Sternoclavicular xanthogranulomatous osteomyelitis in a patient after kidney transplantation: a case report.

Xanthogranulomatous osteomyelitis (XO) is a rare chronic inflammatory bone disease characterized by the presence of cholesterol-laden foam macrophages, histiocytes, and plasma cells. We report the case of a 41-year-old man with end-stage renal disease who had undergone deceased donor kidney transplantation 4 years earlier. He presented with a chest wall mass that he had first identified 2 weeks prior to admission. Computed tomography revealed a periosseous heterogeneously enhancing soft tissue mass adjacent to the sternal end of the left clavicle, accompanied by irregular and destructive osteolytic lesions on the left side of the sternal manubrium. A total mass resection, which included partial clavicle and sternum removal, was performed. Pathological examination revealed foamy histiocytes along with numerous lymphoplasmacytic cells, confirming the diagnosis of XO. This case underscores the potential for XO to develop following kidney transplantation.

Analysis of single umbilical artery with concurrent congenital anomaly: Is it a risk factor for poor prognosis? A cross-sectional study.

Background: A single umbilical artery (SUA) may coexist with a single anomaly or multiple congenital anomalies. Although anomalies associated with SUA can primarily cause high perinatal mortality, their clinical significance has not been evaluated. Objective: We investigated the relationship between the clinical features and the type or number of concurrent anomalies in neonates with SUA. Materials and Methods: In this cross-sectional study, 104 neonates with SUA were enrolled from January 2000 to December 2020 at Dongsan hospital, Daegu, South Korea. Data on the maternal history and the neonates demographic characteristics, clinical course, chromosomal analysis, and congenital anomalies, were collected. Results: Among the neonates with SUA included, 77 (74.0%) had one or more congenital anomalies; 66 (63.5%) were cardiac, 20 (19.2%) were genitourinary, 12 (11.5%) were gastrointestinal, 5 (4.8%) were central nervous system, 12 (11.5%) were skeletal, and 5 (4.8%) were facial anomalies. The number of concurrent anomalies ranged from 0-4. Neonates with SUA and concurrent gastrointestinal anomaly had a high incidence of initial positive ventilation, intubation, and inotropic drug use and lower Apgar score at 1 min and 5 min. 7 (6.7%) neonates with SUA died. Low birth weight (odds ratio = 6.16, p = 0.05), maternal multiparity (2.41, p = 0.13), gastrointestinal anomaly (5.06, p = 0.11), and initial cardiac resuscitation (7.77, p = 0.11) were risk factors for mortality in neonates with SUA. Conclusion: Neonates with SUA and concurrent gastrointestinal anomaly, low birth weight, maternal multiparity, and initial cardiac resuscitation had poor outcomes.

Association between Neck Circumference and Chronic Kidney Disease in Korean Adults in the 2019-2021 Korea National Health and Nutrition Examination Survey.

Chronic kidney disease (CKD) is a major public health problem and a leading cause of cardiovascular disease and death. Early recognition and management of CKD risk factors are necessary to prevent its onset and progression. Neck circumference (NC) is a non-invasive and easily accessible anthropometric measure associated with central obesity and subcutaneous fat accumulation in the upper body. Our study aimed to explore the relationship between NC and the prevalence of CKD using data from the nationally representative Korea National Health and Nutrition Examination Survey (2019-2021). We analyzed data from 10,219 subjects (age > 19 years, no missing values). CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Logistic regression analysis was performed, which revealed a significant association between NC and CKD prevalence even after adjusting for confounding factors, both when NC was considered a continuous variable (OR [95% CI], 1.11 [1.03-1.19]) and in quartiles (Q1 as reference; Q2 OR [95% CI], 1.23 [0.91-1.67]; Q3 OR [95% CI], 1.59 [1.16-2.18]; Q4 OR [95% CI], 1.70 [1.16-2.50]). Our findings suggest that NC could be a simple and effective anthropometric measurement for identifying individuals at risk for CKD.

Assessment of the proarrhythmic effects of repurposed antimalarials for COVID-19 treatment using a comprehensive in vitro proarrhythmia assay (CiPA).

Due to the outbreak of the SARS-CoV-2 virus, drug repurposing and Emergency Use Authorization have been proposed to treat the coronavirus disease 2019 (COVID-19) during the pandemic. While the efficiency of the drugs has been discussed, it was identified that certain compounds, such as chloroquine and hydroxychloroquine, cause QT interval prolongation and potential cardiotoxic effects. Drug-induced cardiotoxicity and QT prolongation may lead to life-threatening arrhythmias such as torsades de pointes (TdP), a potentially fatal arrhythmic symptom. Here, we evaluated the risk of repurposed pyronaridine or artesunate-mediated cardiac arrhythmias alone and in combination for COVID-19 treatment through in vitro and in silico investigations using the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. The potential effects of each drug or in combinations on cardiac action potential (AP) and ion channels were explored using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and Chinese hamster ovary (CHO) cells transiently expressing cardiac ion channels (Nav1.5, Cav1.2, and hERG). We also performed in silico computer simulation using the optimized O'Hara-Rudy human ventricular myocyte model (ORd model) to classify TdP risk. Artesunate and dihydroartemisinin (DHA), the active metabolite of artesunate, are classified as a low risk of inducing TdP based on the torsade metric score (TMS). Moreover, artesunate does not significantly affect the cardiac APs of hiPSC-CMs even at concentrations up to 100 times the maximum serum concentration (Cmax). DHA modestly prolonged at APD90 (10.16%) at 100 times the Cmax. When considering Cmax, pyronaridine, and the combination of both drugs (pyronaridine and artesunate) are classified as having an intermediate risk of inducing TdP. However, when considering the unbound concentration (the free fraction not bound to carrier proteins or other tissues inducing pharmacological activity), both drugs are classified as having a low risk of inducing TdP. In summary, pyronaridine, artesunate, and a combination of both drugs have been confirmed to pose a low proarrhythmogenic risk at therapeutic and supratherapeutic (up to 4 times) free Cmax. Additionally, the CiPA initiative may be suitable for regulatory use and provide novel insights for evaluating drug-induced cardiotoxicity.

Dynamic nature and prognostic value of the neutrophil-to-lymphocyte ratio in critically ill patients with acute kidney injury on continuous renal replacement therapy: A multicenter cohort study.

Introduction: Patients with acute kidney injury (AKI) receiving renal replacement therapy constitute the subgroup of AKI with the highest risk of mortality. Despite recent promising findings on the neutrophil-to-lymphocyte ratio (NLR) in AKI, studies have not yet addressed the clinical implication of the NLR in this population. Therefore, we aimed to examine the prognostic value of NLR in critically ill patients requiring continuous renal replacement therapy (CRRT), especially focusing on temporal changes in NLR. Methods: We enrolled 1,494 patients with AKI who received CRRT in five university hospitals in Korea between 2006 and 2021. NLR fold changes were calculated as the NLR on each day divided by the NLR value on the first day. We performed a multivariable Cox proportional hazard analysis to assess the association between the NLR fold change and 30-day mortality. Results: The NLR on day 1 did not differ between survivors and non-survivors; however, the NLR fold change on day 5 was significantly different. The highest quartile of NLR fold change during the first 5 days after CRRT initiation showed a significantly increased risk of death (hazard ratio [HR], 1.65; 95% confidence intervals (CI), 1.27-2.15) compared to the lowest quartile. NLR fold change as a continuous variable was an independent predictor of 30-day mortality (HR, 1.14; 95% CI, 1.05-1.23). Conclusion: In this study, we demonstrated an independent association between changes in NLR and mortality during the initial phase of CRRT in AKI patients receiving CRRT. Our findings provide evidence for the predictive role of changes in the NLR in this high-risk subgroup of AKI.

Hydrophobically modified silica nanolaces-armored water-in-oil pickering emulsions with enhanced interfacial attachment energy.

HYPOTHESIS: Anisotropic particles with a high aspect ratio led to favorable interfacial adhesion, thus enabling Pickering emulsion stabilization. Herein, we hypothesized that pearl necklace-shaped colloid particles would play a key role in stabilizing water-in-silicone oil (W/S) emulsions by taking advantage of their enhanced interfacial attachment energy. EXPERIMENTS: We fabricated hydrophobically modified silica nanolaces (SiNLs) by depositing silica onto bacterial cellulose nanofibril templates and subsequently grafting alkyl chains with tuned amounts and chain lengths onto the nanograins comprising the SiNLs. FINDINGS: The SiNLs, of which nanograin has the same dimension and surface chemistry as the silica nanospheres (SiNSs), showed more favorable wettability than SiNSs at the W/S interface, which was supported by the approximately 50 times higher attachment energy theoretically calculated using the hit-and-miss Monte Carlo method. The SiNLs with longer alkyl chains from C6 to C18 more effectively assembled at the W/S interface to produce a fibrillary interfacial membrane with a 10 times higher interfacial modulus, preventing water droplets from coalescing and improving the sedimentation stability and bulk viscoelasticity. These results demonstrate that the SiNLs acted as a promising colloidal surfactant for W/S Pickering emulsion stabilization, thereby allowing the exploration of diverse pharmaceutical and cosmetic formulations.

Self-rated health and the risk of incident chronic kidney disease: a community-based Korean study.

BACKGROUND: The relationship between self-rated health (SRH) and the development of incident chronic kidney disease (CKD) has not been explored in the general population. METHODS: We reviewed the data of 7027 participants in the Ansung-Ansan cohort study. SRH was categorized as poor, fair, or good, and the outcome was the development of CKD, defined as the first event of an estimated glomerular filtration rate < 60 mL/min/1.73 m2, at least twice during the follow-up period. Hazard ratios (HRs) and confidence intervals (CIs) were calculated using Cox proportional hazards regression analysis. RESULTS: Over a mean follow-up duration of 11.9 years, 951 participants (13.5%) developed CKD. Compared with poor self-rated health, the HR (95% CI) of fair self-rated health for incident CKD development was 0.771 (0.657-0.905; P = 0.001), whereas that of good self-rated health was 0.795 (0.676-0.935; P = 0.006). However, the renal hazard of good self-rated health did not differ from that of fair self-rated health. In the fully adjusted model, the HR (95% CI) of poor self-rated health compared to non-poor self-rated health for incident CKD was 1.278 (1.114-1.465, P < 0.001). Old age, smoking, cardiovascular disease, diabetes, hypertension, impaired sleep, and high levels of C-reactive protein and white blood cell counts were associated with increased odds of poor self-rated health, whereas male sex, college graduate level of education, and alcohol consumption were associated with decreased odds of poor self-rated health. CONCLUSION: Poor self-rated health is independently associated with CKD development. Therefore, the early detection of potential CKD patients through a brief questionnaire assessment may help control the incidence of CKD.

The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea

Background@#Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. @*Methods@#From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. @*Results@#Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). @*Conclusion@#In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Recent Prevalence of and Factors Associated With Chronic Obstructive Pulmonary Disease in a Rapidly Aging Society: Korea National Health and Nutrition Examination Survey 2015–2019

Background@#The prevalence of chronic obstructive pulmonary disease (COPD) increases with age, and aging is an important risk factor for COPD development. In the era of global aging, demographic information about the prevalence of and factors associated with COPD are important to establish COPD care plans. However, limited information is available in rapidly aging societies, including Korea. @*Methods@#We conducted a cross-sectional observational study using Korea National Health and Nutrition Examination Survey data from 2015–2019. We included 15,613 participants and analyzed trends of and factors associated with COPD. @*Results@#During the study period, the overall prevalence of COPD was 12.9%. Over five years, the yearly prevalence of COPD was fairly constant, ranging from 11.5% to 13.6%. Among individuals aged ≥ 70 years, nearly one-third met COPD diagnostic criteria. In the multivariable analysis, age 70 years or older was the most strong factor associated with COPD (adjusted odds ratio [aOR], 17.86; 95% confidence interval [CI], 14.16–22.52; compared with age 40–49), followed by asthma (aOR, 3.39; 95% CI, 2.44–4.71), male sex (aOR, 2.64; 95% CI, 2.18–3.19), and current smokers (aOR, 2.60; 95% CI, 2.08–3.25). Additionally, exsmokers, low income, decreased forced expiratory volume in 1 second %pred, and a history of pulmonary tuberculosis were associated with COPD. On the other hand, body mass index (BMI) ≥ 25 kg/m 2 (aOR, 0.62; 95% CI, 0.54–0.71; compared with BMI 18.5–24.9 kg/m 2 ) had an inverse association with COPD. @*Conclusion@#Recent trends in the prevalence of COPD in South Korea are relatively stable.Approximately one-third of participants aged 70 years and older had COPD. Aging was the most important factor associated with COPD.

The Optimal Time between Embolization and Surgery for Hypervascular Spinal Metastatic Tumors : A Systematic Review and Meta-Analysis

Objective@#: Preoperative transarterial embolization (TAE) of tumor feeders in hypervascular spine metastasis is known to reduce intraoperative estimated blood loss (EBL) during surgery. The effect of TAE varies for several reasons, and one controllable factor is the timing between embolization and surgery. However, the adequate timing remains unclear. This study aimed to evaluate the timing and other factors that reduce EBL in spinal metastasis surgery through a meta-analysis. @*Methods@#: A comprehensive database search was performed to identify direct comparative studies of EBL stratified by the timing of surgery after TAE for spinal metastasis. EBL was analyzed according to the timing of surgery and other factors. Subgroup analyses were also performed. The difference in EBL was calculated as the mean difference (MD) and 95% confidence interval (CI). @*Results@#: Among seven studies, 196 and 194 patients underwent early and late surgery after TAE, respectively. The early surgery was defined as within 1–2 days after TAE, while the late surgery group received surgery at least 1 day after TAE. Overall, the MD in EBL was not different according to the timing of surgery (MD, 86.3 mL; 95% CI, -95.5 to 268.1 mL; p=0.35). A subgroup analysis of the complete embolization group demonstrated that patients who underwent early surgery within 24 hours after TAE had significantly less bleeding (MD, 233.3 mL; 95% CI, 76.0 to 390.5 mL; p=0.004). In cases of partial embolization, EBL was not significantly different regardless of the time interval. @*Conclusion@#: Complete embolization followed by early spinal surgery within 24 hours may reduce intraoperative bleeding for the patients with hypervascular spinal metastasis.

Resident Education on the Surgical Treatment of Distal Radius Fractures Using a Point-of-View Camera

Background@#In the coronavirus disease 2019 (COVID-19) era, surgical resident education depends largely on virtual materials.With the help of point-of-view (POV) cameras, educational videos have become widely used for surgical training. A video recorded from the surgeon’s POV helps demonstrate the procedure. We made training movies of the surgical approach to distal radius fractures for residents using a head-mounted video recording system with a laser point targeting device (LPTD). @*Methods@#A 15-minnute movie of the trans-flexor carpi radialis approach for distal radius fractures was made. A POV camera was assembled with an LPTD and strapped on the surgeon’s head. This enabled maintenance of the surgical field while recording the procedure. A shorter version of the clip was also made to investigate trainee preference. We asked 24 trainees to watch the two versions of the video and complete a short questionnaire. @*Results@#All trainees felt that the movie made with a POV camera was more efficient than existing materials. Only 1 (4.2%) felt that the laser pointer hindered the view. Four of the 23 trainees (16.7%) felt dizzy while watching the video. Of the two versions, 16 trainees (66.7%) preferred the shorter, edited version. The average score for the video was 8.42 out of 10. @*Conclusions@#A video recording system in the operating room that uses an LPTD-POV camera is an efficient way to produce educational material, particularly for surgical residents during the COVID-19 era.

PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer. @*Materials and Methods@#We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment. @*Results@#Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors. @*Conclusion@#Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Association between ischemic stroke and pyogenic spondylitis in Korea: Nationwide longitudinal cohort study

Objective@#The purpose of this nationwide age- and sex- matched longitudinal study was to determine the pyogenic spondylitis (PS) increases the incidence of ischemic stroke (IS) in Korea. @*Methods@#From the National Health Insurance Service (NHIS), we collected the patient data for the period from January 1, 2004 to December 31, 2015. PS was classified according to the International Classification of Disease codes M46.2-M46.8, M49.2, and M49.3. By using a 1:5 age- and sex- stratified matching, a total of 628 patients and 3140 control subjects were included in the study. The IS incidence rates in PS and control group was calculated by using the Kaplan-Meier method. The outcome of hazard ratio of IS was estimated by Cox proportional hazards regression analyses. This study did not exclude PS as a result of postoperative complications. @*Results@#According to the study, 51 patients (8.12%) in the PS group and 201 patients (6.4%) in the control group experienced IS. The adjusted hazard ratio of IS in the PS group was 3.419 (95% CI: 2.473-4.729) after adjusting individual medical condition and demographics. Following the results of subgroup analysis, the risk ratio of IS was greater in most of the subgroup categories (male, female, age 65, non-diabetic, hypertensive, non-hypertensive, dyslipidemic and non-dyslipidemic subgroup). However, the risk of IS did not differ significantly in diabetic subgroup (95% CI: 0.953-4.360). @*Conclusions@#The risk rate of IS increased in patient with pyogenic spondylitis.

Spinal Sagittal Imbalance is Associated with Vertebral Fracture without a Definite History of Falls: Cross-Sectional, Comparative Study of Cohort with and without a Distal Radius Fracture

Background@#Treating osteoporosis in patients with a distal radius fracture (DRF) became paramount at the Fracture Liaison Service. Spinal sagittal imbalance emerged as a risk factor for subsequent fractures. Therefore, here we investigated the spinal profile of patients with DRF to investigate its association with a history of falls and prevalent vertebral fractures. @*Methods@#We reviewed the cases of 162 women presenting with DRF and 162 age-matched women without fracture who underwent an osteoporosis evaluation including bone mineral density (BMD) and lateral spine imaging. We compared the incidence of prevalent vertebral fracture and sagittal vertical axis (SVA) to measure spinal sagittal imbalance. We also performed a regression analysis of the risks of prevalent vertebral fracture, such as age, body mass index (BMI), BMD, and SVA. @*Results@#The SVA was significantly smaller (indicating more stable sagittal balance) in patients with a DRF versus controls (16 mm vs. 34 mm, respectively; p<0.001). The incidence of a prevalent vertebral fracture was similar between groups (12% vs. 15%, respectively; p=0.332). In both groups, the SVA was significantly greater in those with versus without a vertebral fracture. The vertebral fracture was significantly associated with age and SVA but not BMI or spinal BMD. @*Conclusions@#Spinal sagittal balance was superior in DRF patients, yet the frequency of prevalent vertebral fractures was similar. The identification of this unique spinal profile in patients with DRF may increase our understanding of osteoporotic fractures.

Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids

In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell–cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.

The Essential Function of miR-5739 in Embryonic Muscle Development

Background and Objectives@#Embryologically, mesodermal development is closely related to the development of various organs such as muscles, blood vessels, and hearts, which are the main organs that make up the body. However, treatment for mesoderm developmental disorders caused by congenital or acquired factors has so far relied on surgery and drug treatment for symptom relief, and more fundamentally, treatment for mesoderm developmental disorders is needed. @*Methods@#and Results: In our study, microRNA (miRNA), which plays an important role in the mesoderm development process, was identified and the developmental function was evaluated. miRNAs consist of small nucleotides, which act as transcription factors that bind to the 3’ untranslated region and suppressed target gene expression. We constructed the human embryonic stem cell (hESC) knockout cell line and analyzed the function and characteristics of miR-5739, which plays an important role in mesoderm lineage. miR-5739 acts as a transcription factor targeting SMA, Brachyury T, Hand1, which controls muscle proliferation and differentiation, and KDR gene, which regulates vessel formation in vitro. In vivo results suggest a role in regulating muscle proliferation and differentiation. Gene ontology analysis confirmed that the miR-5739 is closely related to genes that regulate muscle and vessel proliferation and differentiation. Importantly, abnormal expression of miR-5739 was detected in somatic cells derived from patients with congenital muscle disease. @*Conclusions@#Our study demonstrate that miR-5739 gene function significantly affects transcriptional circuits that regu-late muscle and vascular differentiation during embryonic development.

Development and Verification of Time-Series Deep Learning for Drug-Induced Liver Injury Detection in Patients Taking Angiotensin II Receptor Blockers: A Multicenter Distributed Research Network Approach / 대한의료정보학회지

Objectives@#The objective of this study was to develop and validate a multicenter-based, multi-model, time-series deep learning model for predicting drug-induced liver injury (DILI) in patients taking angiotensin receptor blockers (ARBs). The study leveraged a national-level multicenter approach, utilizing electronic health records (EHRs) from six hospitals in Korea. @*Methods@#A retrospective cohort analysis was conducted using EHRs from six hospitals in Korea, comprising a total of 10,852 patients whose data were converted to the Common Data Model. The study assessed the incidence rate of DILI among patients taking ARBs and compared it to a control group. Temporal patterns of important variables were analyzed using an interpretable timeseries model. @*Results@#The overall incidence rate of DILI among patients taking ARBs was found to be 1.09%. The incidence rates varied for each specific ARB drug and institution, with valsartan having the highest rate (1.24%) and olmesartan having the lowest rate (0.83%). The DILI prediction models showed varying performance, measured by the average area under the receiver operating characteristic curve, with telmisartan (0.93), losartan (0.92), and irbesartan (0.90) exhibiting higher classification performance. The aggregated attention scores from the models highlighted the importance of variables such as hematocrit, albumin, prothrombin time, and lymphocytes in predicting DILI. @*Conclusions@#Implementing a multicenter-based timeseries classification model provided evidence that could be valuable to clinicians regarding temporal patterns associated with DILI in ARB users. This information supports informed decisions regarding appropriate drug use and treatment strategies.

The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study

Background@#To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM). @*Methods@#This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints. @*Results@#A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185). @*Conclusion@#In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Importance of Whole-Body Scintigraphy or Positron Emission Tomography for Early Detection of Femoral Lesions in Breast Cancer Patients Treated with Bisphosphonates

Background@#We hypothesized that most of the atypical femoral fractures (AFFs) associated with bisphosphonate treatment for breast cancer (BC) could be found before the fracture event in another radiological examination already performed by breast surgeons, rather than on simple radiographs (SRs). @*Methods@#We thoroughly inspected the clinical charts of BC patients treated at our institute between 2008 and 2017. In total, 228 patients were categorized into three groups based on SRs: complete AFF on at least one side (group 1); incomplete fracture on at least one side, but not any complete fracture (group 2); and no suspicious lesion (group X) on either femur. Then, we inspected whole-body scintigraphy (WBS) and positron emission tomography (PET)-computed tomography (CT) images in all groups. For group X, patients with radiological clues from at least one femur were categorized, ultimately, into final group 3 and the rest made up the normal group. @*Results@#About 35% of the patients showed AFFs (complete or incomplete) or suspicious lesions as AFFs, associated with the side effect of Bisphosphonate. In group 1, bilateral lesions (complete or incomplete fractures) were more frequently seen on SRs than unilateral lesions (p = 0.008). The initially identified findings in WBS and PET-CT for the respective complete and incomplete fractures on SRs of groups 1 and 2 were seen at a mean of 7 months previously. SRs did not reveal the lesions in group 3 until 5 months after the initial identification of the lesions in WBS and PET-CT. @*Conclusions@#Even before incomplete AFFs were detectable on SRs, they could be found at check-ups using WBS and PET-CT that had been previously examined by breast surgeons and radiologists for metastasis surveillance. Awareness of the lesions creates an opportunity for prophylactic surgery before complete fractures occur.

Machine Learning Algorithms for the Prediction of Locomotor Activity by an Infrared Motion Detector on the Sleep-wake States in Mice

Objective@#Even though studies using machine learning on sleep-wake states have been performed, studies in various conditions are still necessary. This study aimed to examine the performance of the prediction model of locomotor activities on sleep-wake states using machine learning algorithms. @*Methods@#The processed data using moving average of locomotor activities were used as predicting features. The sleep-wake states were used as true labels. The prediction models were established by machine learning classifiers such as support vector machine with radial basis function (SVM-RBF), linear discriminant analysis (LDA), naïve Bayes, and random forest (RF). The prediction model was evaluated by a six-fold cross validation. @*Results@#The SVM-RBF and RF showed acceptable performance within a window of moving average from 480 to 1,200 seconds. The highest accuracy (0.869) was shown by the RF at the interval of 480 seconds. Meanwhile, the highest area under the curve (0.939) was shown by LDA at the interval of 870 seconds. @*Conclusion@#This study suggested that the prediction model on sleep-wake state using machine learning could show an improvement of the model performance when using moving average with raw data. The prediction model using locomotor activity can be useful in research on sleep-wake state.