Purpose: This study examined the characteristics and outcomes of resective epilepsy surgery following corpus callosotomy (CC) in children with Lennox-Gastaut syndrome (LGS). Methods: We retrospectively analyzed 17 children with LGS who underwent resective surgery (RS) after CC over a span of 10 years, with a minimum of 2 years of follow-up, at a single tertiary epilepsy center in Korea. Results: Of the 17 patients, 13 (73.5%) demonstrated favorable surgical outcomes (Engel class I or II) at 1 year after RS, and eight (47.1%) were ultimately free of seizures 2 years after surgery. A significantly larger decrease in the number of anti-seizure medications taken from before to 2 years after the final surgical procedure was observed in the group that became seizure-free than in the group with persistent seizures (P=0.062). Furthermore, a significantly greater decline in daily adaptive function was found in the persistent seizure group (P=0.059). The baseline characteristics, results of presurgical evaluation, and treatment-related factors assessed prior to surgery showed no significant differences between the seizure-free group and the group with persistent seizures. Conclusion In conclusion, RS may be a viable option for patients with LGS who exhibit lateralization and/or localization on presurgical evaluation after CC, as the procedure may reveal a concealed primary focus. The proactive implementation of two-stage epilepsy surgery could provide significant seizure reduction and preservation of cognitive function in carefully selected patients with LGS.

Purpose: We report two cases of retinal dystrophy with high myopia associated with a novel retinitis pigmentosa 2 (RP2) exon1 deletion and a simultaneous transforming growth factor β-induced (TGFBI) point mutation.Case summary: The patients were two male siblings previously diagnosed with retinitis pigmentosa. They had a maternal family history of granular corneal dystrophy, and both presented with high myopia of ≥ -7.00 diopters (D). On ophthalmologic imaging, they displayed identical symmetric diffuse retinal dystrophy with hyperpigmented bony spicules in both eyes. Optical coherence tomography revealed diffuse thinning of the neurosensory retina and disruption of the ellipsoid zone. Full-field electroretinography showed nearly flattened cone and rod responses. Although targeted next-generation sequencing did not reveal any mutations in either case, whole-exome sequencing confirmed the existence of a single heterozygous TGFBI point mutation (c.371G>A(p.(Arg124His))) in both patients. Subsequent whole genome sequencing (WGS) confirmed novel RP2 exon1 deletion (c.-37_c.102+581del (720bp)). Conclusions In this case of familial hereditary granular corneal dystrophy, there were difficulties diagnosing and interpreting the genetic test results because of the very rare RP2 deletion. Prior to WGS, it was thought that retinal dystrophy could be attributed to an atypical clinical feature associated with the TGFBI mutation and high myopia. Retinal specialists who diagnose and manage these patients are advised to compile plans that consider appropriate genetic testing and interpretation of the outcomes.

Background: The Pandemic Grief Risk Factors (PGRFs) was developed as a self-report tool to compile a comprehensive list of unique risk factors related to grief when experiencing a coronavirus disease 2019 (COVID-19) loss. We explored the reliability and validity of the PGRF among healthcare workers who witnessed their patients’ deaths during the COVID-19 pandemic. Further, we examined whether the general severity of PGRF may have been associated with work-related stress and pandemic grief reactions. Methods: An online survey was conducted among tertiary hospital healthcare workers (doctors and nursing professionals) who had witnessed the deaths of patients they cared for.Pandemic Grief Scale for healthcare workers, the Stress and Anxiety to Viral Epidemics-3 items, the Patient Health Questionnaire-9, and the Generalized Anxiety Disorder-7 responses were collected. Results: In total, 267 responses were analyzed. The single-factor structure of the Korean version of the PGRF showed a good fit for the model. The scale demonstrated good internal consistency and convergent validity with other depression and anxiety rating scales. The mediation analysis revealed that work-related stress directly influenced pandemic grief reactions positively, and depression, anxiety, and general severity of grief risk factors partially mediated the association positively. Conclusion Among healthcare workers who witnessed the deaths of their patients due to COVID-19, the Korean version of the PGRF was valid and reliable for measuring the overall severity of PGRF. The PGRF can be used to identify individuals at risk for dysfunctional grief.

Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell–derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

Background: Carvedilol is a beta-adrenergic receptor antagonist primarily metabolized by cytochromes P450 (CYP) 2D6. This study established a carvedilol population pharmacokinetic (PK)–pharmacodynamic (PD) model to describe the effects of CYP2D6 genetic polymorphisms on the inter-individual variability of PK and PD. Methods: The PK–PD model was developed from a clinical study conducted on 21 healthy subjects divided into three CYP2D6 phenotype groups, with six subjects in the extensive metabolizer (EM, *1/*1, *1/*2), seven in the intermediate metabolizer-1 (IM-1, *1/*10, *2/*10), and eight in the intermediate metabolizer-2 (IM-2, *10/*10) groups. The PK–PD model was sequentially developed, and the isoproterenol-induced heart rate changes were used to establish the PD model. A direct effect response and inhibitory E max model were used to develop a carvedilol PK–PD model. Results: The carvedilol PK was well described by a two-compartment model with zeroorder absorption, lag time, and first-order elimination. The carvedilol clearance in the CYP2D6*10/*10 group decreased by 32.8% compared with the other groups. The inhibitory concentration of carvedilol estimated from the final PK–PD model was 16.5 ng/mL regardless of the CYP2D6 phenotype. Conclusion The PK–PD model revealed that the CYP2D6 genetic polymorphisms were contributed to the inter-individual variability of carvedilol PK, but not PD.

Purpose: The purpose of this study was to estimate the medical expenditures for poisoning patients in Korea using data from National Health Insurance and the Korea Health Panel Survey. Methods: The operational definition of poisoning was the presence of Korean Standard Classification of Diseases codes from T36 to T65. The number of poisoning patients, the amount of legal copayments, and benefit and non-benefit costs were extracted from both databases. The frequency of emergency, inpatient, and outpatient treatment utilization by poisoning patients was determined, and medical expenses were calculated. Linear regression analyses were performed to investigate factors affecting the medical expenses of poisoning patients. Results: The number of poisoning patients increased from 97,965 in 2011 to 147,984 persons in 2020. Medical expenses also increased by 74% from Korean won (KRW) 30.1 billion to KRW 52.3 billion, and benefit costs also increased by 79%. The average outpatient cost per person was KRW 67,660, and the inpatient cost was KRW 1,485,103. The average non-benefit medical expenses were KRW 80,298, accounting for about 16.2% of the total expenses. Multivariable analysis showed that the total expenditure was associated with economic status and disabilities. Conclusion The average medical expenditure per poisoning patient was KRW 534,302 in 2020, and poisoning-related costs gradually increased during the study period. Further research on the economic burden of poisoning should include indirect costs and reflect disease-adjusted life years.

Purpose: Fertility preservation (FP) is an important issue for young survivors of breast cancer. Although international guidelines recommend pre-treatment fertility counseling for women with breast cancer, there is no standardized protocol or referral system for FP in South Korea. There are also barriers to discussing FP that make patient-centered decision making difficult. This study aimed to develop a shared decision making program for FP and compare the rates of FP procedures between the usual care and shared decision making groups. We hypothesized that multidisciplinary shared decision making for FP would increase the rate of FP procedures and patient satisfaction. Methods The multidisciplinary shared decision making for FP in young women with breast cancer (MYBC) is a multicenter, clustered, stepped-wedge, randomized trial. A total of 1100patients with breast cancer, aged 19–40 years, from nine hospitals in South Korea, will be enrolled. They will be randomized at the institutional level and assigned to usual care and shared decision making groups. Four institutions, each of which can recruit more than 200 patients, will each become a cluster, whereas five institutions, each of which can recruit more than 50 patients, will become one cluster, for a total of five clusters. The shared decision making groups will receive multidisciplinary programs for FP developed by the investigator. The primary outcome is the rate of FP procedures; secondary outcomes include fertility results, satisfaction, and quality of life. Outcomes will be measured at enrollment, treatment initiation, and the 1-, 3-, and 5-year follow-ups after starting breast cancer treatment.Discussion: A multidisciplinary shared decision making program for FP is expected to increase fertility rates and satisfaction among young patients with breast cancer. This study will provide the evidence to implement a multidisciplinary system for patients with breast cancer.

Objective: The aim of the present study was to explore whether or not cancer patients’ viral anxiety and depression during the coronavirus-2019 (COVID-19) pandemic were associated with a fear of cancer progression. We also assessed whether coping strategies affected the relationship. Methods: The present cross-sectional survey included cancer patients who visited Ulsan University Hospital in Ulsan, Korea. The participants’ demographic information and responses to the following symptoms rating scales were collected: Stress and Anxiety to Viral Epidemic–6; Patient Health Questionnaire–9; Cognitive Emotion Regulation Questionnaire-short version; or Fear of Progression Questionnaire-short version. Results: Of the 558 cancer patients surveyed, 25 (4.5%) reported that their treatment schedule was delayed during the COVID-19 pandemic. The patients’ fear of progression was found to be related to age (β=-0.08; p=0.011), viral anxiety (β=0.40; p<0.001), depression (β=0.26; p<0.001), and catastrophizing coping strategies (β=0.15; p=0.004), for an overall adjusted R2 of 0.46 (F=66.8; p<0.001). Mediation analysis showed that viral anxiety and depression were directly associated with fear of progression, while catastrophizing mediated this relationship. Conclusion Fear of progression in cancer patients was associated with viral anxiety, depression, and maladaptive coping techniques, such as catastrophizing, during the COVID-19 pandemic.

Purpose: Given the morphological characteristics of schistocytes, thrombotic microangiopathy (TMA) score can be beneficial as it can be automatically and accurately measured. This study aimed to investigate whether serial TMA scores until 48 h post admission are associated with clinical outcomes in patients undergoing targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). Materials and Methods: We retrospectively evaluated a cohort of 185 patients using a prospective registry. We analyzed TMA scores at admission and after 12, 24, and 48 hours. The primary outcome measures were poor neurological outcome at discharge and 30-day mortality. Results: Increased TMA scores at all measured time points were independent predictors of poor neurological outcomes and 30-day mortality, with TMA score at time-12 showing the strongest correlation [odds ratio (OR), 3.008; 95% confidence interval (CI), 1.707–5.300; p<0.001 and hazard ratio (HR), 1.517; 95% CI, 1.196–1.925; p<0.001]. Specifically, a TMA score ≥2 at time-12 was closely associated with an increased predictability of poor neurological outcomes (OR, 6.302; 95% CI, 2.841–13.976; p<0.001) and 30-day mortality (HR, 2.656; 95% CI, 1.675–4.211; p<0.001). Conclusion Increased TMA scores predicted neurological outcomes and 30-day mortality in patients undergoing TTM after OHCA. In addition to the benefit of being serially measured using an automated hematology analyzer, TMA score may be a helpful tool for rapid risk stratification and identification of the need for intensive care in patients with return of spontaneous circulation after OHCA.

Purpose: Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated. Materials and Methods: A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery. Results: A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group (p=0.024). In multivariable analyses, peak FiO2 within 3 days and tocilizumab combination were consistently significant for 30-day recovery (all p<0.05). The DexaToci group showed a significantly steeper decrease in FiO2 (-4.2±2.6) than the Dexa group (−2.7±2.6; p=0.021) by hospital day 15. The duration of oxygen requirement was significantly shorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p=0.006). Infectious complications and cellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescence stage were not different between the two groups. Conclusion A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.