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Ji Young Kang, Sook Young Lee, Chin Kook Rhee, Seung Joon Kim, Soon Seog Kwon, Young Kyoon KimDepartment of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground and objectives: The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma. Methods: Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA) for 1 month (n = 8–12 per group). We analyzed inflammatory cells and T-helper (Th)2 cytokines in bronchoalveolar lavage (BAL) fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue. Results: Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old) mice than in the young (6-week-old) mice. Interleukin (IL) 4 (IL-4) concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. periodic acid-Schiff (PAS) staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age. Conclusion: The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice.Keywords: aging, asthma, airway remodeling, muscarinic receptor

Childhood trauma can cause deficits in emotional regulation. However, few studies have investigated childhood trauma and emotional regulation skills in patients with mood disorders. We aimed to investigate how childhood trauma and Emotion Regulation Skills Questionnaire (ERSQ) scores are associated with mood disorders.This study included 779 patients with mood disorders (major depressive disorder [MDD, n = 240], bipolar I disorder [BDI, n = 121], and bipolar II disorder [BDII, n = 418]). We used their Childhood Trauma Questionnaire-Short Form (CTQ) and ERSQ scores for the evaluation.The between-group differences in CTQ and ERSQ scores were examined. The CTQ and ERSQ total scores were negatively correlated. Among the CTQ subscales, emotional neglect showed a significant correlation with the ERSQ total score, whereas acceptance and tolerance showed higher negative correlations with the CTQ than with the other ERSQ subscales. The negative relationship between emotional regulation and childhood trauma varied significantly depending on the group, with the BDI group showing a more prominent association than the other groups.Based on various mood disorders, we observed associations between childhood trauma and emotional regulation skills. Consequently, our study offers notable insights for future research on the impact of childhood trauma on ERSQ.

Background: Although ABO-incompatible liver transplantation (ABOi LT) has undergone remarkable progress, the prognostic factors are poorly understood. This study aimed to elucidate the preoperative factors affecting graft survival after ABOi LT., Methods: Patients who underwent ABOi LT between January 2012 and December 2020 at a single institution in South Korea were retrospectively reviewed. A total of 146 recipients, including 34 patients with graft loss, were analyzed., Results: In the multivariate Cox proportional hazard model, recipient age (≥55 y; hazard ratio, 2.47; 95% confidence interval, 1.18-5.19; P = 0.017) and donor ABO type (donor A, hazard ratio, 3.12; 95% confidence interval, 1.33-7.33; P = 0.009) were significantly associated with an increased risk of graft loss. The most common cause of graft loss was recipient death due to bacterial infection (15/34, 44.1%). Both recipient age and donor ABO type were associated with an increased risk of recipient death due to bacterial infections. The incidence of complications after ABOi LT, including antibody-mediated rejection and diffuse intrahepatic biliary stricture, did not differ according to recipient age or donor ABO type., Conclusions: These findings suggest that recipient age and donor ABO type should be considered when preparing for ABOi LT. Careful monitoring and care after transplantation are required for recipients with preoperative risk factors., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Transcranial direct current stimulation (tDCS) has been proposed as a new treatment in major depressive disorder (MDD). This is a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of 10-week home-based tDCS in MDD. Participants were 18 years or older, with MDD in current depressive episode of at least moderate severity as measured using the Hamilton Depression Rating Scale (mean = 19.07 ± 2.73). A total of 174 participants (120 women, 54 men) were randomized to active (n = 87, mean age = 37.09 ± 11.14 years) or sham (n = 87, mean age = 38.32 ± 10.92 years) treatment. tDCS consisted of five sessions per week for 3 weeks then three sessions per week for 7 weeks in a 10-week trial, followed by a 10-week open-label phase. Each session lasted 30 min; the anode was placed over the left dorsolateral prefrontal cortex and the cathode over the right dorsolateral prefrontal cortex (active tDCS 2 mA and sham tDCS 0 mA, with brief ramp up and down to mimic active stimulation). As the primary outcome, depressive symptoms showed significant improvement when measured using the Hamilton Depression Rating Scale: active 9.41 ± 6.25 point improvement (10-week mean = 9.58 ± 6.02) and sham 7.14 ± 6.10 point improvement (10-week mean = 11.66 ± 5.96) (95% confidence interval = 0.51-4.01, P = 0.012). There were no differences in discontinuation rates. In summary, a 10-week home-based tDCS treatment with remote supervision in MDD showed high efficacy, acceptability and safety. ClinicalTrials.gov registration: NCT05202119., (© 2024. The Author(s).)

Background: Severe forms of depression have been linked to excessive subcallosal cingulate (SCC) activity. Stimulation of SCC with surgically implanted electrodes can alleviate depression, but current noninvasive techniques cannot directly and selectively modulate deep targets. We developed a new noninvasive neuromodulation approach that can deliver low-intensity focused ultrasonic waves to the SCC., Methods: Twenty-two subjects with treatment-resistant depression participated in a randomized, double-blind, sham-controlled study. Ultrasonic stimulation was delivered to bilateral SCC during concurrent functional MRI to quantify target engagement. Mood state was measured with the Sadness subscale of the Positive and Negative Affect Schedule before and after 40 minutes of real or sham SCC stimulation. Change in depression severity was measured with the 6-item Hamilton Depression Rating Scale (HDRS- 6) at 24 hours and 7 days., Results: Functional MRI demonstrated a target-specific decrease in SCC activity during stimulation (p=0.028, n=16). In 7 of 16 participants, SCC neuromodulation was detectable at the individual-subject level with a single 10-minute scan (p<0.05, small-volume-correction). Mood and depression scores improved more with real than with sham stimulation. In the per-protocol sample (n=19), real stimulation was superior to sham for HDRS-6 at 24 hours and for Sadness (both p<0.05, d>1). Non-significant trends were found in the intent-to-treat sample., Conclusions: This small pilot study indicates that ultrasonic stimulation modulates SCC activity and can rapidly reduce depressive symptoms. The capability to noninvasively and selectively target deep brain areas creates new possibilities for future development of circuit-directed therapeutics, and for the dissection of deep-brain circuit function in humans., (Copyright © 2024. Published by Elsevier Inc.)

The effect of the duration of red blood cell (RBC) storage on the outcomes of transfused patients remains controversial, and studies on patients in the emergency department (ED) are limited. This study aimed to determine the association between RBC storage duration and outcomes of patients receiving transfusions in the ED. For RBCs issued to patients in the ED between 2017 and 2022, the storage period of the RBC and data on the transfused patient were obtained. Patients were divided into fresh (≤ 7 days) and old (> 7 days) RBC groups, and the associations between storage duration, outcomes, and laboratory changes were evaluated. There was no significant difference in outcomes between the two groups in the 28-day mortality (adjusted odds ratio [OR] 0.91, 95% confidence interval [CI] 0.75-1.10, P = 0.320) and the length of stay (fresh 13.5 ± 18.1 vs. old 13.3 ± 19.8, P = 0.814). Regarding changes in laboratory test results, the increase in hemoglobin and hematocrit levels was not affected by the storage durations. The study revealed that transfusion of older RBCs is not associated with inferior outcomes or adverse clinical consequences when compared to that of fresh RBCs in patients in the ED., (© 2024. The Author(s).)

Background: The Jr a antigen is a high-prevalence red blood cell (RBC) antigen. Reports on cases of fatal hemolytic disease of the fetus and newborn and acute hemolytic transfusion reactions suggest that antibodies against Jr a (anti-Jr a ) have potential clinical significance. Identifying anti-Jr a is challenging owing to a lack of commercially available antisera. We developed an alternative approach to rapidly predict the presence of anti-Jr a using the TaqMan single-nucleotide polymorphism (SNP)-genotyping method., Methods: Residual peripheral blood samples from 10 patients suspected of having the anti-Jr a were collected. Two samples with confirmed Jr(a-) RBCs and anti-Jr a were used to validate the TaqMan genotyping assay by comparing the genotyping results with direct sequencing. The accuracy of the assay in predicting the presence of anti-Jr a was verified through crossmatching with in-house Jr(a-) O+ RBCs., Results: The TaqMan-genotyping method was validated with two Jr(a-) RBC- and anti-Jr a -confirmed samples that showed concordant Jr a genotyping and direct sequencing results. Jr a genotyping for the remaining samples and crossmatching the serum samples with inhouse Jr(a-) O+ RBCs showed consistent results., Conclusions: We validated a rapid, simple, accurate, and cost-effective method for predicting the presence of anti-Jr a using a TaqMan-based SNP-genotyping assay. Implementing this method in routine practice in clinical laboratories will assist in solving difficult problems regarding alloantibodies to high-prevalence RBC antigens and ultimately aid in providing safe and timely transfusions and proper patient care.

Background & Objective: Epilepsy has long been associated with stigma and misconceptions. In response, the Korean Epilepsy Society initiated the Epilepsy Renaming project in 2008 to replace the stigmatizing term with a neutral and scientifically grounded name, "cerebroelectric disorder". This study explores the impact of changing terminology on the public discourse surrounding epilepsy., Methods: Online news articles from distinct time periods (2001-2003, 2011-2014, 2017-2018, and 2020-2022) were analyzed using text data analysis techniques, including Latent Dirichlet Allocation topic modeling, frequency analysis, and sentiment analysis. The inclusion of data from 2017 to 2018 allowed for an examination of discourse trends independent of the COVID-19 pandemic's influence. Correlation of words in each period was visualized via network maps. Migraine was set as control term to highlight changes in perception devoid of significant stigma intervention efforts., Results: The analysis revealed a significant shift in terminology preference, with cerebroelectric disorder gradually replacing epilepsy in news articles. The discourse surrounding epilepsy evolved over time from focusing on healthcare and economic aspects to patient-centered discussions, emphasizing the daily lives of individuals with epilepsy. This shift towards more empathetic and less stigmatized language was contrasted against the discourse on migraine, highlighting the specific impact of the terminological change on epilepsy's perception., Conclusion: The adoption of the neutral term "cerebroelectric disorder" in South Korea has influenced the discourse surrounding epilepsy, leading to more patient-centered discussions and a reduction in stigma. This study highlights the importance of terminology in shaping public perceptions of diseases and suggests that changing terminology can positively impact the understanding and destigmatization of epilepsy., 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 Inc. All rights reserved.)

Background: Regarding the pathophysiology of renal infarction (RI), cardioembolic causes could have large proportion. However, there are notable variations in prevalence of atrial fibrillation (AF) among patients with RI across different studies, ranging from 17 to 65%. The primary objective of this study is to analyze the incidence of AF in patients with RI., Methods: This nationwide retrospective cohort study enrolled 5200 patients with RI from the Korean National Institute of Health Services database spanning the years 2013 to 2019. The study accessed the AF incidence rate within 12 months in patients without a prior history of AF. Events occurring within 3 months of RI diagnosis were excluded to mitigate cases diagnosed during the initial screening or those with AF diagnoses that were potentially overlooked in the past., Results: AF occurred in 19.1% of patients with RI over the entire period (median: 2.5 years, interquartile range 1.04-4.25 years). The majority of AF cases (16.1%) occured within the first year, resulting in an overall incidence rate of 7.0 per 100 person-years. Patients with newly developed AF were, on average, older than those who did not develop AF (64.1 vs. 57.3 years, P < 0.001). The independent predictors of AF were identified as age, male sex, higher body mass index, current smoking, ischemic heart disease, and heart failure., Conclusions: Physicians should consider the implementation of active rhythm monitoring for patients with RI to identify potential occurrence of subclinical AF, even if not initially diagnosed during the initial screening after RI diagnosis., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

Background: The rotational change after using a flexible intramedullary (IM) nail for femoral shaft fractures has been a concern for many surgeons. Recently, a statistical shape model (SSM) was developed for the three-dimensional reconstruction of the femur from two-dimensional plain radiographs. In this study, we measured postoperative femoral anteversion (FAV) in patients diagnosed with femoral shaft fractures who were treated with flexible IM nails and investigated age-related changes in FAV using the SSM., Methods: This study used radiographic data collected from six regional tertiary centers specializing in pediatric trauma in South Korea. Patients diagnosed with femoral shaft fractures between September 2002 and June 2020 and patients aged < 18 years with at least two anteroposterior (AP) and lateral (LAT) femur plain radiographs obtained at least three months apart were included. A linear mixed model (LMM) was used for statistical analysis., Results: Overall, 72 patients were included in the study. The average patient age was 7.6 years and the average follow-up duration was 6.8 years. The average FAV of immediate postoperative images was 27.5 ± 11.5°. Out of 72 patients, 52 patients (72.2%) showed immediate postoperative FAV greater than 20°. The average FAV in patients with initial FAV > 20° was 32.74°, and the LMM showed that FAV decreased by 2.5° (p = 0.0001) with each 1-year increase from the time of initial trauma., Conclusions: This study explored changes in FAV after femoral shaft fracture using a newly developed technology that allows 3D reconstruction from uncalibrated 2D images. There was a pattern of change on the rotation of the femur after initial fixation, with a 2.5° decrease of FAV per year., (© 2024. The Author(s).)

Background: Epicardial adipose tissue (EAT) is associated with the development of cardiovascular disease and long-term survival. This study aimed to assess the characteristics of EAT according to the metabolic health and obesity status using low-dose chest computed tomography (CT)., Methods: A total of 1074 asymptomatic adults who underwent a medical health check-up were enrolled. Subjects were categorized into the following four groups according to the metabolic health and obesity status: metabolically healthy non-obese (MHNO); metabolically unhealthy non-obese (MUNO); metabolically healthy obese (MHO); and metabolically unhealthy obese (MUO). EAT on low-dose chest CT was measured by using automatic, quantitative measurement software., Results: MUO showed the highest EAT volume and lowest EAT radiodensity in comparison with MHNO (p < 0.001). The MUNO (n = 70), MHO (n = 259), and MUO (n = 231) groups had increased EAT volume (β [95 % CI], 37.65 [23.11,52.18], 56.79 [47.56,66.02], 84.85 [74.59,95.11] respectively, all p < 0.001), decreased EAT radiodensity (β [95 % CI], - 3.22 [- 4.59,- 1.85], - 4.48 [- 5.30,- 3.66], - 6.03 [- 6.90,- 5.16] respectively, all p < 0.001) in comparison with the MHNO (n = 514) group by using multivariable linear regression models., Conclusions: Both metabolic abnormalities and obesity were closely associated with EAT characteristics. Characteristics of EAT are similar in MHO and MUNO. This finding suggests that MHO is not a favorable condition in terms of cardiac health, as assessed by the characteristics of EAT. The combination of obesity and metabolically unhealthy status has a synergistic adverse effect on EAT. Measurement of EAT could be a useful imaging biomarker for evaluation of an individual's metabolic health/obesity status., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Peripheral blood stem cell transplantation (PBSCT) is an important therapeutic measure for both hematologic and non-hematologic diseases. For PBSCT to be successful, sufficient CD34 + cells need to be mobilized and harvested. Although risk factors associated with poor mobilization in patients with hematologic diseases have been reported, studies of patients with non-hematologic diseases and those receiving plerixafor are rare. To identify factors associated with poor mobilization, data from autologous PBSC harvest (PBSCH) in 491 patients were retrospectively collected and analyzed. A multivariate analysis revealed that in patients with a hematologic disease, an age older than 60 years (odds ratio [OR] 1.655, 95% confidence interval [CI] 1.049-2.611, p = 0.008), the use of myelotoxic agents (OR 4.384, 95% CI 2.681-7.168, p < 0.001), and a low platelet count (OR 2.106, 95% CI 1.205-3.682, p = 0.009) were associated with poor mobilization. In patients with non-hematologic diseases, a history of radiation on the pelvis/spine was the sole associated factor (OR 12.200, 95% CI 1.934-76.956, p = 0.008). Among the group of patients who received plerixafor, poor mobilization was observed in 19 patients (19/134, 14.2%) and a difference in the mobilization regimen was noted among the good mobilization group. These results show that the risk factors for poor mobilization in patients with non-hematologic diseases and those receiving plerixafor differ from those in patients with hematologic diseases; as such, non-hematologic patients require special consideration to enable successful PBSCH.

Objective: Serum hemoglobin (Hb) level affects the viscosity of blood. Several studies have reported that Hb level is associated with adverse cardiovascular outcome. However, there is a paucity of evidence on the association between serum Hb level and the risk of subclinical atherosclerosis. Thus, the objective of this study was to investigate the relationship between Hb level and risk of carotid plaque in a health checkup cohort., Methods: This retrospective study analyzed a total of 3,805 individuals without history of cardiovascular disease (CVD) who underwent carotid ultrasonography (USG) between January 2016 and June 2018. Participants were divided into 4 groups based on Hb quartiles in each of male and female. Carotid plaque score was calculated based on USG reports. Multivariable logistic regression analysis was performed for each index of quartile groups regarding the risk of carotid plaque., Results: Of 3,805 individuals (mean age, 52.62±10.25 years; 2,674 [70.28%] males), mean Hb level was 15.11±0.75 g/dL in male and 13.35±0.74 g/dL in female. When the Q1 group was compared to the Q4, increasing quartile of Hb was associated with the presence of significant carotid plaque (plaque score ≥3) in male (adjusted odds ratio [OR], 1.538; 95% confidence interval [CI], 1.182-2.001; p =0.001) and female (adjusted OR, 1.749; 95% CI, 1.058-2.676; p =0.01)., Conclusion: A high Hb level is associated with an increased risk of carotid plaques in individuals without history of CVD. This finding may support the need for early screening of CVD in individuals with high Hb levels., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (© 2024 The Korean Society of Lipid and Atherosclerosis.)

Childhood trauma and interpersonal sensitivity impact the development of mood disorders. In this study, we investigate the association between childhood trauma and interpersonal sensitivity in patients with mood disorders. A total 775 patients (major depressive disorder [MDD, n = 241], bipolar I disorder [BD I, n = 119], and bipolar II disorder [BD II, n = 415]) and 734 controls. For evaluation, we used the Childhood Trauma Questionnaire-Short Form (CTQ) and Interpersonal Sensitivity Measure (IPSM). We examined between-group differences for each subscale in the CTQ and IPSM. Patients with BD II had significantly higher IPSM total scores than patients with MDD, BD I, or controls. The CTQ total score was related to the IPSM total score in all participants and subgroups. Among the CTQ subscales, emotional abuse showed the highest correlation with the IPSM total score, while separation anxiety and fragile inner self showed higher positive correlations with CTQ than the other subscales of IPSM in all patient groups and the control group, respectively. The findings reveal that childhood trauma and interpersonal sensitivity are positively correlated among patients with MDD, BD I, and BD II, and that interpersonal sensitivity is higher in patients with BD II than those with BD I or MDD. Childhood trauma is associated with interpersonal sensitivity, and each trauma type has a different impact on mood disorders. We expect that this study will encourage future research on interpersonal sensitivity and childhood trauma in mood disorders to improve treatment approaches., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Abstract: ABO antigen weakness is rarely observed in ABO typing for transfusion. Hematologic diseases and associated gene mutations have been suggested as potential causes of this phenomenon, yet the precise etiology has not been elucidated. Through ABO typing and genetic analysis data conducted over 7 years, we have reconfirmed the association between ABO antigen weakness and hematologic diseases, especially acute myeloid leukemia (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.12-5.83) and myelodysplastic syndrome (OR, 6.94; 95% CI, 2.86-16.83), and discovered previously unidentified candidate genes, CEBPA (OR, 43.70; 95% CI, 18.12-105.40), NRAS (OR, 3.37; 95% CI, 1.46-7.79), U2AF1 (OR, 8.12; 95% CI, 2.86-23.03), and PTPN11 (OR, 4.52; 95% CI, 1.51-13.50), seemingly associated with this phenomenon. Among these, CEBPA double mutations displayed a significant association, with ABO antigen weakness being observed in 20 of the 25 individuals (80.0%) possessing these mutations. From this study, new factors associated with ABO antigen weakness have been identified., (© 2024 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.)

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee 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.)

Objective: We aimed to identify common genes and recurrent causative variants in a large group of Asian patients with different epilepsy syndromes and subgroups., Methods: Patients with unexplained pediatric-onset epilepsy were identified from the in-house Severance Neurodevelopmental Disorders and Epilepsy Database. All patients underwent either exome sequencing or multigene panels from January 2017 to December 2019, at Severance Children's Hospital in Korea. Clinical data were extracted from the medical records., Results: Of the 957 patients studied, 947 (99.0%) were Korean and 570 were male (59.6%). The median age at testing was 4.91 years (interquartile range, 1.53-9.39). The overall diagnostic yield was 32.4% (310/957). Clinical exome sequencing yielded a diagnostic rate of 36.9% (134/363), whereas the epilepsy panel yielded a diagnostic rate of 29.9% (170/569). Diagnostic yield differed across epilepsy syndromes. It was high in Dravet syndrome (87.2%, 41/47) and early infantile developmental epileptic encephalopathy (60.7%, 17/28), but low in West syndrome (21.8%, 34/156) and myoclonic-atonic epilepsy (4.8%, 1/21). The most frequently implicated genes were SCN1A (n = 49), STXBP1 (n = 15), SCN2A (n = 14), KCNQ2 (n = 13), CDKL5 (n = 11), CHD2 (n = 9), SLC2A1 (n = 9), PCDH19 (n = 8), MECP2 (n = 6), SCN8A (n = 6), and PRRT2 (n = 5). The recurrent genetic abnormalities included 15q11.2 deletion/duplication (n = 9), Xq28 duplication (n = 5), PRRT2 deletion (n = 4), MECP2 duplication (n = 3), SCN1A, c.2556+3A>T (n = 3), and 2q24.3 deletion (n = 3)., Significance: Here we present the results of a large-scale study conducted in East Asia, where we identified several common genes and recurrent variants that varied depending on specific epilepsy syndromes. The overall genetic landscape of the Asian population aligns with findings from other populations of varying ethnicities., (© 2023 International League Against Epilepsy.)

Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase the susceptibility of individuals to AT-DILI and to examine genetic interactions that may lead to isoniazid (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis of 380 pharmacogenes in a discovery cohort of 112 patients (35 AT-DILI patients and 77 controls) receiving AT treatment for active tuberculosis. Pharmacogenome-wide association analysis was also conducted using 1048 population controls (Korea1K). NAT2 and ATP7B genotypes were analyzed in a replication cohort of 165 patients (37 AT-DILI patients and 128 controls) to validate the effects of both risk genotypes. NAT2 ultraslow acetylators (UAs) were found to have a greater risk of AT-DILI than other genotypes (odds ratio [OR] 5.6 [95% confidence interval; 2.5-13.2], P = 7.2 × 10 -6 ). The presence of ATP7B gene 832R/R homozygosity (rs1061472) was found to co-occur with NAT2 UA in AT-DILI patients (P = 0.017) and to amplify the risk in NAT2 UA (OR 32.5 [4.5-1423], P = 7.5 × 10 -6 ). In vitro experiments using human liver-derived cell lines (HepG2 and SNU387 cells) revealed toxic synergism between INH and Cu, which were strongly augmented in cells with defective NAT2 and ATP7B activity, leading to increased mitochondrial reactive oxygen species generation, mitochondrial dysfunction, DNA damage, and apoptosis. These findings link the co-occurrence of ATP7B and NAT2 genotypes to the risk of INH-induced hepatotoxicity, providing novel mechanistic insight into individual AT-DILI susceptibility. Yoon et al. showed that individuals who carry NAT2 UAs and ATP7B 832R/R genotypes are at increased risk of developing isoniazid hepatotoxicity, primarily due to the increased synergistic toxicity between isoniazid and copper, which exacerbates mitochondrial dysfunction-related apoptosis., (© 2024. The Author(s).)

Background: Patient safety incidents lead to performance difficulties for nurses when providing nursing practice. This affects work-life balance and causes second and third-victimization. This study predicts factors affecting clinical nurses' work-life balance due to patient safety incidents using classification and regression tree analysis techniques., Methods: This study was a secondary analysis of data from a cohort research project, which used a descriptive survey for data collection. Participants comprised 372 nurses. Data were collected using SurveyMonkey, a mobile-based survey software solution, from January to September 2021. Data included the general characteristics of clinical nurses, second damage, second damage support, third damage, and work-life balance. The specific variables included in the analysis chosen through rigorous Lasso analysis form the foundation for predicting work-life balance. Variables with low explanatory power were excluded, thereafter, the variables selected by Lasso were analyzed with a classification and regression tree model to predict work-life balance., Results: A regression tree was applied to predict work-life balance using seven variables-education level, marital status, position, physical distress, second-victim support, turnover intentions, and absenteeism (selected through Lasso analysis). After pruning, at tree size four, when turnover intentions were < 4.250, physical distress < 2.875, and second-victim support < 2.345, the predicted work-life balance was 3.972. However, when turnover intentions were < 4.250, physical distress < 2.875, and second-victim support ≥ 2.345, then the predicted work-life balance was 2.760., Conclusions: This study's insights offer crucial groundwork for crafting targeted workforce risk management strategies and fostering a conducive organizational culture to mitigate nursing occupational stress, potentially curbing the recurrence of patient safety incidents and improving nursing practice while enhancing patient outcomes. Future research should explore second and third victim experiences across various healthcare settings globally to understand their impact on WLB and patient safety outcomes., (© 2024. The Author(s).)

Introduction: The role of inflammation in the pathophysiology of polycythemia vera (PV) is important. The presence of JAK2 mutations is important in the diagnosis of PV, and serum levels of erythropoietin (EPO) also play a supporting role. However, serum EPO levels show some limitations. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are a readily available marker of inflammation. Thus, we examined whether NLR & PLR might diagnose PV in erythrocytosis patients. We compared NLR & PLR and EPO diagnostic values., Methods: We retrospectively reviewed clinical and laboratory data from two referral hospitals. Two hundred and eighty-five patients with erythrocytosis who underwent a test for the JAK2 mutation were included. It wac classified as the PV group and the secondary polycythemia (SP) group., Results: The median NLR & PLR in the PV group (n = 70) was significantly higher than that in the SP group (n = 170) (NLR: 6.04 vs. 1.77, PLR: 283.18 vs. 101.56, respectively, p < 0.001). In the receiver operating characteristic analysis, the area under the curve of NLR & PLR was significantly higher than that of serum EPO (NLR vs EPO: 0.921 vs. 0.827, p = 0.003; PLR vs EPO: 0.917 vs 0.827, p = 0.003)., Conclusion: In conclusion, NLR & PLR were higher in PV than in SP and showed better diagnostic value than serum EPO level, highlighting their potential as minor diagnostic criteria in patients with PV., (© 2023 John Wiley & Sons Ltd.)

Background: The Gross Motor Function Classification System (GMFCS) is a widely used tool for assessing the mobility of people with Cerebral Palsy (CP). It classifies patients into different levels based on their gross motor function and its level is typically determined through visual evaluation by a trained expert. Although gait analysis is commonly used in CP research, the functional aspects of gait patterns has yet to be fully exploited. By utilizing the gait patterns to predict GMFCS, we can gain a more comprehensive understanding of how CP affects mobility and develop more effective interventions for CP patients., Result: In this study, we propose a multivariate functional classification method to examine the relationship between kinematic gait measures and GMFCS levels in both normal individuals and CP patients with varying GMFCS levels. A sparse linear functional discrimination framework is utilized to achieve an interpretable prediction model. The method is generalized to handle multivariate functional data and multi-class classification. Our method offers competitive or improved prediction accuracy compared to state-of-the-art functional classification approaches and provides interpretable discriminant functions that can characterize the kinesiological progression of gait corresponding to higher GMFCS levels., Conclusion: We generalize the sparse functional linear discrimination framework to achieve interpretable classification of GMFCS levels using kinematic gait measures. The findings of this research will aid clinicians in diagnosing CP and assigning appropriate GMFCS levels in a more consistent, systematic, and scientifically supported manner., (© 2023. The Author(s).)

Background: Variants in the dynamin-1 ( DNM1 ) gene typically cause synaptopathy, leading to developmental and epileptic encephalopathy (DEE). We aimed to determine the genotypic and phenotypic spectrum of DNM1 encephalopathy beyond DEE., Methods: Electroclinical phenotyping and genotyping of patients with a DNM1 variant were conducted for patients undergoing next-generation sequencing at our centre, followed by a systematic review., Results: Six patients with heterozygous DNM1 variants were identified in our cohort. Three had a typical DEE phenotype characterised by epileptic spasms, tonic seizures and severe-to-profound intellectual disability with pathogenic variants located in the GTPase or middle domain. The other three patients had atypical phenotypes of milder cognitive impairment and focal epilepsy. Genotypically, two patients with atypical phenotypes had variants located in the GTPase domain, while the third patient had a novel variant (p.M648R) in the linker region between pleckstrin homology and GTPase effector domains. The third patient with an atypical phenotype showed normal development until he developed febrile status epilepticus. Our systematic review on 55 reported cases revealed that those with GTPase or middle domain variants had more severe intellectual disability (p<0.001) and lower functional levels of ambulation (p=0.001) or speech and language (p<0.001) than the rest., Conclusion: DNM1- related phenotypes encompass a wide spectrum of epilepsy and neurodevelopmental disorders, with specific variants underlying different phenotypes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Abnormal myocardial metabolism is a common pathophysiological process underlying ischemic heart disease and heart failure (HF). Trimetazidine is an antianginal agent with a unique mechanism of action that regulates myocardial energy metabolism and might have a beneficial effect in preventing HF in patients undergoing myocardial revascularization. We aimed to evaluate the potential benefit of trimetazidine in preventing incident hospitalization for HF after myocardial revascularization. Using the common data model, we identified patients without prior HF undergoing myocardial revascularization from 8 hospital databases in Korea. To compare clinical outcomes using trimetazidine, database-level hazard ratios (HRs) were estimated using large-scale propensity score matching for each database and pooled using a random-effects model. The primary outcome was incident hospitalization for HF. The secondary outcome of interest was major adverse cardiac events (MACEs). After propensity score matching, 6724 and 11,211 patients were allocated to trimetazidine new-users and nonusers, respectively. There was no significant difference in the incidence of hospitalization for HF between the 2 groups (HR: 1.08, 95% confidence interval [CI], 0.88-1.31; P = 0.46). The risk of MACE also did not differ between the 2 groups (HR: 1.07, 95% CI, 0.98-1.16; P = 0.15). In conclusion, the use of trimetazidine did not reduce the risk of hospitalization for HF or MACE in patients undergoing myocardial revascularization. Therefore, the role of trimetazidine in contemporary clinical practice cannot be expanded beyond its current role as an add-on treatment for symptomatic angina., Competing Interests: The authors reports no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Blood group antigens, which are prominently expressed in red blood cells, are important in transfusion medicine. The advent of high-throughput genome sequencing technology has facilitated the prediction of blood group antigen phenotypes based on genomic data. In this study, we analyzed data from a large Korean population to provide an updated prevalence of blood group antigen phenotypes, including rare ones. A robust dataset comprising 72,291 single nucleotide polymorphism arrays, 5318 whole-exome sequences, and 4793 whole-genome sequences was extracted from the Korean Genome and Epidemiology Study, Genome Aggregation Database, and Korean Variant Archive and then analyzed. The phenotype prevalence of clinically significant blood group antigens, including MNSs, RHCE, Kidd, Duffy, and Diego, was predicted through genotype analysis and corroborated the existing literature. We identified individuals with rare phenotypes, including 369 (0.51%) with Fy(a-b+), 188 (0.26%) with Di(a+b-), and 16 (0.02%) with Jr(a-). Furthermore, we calculated the frequencies of individuals with extremely rare phenotypes, such as p (0.000004%), Kell-null (0.000310%), and Jk(a-b-) (0.000438%), based on allele frequency predictions. These findings offer valuable insights into the distribution of blood group antigens in the Korean population and have significant implications for enhancing the safety and efficiency of blood transfusion., (© 2023. Springer Nature Limited.)

Background: Large-scale studies about epidemiologic characteristics of renal infarction (RI) are few. In this study, we aimed to analyze the incidence and prevalence of RI with comorbidities in the South Korean population., Methods: We investigated the medical history of the entire South Korean adult population between 2013 and 2019 using the National Health Insurance Service database (n = 51,849,591 in 2019). Diagnosis of RI comorbidities were confirmed with International Classification of Disease, Tenth Revision, Clinical Modification codes. Epidemiologic characteristics, distribution of comorbidities according to etiologic mechanisms, and trend of antithrombotic agents were estimated., Results: During the 7-years, 10,496 patients were newly diagnosed with RI. The incidence rate increased from 2.68 to 3.06 per 100,000 person-years during the study period. The incidence rate of RI increased with age peaking in the 70s with 1.41 times male predominance. The most common comorbidity was hypertension, followed by dyslipidemia and diabetes mellitus. Regarding etiologic risk factor distribution, high embolic risk group, renovascular disease group, and hypercoagulable state group accounted for 16.6%, 29.1%, and 13.7% on average, respectively. For the antithrombotic treatment of RI, the prescription of antiplatelet agent gradually decreased from 17.0% to 13.0% while that of anticoagulation agent was maintained around 35%. The proportion of non-vitamin K antagonist oral anticoagulants remarkably increased from only 1.4% to 17.6%., Conclusion: Considering the progressively increasing incidence of RI and high prevalence of coexisting risk factors, constant efforts to raise awareness of the disease are necessary. The current epidemiologic investigation of RI would be the stepping-stone to establishing future studies about clinical outcomes and optimal treatment strategies., Competing Interests: Minae Park and Sojeong Park are employees of the Hanmi Pharaceutical Co. They independently performed statistical analysis of the work as coauthors. All other authors have no potential conflict of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Growing evidence indicates that early and late postzygotic mosaicism can cause neurodevelopmental disorders (NDDs), but detection of low variant allele frequency (VAF) mosaic variants from blood remains a challenge. Data of 2162 patients with NDDs who underwent conventional genetic tests were reviewed and a deep sequencing was performed using a specifically designed mosaic next-generation sequencing (NGS) panel in the patients with negative genetic test results. Forty-four patents with neurocutaneous syndrome, malformation of cortical development, or nonlesional epileptic encephalopathies were included. In total, mosaic variants were detected from blood in 1.2% (25/2162) of the patients. Using conventional NGS panels, 22 mosaic variants (VAF, 8.8% to 29.8%) were identified in 18 different genes. Using a specifically designed mosaicism NGS panel, three mosaic variants of the NF1, TSC2, and AKT3 genes were identified (VAF, 2.0% to 11.2%). Mosaic variants were found frequently in the patients who had neurocutaneous syndrome (2/7, 28.6%), whereas only one or no mosaic variant was detected for patients who had malformations of cortical development (1/20, 5%) or nonlesional epileptic encephalopathies (0%, 0/17). In summary, mosaic variants that contribute to the spectrum of NDDs can be detected from blood via conventional NGS and specifically designed mosaicism NGS panels, and detection of mosaic variants using blood will increase diagnostic yield., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background and Importance: Appropriate decision-making is critical for transfusions to prevent unnecessary adverse outcomes; however, transfusion in the emergency department (ED) can only be decided based on sparse evidence in a limited time window., Objectives: This study aimed to identify factors associated with appropriate red blood cell (RBC) transfusion in the ED by analyzing retrospective data of patients who received transfusions at a single center., Outcome Measures and Analysis: This study analyzed associations between transfusion appropriateness and sex, age, initial vital signs, an ED triage score [the Korean Triage and Acuity Scale (KTAS)], the length of stay, and the hemoglobin (Hb) concentration., Main Results: Of 10 490 transfusions, 10 109 were deemed appropriate, and 381 were considered inappropriate. A younger age ( P  < 0.001) and a KTAS level of 3-5 ( P  = 0.028) were associated with inappropriate transfusions, after adjusting for O 2 saturation and the Hb level., Conclusions: In this single-center retrospective study, younger age and higher ED triage scores were associated with the appropriateness of RBC transfusions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Clonal hematopoiesis (CH) is a condition in which healthy individuals have somatic mutations in hematopoietic stem cells. It has been reported with increased risk of hematologic malignancy and cardiovascular disease in the general population, but studies of Korean populations with comorbid disease entities are scarce., Methods: White blood cells (WBCs) from patients with gastric cancer (GC) (n=121) were analyzed using a DNA-based targeted (531 genes) panel with customized pipeline designed to detect single nucleotide variants and small indels with low-allele-frequency of ≥0.2 %. We defined significant CH variants as having variant allele frequency (VAF) ≥2 % among variants found in WBCs. Matched cell-free DNA (cfDNA) samples were also analyzed with the same pipeline to investigate the false-positive results caused by WBC variants in cfDNA profiling., Results: Significant CH variants were detected in 29.8 % of patients and were associated with age and male sex. The number of CH variants was associated with a history of anti-cancer therapy and age. DNMT3A and TET2 were recurrently mutated. Overall survival rate of treatment-naïve patients with stage IV GC was higher in those with CH, but Cox regression showed no significant association after adjustment for age, sex, anti-cancer therapy, and smoking history. In addition, we analyzed the potential interference of WBC variants in plasma cell-free DNA testing, which has attracted interest as a complementary method for tissue biopsy. Results showed that 37.0 % (47/127) of plasma specimens harbored at least one WBC variant. VAFs of interfering WBC variants in the plasma and WBC were correlated, and WBC variants with VAF ≥4 % in WBC were frequently detected in plasma with the same VAF., Conclusions: This study revealed the clinical impact of CH in Korean patients and suggests the potential for its interference in cfDNA tests., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Inborn errors of immunity (IEI) include a variety of heterogeneous genetic disorders in which defects in the immune system lead to an increased susceptibility to infections and other complications. Accurate, prompt diagnosis of IEI is crucial for treatment plan and prognostication. In this study, clinical utility of clinical exome sequencing (CES) for diagnosis of IEI was evaluated. For 37 Korean patients with suspected symptoms, signs, or laboratory abnormalities associated with IEI, CES that covers 4,894 genes including genes related to IEI was performed. Their clinical diagnosis, clinical characteristics, family history of infection, and laboratory results, as well as detected variants, were reviewed. With CES, genetic diagnosis of IEI was made in 15 out of 37 patients (40.5%). Seventeen pathogenic variants were detected from IEI-related genes, BTK , UNC13D, STAT3 , IL2RG , IL10RA , NRAS, SH2D1A, GATA2, TET2, PRF1 , and UBA1 , of which four variants were previously unreported. Among them, somatic causative variants were identified from GATA2, TET2 , and UBA1 . In addition, we identified two patients incidentally diagnosed IEI by CES, which was performed to diagnose other diseases of patients with unrecognized IEI. Taken together, these results demonstrate the utility of CES for the diagnosis of IEI, which contributes to accurate diagnosis and proper treatments., 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 Kwon, Cho, Hahn, Oh, Won, Shin, Kang, Ahn, Lee and Choi.)

Background: Blood transfusion is an essential part of medicine. However, many countries have been facing a national blood crisis. To address this ongoing blood shortage issue, there have been efforts to generate red blood cells (RBCs) in vitro, especially from human-induced pluripotent stem cells (hiPSCs). However, the best source of hiPSCs for this purpose is yet to be determined., Methods: In this study, hiPSCs were established from three different hematopoietic stem cell sources-peripheral blood (PB), cord blood (CB) and bone marrow (BM) aspirates (n = 3 for each source)-using episomal reprogramming vectors and differentiated into functional RBCs. Various time-course studies including immunofluorescence assay, quantitative real-time PCR, flow cytometry, karyotyping, morphological analysis, oxygen binding capacity analysis, and RNA sequencing were performed to examine and compare the characteristics of hiPSCs and hiPSC-differentiated erythroid cells., Results: hiPSC lines were established from each of the three sources and were found to be pluripotent and have comparable characteristics. All hiPSCs differentiated into erythroid cells, but there were discrepancies in differentiation and maturation efficiencies: CB-derived hiPSCs matured into erythroid cells the fastest while PB-derived hiPSCs required a longer time for maturation but showed the highest degree of reproducibility. BM-derived hiPSCs gave rise to diverse types of cells and exhibited poor differentiation efficiency. Nonetheless, erythroid cells differentiated from all hiPSC lines mainly expressed fetal and/or embryonic hemoglobin, indicating that primitive erythropoiesis occurred. Their oxygen equilibrium curves were all left-shifted., Conclusions: Collectively, both PB- and CB-derived hiPSCs were favorably reliable sources for the clinical production of RBCs in vitro, despite several challenges that need to be overcome. However, owing to the limited availability and the large amount of CB required to produce hiPSCs, and the results of this study, the advantages of using PB-derived hiPSCs for RBC production in vitro may outweigh those of using CB-derived hiPSCs. We believe that our findings will facilitate the selection of optimal hiPSC lines for RBC production in vitro in the near future., (© 2023. The Author(s).)

Background and Aims: Glomerular hyperfiltration (GHF) is a hemodynamic change of the kidney as an adaptive response to nephron loss. Although GHF is associated with metabolic risk factors and cardiovascular disease (CVD), the mechanisms that explain these relationships remain largely unknown. This is partially caused by a non-unified definition of GHF based on pathophysiologic vascular changes. Thus, the objective of this study was to evaluate the association between various definitions of GHF and carotid plaque in a health checkup cohort., Methods: A total of 4493 individuals without history of CVD who had carotid ultrasonography (USG) results available between January 2016 and June 2018 were enrolled. GHF was defined as >90th percentile of eGFR residuals after adjusting for confounding factors. Carotid plaque score was calculated based on carotid USG results., Results: Of 4493 individuals (mean age, 52.3 ± 10.1 years; 3224 [71.8%] males), 449 subjects were included in the GHF group (mean eGFR, 107.0 ± 7.1 ml/min/1.73 m 2 ) and 4044 subjects were included in the non-GHF group (mean eGFR, 92.5 ± 12.3 ml/min/1.73 m 2 ). When the GHF group was compared to the non-GHF group, GHF was associated with the presence of significant carotid plaque (carotid plaque score ≥2) (adjusted OR: 1.46; 95% CI: 1.16 to 1.83; p = 0.001). GHF defined in this study showed higher sensitivity to the presence of carotid plaque than other definitions of GHF., Conclusions: GHF status was associated with risk of carotid plaque in individuals without history of CVD. Presence of subclinical carotid plaque was associated with risk of future CVD. Therefore, GHF based on creatinine could be a useful surrogate marker for surveillance of CVD in asymptomatic individuals., 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.)

Graphene/polymer actuators were developed using bilayer graphene and various polymer substrates for use as transparent, flexible, and robust electrostatic speaker units. Additionally, a resonant frequency shift was induced using a polymer substrate on which various micropatterns were transferred to boost bass. The total sound pressure level (SPL) in the graphene/polymer actuator was measured by a sweep, and the frequency of the spectrum was confirmed to be one-third that of the octave band frequency. The change in the vibroacoustic characteristic with changes in Young's modulus and density was studied for the polymers of the same size and thickness. Particularly, the possibility of boosting bass was confirmed by inducing a resonant frequency shift and increasing the total SPL by adding micropatterns on a polymer substrate under the same conditions. The resonance frequency of 523 Hz and the SPL of 54 dBA in flat polymer film became 296 Hz and 69 dBA in a specific pattern, which produced a sound of >15 dB based on the same flat polymer. We expect that the design and information provided herein can provide the key parameters required to change the resonant frequency in small-size devices for the application of graphene/polymer thin-film actuators.

As genomic analysis technology has advanced, it has become possible to sub-classify intrahepatic cholangiocarcinoma (ICC) at the histological or molecular level. Here, we verify the recently suggested two subgroups of ICC in the organoids model, compare the characteristics between types. ICC patients are subclassified into small-duct (SD) and large-duct (LD) subtype according to histological characteristics. ICC organoids are established, and unsupervised principal component analysis clustering separates each type of ICC. Differential gene expression reveals enrichment on KRAS, TGFβ and ERBB2 signaling pathways in LD-type compared with SD-type (P < 0.05). Gene set enrichment analysis demonstrates that the cholangiocarcinoma class 2 signature, defined by Andersen et al., is enriched in the LD-type (enrichment Score = 2.19, P < 0.001). A protein-protein interaction network analysis identifies ZNF217 as a significant hub protein (odds ratio = 4.96, P = 0.0105). We perform prospective modeling of histological subtype using patient-derived organoids. Moreover, gene expression profiling of ICC organoids enables identification of type-specific targetable pathways., (© 2023. The Author(s).)

Background: Recent studies have indicated that the triglyceride-glucose (TyG) index or subclinical thyroid dysfunction is associated with carotid plaques, a predictor of cardiovascular disease risk. However, evidence for this association is limited and inconsistent. This study aimed to evaluate the risk of carotid plaques according to TyG index and thyroid function status in the general population., Methods: A total of 2,931 individuals who underwent carotid ultrasound as part of a comprehensive health examination at the Health Promotion Center of Soonchunhyang University Hospital were retrospectively reviewed. Based on the TyG index and thyroid function status, the participants were divided into six groups: LoTyG-SHyper (low TyG index with subclinical hyperthyroidism), LoTyG-Eu (low TyG index with euthyroidism), LoTyG-SHypo (low TyG index with subclinical hypothyroidism), HiTyG-SHyper (high TyG index with subclinical hyperthyroidism), HiTyG-Eu (high TyG index with euthyroidism), and HiTyG-SHypo (high TyG index with subclinical hypothyroidism). A multivariate logistic regression analysis was conducted to determine the risk of carotid plaques., Results: The proportion of participants with significant carotid plaques was significantly different among the six groups (p<0.001, p for trend<0.001). The odds ratio (OR) and 95% confidence interval (CI) for significant carotid plaques were significantly higher in the HiTyG-SHypo group than in the LoTyG-Eu group, even after adjusting for confounding variables including sex, age, smoking, obesity, hypertension and diabetes mellitus (OR 1.506, 95% CI 1.045-2.170, p = 0.028). The OR of significant carotid plaques was higher in the HiTyG-Eu group than in the LoTyG-Eu group; however no associations were observed after additional adjustment for confounding variables., Conclusion: The TyG index and thyroid function status are important predictors of the risk of carotid plaques in healthy individuals. Early evaluation of carotid plaques may be necessary for subjects with high insulin resistance and subclinical hypothyroidism., Competing Interests: The authors have no competing interests to disclose., (Copyright: © 2022 Kim 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.)

Background: Trio test has been widely used for diagnosis of various hereditary disorders. We aimed to investigate the contribution of trio test in genetically diagnosing neurodevelopmental disorders (NDD)., Methods: We retrospectively reviewed 2,059 NDD cases with genetic test results. The trio test was conducted in 563 cases. Clinical usefulness, optimal timing, and methods for the trio test were reviewed., Results: Pathogenic or likely pathogenic variants were detected in 112 of 563 (19.9%) patients who underwent the trio test. With trio test results, the overall diagnostic yield increased by 5.4% (112/2,059). Of 165 de novo variants detected, 149 were pathogenic and we detected 85 novel pathogenic variants. Pathogenic, de novo variants were frequently detected in CDKL5 , ATP1A3 , and STXBP1 ., Conclusion: The trio test is an efficient method for genetically diagnosing NDD. We identified specific situations where a certain trio test is more appropriate, thereby providing a guide for clinicians when confronted with variants of unknown significance of specific genes., 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., (© 2022 Kim, Kwon, Lee, Kim, Lee, Choi, Shin and Kang.)

Background: Hypotensive transfusion reaction (HyTR) is rare. It is characterized by a rapid onset of hypotension during transfusion, which usually resolves quickly upon cessation of transfusion. Information on the incidence and clinical characteristics of HyTR has been reported in only a few studies., Study Design and Methods: We retrospectively reviewed HyTR cases from 10-year hemovigilance data in a tertiary care hospital in Seoul, Korea., Results: We identified 37 HyTRs in 35 patients, and the overall incidence of HyTR was 0.50 per 10,000 transfused units. Among the blood components, the incidence of HyTR was highest in filtered random donor platelets (0.75 per 10,000 units). About half of the HyTRs occurred within 15 min after the start of transfusion (19/37). Blood pressure returned to the normal range within an hour in 73.0% of the cases (27/37). All HyTR cases recovered without severe complications. Known risk factors for HyTR were not prominent in our cohort of patients, with no patients taking angiotensin-converting enzyme inhibitors and only five patients transfused with bedside filtered platelets., Discussion: HyTR can occur in patients with various conditions and types of blood components. Understanding the clinical characteristics of HyTR facilitates proper management, leading to improved transfusion safety., (© 2022 AABB.)

Purpose: Chemotherapy-induced cardiotoxicity is a critical issue for patients with breast cancer. Change of epicardial adipose tissue (EAT) is associated with cardiac dysfunction. The objective of this study was to investigate the relationship between EAT and chemotherapy-induced cardiotoxicity., Methods: This retrospective study analyzed EAT on chest computed tomography (CT) of patients with early breast cancer using automatic, quantitative measurement software between November 2015 and January 2020. Changes in EAT before and after initiation of chemotherapy were compared according to the type of anticancer drug. Subclinical cardiotoxicity was defined as worsening ≥ 10% in left ventricular ejection fraction to an absolute value > 50% with a lower limit of normal measured with standard echocardiography., Results: Among 234 patients with breast cancer, 85 were treated with adjuvant anthracycline-based (AC) and 149 were treated with non-anthracycline-based (non-AC) chemotherapy. There was a significant increase in EAT volume index (mL/kg/m 2 ) at the end of chemotherapy compared to that at the baseline in the AC group (3.33 ± 1.53 vs. 2.90 ± 1.52, p < 0.001), but not in the non-AC group. During the follow-up period, subclinical cardiotoxicity developed in 20/234 (8.6%) patients in the total population [13/85 (15.3%) in the AC group and 7/149 (4.8%) in the non-AC group]. In the multivariable analysis, EAT volume index increment after chemotherapy was associated with a lower risk of subclinical cardiotoxicity in the AC group (Odds ratio: 0.364, 95% CI 0.136-0.971, p = 0.044)., Conclusions: Measurement of EAT during anthracycline-based chemotherapy might help identify subgroups who are vulnerable to chemotherapy-induced cardiotoxicity. Early detection of EAT volume change could enable tailored chemotherapy with cardiotoxicity prevention strategies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Mood disorder and borderline personality pathology (BPP) are frequently comorbid and relate to childhood trauma. We investigated the relationship between childhood trauma and BPP features in mood disorder patients versus controls., Methods: A total of 488 mood disorder patients, particularly major depressive disorder (MDD), bipolar I disorder (BD I), and bipolar II disorder (BD II), and 734 controls were included. We examined between-group BPP-related differences and correlated between BPP and childhood trauma using the Childhood Trauma Questionnaire-Short Form (CTQ) and the Personality Assessment Inventory-Borderline Features Scale., Results: BD II patients showed significantly higher BPP. Emotional abuse and neglect were prominently associated with BPP, while affective instability and negative relationships exhibited a stronger association with childhood trauma. We also found a positive relationship between childhood trauma and BPP in MDD, BD I, and BD II patients., Conclusion: The findings of the present study imply that BPP features are more likely to be found in patients with BD II than BD I or MDD. Mood disorder patients with severe childhood trauma may have higher BPP features. Thus, further study of the relationship between childhood trauma and BPP features could improve the therapeutic approaches and help understand patients with mood disorders.

Background and Aims: Chronic inflammation plays a critical role in the pathogenesis of myeloproliferative neoplasm (MPN), and inflammatory conditions are closely related to the development and exacerbation of atherosclerosis. This study aimed to compare carotid plaque burden and neutrophil-lymphocyte ratio (NLR) in the essential thrombocythemia (ET)/polycythemia vera (PV) and control groups., Methods and Results: We retrospectively assessed carotid plaque burden and NLR in patients with ET/PV between January 2010 and September 2021 and propensity-score matched these patients to control subjects from the general population. All patients underwent carotid imaging using carotid ultrasonography for atherosclerosis screening. After 3:1 propensity-score matching, 140 patients in the control group were matched to 51 patients in ET/PV group. The mean NLR was significantly higher in the MPN group than in the control group (4.77 ± 3.96 vs. 1.93 ± 1.03, p < 0.001). The carotid plaque score was also higher in MPN group than in the control group (2.37 ± 1.47 vs. 1.94 ± 1.17, p = 0.038)., Conclusion: Patients with PV/ET show a higher NLR and carotid plaque burden than the normal population. This reflected that PV/ET was a highly inflammatory and atherosclerotic condition expressing potentially increased cardiovascular risk., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The current treatments for chronic knee osteoarthritis (OA), a disabling and costly healthcare condition in the United States, vary in their level of supporting evidence. Although total knee replacement is one of the best-supported interventions, its associated risks should not be taken lightly, especially in older patients with comorbidities. Genicular nerve block with subsequent genicular nerve radiofrequency neurotomy (GN-RFN) has emerged as a promising intervention for refractory pain in knee OA. Purposes/Questions: We sought to assess the pain and functional outcomes of genicular nerve bipolar radiofrequency neurotomy (B-RFN) for the treatment of chronic pain due to knee OA. Methods: A total of 21 patients who underwent unilateral genicular nerve B-RFN after positive diagnostic genicular nerve block (50% or greater pain relief) treated between July 2018 to December 2018 were included. Pain numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were collected at baseline, 3 months, and 6 months post-B-RFN. Changes at each time point were compared to baseline scores using paired sample t tests. Results: At 3 months, 62% of patients had a greater than 50% improvement in NRS scores and 57% of patients had a greater than 50% improvement in WOMAC scores. At 6 months, 81% of patients had a greater than 50% improvement in NRS scores and 67% had a greater than 50% improvement in WOMAC scores. The absolute change in mean NRS (± standard deviation) at 6 months went from 7.5 ± 1.9 to 2.5 ± 1.2. The absolute change in mean WOMAC scores at 6 months went from 46.9 ± 8.0 to 19.0 ± 6.2. Conclusion: Of 21 patients, 14 (67%) saw greater than 50% improvements in both NRS and WOMAC scores at 6 months after genicular nerve B-RFN. Further prospective studies are needed to determine the selection criteria of patients most likely to benefit from this procedure., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

We aimed to investigate the progression of patella alta (PA) in patients with cerebral palsy (CP) using the Koshino-Sugimoto (KS) index and assess associated risk factors. Participants in our retrospective study met the following inclusion criteria: patients with CP who visited our institute from May 2003 to December 2019, were ≤18 years of age, were followed up for >2 years and had at least two lateral knee radiographs. KS indices of both knee radiographs were measured for each patient. A linear mixed model was implemented. Our participants included 222 CP patients. KS index values were measured via 652 knee radiographs. Reference values of the KS index for those between 4 and 18 years of age were determined according to Gross Motor Function Classification System (GMFCS) levels. In all GMFCS levels, the KS index decreased with patients' ages (P < 0.0001). In groups where the KS index increased, GMFCS levels IV (P = 0.0045) and V (P = 0.0040) were statistically significant. Change in the KS index values indicates that PA improves as patients age within all GMFCS levels. However, in patients with GMFCS levels of IV and V, progressive PA is expected., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Asian Americans (AA) are the only racial group in the United States to experience cancer as the number one cause of mortality. Yet, Asian Americans have one of the lowest rates of cancer screenings of all minority groups in the United States., Methods: A cross-sectional and population-based study design was used. Cross-sectional data was collected from 1,650 AA participants via a survey given during two annual community health festivals in 2017 and 2018. Survey variables included sociodemographic measures, self-reported English-language proficiency level, access to primary care, attitudes on preventative cancer screening, current screening status and barriers to undergoing cancer screening., Results: Nearly 66% (n=1,081) reported not having a primary care physician (PCP). While the majority of the participants (n=1,510, 92%) stated that preventative cancer screenings were important, only a small portion (n=1,091, 16%) were up-to-date on cancer screening procedures. The biggest barriers to preventative cancer screening were: 1) Lack of insurance (n=840, 40%); 2) Cost of seeing a physician (n=517, 24%); and 3) Do not feel the need (n=299, 14%)., Conclusions: To overcome the barriers we identified and effectively increase cancer screenings in Asian Americans, community outreach should be considered to provide linkage to primary care physicians and navigation to low-cost screening programs.