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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.

Although large-scale genome-wide association studies (GWASs) have revealed the genetic architecture of schizophrenia, these studies have mainly focused on populations of European ancestry. This study aimed to identify common genetic variants associated with schizophrenia in the Korean population and evaluate the performance of polygenic risk scores (PRSs) derived from large-scale GWASs across ancestries. In the Korean psychiatric GWAS project (KPGP), seven academic institutes and their affiliated hospitals across South Korea recruited a cohort of 1670 patients with DSM-IV-defined schizophrenia and 2271 healthy controls. A total of 6690,822 SNPs were tested for association with schizophrenia. We identified one previously unreported genome-wide significant locus rs2423464 (P = 2.83 × 10 -11 ; odds ratio = 1.65; 95 % confidence interval = 1.43-1.91, minor allele frequency = 0.126). This variant was also associated with increased lysosomal-associated membrane protein family member 5 (LAMP5) gene expression. The PRS derived from the meta-analysis results of East Asian and European GWASs explained a larger proportion of the phenotypic variance in the Korean schizophrenia sample than the PRS of an East Asian or European GWAS. (R 2 = 0.073 for meta-analysis; 0.028 for East Asian GWAS; 0.037 for European GWAS). GWASs involving diverse ethnic groups will expand our understanding of the genetic architecture of schizophrenia., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate the viability of robot-assisted appendiceal ureteroplasty as an innovative surgical approach for the reconstruction of ureteral strictures in cases where traditional methods are unsuitable., Methods: We conducted a retrospective review of 14 patients who underwent robot-assisted appendiceal ureteroplasty for right-sided ureteral stricture disease at three academic centers between March 2018 and November 2022. Patients were selected based on stricture characteristics, tissue quality, and the need for tissue transfer techniques. Surgical outcomes, including stricture-free rates, renal function, and complication rates, were analyzed., Results: The median patient age was 63years, with a balanced gender distribution. The median stricture length was 4.75 cm. The majority of strictures were located in the proximal ureter (50%). Surgical approaches included appendiceal onlay flaps (71.4%) and interposition flaps (28.6%). The median operative time was 268 minutes, with an average estimated blood loss of 75 mL. Postoperatively, ureteral patency was achieved in 92.9% of patients. Two patients (14.3%) experienced urinary tract infections requiring readmission. There was no significant change in serum creatinine levels postoperatively. Hydronephrosis grade significantly improved following surgery (P = .025)., Conclusion: Robot-assisted appendiceal ureteroplasty is a safe and effective technique for managing ureteral strictures. It offers a high success rate with minimal complications, making it a valuable addition to the urologic surgeon's armamentarium for complex ureteral reconstructions., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Background/aim: TP53 mutation in breast cancer (BC) is associated with chemoresistance, endocrine therapy resistance, and late recurrence, resulting in poor prognosis. Nuclear accumulation of p53 in immunohistochemistry (IHC) is a surrogate marker of TP53 mutation. This study analyzed the frequency, type, and distribution of TP53 mutations in BCs and assessed the efficacy of p53 IHC as a surrogate marker of TP53 mutation., Patients and Methods: We collected data from 112 BC cases, including the results of p53 IHC and next-generation sequencing (NGS)., Results: Over-expression of p53 IHC was observed in 36 patients (32.1%), complete absence in 19 patients (17.0%), aberrant cytoplasmic staining in 1 patient (0.9%), and wild-type in 56 (50.0%) patients. The concordance rate between TP53 mutation and p53 IHC was 88.4% in all BCs, 89.9% in luminal BCs, and 86.0% in triple-negative BCs (TNBC). TNBC, abnormal p53 IHC pattern, p53 IHC over-expression, neoadjuvant chemotherapy (NAC) history, TP53 mutation, and high pre-treatment ki-67 labeling index (≥50%) were significantly associated with worse distant metastasis-free survival (DMFS) and overall survival (OS) (p<0.05). Pre-NAC clinical stage III was associated with worse DMFS but not OS. Multivariate analysis showed that NAC history, TNBC, and p53 IHC over-expression were independent predictors of worse DMFS. An abnormal p53 IHC pattern and NAC history were independent predictors of worse OS., Conclusion: P53 IHC is a valid surrogate marker of TP53 mutation in BC. Accumulation of abnormal p53 alone, regardless of TP53 mutation, was associated with worse DMFS and can be used as an easily accessible biomarker to predict chemoresistance., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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.

Although the associations between a patient's body mass index (BMI) and metabolic diseases, as well as their breath test results, have been studied, the relationship between breath hydrogen/methane levels and metabolic diseases needs to be further clarified. We aimed to investigate how the composition of exhaled breath gases relates to metabolic disorders, such as diabetes mellitus, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD), and their key risk factors. An analysis was performed using the medical records, including the lactulose breath test (LBT) data of patients who visited the Ajou University Medical Center, Suwon, Republic of Korea, between January 2016 and December 2021. The patients were grouped according to four different criteria for LBT hydrogen and methane levels. Of 441 patients, 325 (72.1%) had positive results for methane only (hydrogen < 20 parts per million [ppm] and methane ⩾ 3 ppm). BMIs and NAFLD prevalence were higher in patients with only methane positivity than in patients with hydrogen and methane positivity (hydrogen ⩾ 20 ppm and methane ⩾ 3 ppm). According to a multivariate analysis, the odds ratio of only methane positivity was 2.002 (95% confidence interval [CI]: 1.244-3.221, P = 0.004) for NAFLD. Our results demonstrate that breath methane positivity is related to NAFLD and suggest that increased methane gas on the breath tests has the potential to be an easily measurable biomarker for NAFLD diagnosis., (© 2024 IOP Publishing Ltd.)

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: Bipolar disorder (BD) shows heterogeneous illness presentation both cross-sectionally and longitudinally. This phenotypic heterogeneity might reflect underlying genetic heterogeneity. At the same time, overlapping characteristics between BD and other psychiatric illnesses are observed at clinical and biomarker levels, which implies a shared biological mechanism between them. Incorporating these two issues in a single study design, this study investigated whether phenotypically heterogeneous subtypes of BD have a distinct polygenic basis shared with other psychiatric illnesses., Methods: Six lifetime phenotype dimensions of BD identified in our previous study were used as target phenotypes. Associations between these phenotype dimensions and polygenic risk scores (PRSs) of major psychiatric illnesses from East Asian (EA) and other available populations were analyzed., Results: Each phenotype dimension showed a different association pattern with PRSs of mental illnesses. PRS for EA schizophrenia showed a significant negative association with the cyclicity dimension ( p = 0.044) but a significant positive association with the psychotic/irritable mania dimension ( p = 0.001). PRS of EA major depressive disorder demonstrated a significant negative association with the elation dimension ( p = 0.003) but a significant positive association with the comorbidity dimension ( p = 0.028)., Conclusion: This study demonstrates that well-defined phenotype dimensions of lifetime-basis in BD have distinct genetic risks shared with other major mental illnesses. This finding supports genetic heterogeneity in BD and suggests a pleiotropy among BD subtypes and other psychiatric disorders beyond BD. Further genomic analyses adopting deep phenotyping across mental illnesses in ancestrally diverse populations are warranted to clarify intra-diagnosis heterogeneity and inter-diagnoses commonality issues in psychiatry.

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).)

Residual pure intralymphatic carcinoma (PIC) component only after neoadjuvant chemotherapy (NAC) is lymphovascular tumor emboli without invasive carcinoma and extremely rare form of residual tumor after NAC. Although several studies have been published, the prognostic influence of residual PIC component only had not been fully evaluated. This study aims to evaluate the clinicopathologic features and the prognostic value of residual PIC component only. We reviewed the 251 patients with no residual invasive carcinoma in breast after NAC and found 12 patients with residual PIC component only after NAC. Five cases were triple negative, 6 were HER2 positive, and 1 was estrogen receptor positive and HER2 negative. The extent of PIC component ranged from 0.18 to 50.00 mm. The detailed microscopic PIC component findings did not significantly correlate with regional lymph node metastasis, local recurrence, or distant metastasis (p > 0.05). In multivariate survival analysis, the presence of lymph node metastasis and pretreatment ki-67 labeling index more than 50 % was statistically associated with greater risk of relapse [Cox proportional hazards ratio (HR) = 3.236, 95 % confidence interval (CI), 1.461-7.280, p = 0.004; HR = 3.046, 95 % CI, 1.421-6.529, p = 0.004, respectively) and residual PIC component only tended to be associated with greater risk of relapse (HR = 2.378, 95 % CI, 0.853-6.631; p = 0.098), but not reached to statistically significance. In patients without lymph node metastasis, the presence of residual PIC component only was associated with worse disease-free survival (p = 0.004). Although the number of published studies still limited, residual residual PIC component only after NAC is associated with poor outcome, and it should not be considered as pathological complete response., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To determine whether a simple point-of-care measurement system estimating renal parenchymal volume using tools ubiquitously available could be used to replace nuclear medicine renal scintigraphy (NMRS) in current clinical practice to predict estimated glomerular filtration rate (eGFR) after nephrectomy by estimating preoperative split renal function., Patients and Methods: We performed a retrospective review of patients who underwent abdominal cross-sectional imaging (computed tomography/magnetic resonance imaging) and mercaptoacetyltriglycine (MAG3) NMRS prior to total nephrectomy at a single institution. We developed the real-time estimation of nephron activity with a linear measurement system (RENAL-MS) method of estimating postoperative renal function via the following technique: renal parenchymal volume of the removed kidney relative to the remaining kidney was estimated as the product of renal length and the average of six renal parenchymal thickness measurements. The utility of this value was compared to the utility of the split renal function measured by MAG3 for prediction of eGFR and new onset Stage 3 chronic kidney disease (CKD) at ≥90 days after nephrectomy using uni- and multivariate linear and logistic regression., Results: A total of 57 patients met the study criteria. The median (interquartile range [IQR]) age was 69 (61-80) years. The median (IQR) pre- and postoperative eGFR was 74 (IQR 58-90) and 46 (35-62) mL/min/1.73 m 2 , respectively. [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] Correlations between actual and predicted postoperative eGFR were similar whether the RENAL-MS or NMRS methods were used, with correlation using RENAL-MS being slightly numerically but not statistically superior (R = 0.82 and 0.76; P = 0.138). Receiver operating characteristic curve analysis using logistic regression estimates incorporating age, sex, and preoperative creatinine to predict postoperative Stage 3 CKD were similar between RENAL-MS and NMRS (area under the curve 0.93 vs. 0.97). [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] CONCLUSION: A point-of-care tool to estimate renal parenchymal volume (RENAL-MS) performed equally as well as NMRS to predict postoperative eGFR and de novo Stage 3 CKD after nephrectomy in our population, suggesting NMRS may not be necessary in this setting., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

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.

Objective: To describe the characteristics, management, and functional outcomes of patients with synchronous urethral stricture disease (SUSD) utilizing a multi-institutional cohort., Methods: Data were collected and assessed from a prospectively maintained, multi-institutional database. Patients who underwent anterior urethroplasty for urethral stricture disease (USD) were included and stratified by the presence or absence of SUSD. USD location and etiology were classified according to the Trauma and Urologic Reconstruction Network of Surgeons Length, Segment and Etiology Anterior Urethral Stricture Classification System. Anterior urethroplasty techniques were recorded for both strictures. Functional failure was compared between groups., Results: One thousand nine hundred eighty-three patients were identified, of whom, 137/1983 (6.9%) had SUSD. The mean primary stricture length for patients with SUSD was 3.5 and 2.6 cm for the secondary stricture. Twelve anterior urethroplasty technique combinations were utilized in treating the 27 different combinations of SUSD. Functional failure was noted in 18/137 (13.1%) patients with SUSD vs 192/1846 (10.4%) patients with solitary USD, P = .3. SUSD was not associated with increased odds of functional failure. S classifications: S1b, P = .003, S2a, P = .001, S2b, P = .01 and S2c, P = .02 and E classifications: E3a, P = .004 and E6, P = .03, were associated with increased odds of functional failure., Conclusion: Repair of SUSD in a single setting does not increase the risk of functional failure compared to patients with solitary USD. Increasing S classification, S1b through S2c and E classifications E3a and E6 were associated with increased functional failure. This reinforces the importance of the Trauma and Urologic Reconstruction Network of Surgeons Length, Segment and Etiology Anterior Urethral Stricture Classification System as a necessary tool in large-scale multi-institutional analysis when assessing highly heterogenous patient populations., Competing Interests: Declaration of Competing Interest No conflict., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

Background and Objective: Fluticasone furoate/vilanterol (FF/VI; RELVAR ELLIPTA) is approved in Korea for patients with asthma or chronic obstructive pulmonary disease (COPD). This study evaluated the effectiveness and safety of FF/VI in Korean patients with asthma and/or COPD over a 6-year period., Methods: This was an open-label, multicentre, observational, post-marketing surveillance study in patients newly treated with FF/VI (100 or 200 μg/25 μg once daily). Safety endpoints were the incidence of adverse events (AEs), including unexpected AEs/adverse drug reactions (ADRs) and serious AEs/ADRs. Effectiveness was assessed after 24 weeks by Global Physician Assessment (logistic regression) and forced expiratory volume in 1 s (FEV 1 ; paired t-tests)., Results: Of the 3426 patients enrolled across 45 hospitals between July 2014 and June 2020, 3216 were included in the safety analysis (50.5% female; mean age ± standard deviation [SD]: 58.6 ± 16.3 years). Overall incidence of AEs was 30.9% (n = 992); 4.1% (n = 132) were ADRs. Serious AEs were reported in 4.1% (n = 132) of patients; 0.1% (n = 4) were ADRs. Of 1543 patients analysed for symptomatic improvement, 89.2% (n = 1377) improved, 9.4% (n = 145) were unchanged, and 1.4% (n = 21) worsened. Mean FEV 1 (difference ± SD) increased significantly in patients with asthma (0.09 ± 0.29 L; p < 0.0001), COPD (0.11 ± 0.24 L; p = 0.0011), or both (0.05 ± 0.18 L; p = 0.0399), indicating improved lung function., Conclusion: In this real-world study, FF/VI administered to Korean patients was well tolerated and effective for the treatment of asthma and COPD. These results were consistent with other studies in Asian and global populations., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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.)

Competing Interests: Declaration of Competing Interest Dr Eric Cho and Dr Jill Buckley have nothing to disclose.

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.