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Seung Taek Lim,1 Ye Won Jeon,1 Hongki Gwak,1 Ja Seong Bae,2 Young Jin Suh1 1Division of Breast & Thyroid Surgical Oncology, Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea; 2Division of Thyroid Surgical Oncology, Department of Surgery, Seoul St. Mary’s Hospital, Catholic University of Korea College of Medicine, Seoul, KoreaCorrespondence: Young Jin SuhDivision of Breast & Thyroid Surgical Oncology, Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, KoreaTel +82-31-249-8169Fax +82-31-247-5347Email yjsuh@catholic.ac.krPurpose: To develop a nomogram for predicting biochemical incomplete response (BIR) in the dynamic risk stratification (DRS) of papillary thyroid carcinoma (PTC) patients without structural recurrence, and to investigate its validity.Patients and Methods: Overall, 1705 (1005 and 700 in the training and validation cohorts, respectively) PTC patients treated with total thyroidectomy without structural recurrence were included. multivariate logistic regression analyses were performed to determine the significant predictors of BIR in the training cohort. A nomogram was subsequently constructed for BIR risk prediction. Assessments for the predictive accuracy, discrimination, and calibration of the nomogram were performed. Subsequently, internal and external validations were conducted.Results: In the multivariate analysis, age, sex, lymph node metastasis site, extrathyroidal extension, and lymphovascular invasion showed significant predictive value; using these predictive factors and tumor size, a nomogram for BIR risk prediction was constructed. In the training cohort, the nomogram showed good predictive performance and discrimination in the receiver operating characteristic (ROC) curve analysis, with an area under the curve (AUC) of 0.765. In internal validation, the bootstrap-corrected AUC was 0.76. The calibration plot showed good agreement between the predicted and actual observation. The Hosmer–Lemeshow (HL) test did not suggest a lack of fit (p=0.1613). In the external validation, the AUC was 0.828 in the ROC curve analysis; the calibration plot showed good quality, and the HL test did not suggest a lack of fit (p=0.2161).Conclusion: The constructed nomogram may effectively predict the risk of BIR in DRS in PTC patients without structural recurrence.Level of Evidence: Level 4.Keywords: papillary thyroid carcinoma, dynamic risk stratification, nomogram, biochemical incomplete response

Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein, Bax. Elucidating the molecular mechanisms by which nanosized particles induce activation of cell death signaling pathways would be critical for the development of prevention strategies to minimize the cytotoxicity of nanomaterials.Keywords: TiO2, reactive oxygen species, apoptotic cell death, Fas upregulation, Bax activation, mitochondrial membrane potential loss, caspase activation

To compare the diagnostic accuracies of the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental Status Examination (MMSE) for Alzheimer's diseases (AD), we administered them simultaneously to 82 AD patients and 82 age- and sex-matched nondemented control subjects. The area under the receiver operator curve (AUC) for AD of the HDS-R (AUCHDS-R) and MMSE (AUCMMSE) were bigger than 0.90 indicating that both tests are useful for detecting AD. However, AUCHDS-R (0.952) was significantly larger than that of the AUCMMSE (0.902) regard-less of the educational level of the subjects, indicating that the HDS-R is more accurate than MMSE in diagnosing AD. Moreover, the superiority of the HDS-R (AUCHDS_R = 0.894) to the MMSE (AUCMMSE = 0.704) remained significant in mild AD patients alone, who are the focus of screening. In conclusion, the HDS-R is better than the MMSE as a screening instrument for AD. [ABSTRACT FROM AUTHOR]

Cisplatin has been one of the most widely used anticancer agents, but its nephrotoxicity remains a dose-limiting complication. Here, we evaluated the idiopathic nature and the predose prediction of cisplatin-induced nephrotoxicity using a nuclear magnetic resonance (NMR)-based pharmacometabonomic approach. Cisplatin produced serious toxic responses in some animals (toxic group), but had little effect in others (nontoxic group), as judged by hematological and histological results. The individual metabolic profiles, assessed by urine NMR spectra, showed large differences between the post-administration profiles of the two groups, indicating the relevance of the NMR approach. Importantly, multivariate analysis of the NMR data showed that the toxic and nontoxic groups can be differentiated based on the pretreatment metabolite profiles. Leave-one-out analysis, performed to evaluate the practical performance of our approach, gave a 66% accuracy rate in predicting toxic responses based on the pretreatment metabolite profiles. Hence, we provide a working model that can explain the idiopathic toxicity mechanism based on marker metabolites found by NMR analysis consistent with tissue NADH measurements. Thus, a pharmacometabonomic approach using pretreatment metabolite profiles may help expedite personalized chemotherapy of anticancer drugs. [ABSTRACT FROM AUTHOR]

Objective: Due to the application of multiple treatment modalities, a substantial proportion of patients with head and neck cancer (HNC) experience one or more emergency room (ER) visits or unplanned hospitalizations during or after treatment. We investigated HNC cases that visited ERs after cancer treatment to identify potential risk factors in the context of the Korean healthcare system., Methods: This was a single-center cohort study of HNC patients who underwent cancer treatments at OOOO in 2019 (N = 566). The patients were treated with surgery alone (N = 184), surgery plus adjuvant therapy (N = 138), curative non-surgical treatment (radiation or chemo-radiation) (N = 209), or palliative treatments (N = 35). We followed up cases for up to 3 years, who visited the ER after (or during) cancer treatments and analyzed the main reasons and risk factors for ER visits., Results: The rate of ER visits was 8.0% (N = 45) of patients with HNC (no. of ER visits, N = 70, 12.4%, mean = 1.56, range = 1-4), among which treatment-related ER visits made up 4.6%. Common reasons for ER visits were surgical site or wound problems (31.1% per patient, 22.9% per ER visits), and oral intake or feeding problems (22.2% per patient, 31.4% per ER visit). Tumor subsite (17.9% of treatment-related ER visits in hypopharynx cancer), tumor burden (8.6-12.2% in T2-4 and 6.7% in N+ status), and treatment modalities (surgery with adjuvant chemo-radiation, 19.4%) were identified as significant risk factors for ER visits, while patient age and comorbidities were not., Conclusion: The most common causes for ER visits were wound and feeding problems in HNC patients, and tumor factors and treatment modalities were independent risk factors for ER visits. Adequate planning and management to address these problems could help reduce ER visits and costs and improve patient care.

By investigating the characteristics and prognosis of breast cancer (BC) patients who have undergone hormone replacement therapy (HRT), this study addresses a gap in the existing literature. A total of 17,355 postmenopausal patients with BC were analyzed using data from the Korea Breast Cancer Society database (2000-2014). Among them, 3,585 (20.7%) had a history of HRT before BC diagnosis (HRT group), while 13,770 (79.3%) never received HRT (non-HRT group). The HRT group exhibited an earlier pathologic stage, lower histologic and nuclear grades, and a higher rate of breast conservation surgery compared to the non-HRT group. Furthermore, this group had a higher rate of screening participation and a greater proportion of patients with a normal or overweight body mass index (BMI). The prognosis of the HRT group was better than that of the non-HRT group, with a 5-year overall survival rate of 93.9% versus 91.7% ( p < 0.001). The hazard ratio for the HRT group was 0.7 (95% confidence interval, 0.608-0.805; p < 0.001). Increased screening participation, longer HRT duration, and a normal or overweight BMI were associated with a better prognosis in the HRT group. Patients with BC who underwent HRT showed better clinicopathological characteristics and prognosis than those who did not receive HRT. The results highlighted significant differences in patients who underwent screening and those with a normal or overweight BMI. Furthermore, a longer HRT duration was associated with a better prognosis., Competing Interests: The authors declare that they have no competing interests., (© 2024 Korean Breast Cancer Society.)

Objective: The aim of this study was to assess the effectiveness of a deep learning-based image contrast-boosting algorithm by enhancing the image quality of low-dose computed tomography pulmonary angiography at reduced iodine load., Methods: This study included 179 patients who underwent low-dose computed tomography pulmonary angiography with a reduced iodine load using 64 mL of a 1:1 mixture of contrast medium from January 1 to June 30, 2023. For single-energy computed tomography, the noise index was set at 15.4 to maintain a CTDIvol of <2 mGy at 80 kVp, and for dual-energy computed tomography, fast kV-switching between 80 and 140 kVp was employed with a fixed tube current of 145 mA. Images were reconstructed by 50% adaptive statistical iterative reconstruction (AR50) and a commercially available deep learning image reconstruction (TrueFidelity) package at a high strength level (TFH). In addition, AR50 images were further processed using a deep learning-based contrast-boosting algorithm (AR50-CB). Quantitative and qualitative image qualities and numbers of involved vessels with thrombus at each pulmonary artery level were compared in the 3 image types using the Friedman test and Wilcoxon signed rank test., Results: Five hundred thirty-seven reconstructed image datasets of 179 patients were analyzed. Quantitative image analysis showed AR50-CB (30.8 ± 10.0 and 28.1 ± 9.6, respectively) had significantly higher signal-to-noise ratio and contrast-to-noise ratio values than AR50 (20.2 ± 6.2 and 17.8 ± 6.2, respectively) (P < 0.001) or TFH (28.3 ± 8.3 and 24.9 ± 8.1, respectively) (P < 0.001). Qualitative image analysis showed that contrast enhancement and noise scores of AR50-CB were significantly greater than those of AR50 (P < 0.001) and that AR50-CB enhancement scores were significantly higher than TFH enhancement scores (P < 0.001). The number of subsegmental pulmonary arteries affected by thrombus detected was significantly greater for AR50-CB (30 for AR50, 30 for TFH, and 55 for AR50-CB, P < 0.001)., Conclusions: The use of a deep learning-based contrast-boosting algorithm improved image quality in terms of signal-to-noise ratio and contrast-to-noise ratio values and the detection of thrombi in subsegmental pulmonary arteries., Competing Interests: C.A. is an employee of ClariPi. His role was confined to providing the deep learning–based contrast-boosting image sets, and he did not participate in data analysis or data control. Other authors declare that there is no conflict of interest. This study was supported by Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital (30-2023-016)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Surgical occlusion of the left atrial appendage (LAA) during cardiac surgery in patients with atrial fibrillation (AF) is known to reduce thromboembolism. However, data on the clinical significance of LAA occlusion (LAAO) in patients with mitral regurgitation (MR) are lacking. A total of 237 AF patients with chronic severe MR who underwent mitral valve (MV) surgery were retrospectively analyzed. Patients were divided into two groups according to concomitant LAAO or LAA preservation. The primary outcome was a composite of all-cause death and thromboembolic events (ischemic stroke or systemic embolism). The LAA was surgically occluded in 98 (41%) patients and preserved in 139 (59%) patients. During the follow-up period (median, 37 months), 29 primary outcomes occurred. In the Kaplan-Meyer analysis, the LAA preservation group showed a greater cumulative incidence of the primary outcome (P = 0.002) and thromboembolic events (P = 0.003) than the LAAO group. In the univariate Cox regression analysis, coronary artery disease, CHA 2 DS 2 -VASc score, a cauliflower-shaped LAA, Maze, and no LAAO were significantly associated with the primary outcome. In the multivariate Cox regression analysis, concomitant LAAO was significantly linked to the primary outcome (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.10-0.91, P = 0.033) and thromboembolic events (HR: 0.19, 95% CI: 0.04-0.87, P = 0.032). These benefits from LAAO were consistent, even after propensity score-matched analysis. For patients undergoing surgery for chronic MR who also have AF, concomitant surgical LAAO is associated with favorable clinical outcome., (© 2024. The Author(s).)

Objectives: To investigate the value of body composition indices derived from pre-procedural computed tomography (CT) in predicting 1-year mortality among patients who underwent transcatheter aortic valve replacement (TAVR)., Materials and Methods: We assessed consecutive patients who underwent TAVR between June 2016 and December 2021 at a single academic medical center. Skeletal muscle and subcutaneous fat area at the T4, T12, and L3 levels on pre-procedural CT were measured. The association between body composition and 1-year mortality was evaluated using Cox proportional hazard regression analysis., Results: Finally, 408 patients were included (185 men and 223 women; mean age, 81.7 ± 5.1 years; range, 62-98 years). Post-procedural death occurred in 13.2% of patients. The muscle-height index and fat-height index at the L3 level were more strongly correlated with those at the T12 level (r = 0.765, p < 0.001 and r = 0.932, p < 0.001, respectively) than with those at the T4 level (r = 0.535, p < 0.001 and r = 0.895, p < 0.001, respectively). The cumulative 1-year mortality rate was highest for patients with both sarcopenia and adipopenia (26%), followed by those with adipopenia only (17%), those with sarcopenia only (12%), and those with neither sarcopenia nor adipopenia (8%, p = 0.002). Multivariable analysis revealed that body composition at the T12 level was an independent risk factor for 1-year mortality (hazard ratio: 4.09, 95% confidence interval: 2.01-8.35) in patients with both sarcopenia and adipopenia (p < 0.001)., Conclusion: Sarcopenia or adipopenia assessed with CT at the thoracic level may be valuable for stratifying 1-year all-cause mortality in patients who undergo TAVR., Clinical Relevance Statement: Skeletal muscle and subcutaneous fat mass indices at the level of T12, measured on pre-procedural CT, have value for risk stratification of 1-year all-cause mortality in patients who undergo transcatheter aortic valve replacement., Key Points: Sarcopenia and adipopenia are associated with the prognosis of patients undergoing transcatheter aortic valve replacement. Body composition at the T12 level was an independent risk factor for 1-year all-cause mortality. Sarcopenia or adipopenia assessed at T12 with pre-procedural CT is valuable for risk stratification., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Y.J.K. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: One of the authors (Mr. Yun Ho Roh) has significant statistical expertise. Informed consent: Written informed consent was waived by the Institutional Review Board. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: No study subjects have been previously reported. Methodology: Diagnostic or prognostic study Performed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that leads to respiratory failure and death due to irreversible scarring of the distal lung. While historically considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now recognized to play a central role in IPF pathophysiology., Purpose: This study aimed to investigate the regenerative capacity of AT2 cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity., Method: Lung tissues from 3 pneumothorax patients and 6 IPF patients (early and advanced stages) were obtained by VATS and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-EpCAM+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immuno-staining was used to confirm the presence of AT2 cells., Results: FACS sorting yielded approximately 1% AT2 cells of the total cells in early IPF tissue, and the number decreased as the disease progressed, compared with 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller in size and fewer in number compared to those from pneumothorax patients. The colony-forming efficiency decreased as the disease progressed. In immuno-staining results, the IPF organoids showed lower expression of SFTPC compared to the pneumothorax group and contained KRT5+ cells., Conclusion: This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, and IPF AT2 cells inherently exhibit functional abnormalities and altered differentiation plasticity.

Background : The 2015 American Thyroid Association guidelines recommend the maintenance of serum thyroid stimulating hormone (TSH) levels ≤2 mIU/L in patients with low-risk papillary thyroid carcinoma (PTC) who underwent lobectomy; however, the evidence is insufficient. We investigated the association between maintaining the TSH status at ≤2 mIU/L and tumor recurrence in patients with low-risk PTC who underwent lobectomy through a 5-year landmark analysis. Methods : Between 2010 and 2016, 662 patients with low-risk PTC were included. The postoperative TSH status was determined using the 'TSH > 2 ratio', which was calculated using the TSH test results during the 5-year follow-up. The optimal cutoff value of 'TSH > 2 ratio' for tumor recurrence was determined using a receiver operating characteristic curve analysis. Recurrence-free survival (RFS) was compared between the groups using Kaplan-Meier and Cox proportional hazard regression analyses. Results : Patients with 'TSH > 2 ratio' > 0.1833 ( n = 498) had a worse RFS outcome compared to patients with 'TSH > 2 ratio' ≤ 0.1833 ( n = 164; p < 0.001). 'TSH > 2 ratio' > 0.1833 was a significant risk factor for tumor recurrence after the 5-year landmark (hazard ratio: 4.795, 95% confidence interval: 2.102-10.937, p < 0.001). Conclusions : Maintaining TSH levels ≤ 2 mIU/L below a certain percentage among the total TSH tests during the 5-year follow-up period has a negative impact on tumor recurrence.

Backgrounds/aims: This meta-analysis examined whether preoperative vibration-controlled transient elastography (VCTE) can predict postoperative complications and recurrence in patients undergoing hepatic resection for hepatocellular carcinoma (HCC)., Methods: A systematic literature search was conducted using Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases. Out of 431 individual studies, thirteen published between 2008 and 2022 were included. Five studies focused on HCC recurrence, while eight examined postoperative complications., Results: The meta-analysis of five studies on HCC recurrence showed that the high-risk group with a high VCTE score had a significantly increased recurrence rate after hepatic resection (hazard ratio 2.14). The cutoff value of VCTE in the high-risk group of HCC recurrence was 7.4-13.4 kPa, the sensitivity was 0.60 (95% confidence interval [CI] 0.47-0.72), and the specificity was 0.60 (95% CI 0.46-0.72). The area under the receiver operating characteristic curve (AUC) of the liver stiffness measured by VCTE to predict the HCC recurrence was 0.63 (95% CI 0.59-0.67). The meta-analysis on the postoperative complications revealed a significantly increased risk of postoperative complications in the high-risk group (12-25.6 kPa) with a high VCTE value (odds ratio [OR], 8.32). The AUC of the liver stiffness measured by VCTE to predict the postoperative complications was 0.87 (95% CI 0.84-0.90), the sensitivity was 0.76 (95% CI 0.55-0.89) and the specificity was 0.85 (95% CI 0.73-0.92)., Conclusion: This meta-analysis suggests that preoperative VCTE in patients undergoing hepatic resection for HCC is useful in identifying individuals at a high risk of postoperative complications and HCC recurrence.

Purpose: This study aimed to investigate the correlation between serum creatinine levels and the presence and severity of radiographic knee osteoarthritis (OA) in individuals aged ≥50 years while adjusting for potential confounders., Materials and Methods: Cross-sectional data from the 2009-2011 Korea National Health and Nutrition Examination Survey comprising 3428 individuals aged ≥50 years were utilized. The Kellgren-Lawrence (K-L) grading scale was used to assess the radiographic presence and severity of knee OA. Logistic regression and receiver operating characteristic analyses were used to investigate the association between serum creatinine levels and the presence of knee OA, whereas ordinal regression was used to assess the impact of creatinine levels on knee OA severity., Results: The presence of radiographic knee OA conferred by low serum creatinine levels was found to be significant in both sexes [odds ratio (OR), 0.118; 95% confidence interval (CI), 0.045-0.314, p <0.001 for men; OR, 0.148; 95% CI, 0.040-0.549, p =0.004 for women]. Low serum creatinine was significantly associated with knee OA-graded K-L severity in each sex-based group [β, -1.923; standard error, 0.478; p <0.001 for men and β, -1.532; SE, 0.575; p =0.008 for women]., Conclusion: Low serum creatinine level was associated with a higher presence of knee OA in both men and women, and was also linked to the severity of the disease. These findings suggest that the serum creatinine level may be a potential biomarker for assessing the presence and severity of knee OA., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Backgrounds/aims: Liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using VCTE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients., Methods: A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used VCTE were finally registered. Hazard ratios (HRs) and the 95% confidence intervals (CIs) were considered summary estimates of treatment effect sizes of ≥11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model., Results: Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45-4.54) in CHB patients with a baseline LSM of ≥11 kPa compared to patients who did not. In ten studies included, LSM of ≥11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50-71%) and 78% (95% CI, 66-86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70-0.77)., Conclusion: The risk of HCC development was elevated in CHB patients with VCTE-determined LSM of ≥11 kPa. This finding suggests that VCTE-determined LSM values may aid the risk prediction of HCC development in CHB patients.

Purpose: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM., Materials and Methods: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies., Results: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07-1.97, p =0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p <0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61-8.87), p =0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p <0.05)., Conclusion: Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Living cells can perform incredible tasks that man-made micro/nano-sized robots have not yet been able to accomplish. One example is that white blood cells can sense and move to the site of pathogen attack within minutes. The robustness and precision of cellular functions have been perfected through billions of years of evolution. In this context, we ask the question whether cells follow a set of physical principles to sense, adapt, and migrate. Microfluidics has emerged as an enabling technology for recreating well-defined cellular environment for cell migration studies, and its ability to follow single cell dynamics allows for the results to be amenable for theoretical modeling. In this review, we focus on the development of microfluidic platforms for recreating cellular biophysical (e.g., mechanical stress) and biochemical (e.g., nutrients and cytokines) environments for cell migration studies in 3D. We summarize the basic principles that cells (including bacteria, algal, and mammalian cells) use to respond to chemical gradients learned from microfluidic systems. We also discuss about novel biological insights gained from studies of cell migration under biophysical cues and the need for further quantitative studies of cell function under well-controlled biophysical environments in the future., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications., (© 2024. The Author(s).)

Continued advances in the diagnosis and treatment of breast cancer (BC) have led to an increase in the number of long-term BC survivors and an increase in the incidence of metachronous BC in the contralateral breast. Therefore, it is important to understand the factors that influence the development of metachronous BC; however, the impact of the laterality of the initial ipsilateral (I)BC as a risk factor for the development of metachronous contralateral (MC)BC has not been extensively investigated. The present study included 17,082 female patients with stage 0-3 IBC from the prospectively maintained Korean Breast Cancer Registry from 1989-2013 and divided them into two groups: Patients with MCBC (n=88) and those without MCBC (n=16,994). Risk factors that present at the initial BC diagnosis that could significantly influence the development of MCBC were screened for and risks were evaluated using the Fine-Gray subdistribution hazard model. Significant differences in baseline characteristics between MCBC and non-MCBC groups were demonstrated. Patients aged <40 years, those with histological and nuclear grade 3 tumors, and those with the triple-negative BC subtype were significantly more prevalent in the MCBC group than in the non-MCBC group. Additionally, the cumulative incidence of MCBC increased over time, with a notable increase from 0.1% in year 1 to 1.6% in year 10. Survival analysis revealed no significant differences in overall or BC-specific survival between the two groups. Key predictive factors identified for MCBC included an age of <40 years at initial diagnosis, a negative progesterone receptor status, and a Ki-67 score of >14%. Overall, the present study revealed several factors associated with MCBC and emphasized the need for long-term monitoring of BC survivors, considering these newly identified risk factors., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Park et al.)

Background: World Health Organization defined pheochromocytomas/paragangliomas (PPGL) as malignant tumors in 2017 because the existing classification system could not reflect locally aggressive behavior sufficiently. However, predicting the likelihood of metastasis remains a crucial part of the treatment strategy., Methods: From one tertiary care hospital and one secondary hospital, 97 PPGL cases were selected. Medical records of PPGL cases with the presence of formalin-fixed and paraffin-embedded (FFPE) tissue of primary lesion were reviewed. For FFPE tissues, a nCounter assay was conducted to determine differently expressed genes between metastatic and non-metastatic PPGL groups. Performances of prediction models for the likelihood of metastasis were calculated., Results: Of a total of 97 PPGL cases, 39, 20, and 38 were classified as benign, malignant, and validation, respectively. In the nCounter assay, CDK1, TYMS, and TOP2A genes showed significant differences in expression. Tumor size was positively correlated with CDK1 expression level. The Lasso regression model showed supreme performance of sensitivity 91.7% and specificity 95.5% when those significant factors were considered., Conclusion: Machine learning of multi-modal classifiers can be used to create a prediction model for metastasis of PPGL with high sensitivity and specificity using nCounter assay. Moreover, CDK1 inhibitors could be considered for developing drug treatment., (© 2024 Wiley Periodicals LLC.)

Objectives: Laryngeal keel insertion, mucosal suture, application of mitomycin-C (MMC), and staged operations are approaches to prevent the anterior glottic web, but there are limitations. Our study suggests a modified approach to prevent the formation of an anterior glottic web. Methods: This retrospective single-institution tertiary center study (N = 23) involved the simultaneous removal of bilateral vocal fold lesions with topical MMC application. If exudate was identified after 4 to 6 weeks, second laryngomicroscopic surgery (LMS) was performed to remove it with topical MMC application. Extent of anterior glottic web was measured as a percentage of the total length of the membranous vocal fold. Results: After the initial surgery, 18 patients recovered without anterior web or fibrin exudate. Thick exudate was observed in 5 patients. After the second LMS, all patients showed improvement and did not develop anterior web. Conclusion: This modified method has been developed to prevent the anterior glottic web without complications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Non-infectious erythema, or Red Breast Syndrome (RBS), has been observed on the skin where acellular dermal matrix was implanted, although the exact cause is yet to be determined., Patients and Methods: A total of 214 female patients underwent breast-conserving surgery (BCS) and volume replacement using diced acellular dermal matrix (dADM) for breast cancer between December 2017 and December 2018. After collecting and evaluating relevant clinical data, inflammation markers, along with NK cell status presented by IFN-γ secretion assay, were measured using ELISA., Results: Nineteen patients (8.88%) presented with RBS after BCS and dADM use. A significant increase of platelet-to-lymphocyte ratio was noted in the non-RBS group ( p = 0.02). Compared to the RBS group ( p = 0.042), the WBC level of the non-RBS group showed significant decrease over time. Eosinophil counts increased significantly at follow-up but went up higher in the RBS group. Multivariate analysis showed preoperative chemotherapy significantly increased the hazard of RBS (OR 3.274, p = 0.047 and OR 17.098, p < 0.001, respectively)., Discussion: Though no causal relationship between RBS and immune status was proven, the results suggest an association between preoperative chemotherapy and RBS in addition to the possible role of eosinophilia in leading to eosinophilic dermatoses, which warrants further exploration and elucidation.

Objectives: To assess the feasibility of the UTE-MRI radiomic model in predicting the micropapillary and/or solid (MP/S) patterns of surgically resected lung adenocarcinoma., Materials and Methods: We prospectively enrolled 74 lesions from 71 patients who underwent UTE-MRI and CT before curative surgery for early lung adenocarcinoma. For conventional radiologic analysis, we analyzed the longest lesion diameter and lesion characteristics at both UTE-MRI and CT. Radiomic features were extracted from the volume of interest of the lesions and Rad-scores were generated using the least absolute shrinkage and selection operator with fivefold cross-validation. Six models were constructed by combining the conventional radiologic model, UTE-MRI Rad-score, and CT Rad-score. The areas under the curves (AUCs) of each model were compared using the DeLong method. Early recurrence after curative surgery was analyzed, and Kaplan-Meier survival analysis was performed., Results: Twenty-four lesions were MP/S-positive, and 50 were MP/S-negative. The longitudinal size showed a small systematic difference between UTE-MRI and CT, with fair intermodality agreement of lesion characteristic (kappa = 0.535). The Rad-scores of the UTE-MRI and CT demonstrated AUCs of 0.84 and 0.841, respectively (p = 0.98). Among the six models, mixed conventional, UTE-MRI, and CT Rad-score model showed the highest diagnostic performance (AUC = 0.879). In the survival analysis, the high- and low-risk groups were successfully divided by the Rad-score in UTE-MRI (p = 0.01) and CT (p < 0.01)., Conclusion: UTE-MRI radiomic model predicting MP/S positivity is feasible compared with the CT radiomic model. Also, it was associated with early recurrence in the survival analysis., Clinical Relevance Statement: A radiomic model utilizing UTE-MRI, which does not present a radiation hazard, was able to successfully predict the histopathologic subtype of lung adenocarcinoma, and it was associated with the patient's recurrence-free survival., Key Points: • No studies have reported the ultrashort echo time (UTE)-MRI-based radiomic model for lung adenocarcinoma. • The UTE-MRI Rad-score showed comparable diagnostic performance with CT Rad-score for predicting micropapillary and/or solid histopathologic pattern. • UTE-MRI is feasible not only for conventional radiologic analysis, but also for radiomics analysis., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Even though some studies have shown possible clinical relationship between molecular subtypes and tumor infiltrating natural killer (NK) cells around tumors, there are few studies showing the clinical relevance of peripheral NK cell activity at diagnosis in female patients with invasive breast cancer. A total of 396 female invasive breast cancer patients who received curative surgical treatment from March 2017 to July 2021 were retrospectively analyzed. NK cell activation-induced interferon-gamma (IFN-γ) secretion measured by enzyme-linked immunosorbent assay was used to measure the activity of peripheral NK cells. Statistical analyses were performed to determine clinical relationships with major clinicopathologic parameters. Quadripartite NK cell activity measured by induced interferon-gamma showed significant relevance with staging and body mass index, and some of the inflammatory serological markers, namely N/L (neutrophil/lymphocyte), P/N (platelet/neutrophil), and P/L (platelet/lymphocyte), showed significantly different NK activity in each interval by univariate analysis. A binary subgroup analysis, setting the IFN-γ secretion cut-off at 100 pg/mL, showed that stage III was significantly increased and axillary lymph node metastasis positivity was increased in the group of IFN-γ < 100 pg/mL, and IFN-γ secretion decreased with an increasing N stage, increased BMI (body mass index), and decreased production of IFN-γ. Following this, the same binary analysis, but with the IFN-γ secretion cut-off at 250 pg/mL, also showed that secretion in stage III was increased in those concentrations with <250 pg/mL, axillary lymph node positivity appeared to be correlated, and BMI ≥ 30 increased in prevalence. Additional ANOVA post hoc tests (Bonferroni) were performed on some serological markers that tended to be somewhat inconsistent. By subgroup analysis with Bonferroni adjustment between the IFN-γ secretion and TNM stage, no significant difference in IFN-γ secretion could be identified at stages I, II, and IV, but at stage III, the IFN-γ secretion < 100 pg/mL was significantly higher than 250 ≤ IFN-γ secretion < 500 pg/mL or IFN-γ secretion ≥ 500 pg/mL. According to this study, stage III was significantly associated with the lowest IFN-γ secretion. Compared to a higher level of IFN-γ secretion, a lower level of IFN-γ secretion seemed to be associated with increased body mass index. Unlike when IFN-γ secretion was analyzed in quartiles, as the IFN-γ secretion fell below 100 pg/mL, the correlation between axillary lymph node positivity and increased N stage, increased BMI, and increased N/L and P/L, which are suggested poor prognostic factors, became more pronounced. We think a peripheral IFN-γ secretion test might be convenient and useful tool for pretreatment risk assessment and selecting probable candidates for further treatment such as immunotherapy in some curable but high-risk invasive breast cancer patients, compared to other costly assaying of tissue NK cell activity at diagnosis.

Uncontrolled growth of tumor cells in confined spaces leads to the accumulation of compressive stress within the tumor. Although the effects of tension within 3D extracellular matrices (ECMs) on tumor growth and invasion are well established, the role of compression in tumor mechanics and invasion is largely unexplored. In this study, we modified a Transwell assay such that it provides constant compressive loads to spheroids embedded within a collagen matrix. We used microscopic imaging to follow the single cell dynamics of the cells within the spheroids, as well as invasion into the 3D ECMs. Our experimental results showed that malignant breast tumor (MDA-MB-231) and non-tumorigenic epithelial (MCF10A) spheroids responded differently to a constant compression. Cells within the malignant spheroids became more motile within the spheroids and invaded more into the ECM under compression; whereas cells within non-tumorigenic MCF10A spheroids became less motile within the spheroids and did not display apparent detachment from the spheroids under compression. These findings suggest that compression may play differential roles in healthy and pathogenic epithelial tissues and highlight the importance of tumor mechanics and invasion., (Creative Commons Attribution license.)

Venous thromboembolism (VTE) is a common occurrence in cancer and chemotherapy increases thrombosis risk. Current risk assessment models such as the Khorana score (KS) and its modifications have limitations in female cancers. We assessed the coagulation profile of a group of women cancer patients under chemotherapy using thromboelastography (TEG) to determine if this can inform VTE risk assessment. Cancer patients who planned to receive chemotherapy were recruited. Baseline demographics, cancer data, BMI, Khorana Score (KS), and VTE risk factors were recorded and patients were followed for 6 months, for any thrombotic events. A total of 36 patients aged 35-85 (18 breast, 11 endometrial, 7 ovarian cancer) were evaluated. Hypercoagulability was detected in 63% of patients post-chemo cycle 1 and 75% post-cycle 2, with a significant increase in MA (maximum amplitude) and CI (clotting index), reduction in R (reaction time), K (clot kinetics), and LY30 (lysis time after 30 min of MA). KS showed only 7% of patients were high risk, 23% were low, and 70% were intermediate risk. MA and CI significantly increased in patients with intermediate and high-risk KS when compared with the low-risk patients and MA was positively correlated with KS. Five patients developed actual VTE; 100% of the tested ones were hypercoagulable either post-cycle 1 or 2 and 80% were KS intermediate risk. TEG is a hypercoagulability marker and TEG-MA and CI can potentially assess VTE risk. Larger studies are needed to assess the utility of TEG as an adjuvant to KS to better predict VTE in specific female cancers., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Purpose: This study aimed to analyze the treatment outcomes and adverse effects of moderately hypofractionated partial breast irradiation (PBI) in patients with early breast cancer., Methods: In total, 473 patients with early breast cancer or carcinoma in situ were diagnosed with Tis or T1N0 disease and underwent PBI following breast-conserving surgery. All histologic tumor types, close surgical margins within 1 mm of the tumor, and multifocal tumors were included in this study. A radiation dose of 50 Gy in 20 fractions was delivered over 4 weeks using intensity-modulated radiotherapy technique. Dosimetric data, recurrence patterns, survival outcomes, and adverse events were retrospectively analyzed., Results: During a median follow-up of 28.9 months, seven patients (1.5%) experienced ipsilateral breast tumor recurrence (IBTR). Two patients had regional recurrence, four patients developed contralateral breast cancer, and no distant metastases were observed. The locoregional recurrence rate in the ipsilateral breast was 1.8%. Two deaths occurred during the follow-up period, but were not attributed to breast cancer. The 2-year disease-free survival and 2-year overall survival rates were was 94.0% and 99.8%, respectively. Acute adverse events occurred in 131 patients (27.1%), and were distributed among all grades, with only two patients (0.4%) experiencing grade 3 events. Late adverse events were noted in 16 patients (3.4%), and were distributed among all grades, including grade 3 events in four patients (0.8%). No grade 4 or 5 events were observed., Conclusion: Hypofractionated PBI demonstrated favorable IBTR rates in patients with early breast cancer, with low incidence of acute and late toxicities in the short-term analysis., Competing Interests: The authors declare that they have no competing interests., (© 2024 Korean Breast Cancer Society.)

Vitamin D deficiency is a worldwide health issue especially in women. Serum vitamin D concentrations vary depending on the weather. However, the ideal vitamin D supplementation strategy related to weather remains uncertain. We aimed to investigate the relationship between climate factors and serum 25-hydroxy vitamin D [25(OH)D] concentrations. This study included 11,272 women aged 20-79 who visited a health promotion center for annual checkups between January 2013 and December 2015. We reviewed medical records and collected daily meteorological data. We analyzed the association between serum 25(OH)D concentration and climate factors using simple and multiple regression models and then predicted serum 25(OH)D concentration using multiple fractional polynomial models. The median age of the participants was 51 years (20-79 years), and the mean serum 25(OH)D level was 17.4 ± 8.6 ng/mL. The serum 25(OH)D concentration was lower in young women than in older women. The proportions of women with adequate 25(OH)D levels were 14.9% and 47.0% in the age groups 20-29 and 70-79, respectively. The maximum level of predicted log 25(OH)D was found in September, and the minimum was found in January. In multiple regression analysis, age and monthly mean temperature were associated with 25(OH)D concentrations. Serum 25(OH)D level was predicted using the following formula: log (25(OH)D) = 2.144 + 0.009 × age + 0.018 × ((temperature + 12.4)/10)2 (P < 0.001, adjusted R2 = 0.091). Serum 25(OH)D concentrations changed according to air temperature. An adequate strategy for vitamin D supplementation, based on air temperature, is necessary to maintain healthy serum 25(OH)D levels., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy., (© 2024. The Author(s).)

Purpose: To assess the added value of radiomics models from preoperative chest CT in predicting the presence of spread through air spaces (STAS) in the early stage of surgically resected lung adenocarcinomas using multiple validation datasets., Materials and Methods: This retrospective study included 550 early-stage surgically resected lung adenocarcinomas in 521 patients, classified into training, test, internal validation, and temporal validation sets (n=211, 90, 91, and 158, respectively). Radiomics features were extracted from the segmented tumors on preoperative chest CT, and a radiomics score (Rad-score) was calculated to predict the presence of STAS. Diagnostic performance of the conventional model and the combined model, based on a combination of conventional and radiomics features, for the diagnosis of the presence of STAS were compared using the area under the curve (AUC) of the receiver operating characteristic curve., Results: Rad-score was significantly higher in the STAS-positive group compared to the STAS-negative group in the training, test, internal, and temporal validation sets. The performance of the combined model was significantly higher than that of the conventional model in the training set {AUC: 0.784 [95% confidence interval (CI): 0.722-0.846] vs. AUC: 0.815 (95% CI: 0.759-0.872), p =0.042}. In the temporal validation set, the combined model showed a significantly higher AUC than that of the conventional model ( p =0.001). The combined model showed a higher AUC than the conventional model in the test and internal validation sets, albeit with no statistical significance., Conclusion: A quantitative CT radiomics model can assist in the non-invasive prediction of the presence of STAS in the early stage of lung adenocarcinomas., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Aims: We aimed to investigate the association between the age at diagnosis of type 2 diabetes and the risk of cardiovascular (CVD) outcomes in comparison with nondiabetic counterparts., Methods: A total of 634,350 patients with newly diagnosed type 2 diabetes between January 1, 2012, and December 31, 2014 were included in a Korean population cohort study. Nondiabetic matched controls were selected from the general population in a 1:2 ratio. Participants were followed until the end of 2019 for CVD outcomes and mortality., Results: During 5.7 years of follow-up, patients with type 2 diabetes diagnosed at ≤40 years of age had the highest excess risk for most outcomes relative to controls, with an adjusted hazard ratio (HR) (95 % CI) of 6.08 (5.51-6.70) for total mortality, 7.10 (6.66-7.58) for hospitalization for heart failure, and 5.04 (4.86-5.24) for coronary heart disease. All risks attenuated progressively with each increasing decade of diagnostic age., Conclusion: In this population-based cohort study, a younger age at diagnosis of type 2 diabetes was associated with a higher relative risk of mortality and CVD outcomes. Therefore, primary prevention of type 2 diabetes is desirable at all ages but is particularly important at younger ages., Competing Interests: Declaration of competing interest The authors 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 © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to investigate clinical practices and factors related to the outcomes of T-DM1 use in patients with HER2-positive metastatic breast cancer (mBC)., Methods: We included patients with HER2-positive mBC who received T-DM1 as a palliative therapy between August 2017 and December 2018. The safety and outcomes of T-DM1, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) for mortality or progression to HER2-positive mBC., Results: In total, 824 patients were enrolled during the study period. The mean age of patients was 58 years, and 516 (62.6%) patients relapsed after curative treatment. Excluding a history of endocrine therapy, 341 (41.4%) patients previously received none or first-line chemotherapy, 179 (21.7%) received second-line therapy, and 303 (36.9%) received third-or later-line chemotherapy before T-DM1 therapy. During a median follow-up of 16.8 months, the ORR was 35%, the median PFS was 6.6 months, and the median OS was not reached. The clinical factors associated with the hazard of progression were age (<65 years), poor performance status (⩾2), advanced line of palliative chemotherapy (⩾2), prior pertuzumab use, and treatment duration of palliative trastuzumab (<10 months). Common grade 3-4 adverse events were thrombocytopenia ( n = 107, 13.2%), neutropenia ( n = 23, 2.8%), anemia ( n = 21, 2.6%), and elevated liver enzyme ( n = 20, 2.5%). Hypokalemia (⩽3.0 mmol/L) and any-grade bleeding events occurred in 25 (3.1%) and 94 (22.6%) patients, respectively., Conclusion: This is the first nationwide real-world study of T-DM1 use in patients with HER2-positive mBC in Korea. The effectiveness and toxicity profiles of T-DM1 in real-world practice were comparable to those in randomized trials. Moreover, patient factors and previous anti-HER2 therapy could predict the outcomes of T-DM1 therapy., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Backgruound: The onset and progression of sarcopenia are highly variable among individuals owing to genetic and environmental factors. However, there are a limited number of studies measuring the heritability of muscle strength in large numbers of parent-adult offspring pairs. We aimed to investigate the familial correlation and heritability of hand grip strength (HGS) among Korean adults., Methods: This family-based cohort study on data from the Korea National Health and Nutrition Examination Survey (2014 to 2019) included 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations of HGS were calculated in different pairs of relatives. Variance component methods were used to estimate heritability., Results: The heritability estimate of HGS among Korean adults was 0.154 (standard error, 0.066). Correlation coefficient estimates for HGS between parent-offspring, sibling, and spouse pairs were significant at 0.07, 0.10, and 0.23 (P<0.001, P=0.041, and P<0.001, respectively). The total variance in the HGS phenotype was explained by additive genetic (15.4%), shared environmental (11.0%), and unique environmental (73.6%) influences. The odds of weak HGS significantly increased in the offspring of parents with weak HGS (odds ratio [OR], 1.69-3.10; P=0.027-0.038), especially in daughters (OR, 2.04-4.64; P=0.029-0.034)., Conclusion: HGS exhibits a familial correlation and significant heritable tendency in Korean adults. Therefore, Asian adults, especially women, who have parents with weak HGS, need to pay special attention to their muscle health with the help of healthy environmental stimuli.

Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporosis-related measurement has shown controversial results. In this study, we found an age, dose andduration-dependent osteoprotective effect of statins in general older population., Purpose: Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporotic fractures has shown controversial results., Methods: In this study with Korean National Health Insurance Service-Senior cohort database, a total of 365,656 elderly without previous history of osteoporosis and who were started on statin since January 1 2004 were included and observed until December 31 2012. Hazard rations (HR) for major osteoporotic fractures were calculated using the weighted Cox proportional hazards model with inverse-probability of treatment weighting method., Results: During 6.27 years of follow-up period, 54,959 osteoporotic fractures occurred and the majority of fractures (69.5%) were vertebral fractures. Compared with non-users, statin use was associated with a decreased risk of all outcomes with adjusted HR (95% CI) of 0.77 (0.72-0.83; P < 0.001) for major osteoporotic fractures, 0.49 (0.38-0.62; P < 0.001) for hip fractures, and 0.70 (0.64-0.77; P < 0.001) for vertebral fractures. When outcomes were examined separately by sex, the results were broadly comparable in terms of patterns of risk reduction by statin use. The patients with statin initiated at age ≥ 80 years had the highest risk reduction for most outcomes relative to non-users. Higher cumulative dose of statin was negatively associated with the osteoporotic fracture risk; 0.97 (0.91-1.02) for 30-364 cumulative daily defined dose (cDDD), 0.45 (0.40-0.51) for 365-1,094 cDDD, and 0.22 (0.15-0.33) for ≥ 1,095 cDDD., Conclusions: Our results showed that statin use was associated with significant reduction in the risk of osteoporotic fractures in general older population., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background and Purpose: The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs., Methods: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes., Results: Among 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p  = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02)., Conclusion: The progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association., 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 Yoon, Kim, Suh, Kim, Youn, Jeong, Han and Choi.)

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, contributing significantly to morbidity and mortality. In a previous study, we developed a deep neural network for predicting paroxysmal atrial fibrillation (PAF) during sinus rhythm (SR) using digital data from standard 12-lead electrocardiography (ECG). The primary aim of this study is to validate an existing artificial intelligence (AI)-enhanced ECG algorithm for predicting PAF in a multicenter tertiary hospital. The secondary objective is to investigate whether the AI-enhanced ECG is associated with AF-related clinical outcomes., Methods and Analysis: We will conduct a retrospective cohort study of more than 50,000 12-lead ECGs from November 1, 2012, to December 31, 2021, at 10 Korean University Hospitals. Data will be collected from patient records, including baseline demographics, comorbidities, laboratory findings, echocardiographic findings, hospitalizations, and related procedural outcomes, such as AF ablation and mortality. De-identification of ECG data through data encryption and anonymization will be conducted and the data will be analyzed using the AI algorithm previously developed for AF prediction. An area under the receiver operating characteristic curve will be created to test and validate the datasets and assess the AI-enabled ECGs acquired during the sinus rhythm to determine whether AF is present. Kaplan-Meier survival functions will be used to estimate the time to hospitalization, AF-related procedure outcomes, and mortality, with log-rank tests to compare patients with low and high risk of AF by AI. Multivariate Cox proportional hazards regression will estimate the effect of AI-enhanced ECG multimorbidity on clinical outcomes after stratifying patients by AF probability by AI., Discussion: This study will advance PAF prediction based on AI-enhanced ECGs. This approach is a novel method for risk stratification and emphasizes shared decision-making for early detection and management of patients with newly diagnosed AF. The results may revolutionize PAF management and unveil the wider potential of AI in predicting and managing cardiovascular diseases., Ethics and Dissemination: The study findings will be published in peer-reviewed publications and disseminated at national and international conferences and through social media. This study was approved by the institutional review boards of all participating university hospitals. Data extraction, storage, and management were approved by the data review committees of all institutions., Clinical Trial Registration: [cris.nih.go.kr], identifier (KCT0007881)., Competing Interests: Y-SB, S-CL, WC and D-HK were employed by DeepCardio Inc. The remaining 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., (© 2023 Baek, Kwon, You, Lee, Yu, Lee, Roh, Kim, Shin, Lee, Park, Park, Suh, Choi, Lee, Joung, Choi and Kim.)

Background: The reliability and diagnostic performance of deep learning (DL)-based automated T2 measurements on T2 map of 3.0-T cardiac magnetic resonance imaging (MRI) using multi-institutional datasets have not been investigated. We aimed to evaluate the performance of a DL-based software for measuring automated T2 values from 3.0-T cardiac MRI obtained at two centers., Methods: Eighty-three subjects were retrospectively enrolled from two centers (42 healthy subjects and 41 patients with myocarditis) to validate a commercial DL-based software that was trained to segment the left ventricular myocardium and measure T2 values on T2 mapping sequences. Manual reference T2 values by two experienced radiologists and those calculated by the DL-based software were obtained. The segmentation performance of the DL-based software and the non-inferiority of automated T2 values were assessed compared with the manual reference standard per segment level. The software's performance in detecting elevated T2 values was assessed by calculating the sensitivity, specificity, and accuracy per segment., Results: The average Dice similarity coefficient for segmentation of myocardium on T2 maps was 0.844. The automated T2 values were non-inferior to the manual reference T2 values on a per-segment analysis (45.35 vs. 44.32 ms). The DL-based software exhibited good performance (sensitivity: 83.6-92.8%; specificity: 82.5-92.0%; accuracy: 82.7-92.2%) in detecting elevated T2 values., Conclusions: The DL-based software for automated T2 map analysis yields non-inferior measurements at the per-segment level and good performance for detecting myocardial segments with elevated T2 values compared with manual analysis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-375/coif). Two authors (PKK and BWC) are founders of Phantomics, Inc. (Seoul, Korea) and one author (YJY) is an employee of the same company, but the company did not give financial support for this study. The company supported the software (Myomics) for this study. The other authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objectives: To investigate the incremental prognostic value of the 2020 International Association for the Study of Lung Cancer (IASLC) histologic grading system over traditional prognosticators in surgically resected pathologic stage 1 lung adenocarcinomas and to identify the clinical and radiologic characteristics of lung adenocarcinomas reclassified by the 2020 histologic grading system., Materials and Methods: We retrospectively enrolled 356 patients who underwent surgery for pathologic stage 1 adenocarcinoma between January 2016 and December 2017. The histologic grading was classified according to the predominant histologic subtype (conventional system) and the updated 2020 IASLC grading system. The clinical and computed tomography (CT) characteristics were compared according to the reclassification of the updated system. The performance of prognostic models for recurrence-free survival based on the combination of pathologic tumor size, histologic grade, and CT-based information was compared using the c-index., Results: Postoperative recurrence occurred in 6.7% of patients during the follow-up period (mean, 1589.2 ± 406.7 days). Fifty-nine of 244 (24.2%) tumors with intermediate grades in the conventional system were reclassified as grade 3 with the updated grading system. They showed significantly larger solid proportions and higher percentages of pure solid nodules on CT compared to tumors without reclassification (n = 185) (P < 0.05). Prognostic prediction models based on pathology tumor size and histologic grades had significantly higher c-indices (0.754-0.803) compared to the model based on pathologic tumor size only (c-index:0.723, P < 0.05)., Conclusion: The 2020 IASLC histologic grading system has significant incremental prognostic value over the pathologic stage in surgically resected pathologic stage 1 lung adenocarcinoma. Reclassified lung adenocarcinomas using the updated grading system have a larger solid proportion and a higher percentage of pure solid nodules on CT., Competing Interests: Declaration of Competing Interest The authors 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 B.V. All rights reserved.)

During the adsorptive removal of hazardous metal contaminants, dissolution-precipitation of sparingly soluble adsorbents may result in the formation of toxic colloidal suspensions, triggering secondary pollution. Therefore, we studied the prevention of colloid-facilitated contamination in a model adsorption system of dicalcium phosphate dihydrate (DCPD, CaHPO 4 ·2H 2 O) and Cd 2+ as an adsorbent and adsorbate. Upon adding pure DCPD powder into a 500 mg L -1 Cd 2+ solution of pH ≌ 7.0, aggregates of spheroidal Cd-bearing primary particles, within 0.040-0.95 μm size range, were generated via dissolution-precipitation. The accumulated volume of these submicron particles (10.8%) was greater than that of the submicron particles from the exposure of DCPD to deionized water (4.48%). While the Cd-carrying submicron particles, which are responsible for colloidal recontamination, appeared to form via homogeneous nucleation, their formation was suppressed using polyacrylonitrile fibers (PANFs) as supporting substrates. Thus, heterogeneous nucleation on PANFs formed hexagonal columnar microparticles of a new phase, pentacadmium dihydrogen tetrakis (phosphate) tetrahydrate (Cd 5 H 2 (PO 4 ) 4 ·4H 2 O). Together with dissolution-precipitation on the native DCPD, nucleation and growth on the PANFs accelerated the depletion of the dissolved species, reducing the degree of supersaturation along the DCPD-water interface. Although the PANFs decreased the Cd adsorption capacity to 56.7% of that of DCPD, they prevented the formation of small aggregates of Cd-bearing particles. Other sparingly soluble adsorbents can be compounded with PANF to prevent the generation of toxic colloids., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kuk Cho reports financial support was provided by National Research Foundation of Korea. Yong Jae Suh reports financial support was provided by Korea Ministry of Science and ICT., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rationale and Objectives: The aim of this study was to evaluate the usual postoperative imaging findings among patients who underwent oncoplastic breast-conserving surgery (BCS) with acellular dermal matrix (ADM) and to assess the clinical utility of mammography (MG) and ultrasonography (US) in follow-ups., Materials and Methods: This retrospective review of our prospectively collected database of patients who underwent oncoplastic BCS with ADM was conducted with IRB approval and in HIPPA compliance. A total of 105 patients whose follow-up MG and US studies over 2years after surgery were available were included in this study. Postoperative imaging findings were analyzed based on sequential MG and US follow-ups. The clinical outcomes and pathological data were also reviewed. The diagnostic performance of MG and US for postoperative surveillance was assessed., Results: On MG, ADM presented as an oval (99/105, 94.3%), circumscribed/obscured (65/105, 61.9%), and high-density (56/105, 53.3%) mass with calcifications (54/105, 51.4%). On US, the ADM-filled cavity presented as an oval (93/105, 88.6%), circumscribed (70/105, 66.7%), heterogenous echoic (65/105, 61.9%) mass with marginal/posterior acoustic shadowing (95/105, 90.5%) on US. During the follow-up period (mean, 46.1months; range, 26-58 months), four tumor recurrences were diagnosed (4/105, 3.8%). One tumor recurrence detected on MG presented as microcalcifications (1/4, 25%), which were differentiated from benign postoperative calcifications due to their suspicious morphology and location. Two additional recurrences (2/4, 50%), which were MG-negative small masses or intraductal lesions, were detected on US. One tumor recurrence was missed on both MG+US and was detected by magnetic resonance imaging performed at clinician's request. The sensitivity and specificity of MG, US, and MG+US for postoperative surveillance were 25%, 50% and 75% and 100%, 98% and 98%, respectively., Conclusion: Recognition and adequate interpretation of the usual findings after oncoplastic BCS with ADM insertion are important in postoperative imaging surveillance. The sole use of MG is not sufficient for the detection of mass-type tumor recurrence due to the density of inserted ADM fillers. Therefore, the combined use of MG+US could serve as a useful postoperative surveillance tool with increased sensitivity in this population., Competing Interests: Declaration of Competing Interest The authors 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 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Acidic wastewater containing radioactive 137 Cs is difficult to treat by selective adsorption. Abundant H + under acidic conditions damages the structure of adsorbents and competes with Cs + for adsorption sites. Herein, we designed a novel layered calcium thiostannate (KCaSnS) that contains Ca 2+ as a dopant. The dopant Ca 2+ ion is metastable and larger than the ions attempted before. The pristine KCaSnS demonstrated a high Cs + adsorption capacity of 620 mg/g at 8250 mg/L Cs + solution and pH 2, which is 68% higher than that at pH 5.5 (370 mg/g), a trend opposite to all previous studies. The neutral condition allowed the release of Ca 2+ present only in the interlayer (∼20%); whereas the high acidity facilitated the leaching of Ca 2+ from the backbone structure (∼80%). The complete structural Ca 2+ leaching was made possible only by a synergistic interaction of highly concentrated H + and Cs + . Doping a large enough ion, such as Ca 2+ , to accommodate Cs + into the Sn-S matrix upon its liberation opens a new way of designing high-performance adsorbents., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kuk Cho reports financial support was provided by National Research Foundation of Korea. Yong Jae Suh reports financial support was provided by Ministry of Science and ICT of Korea., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Acute myeloid leukemia (AML) generally has an unsatisfactory prognosis despite the recent introduction of new regimens, including targeted agents and antibodies. To find a new druggable pathway, we performed integrated bioinformatic pathway screening on large OHSU and MILE AML databases, discovered the SUMOylation pathway, and validated it independently with an external data set (totaling 2959 AML and 642 normal sample data). The clinical relevance of SUMOylation in AML was supported by its core gene expression which is correlated with patient survival, European LeukemiaNet 2017 risk classification, and AML-relevant mutations. TAK-981, a first-in-class SUMOylation inhibitor currently under clinical trials for solid tumors, showed antileukemic effects with apoptosis induction, cell-cycle arrest, and induction of differentiation marker expression in leukemic cells. It exhibited potent nanomolar activity, often stronger than that of cytarabine, which is part of the standard of care. TAK-981's utility was further demonstrated in in vivo mouse and human leukemia models as well as patient-derived primary AML cells. Our results also indicate direct and cancer cell-inherent anti-AML effects by TAK-981, different from the type 1 interferon and immune-dependent mechanism in a previous solid tumor study. Overall, we provide a proof-of-concept for SUMOylation as a new targetable pathway in AML and propose TAK-981 as a promising direct anti-AML agent. Our data should prompt studies on optimal combination strategies and transitions to clinical trials in AML., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The human epidermal growth factor receptor-2 (HER2) enriched subtype of breast cancer is associated with early recurrence, mostly within 5 years. However, anti-HER2 therapies have improved outcomes and their benefits persist in the long term. This study aimed to determine predictive factors for late survival in patients with HER2-positive breast cancer. We analyzed 20,672 patients with HER2-positive stage I-III breast cancer. The patients were divided into two groups based on a follow-up period of 60 months. The multivariate analysis of factors associated with poor overall survival included old age, advanced pathologic tumor size stage (pT), advanced pathologic regional lymph node stage (pN), high histological grade, presence of lymphatic and vascular invasion, and HR-negative status within 60 months. In the breast cancer-specific survival (BCSS) of the > 60 months follow-up group, the hazard ratios (HRa) based on pN-negative were 3.038, 3.722, and 4.877 in pN1 (p = 0.001), pN2 (p < 0.001), and pN3 (p < 0.001), respectively. Only pT4 level was statistically significant in the pT group (HRa, 4.528; p = 0.007). Age (HRa, 1.045, p < 0.001) and hormone receptor-positive status (HRa, 1.705, p = 0.022) were also associated to worse BCSS. Although lymphatic invasion was not significantly associated with BCSS, there was a tendency toward a relationship (p = 0.079) with worse BCSS. In HER2-positive breast cancer patients, node status had a more significant relationship with long-term prognosis than T stage. Patients with HER2-positive breast cancer who have T4 or node-positive should be considered for clinical observation and education beyond 5 years., (© 2023. The Author(s).)

Objective: To assess the effect of local ablative therapy (LAT) on overall survival in patients with lung metastases from colorectal cancer (CRC) compared with patients treated with systemic therapy., Summary Background Data: CRC affects approximately 1.4 million individuals worldwide every year. The lungs are commonly affected by CRC, and there is no treatment standard for a secondary lung metastasis from CRC., Methods: This longitudinal, retrospective cohort study (2010-2018) quantified the pulmonary and extrapulmonary tumor burden of 1143 patients by retrospectively reviewing computed tomography images captured at diagnosis. A comprehensive multidisciplinary approach informed how and when surgery and/or stereotactic body radiotherapy was administered., Results: Among 1143 patients, 473 patients (41%) received LAT, with surgery first (n = 421) or stereotactic ablative radiation therapy first (n = 52) either at the time of diagnosis (n = 288), within 1 year (n = 132), or after 1 year (n = 53). LAT was repeated in 158 patients (33.4%, 384 total sessions) when new lung metastases were detected. The 5- and 10-year survival rates for patients treated with LAT (71.2% and 64.0%, respectively) were significantly higher than those of patients treated with systemic therapy alone (14.2% and 10.0%, respectively; P <0.001). The overall survival of patients who received LAT intervention increased as the total tumor burden decreased., Conclusions: A high long-term survival rate was achievable in a significant portion of patients with lung metastasis from CRC by the timely administrations of LAT to standard systemic therapy. The tumor burden and LAT feasibility should be included in a discussion during the follow-up period., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)