adverse events occurred in 13.8% of patients. Conclusion In this real-world analysis of one of the largest Asian cohorts of patients with earlystage TNBC treated with neoadjuvant pembrolizumab, the KEYNOTE-522 regimen demonstrated substantial efficacy and manageable toxicity, consistent with the original trial findings.

Purpose: Improvement of left ventricular (LV) diastolic dysfunction (DD) is known to be a good prognostic factor in patients with heart failure with reduced ejection fraction (EF). In the present study, we investigated the predisposing risk factors affecting the reversibility of LV diastolic filling pattern (DFP) in patients with preserved EF. Materials and Methods: A total of 600 patients with pseudonormal LVDFP and preserved EF who underwent follow-up echocardiography were enrolled between 2011 and 2020. We compared their index and follow-up echocardiography findings and determined the predisposing risk factor affecting the reversibility of LVDFP. Results: Comparing the index and follow-up echocardiography findings showed that 379 (63%) patients had improved to normal or impaired relaxation LVDFP (improved group) and 221 (37%) patients had maintained or worsened LVDFP (unimproved group).The incidence of paroxysmal atrial fibrillation (PAF) was significantly higher in the unimproved group than in the improved group (4.7% vs. 9.5%, p=0.026). After adjustment for relevant clinical risk factors of diastolic dysfunction, PAF was determined to be an independent predisposing risk factor for the unimproved LVDFP (odds ratio: 2.10, 95% confidence interval: 1.06–4.15, p=0.033).Among the parameters of diastolic dysfunction in follow-up echocardiography, the left atrial volume index, mean E/A ratio, and E/e' were significantly improved in patients without PAF but remained in patients with PAF. Conclusion We identified that PAF was an independent predisposing risk factor of the unimproved LVDFP in patients with pseudonormal LVDFP and preserved EF. Therefore, early detection and management of PAF might be required in patients with LVDD and preserved EF to prevent adverse cardiovascular events.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Background: The World Health Organization has declared the end of the coronavirus disease 2019 (COVID-19) public health emergency. However, this did not indicate the end of COVID-19. Several months after the infection, numerous patients complain of respiratory or nonspecific symptoms; this condition is called long COVID. Even patients with mild COVID-19 can experience long COVID, thus the burden of long COVID remains considerable. Therefore, we conducted this study to comprehensively analyze the effects of long COVID using multi-faceted assessments. Materials and Methods: We conducted a prospective cohort study involving patients diagnosed with COVID-19 between February 2020 and September 2021 in six tertiary hospitals in Korea. Patients were followed up at 1, 3, 6, 12, 18, and 24 months after discharge. Long COVID was defined as the persistence of three or more COVID-19-related symptoms. The primary outcome of this study was the prevalence of long COVID after the period of COVID-19. Results: During the study period, 290 patients were enrolled. Among them, 54.5 and 34.6% experienced long COVID within 6 months and after more than 18 months, respectively. Several patients showed abnormal results when tested for post-traumatic stress disorder (17.4%) and anxiety (31.9%) after 18 months. In patients who underwent follow-up chest computed tomography 18 months after COVID-19, abnormal findings remained at 51.9%. Males (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05–0.53; P=0.004) and elderly (OR, 1.04; 95% CI, 1.00–1.09; P=0.04) showed a significant association with long COVID after 12–18 months in a multivariable logistic regression analysis. Conclusion Many patients still showed long COVID after 18 months post SARS-CoV-2 infection. When managing these patients, the assessment of multiple aspects is necessary.

Background: Psychological test reports are essential in assessing intellectual functioning, aiding in diagnosing and treating intellectual disability (ID) and attention-deficit/ hyperactivity disorder (ADHD). However, these reports can have several problems because they are diverse, unstructured, subjective, and involve human errors. Additionally, physicians often do not read the entire report, and the number of reports is lower than that of diagnoses. Methods: We developed explainable predictive models for classifying IDs and ADHDs based on written reports to address these issues. The reports of 1,475 patients with IDs and ADHDs who underwent intelligence tests were used for the models. These models were developed by analyzing reports using natural language processing (NLP) and incorporating the physician’s diagnosis for each report. We selected n-gram features from the models’ results by extracting important features using SHapley Additive exPlanations and permutation importance to make the models explainable. Developing the n-gram feature-based original text search system compensated for the lack of human readability caused by NLP and enabled the reconstruction of human-readable texts from the selected n-gram features. Results: The maximum model accuracy was 0.92, and the 80 human-readable texts were restored from four models. Conclusion The results showed that the models could accurately classify IDs and ADHDs, even with a few reports. The models were also able to explain their predictions. The explainability-enhanced model can help physicians understand the classification process of IDs and ADHDs and provide evidence-based insights.

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: The increasing incidence and mortality rates of tuberculosis among older individuals who suffer from multiple morbidities and are vulnerable to malnutrition are major obstacles to efforts to eradicate tuberculosis in the Republic of Korea. Herein, we identified the factors associated with mortality during anti-tuberculosis treatment in patients with pulmonary tuberculosis. Methods: We conducted a case-control study and extracted data from the database of a multi-center prospective observational cohort study in Korea. Among the participants with rifampicin-susceptible pulmonary tuberculosis, the survival group was defined as those who successfully completed treatment within one year, whereas the mortality group was defined as those who died during treatment. Univariable and multivariable logistic regression analyses were performed to identify factors associated with TB mortality. Results: Among 1,119 participants with pulmonary TB registered between 2019 and 2021, 799 and 59 were grouped in the survival and mortality groups, respectively. Age, positive smear results, alarming symptoms, nutrition risk score, Charlson comorbidity index score, and initial standard treatment regimen were significant based on univariable analysis and were selected for the multivariable logistic regression model. Nutrition risk score (adjusted odds ratio, 2.44; 95% confidence interval, 1.72–3.48) and Charlson comorbidity index score (adjusted odds ratio, 1.62; 95% confidence interval, 1.35–1.94) remained statistically significant in the multivariate analysis. Conclusion Nutritional status and comorbidities at baseline were identified as important factors associated with mortality in patients with pulmonary tuberculosis.

Purpose: The opacity of zirconia sometimes requires a veneering material; thus lithium disilicate, a veneer material with excellent strength, can be used. This study investigated the fracture resistance of zirconia–lithium disilicate (Zr-LS2) bi-layered crowns according to the design of the substructure. Materials and Methods: Five groups of posterior Zr-LS2 restorations (Zirtooth and Amber LiSi-POZ) were fabricated with different zirconia substructure coverage (control group, groups half occlusal zirconia coverage; 1/2OZ, and three-quarter occlusal zirconia coverage; 3/4OZ) and margin designs (control group, groups collar margin; C-M, and collarless margin; Cl-M). All restorations were cemented with self-adhesive resin cement followed by 24-h water storage and thermocycling (10,000 cycles, 5°C and 55°C). The fracture load was measured, and failure mode analysis, fractography, and elemental analysis were performed. The one-way analysis of variance and Fisher’s exact test were performed for statistical analyses (α=.05). Results: A significant difference was found in the fracture load of Zr-LS2 restorations according to the zirconia coverage of the occlusal area and margin design (P<.05). Group 3/4OZ was significantly larger than the control group C and 1/2OZ (P<.05). The C-M group had greater fracture loads based on margin design than the control group C and Cl-M (P<.05). Conclusion The fracture resistance of posterior Zr-LS2 restorations increased with the zirconia coverage, occlusal thickness, and collar margin.

Background: Psychological test reports are essential in assessing intellectual functioning, aiding in diagnosing and treating intellectual disability (ID) and attention-deficit/ hyperactivity disorder (ADHD). However, these reports can have several problems because they are diverse, unstructured, subjective, and involve human errors. Additionally, physicians often do not read the entire report, and the number of reports is lower than that of diagnoses. Methods: We developed explainable predictive models for classifying IDs and ADHDs based on written reports to address these issues. The reports of 1,475 patients with IDs and ADHDs who underwent intelligence tests were used for the models. These models were developed by analyzing reports using natural language processing (NLP) and incorporating the physician’s diagnosis for each report. We selected n-gram features from the models’ results by extracting important features using SHapley Additive exPlanations and permutation importance to make the models explainable. Developing the n-gram feature-based original text search system compensated for the lack of human readability caused by NLP and enabled the reconstruction of human-readable texts from the selected n-gram features. Results: The maximum model accuracy was 0.92, and the 80 human-readable texts were restored from four models. Conclusion The results showed that the models could accurately classify IDs and ADHDs, even with a few reports. The models were also able to explain their predictions. The explainability-enhanced model can help physicians understand the classification process of IDs and ADHDs and provide evidence-based insights.