Background: Current guidelines recommend factor IIa- or Xa-specific inhibitors over warfarin analogs for preventing thromboembolic stroke in patients with atrial fibrillation (AF).However, their plasma concentrations in Korean patients are not well understood. Methods: We conducted a single-center laboratory study to determine the distribution ranges of peak and trough concentrations of three factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) prescribed for preventing strokes in patients with AF. Patients receiving one of these drugs and undergoing blood specimen collection for laboratory tests were screened. Blood specimens were obtained from patients who had adhered to the prescribed drug regimen consistently for at least 1 week. Drug plasma concentrations were measured using heparin liquid-reagent technology-based anti-Xa chromogenic assays. Results: We selected 459 patients who were taking standard or on-label-reduced doses of apixaban (N = 252), edoxaban (N = 182), or rivaroxaban (N = 25). The 5th–95th percentile ranges of the peak concentrations were 84–414 ng/mL (apixaban), 72–424 ng/mL (edoxaban), and 97–517 ng/mL (rivaroxaban). The respective 5th–95th percentile ranges of the trough concentrations were 44–237 ng/mL, 23–93 ng/mL, and 13–219 ng/mL. Approximately 19.6% (apixaban), 33.3% (edoxaban), and 64.0% (rivaroxaban) of patients in each group had peak concentrations out of the predicted distribution ranges based on pharmacokinetic data. Approximately 7.3%, 52.8%, and 8.3% of patients had trough concentrations out of the predicted distribution ranges. Conclusions A considerable proportion of Korean patients with AF taking factor Xa inhibitors may require population-specific reference ranges to guide therapeutic monitoring.

Purpose: This study aimed to develop and evaluate the effectiveness of the Trauma-nursing Education and Skill Support (TESS) program based on the ADDIE model (Analysis, Design, Development, Implementation, Evaluation model). The program was designed to enhance trauma nurses’ clinical competencies, including trauma-related knowledge, self-efficacy, and problem-solving ability, through the integration of theoretical education and simulation-based practice. Methods: A quasi-experimental study using a non-equivalent control group pretest–posttest design was conducted. Participants included 108 trauma nurses from regional trauma centers, military trauma centers, and emergency care facilities, who were assigned to an experimental group (n=52) or a control group (n=56). The TESS program consisted of a 2-day, 14-hour blended-learning course that included eight lecture sessions and four simulation-based practice stations. Data were collected at baseline, immediately after the intervention, and at 6 months using validated instruments measuring trauma-related knowledge, self-efficacy, and problem-solving ability. Two-way repeated-measures analysis of variance was used for data analysis. Results: The experimental group demonstrated significant improvements in trauma-related knowledge, self-efficacy, and problem-solving ability compared with baseline (all p<.001). These improvements were sustained at 6 months, although trauma-related knowledge scores showed a slight decline compared with immediate posttest levels. Between-group analyses confirmed significant group-by-time interaction effects for all outcomes: trauma-related knowledge (η2=0.12, p<.001), self-efficacy (η2=0.09, p=.002), and problem-solving ability (η2=0.08, p=.003). Conclusion The TESS program effectively enhanced trauma nurses’ trauma-related knowledge, self-efficacy, and problem-solving ability, with effects sustained for up to 6 months. Incorporating blended learning and simulation-based training into standardized trauma nursing education may strengthen clinical competencies and ultimately contribute to improved patient outcomes.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Early mortality following hemodialysis initiation hinders survival improvement in older patients. This study aimed to develop a clinical risk model for predicting 6-month mortality after dialysis initiation in older Korean hemodialysis patients. Methods: We analyzed data from incident hemodialysis patients aged >70 years from the Korean Society of Geriatric Nephrology (KSGN) database. A prediction model was developed using multivariate logistic regression analysis and externally validated with independent datasets. Results: Among 1,751 incident hemodialysis patients, the 6-month mortality rate was 15.5%. Using multivariate logistic analysis, we constructed the KSGN score as an independent risk factor for 6-month mortality, and its components and score are as follows: old age at dialysis initiation (≥85 years, score 2); hypertension and renovascular disease as a primary etiology of end-stage kidney disease (ESKD) (score 1); malignancy history (yes, score 1); low serum albumin (<3.5 g/dL, score 1); hypertension treatment (yes, score –1); prepared vascular access on maintenance dialysis (arteriovenous fistula/arteriovenous graft, score –3). In the development cohort, the area under the curve (AUC) for the KSGN score was significantly higher than the Alberta Wick’s score (0.707 vs. 0.683, p = 0.001). In the validation cohort, the KSGN score’s performance was comparable to existing models. Conclusion: The KSGN score may be a valuable tool for predicting early mortality after dialysis initiation in older patients with ESKD, aiding in decision-making and management regarding dialysis initiation.

Background: The aim of this study is to investigate the specific pathway involved in human leukocyte antigen (HLA) sensitization using single-cell RNA-sequencing analysis and an allo-sensitized mouse model developed with an HLA.A2 transgenic mouse. Methods: For sensitization, wild-type C57BL/6 mouse received two skin grafts from C57BL/6-Tg(HLA-A2.1)1Enge/J mouse (allogeneic mouse, ALLO). For syngeneic control (SYN), skin grafts were transferred from C57BL/6 to C57BL/6. We performed single-cell RNA-sequencing analysis on splenocytes isolated from ALLO and SYN and compared the gene expression between them. Results: We generated 9,190 and 8,890 single-cell transcriptomes from ALLO and SYN, respectively. Five major cell types (B cells, T cells, natural killer cells, macrophages, and neutrophils) and their transcriptome data were annotated according to the representative differentially expressed genes of each cell cluster. The percentage of B cells was higher in ALLO than it was in SYN. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the highly expressed genes in the B cells from ALLO were mainly associated with antigen processing and presentation pathways, allograft rejection, and the Th17 cell differentiation pathway. Upregulated genes in the T cells of ALLO were involved in the interleukin (IL)-17 signaling pathway. The ratio of Th17 cluster and Treg cluster was increased in the ALLO. On flow cytometry, the percentage of Th17 (IL-17+/CD4+ T) cells was higher and regulatory T cells (FOXP3+/CD4+ T) was lower in the ALLO compared to those in the SYN. Conclusion Our results indicate that not only the B cell lineage but also the Th17 cells and their cytokine (IL-17) are involved in the sensitization to HLA.

Objective: Cognitive reserve has emerged as a concept to explain the variable expression of clinical symptoms in the pathology of Alzheimer’s disease (AD). The association between years of education, a proxy of cognitive reserve, and resting-state functional connectivity (rFC), a representative intermediate phenotype, has not been explored in the preclinical phase, considering risk factors for AD. We aimed to evaluate whether the relationship between years of education and rFC in cognitively preserved older adults differs depending on amyloid-beta deposition and APOE ε4 carrier status as effect modifiers. Methods: A total of 121 participants underwent functional magnetic resonance imaging, [ 18F] flutemetamol positron emission tomography-computed tomography, APOE genotyping, and a neuropsychological battery. Potential interactions between years of education and AD risk factors for rFC of AD-vulnerable neural networks were assessed with wholebrain voxel-wise analysis. Results: We found a significant education years-by-APOE ε4 carrier status interaction for the rFC from the seed region of the central executive (CEN) and dorsal attention networks. Moreover, there was a significant interaction of rFC between right superior occipital gyrus and the CEN seed region by APOE ε4 carrier status for memory performances and overall cognitive function. Conclusion In preclinical APOE ε4 carriers, higher years of education were associated with higher rFC of the AD vulnerable network, but this contributed to lower cognitive function. These results contribute to a deeper understanding of the impact of cognitive reserve on sensitive functional intermediate phenotypic markers in the preclinical phase of AD.

This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. Methods: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. Results: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21–1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78–2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09–1.99; p = 0.01) but not among those with low disease severity. Conclusion: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

Background/Aims: The association between symptomatic knee osteoarthritis (OA) and higher cardiovascular disease (CVD) mortality is established; however, findings from studies that utilized regression analysis were limited, attributed to the strong association between OA and metabolic risk factors. This study aimed to evaluate the association between knee OA and mortality through propensity score matching. Methods: This was a cohort study including Korean National Health and Nutrition Examination Survey (2010–2013) participants aged ≥ 50 years. By linking the survey data to cause of death data (through 2019) from Statistics Korea, mortality and cause-specific mortality data were obtained. Radiographic knee OA (ROA) was defined as bilateral Kellgren–Lawrence grade ≥ 2. Propensity score matching (1:1) was conducted between asymptomatic ROA, knee pain, and symptomatic ROA groups and normal groups, balancing the confounding factors. Time to death was analyzed using Cox proportional hazard modeling. Results: A higher CVD mortality was observed in the symptomatic ROA group, but not in others; the risk estimates were asymptomatic ROA (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.77–1.65), knee pain (HR 0.61; 95% CI 0.27–1.38), and symptomatic ROA (HR 1.39; 95% CI 0.89–2.17). No association was found between the all-cause/cancer mortality and other groups. Conclusions When propensity score matching controls metabolic risk factor imbalances, the association between symptomatic knee OA and higher CVD mortality was weaker compared to results of prior studies that used regression adjustment. The results may be more precise estimates of the total risk of knee OA for mortality in Koreans.

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.

As the field of interventional pain management (IPM) grows, the risk of surgical site infections (SSIs) is increasing. SSI is defined as an infection of the incision or organ/space that occurs within one month after operation or three months after implantation. It is also common to find patients with suspected infection in an outpatient clinic. The most frequent IPM procedures are performed in the spine. Even though primary pyogenic spondylodiscitis via hematogenous spread is the most common type among spinal infections, secondary spinal infections from direct inoculation should be monitored after IPM procedures. Various preventive guidelines for SSI have been published. Cefazolin, followed by vancomycin, is the most commonly used surgical antibiotic prophylaxis in IPM. Diagnosis of SSI is confirmed by purulent discharge, isolation of causative organisms, pain/tenderness, swelling, redness, or heat, or diagnosis by a surgeon or attending physician. Inflammatory markers include traditional (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) and novel (procalcitonin, serum amyloid A, and presepsin) markers. Empirical antibiotic therapy is defined as the initial administration of antibiotics within at least 24 hours prior to the results of blood culture and antibiotic susceptibility testing. Definitive antibiotic therapy is initiated based on the above culture and testing. Combination antibiotic therapy for multidrug-resistant Gramnegative bacteria infections appears to be superior to monotherapy in mortality with the risk of increasing antibiotic resistance rates. The never-ending war between bacterial resistance and new antibiotics is continuing. This article reviews prevention, diagnosis, and treatment of infection in pain medicine.