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Background/Objectives: Radiofrequency ablation (RFA) is an important local treatment for hepatocellular carcinoma (HCC). This study aimed to evaluate the characteristics of tumor recurrence after RFA and analyze predictors of tumor recurrence and survival in patients with HCC. Methods: We retrospectively reviewed data from treatment-naïve patients with HCC who underwent RFA for HCC treatment between 2008 and 2017 at four tertiary hospitals in South Korea. Results: A total of 636 patients with HCC treated with RFA were enrolled in the study. The mean age was 66.3 ± 10.4 years, with 75.0% of patients being male. Most patients (96.7%) had underlying liver cirrhosis, and viral hepatitis (types B and C) accounted for most cases. The average maximum tumor size was 2.2 ± 0.9 cm, with 84.3% of tumors being single lesions. During the follow-up period, 331 patients experienced recurrence, with 95.5% of cases being intrahepatic and one-fifth occurring at the RFA site. Most patients underwent RFA or transarterial chemoembolization as subsequent therapy for recurrence. Multivariate analysis revealed that age, the albumin-bilirubin (ALBI) grade, and Child-Pugh class B status were independent factors associated with tumor recurrence. Only the ALBI grade was significantly associated with mortality. Additionally, the ALBI grade differentiated between recurrence-free survival and overall survival in the Kaplan-Meier survival curve. Conclusions: The ALBI grade was independently associated with tumor recurrence and prognosis in patients with HCC following RFA. This grading system can help clinicians identify high-risk patients, optimize treatment strategies, and enhance patient care.

Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results., Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected., Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients., Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Purpose: This study assessed the use of liver stiffness (LS) and dispersion slope (DS) in classifying patients with chronic hepatitis B (CHB) by the necessity of antiviral treatment., Methods: A retrospective review examined 249 patients with CHB (male:female, 107:142; mean age, 53±14 years) between April 2018 and March 2022. Patients for whom treatment was indicated, termed group 1, exhibited either serum alanine transaminase (ALT) and aspartate aminotransferase levels not exceeding five times the upper limit of normal and LS &gt;13 kPa, or hepatitis B virus DNA &gt;2,000 IU/mL and ALT &gt;40 IU/L. The remaining patients comprised group 2 (treatment not required). In subgroup analysis, patients with LS &lt;13 kPa were further examined., Results: Overall, group 1 exhibited significantly higher LS (12.64±6.76 vs. 6.31±1.67 kPa, P&lt;0.001) and DS (15.52±4.95 vs. 11.04±1.93 [m/s]/kHz, P&lt;0.001) than group 2. In subgroup analysis, group 1 also demonstrated significantly higher values (LS: 8.05±2.12 vs 6.31±1.67 kPa, P&lt;0.001, DS: 13.06±2.75 vs. 11.04±1.93 [m/s]/kHz, P&lt;0.001). The areas under the curve (AUCs) for LS and DS in group 1 were 0.855 (95% confidence interval [CI], 0.80 to 0.90; P&lt;0.001) and 0.810 (95% CI, 0.75 to 0.86; P&lt;0.001), respectively. In subgroup analysis, the AUCs for LS and DS in group 1 were 0.751 (95% CI, 0.69 to 0.81; P&lt;0.001) and 0.711 (95% CI, 0.64 to 0.77; P&lt;0.001), respectively. Within group 1, the AUCs for LS and DS did not differ significantly (P&gt;0.05)., Conclusion: LS and DS assist in classifying patients with CHB by their need for antiviral treatment.

A resurgence of Mycoplasma pneumoniae (MP)-the leading cause of community-acquired bacterial pneumonia, particularly in children-occurred following the COVID-19 pandemic. We aimed to investigate the clinical manifestations, macrolide resistance patterns, and therapeutic approaches related to the MP pneumonia epidemic. Children and adolescents diagnosed with MP pneumonia in September-December 2023 were screened. Clinical data were retrospectively collected from 13 major hospitals using concordant microbiological criteria, including either a positive PCR result or four-fold increase in serological markers. Demographic characteristics, treatment modalities, and clinical outcomes were analyzed. Of the 474 screened patients, 374 (median age: 7.7 [IQR, 5.4-9.6] years; hospitalization rate: 88.6%) met the microbiological confirmation criteria. Most patients experienced fever (98.9%), and lobular/lobar consolidation (59.1%) was the dominant radiological finding. The macrolide resistance rate remained high at 87.0%; corticosteroids were widely used (55.6%) alongside macrolides, despite resistance. Patients with consolidation had prolonged fever (median 8 vs. 7 days, p = 0.020) and higher hospitalization rates (92.3% vs. 83.0%, p = 0.008). Macrolide resistance did not significantly influence radiological outcomes. This study highlights the ongoing challenge of macrolide resistance in MP pneumonia and need for tailored therapeutic approaches. Despite high resistance, macrolides remain commonly prescribed, often concurrently with corticosteroids.

Context.—: Apocrine differentiation and androgen receptor (AR) positivity represent a specific subset of triple-negative breast cancer (TNBC) and are often considered potential prognostic or predictive factors., Objective.—: To evaluate the response of TNBC to neoadjuvant chemotherapy (NAC) and to assess the impact of apocrine morphology, AR status, Ki-67 labeling index (Ki-67LI), and tumor-infiltrating lymphocytes (TILs)., Design.—: A total of 232 TNBC patients who underwent NAC followed by surgical resection in a single institute were analyzed. The study evaluated apocrine morphology and AR and Ki-67LI expression via immunohistochemistry from pre-NAC biopsy samples. Additionally, pre-NAC intratumoral TILs and stromal TILs (sTILs) were quantified from biopsies using a deep learning model. The response to NAC after surgery was assessed based on residual cancer burden., Results.—: Both apocrine morphology and high AR expression correlated with lower Ki-67LI (P < .001 for both). Apocrine morphology was associated with lower postoperative pathologic complete response (pCR) rates after NAC (P = .02), but the difference in TILs between TNBC cases with and without apocrine morphology was not statistically significant (P = .09 for sTILs). In contrast, AR expression did not significantly affect pCR (P = .13). Pre-NAC TILs strongly correlated with postoperative pCR in TNBCs without apocrine morphology (P < .001 for sTILs), whereas TNBC with apocrine morphology demonstrated an indeterminate trend (P = .82 for sTILs)., Conclusions.—: Although TIL counts did not vary significantly based on apocrine morphology, apocrine morphology itself was a more reliable predictor of NAC response than AR expression. Consequently, although apocrine morphology is a rare subtype of TNBC, its identification is clinically important., Competing Interests: Lim and Song are employees of Lunit Inc (Seoul, South Korea) and declare a potential conflict of interest. The other authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Purpose: Oncotype DX (ODX) predicts the risk of recurrence and benefits of adding chemotherapy for patients with estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer. We aimed to develop a simplified scoring system using readily available clinicopathological parameters to predict a high-risk ODX recurrence score (RS) while minimizing reproducibility issues regarding Ki-67 index evaluation methods., Methods: We enrolled 300 patients with ER+/HER2- early breast cancer, for whom ODX RS data were available in the test set. Using the QuPath image analysis platform, we systematically evaluated the average, hotspot, and hottest spot Ki-67 scores in the test set. Logistic regression analyses were conducted to establish a predictive scoring system for high-risk ODX RS. An independent validation set comprising 117 patients over different periods was established., Results: Factors such as age ≤ 50 years, invasive ductal carcinoma tumor type, histologic grade 2 or 3, tumor necrosis, progesterone receptor negativity, and a high Roche-analyzed Ki-67 score (> 20) were associated with high-risk ODX RS. These variables were incorporated into our scoring system. The area under the curve of the scoring system was 0.8057. When applied to both the test and validation sets with a cutoff value of 3, the sensitivity of our scoring system was 92%., Conclusion: We successfully developed a scoring system based on the systematic evaluation of Ki-67 scoring methods. We believe that our user-friendly predictive scoring system for high risk ODX RS could help clinicians in identifying patients who may or may require additional ODX testing., Competing Interests: The authors declare that they have no competing interests., (© 2024 Korean Breast Cancer Society.)

Background: Several genetic studies have been undertaken to elucidate the intricate interplay between genetics and drug responses in bipolar disorder (BD). However, there has been notably limited research on biomarkers specifically linked to valproate, with only a few studies investigating integrated proteomic and genomic factors in response to valproate treatment. Therefore, this study aimed to identify biological markers for the therapeutic response to valproate treatment in BD. Patients with BD in remission were assessed only at baseline, whereas those experiencing acute mood episodes were evaluated at three points (baseline, 8 ± 2 weeks, and 6 ± 1 months). The response to valproate treatment was measured using the Alda scale, with individuals scoring an Alda A score ≥ 5 categorized into the acute-valproate responder (acute-VPAR) group. We analyzed 158 peptides (92 proteins) from peripheral blood samples using multiple reaction monitoring mass spectrometry, and proteomic result-guided candidate gene association analyses, with 1,627 single nucleotide variants (SNVs), were performed using the Korean chip., Results: The markers of 37 peptides (27 protein) showed temporal upregulation, indicating possible association with response to valproate treatment. A total of 58 SNVs in 22 genes and 37 SNVs in 16 genes showed nominally significant associations with the Alda A continuous score and the acute-VPAR group, respectively. No SNVs reached the genome-wide significance threshold; however, three SNVs (rs115788299, rs11563197, and rs117669164) in the secreted phosphoprotein 2 gene reached a gene-based false discovery rate-corrected significance threshold with response to valproate treatment. Significant markers were associated with the pathophysiological processes of bipolar disorders, including the immune response, acute phase reaction, and coagulation cascade. These results suggest that valproate effectively suppresses mechanisms associated with disease progression., Conclusions: The markers identified in this study could be valuable indicators of the underlying mechanisms associated with response to valproate treatment., (© 2024. The Author(s).)

Overexpression of transglutaminase 2 (TGase 2; TG2) has been implicated in the progression of renal cell carcinoma (RCC) through the inactivation of p53 by forming a protein complex. Because most p53 in RCC has no mutations, apoptosis can be increased by inhibiting the binding between TG2 and p53 to increase the stability of p53. In the present study, a novel TG2 inhibitor was discovered by investigating the structure of 1H-benzo[d]imidazole-4,7-dione as a simpler chemotype based on the amino-1,4-benzoquinone moiety of streptonigrin, a previously reported inhibitor. Through structure-activity relationship (SAR) studies, compound 8j (MD102) was discovered as a potent TG2 inhibitor with an IC 50 value of 0.35 µM, p53 stabilization effect and anticancer effects in the ACHN and Caki-1 RCC cell lines with sulforhodamine B (SRB) GI 50 values of 2.15 µM and 1.98 µM, respectively. The binding property of compound 8j (MD102) with TG2 was confirmed to be reversible in a competitive enzyme assay, and the binding interaction was expected to be formed at the β-sandwich domain, a p53 binding site, in the SPR binding assay with mutant proteins. The mode of binding of compound 8j (MD102) to the β-sandwich domain of TG2 was analyzed by molecular docking using the crystal structure of the active conformation of human TG2. Compound 8j (MD102) induced a decrease in the downstream signaling of p-AKT and p-mTOR through the stabilization of p53 by TG2 inhibition, resulting in tumor cell apoptosis. In a xenograft animal model using ACHN cancer cells, oral administration and intraperitoneal injection of compound 8j (MD102) showed an inhibitory effect on tumor growth, confirming increased levels of p53 and decreased levels of Ki-67 in tumor tissues through immunohistochemical (IHC) tissue staining. These results indicated that the inhibition of TG2 by compound 8j (MD102) could enhance p53 stabilization, thereby ultimately showing anticancer effects in RCC. Compound 8j (MD102), a novel TG2 inhibitor, can be further applied for the development of an anticancer candidate drug targeting RCC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yong-Chul Kim reports financial support was provided by Gwangju Institute of Science and Technology. Eun Yi Cho reports financial support was provided by Korea Ministry of Small and Medium Enterprises and Startups. Soo-Youl Kim, Yong-Chul Kim has patent issued to MDbiopharm Corp. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Breast cancer is one of the most common causes of cancer-related death in females. Numerous drug-targetable biomarkers and predictive biomarkers have been developed. Some researchers have expressed doubts about the need for next-generation sequencing (NGS) studies in daily practice. This study analyzed the results of NGS studies on breast cancer at a single institute and evaluated the real-world applications of NGS data to precision medicine for breast cancer., Materials and Methods: We retrospectively collected the results of NGS studies and analyzed the histopathologic features and genetic profiles of patients treated for breast cancer from 2010 to 2021. Seventy cases had data from CancerSCAN, a customized panel of 375 cancer-associated genes, and 110 cases had data from TruSight Oncology 500., Results: The most frequently detected single nucleotide variant was the TP53 mutation (123/180, 68.3%), followed by PIK3CA mutations (51/180, 28.3%). Estrogen receptor 1 (ESR1) mutation was detected in 11 patients (6.1%), of whom 10 had hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, and two had no history of prior endocrine therapy. Based on their NGS study results, 13 patients (7.2%) received target therapy. Among them, four patients had a BRCA1 or BRCA2 germline mutation, and nine patients had a PIK3CA mutation., Conclusion: NGS can provide information about predictive biomarkers and drug-targetable biomarkers that can enable treatment and participation in clinical trials based on precision medicine. Further studies should be conducted to excavate novel drug-targetable biomarkers and develop additional target therapies.

This study was conducted to evaluate the effects of dynamic stretching combined with manual therapy on pain, range of motion, function, and quality of life in patients with adhesive capsulitis. The participants were randomly divided into two groups: the dynamic stretching combined with manual therapy (DSMT) group ( n = 17) and the static stretching combined with manual therapy (SSMT) group ( n = 17). Both groups received manual therapy for 10 min and two sessions per week for 4 weeks. The DSMT group also performed additional dynamic stretching for 20 min per session, two sessions per week for 4 weeks. The SSMT group practiced additional static stretching for 20 min per session, two sessions per week for 4 weeks. The pain, ROM, function, and quality of life were measured and evaluated before and after treatment. There were significant improvements in the outcomes of pain, flexion and abduction of shoulder ROM, Shoulder Pain and Disability Index (SPADI), and the physical component score and mental component score of the Short Form-36 (SF-36) in both groups. Additionally, the external and internal rotation of the shoulder ROM and the SF-36 general health factor increased significantly more in the A group (DSMT group) compared to the B group (SSMT). In conclusion, dynamic stretching plus manual therapy offers the same results as static stretching plus manual therapy, but with additional improvement in internal and external rotation.

Neoadjuvant chemotherapy (NAC) is widely used as a standard treatment for early-stage triple-negative breast cancer (TNBC). While patients who achieve pathologic complete response (pCR) have a highly favorable outcome, patients who do not achieve pCR have variable prognoses. It is important to identify patients who are most likely to have poor survival outcomes to identify candidates for more aggressive therapeutic approaches after NAC. Many studies have demonstrated that cytokines and growth factors packaged into extracellular vesicles (EVs) have an essential role in tumor progression and drug resistance. In this study, we examined the role of serum-derived EV-associated cytokines as prognostic biomarkers for long-term outcomes in patients who underwent anthracycline-taxane-based NAC. We isolated extracellular vesicles from the serum of 190 TNBC patients who underwent NAC between 2015 and 2018 at Samsung Medical Center. EV-associated cytokine concentrations were measured with ProcartaPlex Immune Monitoring 65-plex panels. The prognostic value of EV-associated cytokines was studied. We found that patients with high EV&#95;APRIL, EV&#95;CXCL13, and EV&#95;VEGF-A levels had shorter overall survival (OS). We further evaluated the role of these selected biomarkers as prognostic factors in patients with residual disease (RD) after NAC. Even in patients with RD, high levels of EV&#95;APRIL, EV&#95;CXCL13, and EV&#95;VEGF-A were correlated with poor OS. In all subgroup analyses, EV&#95;CXCL13 overexpression was significantly associated with poor overall survival. Moreover, multivariate analysis indicated that a high level of EV&#95;CXCL13 was an independent predictor of poor OS. Correlation analysis between biomarker levels in EVs and serum showed that EV&#95;VEGF-A positively correlated with soluble VEGF-A but not CXCL13. An elevated level of soluble VEGF-A was also associated with poor OS. These findings suggest that EV&#95;APRIL, EV&#95;CXCL13, and EV&#95;VEGF-A may be useful in identifying TNBC patients at risk of poor survival outcomes after NAC.

Atherosclerosis is associated with various cardiovascular diseases (CVDs). Measurement of arterial stiffness using pulse wave velocity (PWV) enables assessment of atherosclerosis progression in individuals. The authors screened patients with asymptomatic atherosclerosis, based on the PWV findings, to evaluate appropriate early interventions and assess the efficacy of γ-linolenic acid, Vitis vinifera extract, and acetyl-L-carnitine triple combination therapy in atherosclerosis prevention. This retrospective study analyzed the medical records of adult patients between March 2007 and April 2019, with presenting complaints of fatigue and lethargy. Among patients with vascular stiffness beyond their biological age on brachial-ankle PWV (baPWV) testing, those with ≥80% compliance for three drugs were allocated to the experimental group. Those with compliance of <80% for any one drug were allocated to the control group to assess changes in arterial stiffness, fasting plasma glucose (FPG), lipid level, and blood pressure (BP). After 1 year of triple-combination therapy, there were significant decreases in right and left baPWV (1537.16 ± 274.84 and 1519.00 ± 289.32 cm/s, respectively) as compared to baseline (1633.15 ± 271. 20 and 1598.64 ± 267.95 cm/s, respectively; p < .001). There was no difference in baPWV between sexes. Moreover, neither group showed significant changes in FPG and lipid levels. When triple-combination therapy combining γ-linolenic acid, V. vinifera extract, and acetyl-L-carnitine was administered to patients with high arterial stiffness relative to their age, as assessed by baPWV, the experimental group showed a decrease in arterial stiffness in both sexes., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC). In the genetic analysis of 73 TNACs and 32 LK-TNBCs, the most frequently mutated driver gene in TNAC was TP53 (16/56, 28.6%), followed by PIK3CA (9/56, 16.1%), ZNF717 (8/56, 14.3%), and PIK3R1 (6/56, 10.71%). Mutational signature analysis showed enrichment of defective DNA mismatch repair (MMR)-related signatures (SBS6 and SBS21) and the SBS5 signature in TNAC, whereas an APOBEC activity-associated mutational signature (SBS13) was more prominent in LK-TNBC (Student's t test, p < 0.05). In intrinsic subtyping, 38.4% of TNACs were classified as luminal A, 27.4% as luminal B, 26.0% as HER2-enriched (HER2-E), 2.7% as basal, and 5.5% as normal-like. The basal subtype was the most dominant subtype (43.8%) in LK-TNBC (p < 0.001), followed by luminal B (21.9%), HER2-E (21.9%), and luminal A (12.5%). In the survival analysis, TNAC had a five-year disease-free survival (DFS) rate of 92.2% compared to 59.1% for LK-TNBC (P = 0.001) and a five-year overall survival (OS) rate of 95.3% compared to 74.6% for LK-TNBC (P = 0.0099). TNAC has different genetic characteristics and better survival outcomes than LK-TNBC. In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC., (© 2023. The Author(s).)

The genotype-phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype-phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P < 0.001, hazard ratio (HR) 2.8) and splicing and truncating groups (P = 0.002, HR 3.1). Sensorineural hearing loss was detected in 65.1% of male patients, while hearing survival periods showed a highly significant difference between the non-truncating and truncating groups (P < 0.001, HR 5.1). In female patients, approximately 20% developed kidney failure at the median age of 50.2 years. The kidney survival was significantly different between the non-truncating and truncating groups (P = 0.006, HR 5.7). Our findings support the presence of genotype-phenotype correlation not only in male patients but also in female patients with XLAS., (© 2023. The Author(s).)

Background: The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI)., Methods: A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria ( Streptococcus pneumoniae , Haemophilus influenzae , Neisseria meningitidis , Staphylococcus aureus , Streptococcus agalactiae , Streptococcus pyogenes , Listeria monocytogenes , and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed., Results: A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (r s = -0.430, P = 0.036), H. influenzae (r s = -0.922, P < 0.001), while trend toward an increase in the relative proportion of S. aureus (r s = 0.850, P < 0.001), S. agalactiae (r s = 0.615, P = 0.001), and S. pyogenes (r s = 0.554, P = 0.005)., Conclusion: In the proportion of IBIs over a 24-year period between 1996 and 2019, we observed a decreasing trend for S. pneumoniae and H. influenzae and an increasing trend for S. aureus , S. agalactiae , and S. pyogenes in children > 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era., Competing Interests: The authors have no conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

This study aims to investigate the factors affecting shift nurses' retention to solve the nurse shortage problem. The independent variables were general characteristics, stress response, work-life balance, and grit. The subjects for the study were 214 nurses working in three shifts at three general hospitals in Korea. Data were collected from 1 to 31 August 2022. We used structured tools such as the Nurses' Retention Index, Stress Response Inventory, Work-Life Balance Scale, and Clinical Nurse's Grit Scale. Data analysis was conducted using descriptive statistics, independent sample t -test, one-way variance analysis, Pearson correlation analysis, and hierarchical multiple regression analysis. Age, job satisfaction, and grit were factors that had a significant impact on retention intention. Grit had the greatest impact on retention intention. Additionally, retention intention increased in those aged from 30 to 40 years as compared with those under the age of 30. It is necessary to develop and implement a program that can improve grit to enhance the retention intention of shift nurses. Additionally, it is necessary to actively seek measures to reduce dissatisfaction with nursing jobs, increase satisfaction, and manage human resources considering the characteristics of age groups.

Introduction: Immune checkpoint inhibitor (ICI) is one of the standard treatment strategies in triple negative breast cancer (TNBC). However, the benefit of ICI with chemotherapy is limited in metastatic TNBC. In this study, we evaluated the effect of PD-L1 and LAG-3 expression on tissue microenvironment of mTNBC treated with ICI., Methods: We reviewed representative formalin-fixed paraffin embedded specimens from metastatic or archival tumor tissues of TNBCs who treated with PD-1/PD-L1 inhibitors in metastatic setting. We used the Opal multiplex Detection kit with six antibodies (anti-PD-L1, anti-LAG-3, anti-CD68, anti-panCK, anti-CD8, anti-CD107a/LAMP antibody)., Results: We evaluated the association between LAG-3+cells and survival outcome regarding CK expression. Stromal LAG-3+/CK+ and LAG-3+/CK- cells were not associated with ICI-progression free survival(PFS) (P=0.16). However, LAG-3+ cell distributions in the tumor area impacted on ICI-PFS. A high density of LAG-3+CK+ cells was associated with shorter ICI-PFS compared with low densities of both LAG-3+CK+ and LAG-3+CK- cells (1.9 vs. 3.5 months). In addition, a high density of LAG-3+CK- cells had a relatively longer ICI-PFS compared with other groups (P=0.01). In terms of total area, the pattern of densities of LAG-3+CK+ cells and LAG-3+CK- cells were similar to those in the tumor area In addition, ICI-PFS of LAG-3+CK- and LAG-3+CK+ cell densities in the total area was equal to that in the tumor area., Discussion: In conclusion, our findings revealed tumor-intrinsic LAG-3 expression was the resistance mechanism toward PD-1/PD-L1 inhibitors in mTNBCs. Multivariate analysis also suggested that LAG-3 expression in tumor cells was an independent predictive biomarker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Kim, Cho, Park, Ahn, Kim and Im.)

The birth prevalence of symptomatic congenital cytomegalovirus (cCMV) disease among live birth in Korea from a multicenter study was 0.06% during 2001-2015 with increasing frequency. The administrative prevalence of cCMV infection by big-data analysis from the national health insurance system was 0.01% and the average healthcare cost was US$2010 per person., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A measles outbreak with 20 confirmed cases occurred at a local children's hospital in Daejeon from March 28 to April 21, 2019. The index patient was a 7-month-old girl with a recent history of travel to Vietnam. Contact tracing, active surveillance, and post-exposure prophylaxis were conducted by health authorities. Among the 20 patients, 11 (55%) were infants (0-11 months of age), three (15%) were aged 1-3 years, one (5%) was aged 4 years, and five (25%) were adults. Fifteen (75%) patients did not have a history of measles vaccination, and five (25%) had received only one vaccine dose. This study described the importance of prompt application of infection control measures in susceptible environments, including hospitals. Age-appropriate vaccination and providing information on infectious diseases to international travelers and multicultural families in Korea is vital., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: Umeclidinium/vilanterol (UMEC/VI; ANORO ELLIPTA, GSK) is a commonly used dual bronchodilator. This study evaluated the safety and effectiveness of UMEC/VI in Korean patients with chronic obstructive pulmonary disease (COPD) over a 6-year period., Methods: This was an open-label, multicentre, observational, post-marketing surveillance study. A total of 3,375 patients were enrolled consecutively in 52 hospitals, by 53 physicians, between July 2014 and July 2020. Patients who were administered UMEC/VI (fixed-dose 62.5 μg/25 μg) at least once and were monitored for safety and effectiveness were included in the analysis. Incidence and severity of adverse events (AEs) reported after administrating at least one dose of UMEC/VI were monitored, including unexpected adverse events (UAEs) and adverse drug reactions (ADRs). Effectiveness of UMEC/VI after 24 weeks of administration was also assessed using physician's evaluation (effective, ineffective/no change, worsening, indeterminable) and lung function improvement., Results: Of 3,375 patients, 3,086 were included in the safety assessment group (mean age±standard deviation: 69.76±8.80 years; 85.9% male [n=2,652]; 73.1% aged ≥65 years [n=2,255]). The overall incidence of AEs was 28.8% (n=890), of which 2.2% (n=67) were ADRs. Serious AEs and UAEs were reported in 181 (5.9%) and 665 (21.6%) patients, respectively, and two patients (&lt;0.1%) reported unexpected severe ADR. Of the 903/3,086 patients analysed for effectiveness, most (82.8%, n=748) showed overall disease improvement after UMEC/VI treatment., Conclusion: This study confirmed UMEC/VI administered to Korean patients according to the prescribing information was well-tolerated and can be considered an effective option for COPD treatment.

This study aimed to determine the mediating effect of sports confidence on competitive state anxiety and perceived performance basketball game. This study was conducted on 219 Korean basketball players, including 101 men and 118 women who were either high school students (42), university students (96), or professional basketball players (81). The Sources of Sport Confidence Questionnaire (SSCQ), Revised Competitive State Anxiety Inventory-2 (CSAI-2R), and the perceived performance questionnaire was used to measure sports confidence, competitive state anxiety, and perceived performance, respectively. The results showed that self-confidence (β = z 0.552, p < 0.001) and the coaches’ leadership (β = 0.552, p < 0.001) were found to be factors that influenced perceived performance. The perceived performance showed a positive correlation with all the sports confidence subscales and self-confidence of the competitive state anxiety subscales (p < 0.01). However, it showed a negative correlation with cognitive and somatic anxiety (p < 0.01). Sports confidence had a statistically significant mediating effect between somatic anxiety and perceived performance and a statistically significant mediating effect between self-confidence and perceived performance (p < 0.05). It appeared that sports confidence and competitive state anxiety had a statistically significant effect on perceived.

Background: Expansion of the single sequence type 3 (ST3) was associated with a high macrolide resistance rate among Mycoplasma pneumoniae in Korea during the 2014-2016 epidemic. This study investigates the macrolide resistance rate and genetic diversity of the subsequent epidemic of M. pneumoniae pneumonia in 2019-2020., Methods: The culture for M. pneumoniae was developed from 1228 respiratory samples collected from children with pneumonia in four hospitals in Korea between January 2019 and January 2020. Determination of macrolide resistance and multilocus sequence typing analysis were performed on M. pneumoniae isolates. eBURST analysis was applied to estimate the relationships among strains and to assign strains to a clonal complex., Results: M. pneumoniae was cultured in 93 (7.6%) of 1228 clinical samples. The overall macrolide resistance rate of M. pneumoniae strains was 78.5% (73/93). Of the nine STs identified, three were novel. The most common ST was ST3 (66 [71.0%]) followed by ST14 (18 [19.4%]) and ST7/ST15 (2 [2.2%] each). Three STs (ST3, ST14, and ST17) exhibited macrolide resistance. The macrolide resistance rates of ST3 and ST14 were 98.5% (65 of 66) and 38.9% (7 of 18), respectively., Conclusion: Compared to the previous outbreak in 2014-2016, the overall macrolide resistance remained high; however, an increasing proportion of macrolide resistance was observed within ST14 strains in 2019-2020., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Accurate brain meningioma segmentation and volumetric assessment are critical for serial patient follow-up, surgical planning and monitoring response to treatment. Current gold standard of manual labeling is a time-consuming process, subject to inter-user variability. Fully-automated algorithms for meningioma segmentation have the potential to bring volumetric analysis into clinical and research workflows by increasing accuracy and efficiency, reducing inter-user variability and saving time. Previous research has focused solely on segmentation tasks without assessment of impact and usability of deep learning solutions in clinical practice. Herein, we demonstrate a three-dimensional convolutional neural network (3D-CNN) that performs expert-level, automated meningioma segmentation and volume estimation on MRI scans. A 3D-CNN was initially trained by segmenting entire brain volumes using a dataset of 10,099 healthy brain MRIs. Using transfer learning, the network was then specifically trained on meningioma segmentation using 806 expert-labeled MRIs. The final model achieved a median performance of 88.2% reaching the spectrum of current inter-expert variability (82.6-91.6%). We demonstrate in a simulated clinical scenario that a deep learning approach to meningioma segmentation is feasible, highly accurate and has the potential to improve current clinical practice., (© 2022. The Author(s).)

Background: Multiple inhaler triple therapy (MITT), comprising inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA), has been used as an escalation treatment for patients with chronic obstructive pulmonary disease (COPD). However, real-world use of MITT has not been investigated in Asia, including South Korea. This study reports baseline characteristics of patients with COPD initiated on MITT in South Korea, and their treatment patterns. Healthcare resource utilization (HRU) and costs associated with COPD exacerbations following MITT initiation were also assessed., Methods: This was a retrospective cohort study using the South Korea National Health Insurance database (2014-2018). Included patients were ≥ 40 years, had a COPD diagnosis, were newly initiated on MITT and had ≥ 12 months' data both before (baseline) and after index date (the first day with overlapping supply of all MITT components). Treatment immediately before initiation and immediately following discontinuation of MITT were identified, and proportion of days covered (PDC) by MITT was calculated. HRU and costs (per person per year [PPPY]) associated with exacerbations were identified following MITT initiation; costs were calculated using the average 2020 exchange rate (0.0008 USD/KRW)., Results: Among 37,400 patients, the mean age was 69 (SD 10) years and 73% were males; 56% had ≥ 1 COPD exacerbation during the baseline period, with a mean of 2 (SD 5) events/year. ICS/LABA was the most frequent regimen prescribed immediately before initiation (37%) and immediately following discontinuation (41% of 34,264 patients) of MITT. At 3, 6, and 12 months from treatment initiation, mean PDC was 81%, 63% and 49%, respectively; median treatment duration was 102 days. The mean (95% confidence interval [CI]) number of total visits for severe COPD exacerbations was 0.77 PPPY (0.75-0.78); mean PPPY total healthcare costs were 2093 USD., Conclusions: Patients with COPD in South Korea experienced frequent exacerbations prior to MITT, and PDC by MITT was low. Patients may benefit from early optimization of COPD therapy, and greater emphasis on adherence to inhaled COPD therapy. Severe exacerbations were found to incur substantial costs; treatment alternatives that can reduce the rate of severe exacerbations are likely to minimize healthcare costs., (© 2022. The Author(s).)

Objectives: Changes in the epidemiology of group A streptococcus (GAS) infection is related to emm genotype. We studied the distribution of emm genotypes and their antibiotic susceptibility among Korean children., Methods: Isolates from children with GAS infection between 2012 and 2019 were collected. emm typing and cluster analysis was performed according to the Centers for Disease Control emm cluster classification. Antimicrobial susceptibility was tested using the E-test and resistance genes were analyzed for macrolide resistant phenotypes., Results: Among 169 GAS isolates, 115 were from children with scarlet fever. Among invasive isolates, emm1 (6/22, 27.3%), emm12 (4/22, 18.2%), and emm4 (4/22, 18.2%) were most common. In scarlet fever, although emm4 (38/115, 33.0%) was the most prevalent throughout the study period, emm4 was replaced by emm3 (28/90, 31.1%) during an outbreak in 2017-2018. Among all isolates, only 2 (1.2%) exhibited erythromycin resistance and harbored both ermA and ermB genes., Conclusions: In this analysis of GAS isolated from Korean children, emm1 was the most prevalent in invasive infection. In scarlet fever, emm4 was prevalent throughout the study period, with an increase in emm3 during 2017-2018. GAS isolates during 2012-2019 demonstrated low erythromycin resistance., Competing Interests: Declaration of competing interest The authors have no conflict of interests., (Copyright © 2022. Published by Elsevier B.V.)

Background: The development of back pain following epidural analgesia is one reason for patient refusal of neuraxial analgesia. The primary endpoint of this study was to compare the incidence and severity of back pain following midline and paramedian epidural technique. The secondary endpoint was to identify the risk factors associated with the occurrence of back pain., Methods: This prospective randomized study included 114 patients receiving thoracic epidural catheterization for pain management following upper abdominal or thoracic surgery. Patients were allocated to either the midline or the paramedian group by computer-generated randomization. An investigator who was blinded to the patient group interviewed patients at 24, and 48 h, and 3-5 days after surgery about the existence of back pain and its severity., Results: The total incidence of back pain following epidural anesthesia was 23.8% in the midline group and 7.8% in the paramedian group. The numerical rating scale of back pain was not different between the two groups at 24 h and 4 days after surgery. The paramdian technique was associated with a lower incidence of back pain than the midline technique (95% confidence interval 0.05-0.74, odds ratio 0.2, P < 0.01). However, the number of attempts, surgical position, body mass index, and duration of surgery were not associated with back pain., Conclusions: This study showed that the midline group of thoracic epidural analgesia demonstrated higher incidence of back pain than the paramedian group. However, the pain was mild in intensity and decreased with time in both groups.

Background: The immunologic features of children with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not clearly delineated. This study was conducted to evaluate SARS-CoV-2-specific antibody responses in children with COVID-19., Methods: The levels of anti-spike (S) IgG, anti-SARS-CoV-2 IgG, and neutralizing antibody (NAb) were measured during various time points in children <19 years of age with COVID-19 in South Korea from February 2020 to September 2020., Results: One hundred sixty-five blood samples from 114 children with COVID-19 (43.9% asymptomatic and 56.1% mildly symptomatic) were analyzed. In both asymptomatic and mildly symptomatic children, the positive rates of anti-S IgG, anti-SARS-CoV-2 IgG, and NAb were low within 7 days after onset, but they soon reached 100% 14 to <28 days after onset. In symptomatic children, the geometric mean titers (GMTs) of antibodies were all below the positive cutoff during the first 2 weeks from onset and peaked at 28 to <56 days (5.6 for anti-S IgG, 383.6 for anti-SARS-CoV-2 IgG, and 55.0 for NAb, P < .001, respectively). Antibody levels remained detectable up to 3 months after infection. The antibody GMTs during the period 14 to <56 days after symptom onset were highest in children aged 0-4 years., Conclusions: These results collectively present the humoral immune responses during SARS-CoV-2 infection in children. A further longitudinal study is needed to thoroughly understand the immune system and for effective vaccine development in children during the COVID-19 pandemic., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Child poverty situated in different socioeconomic and environmental contexts has long been a central concern for practitioners, researchers, and policy makers. However, concerned research studies are predominantly adult-centric, confined to specific areas, or seldom found in Asian developed economies. Against the backdrop of this research gap, this study examines children's experiences of poverty in relation to economic and material aspects, social relationships and participation, and psychological and emotional wellbeing, and their ways of coping with the effects of poverty. Using a purposive sampling method, a total of 40 children participants aged 8-14 living in or near poverty were recruited for an individual interview. The study showed that children experienced a range of deprivations in relation to falling short of the resources, opportunities, and activities that are commanded by average young persons. Limited living space also stands out as a more severe problem that is difficult to cope with. The various coping strategies include small spending savvy tactics, parental buffering, compensation, and mental coping. Proximity to schools and NGOs can help children in poverty to cope with problems caused by deprivations in different aspects. Implications for research studies and practice for working with children in or near poverty are discussed accordingly.

Hippo signaling is known to maintain balance between cell proliferation and apoptosis via tight regulation of factors, such as metabolic cues, cell-cell contact, and mechanical cues. Cells directly recognize glucose, lipids, and other metabolic cues and integrate multiple signaling pathways, including Hippo signaling, to adjust their proliferation and apoptosis depending on nutrient conditions. Therefore, the dysregulation of the Hippo signaling pathway can promote tumor initiation and progression. Alteration in metabolic cues is considered a major factor affecting the risk of cancer formation and progression. It has recently been shown that the dysregulation of the Hippo signaling pathway, through diverse routes activated by metabolic cues, can lead to cancer with a poor prognosis. In addition, unique crosstalk between metabolic pathways and Hippo signaling pathways can inhibit the effect of anticancer drugs and promote drug resistance. In this review, we describe an integrated perspective of the relationship between the Hippo signaling pathway and metabolic signals in the context of cancer. We also characterize the mechanisms involved in changes in metabolism that are linked to the Hippo signaling pathway in the cancer microenvironment and propose several novel targets for anticancer drug treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Tenofovir disoproxil fumarate (TDF, Viread ® ) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF., Methods: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread ® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated., Results: A total of 122 patients (DA-2802 group: n = 61, Viread ® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was -5.13 ± 1.40 in the DA-2802 group and -4.97 ± 1.40 log 10 copies/mL in the Viread ® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results ( P < 0.001), which confirmed non-inferiority of DA-2802 to Viread ® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread ® group ( P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread ® group ( P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread ® group ( P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity., Conclusion: DA-2802 is considered an effective and safe treatment for patients with CHB., Trial Registration: ClinicalTrials.gov Identifier: NCT02967939., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

In this study, we developed and validated a scale that measures the sense of community among Korean military personnel. We conducted the research in three stages. In the first preliminary stage, we administered an open-ended questionnaire to 47 military officers in order to develop the initial questions. Experts verified the content validity of the 60 preliminary questions, and the questions were modified based on the experts' input. In the second preliminary stage, we extracted preliminary scales for 20 items based on the responses of 457 Army soldiers. In the third stage, we provided the preliminary scale to 656 Korean military personnel, and their responses were used to extract a five-factor matrix with 20 items. The five factors were Needs Fulfillment, Influence, Shared Emotional Connection, Rule Compliance, and Membership; each factor consisted of four items. Finally, after four weeks, we administered the scale to 208 additional military personnel, and the stability of the scale was confirmed, with a test-retest reliability of .90. To conclude the paper, we describe the implications of the scale developed in this study as well as directions for future studies., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 Society for Military Psychology, Division 19 of the American Psychological Association.)

Background: Bipolar disorder (BD) has the greatest suicide risk among mental and physical disorders. A recent genome-wide association study (GWAS) of European ancestry (EUR) samples revealed that the genetic etiology of suicide attempt (SA) was not only polygenic but also, in part, diagnosis-specific. The authors aimed to examine whether the polygenic risk score (PRS) for SA derived from that study is associated with SA or repeated attempts in Korean patients with BD. This study also investigated the shared heritability of SA and mental disorders which showed an increased risk of SA and a high genetic correlation with BD., Methods: The study participants were 383 patients with BD. The history of SA was assessed on a lifetime basis. PRSs for reference disorders were calculated using the aforementioned GWAS data for SA and the Psychiatric Genomics Consortium data of BD, schizophrenia, major depressive disorder (MDD), and obsessive-compulsive disorder (OCD)., Results: The PRS for SA was significantly associated with lifetime SA in the current subjects (Nagelkerke's R 2  = 2.73%, odds ratio [OR] = 1.36, p = 0.007). Among other PRSs, only the PRS for OCD was significantly associated with lifetime SA (Nagelkerke's R 2  = 2.72%, OR = 1.36, p = 0.007). The PRS for OCD was higher in multiple attempters than in single attempters (Nagelkerke's R 2  = 4.91%, OR = 1.53, p = 0.043)., Conclusion: The PRS for SA derived from EUR data was generalized to SA in Korean patients with BD. The PRS for OCD seemed to affect repeated attempts. Genetic studies on suicide could benefit from focusing on specific psychiatric diagnoses and refined sub-phenotypes, as well as from utilizing multiple PRSs for related disorders., (© 2022. The Author(s).)

Patients with a biopsy diagnosis of ductal carcinoma in situ (DCIS) may be diagnosed with invasive breast cancer after excision. We evaluated the preoperative clinical and imaging predictors of DCIS that were associated with an upgrade to invasive carcinoma on final pathology and also compared the diagnostic performance of various statistical models. We reviewed the medical records; including mammography, ultrasound (US), and magnetic resonance imaging (MRI) findings; of 644 patients who were preoperatively diagnosed with DCIS and who underwent surgery between January 2012 and September 2018. Logistic regression and three machine learning methods were applied to predict DCIS underestimation. Among 644 DCIS biopsies, 161 (25%) underestimated invasive breast cancers. In multivariable analysis, suspicious axillary lymph nodes (LNs) on US (odds ratio [OR], 12.16; 95% confidence interval [CI], 4.94-29.95; P < 0.001) and high nuclear grade (OR, 1.90; 95% CI, 1.24-2.91; P = 0.003) were associated with underestimation. Cases with biopsy performed using vacuum-assisted biopsy (VAB) (OR, 0.42; 95% CI, 0.27-0.65; P < 0.001) and lesion size <2 cm on mammography (OR, 0.45; 95% CI, 0.22-0.90; P = 0.021) and MRI (OR, 0.29; 95% CI, 0.09-0.94; P = 0.037) were less likely to be upgraded. No significant differences in performance were observed between logistic regression and machine learning models. Our results suggest that biopsy device, high nuclear grade, presence of suspicious axillary LN on US, and lesion size on mammography or MRI were independent predictors of DCIS underestimation., (© 2022. The Author(s).)

In April 2020, the Ministry of Food and Drug Safety licensed a hexavalent combined diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) conjugated to tetanus protein, and hepatitis B (HepB) (recombinant DNA) vaccine, DTaP-IPV-Hib-HepB (Hexaxim, Sanofi Pasteur), for use as a 3-dose primary series in infants aged 2, 4, and 6 months. The DTaP-IPV-Hib-HepB vaccine is highly immunogenic and safe and provides a long-term immune response based on studies performed in a variety of settings in many countries, including Korea. This report summarizes the Committee on Infectious Diseases of the Korean Pediatric Society guidelines for the use of this newly introduced hexavalent combination vaccine.

Background: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification., Methods: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier)., Results: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems., Conclusions: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Neoadjuvant chemotherapy (NAC) is a standard treatment strategy for patients with locally advanced breast cancer (LABC). However, there are no established predictors of chemosensitivity and survival in LABC patients who undergo NAC. Many studies have demonstrated that exosomes and cytokines are important players in intercellular communication between tumors and their environments, and are involved in chemotherapy resistance. Recently, it was reported that cytokines can be packaged into exosomes, but whether exosomal cytokines serve as biomarkers in breast cancer patients is still unclear. In this study, we examined the roles of cytokines in both serum and exosomes as prognostic biomarkers for long-term outcomes in patients with breast cancer who undergo NAC. We isolated exosomes from the blood of 129 patients with early breast cancer who were receiving neoadjuvant chemotherapy between 2008 and 2011 at Samsung Medical Center. The levels of cytokines and growth factors in serum and exosomes were measured with ProcartaPlex immune-related panels. We investigated correlations between clinic-pathologic variables and patient survival, and Cox proportional hazards regression analysis was performed for prognostic evaluation. We detected significant differences in expression patterns between serum cytokines and exosomal cytokines. In both serum and exosomes, many cytokines were positively correlated with age. In univariate analysis, patients with high serum IP-10, serum MMP-1, and exosomal NGF had shorter overall survival. Exosomal NGF showed significantly poorer overall survival in multivariate analysis. These findings suggest that exosomal NGF is useful for identifying patients with poor survival outcomes.