ASCL1-mediated direct reprogramming: converting ventral midbrain astrocytes into dopaminergic neurons for Parkinson's disease therapy.

Parkinson's disease (PD), characterized by dopaminergic neuron degeneration in the substantia nigra, is caused by various genetic and environmental factors. Current treatment methods are medication and surgery; however, a primary therapy has not yet been proposed. In this study, we aimed to develop a new treatment for PD that induces direct reprogramming of dopaminergic neurons (iDAN). Achaete-scute family bHLH transcription factor 1 (ASCL1) is a primary factor that initiates and regulates central nervous system development and induces neurogenesis. In addition, it interacts with BRN2 and MYT1L, which are crucial transcription factors for the direct conversion of fibroblasts into neurons. Overexpression of ASCL1 along with the transcription factors NURR1 and LMX1A can directly reprogram iDANs. Using a retrovirus, GFP-tagged ASCL1 was overexpressed in astrocytes. One week of culture in iDAN convertsion medium reprogrammed the astrocytes into iDANs. After 7 days of differentiation, TH+/TUJ1+ cells emerged. After 2 weeks, the number of mature TH+/TUJ1+ dopaminergic neurons increased. Only ventral midbrain (VM) astrocytes exhibited these results, not cortical astrocytes. Thus, VM astrocytes can undergo direct iDAN reprogramming with ASCL1 alone, in the absence of transcription factors that stimulate dopaminergic neuron development.

Evaluating the HYDRASHIFT 2/4 Daratumumab assay: a powerful approach to assess treatment response in multiple myeloma.

OBJECTIVES: This study evaluates the HYDRASHIFT assay's effectiveness in mitigating daratumumab interference on serum protein tests during multiple myeloma (MM) treatment, aiming to ensure an accurate assessment of treatment response. METHODS: We analyzed 113 serum samples from 68 MM patients undergoing daratumumab treatment, employing both standard IF and the HYDRASHIFT assay. The assay's precision was determined through intra-day and inter-day variability assessments, while its specificity was verified using serum samples devoid of daratumumab. Comparative analysis of IF results, before and after the application of the HYDRASHIFT assay, facilitated the categorization of treatment responses in alignment with the International Myeloma Working Group's response criteria. RESULTS: The precision underscored the assay's consistent repeatability and reproducibility, successfully eliminating interference of daratumumab-induced Gκ bands. Specificity assessments demonstrated the assay's capability to distinguish daratumumab from both isatuximab and naturally occurring M-proteins. Of the analyzed cases, 91 exhibited successful migration of daratumumab-induced Gκ bands, thereby enhancing the accuracy of treatment response classification. The remaining 22 cases did not show a visible migration complex, likely due to the low concentration of daratumumab in the serum. These findings underscore the assay's critical role in distinguishing daratumumab from endogenous M-protein, particularly in samples with a single Gκ band on standard IF, where daratumumab and endogenous M-protein had co-migrated. CONCLUSIONS: The HYDRASHIFT assay demonstrates high precision, specificity, and utility in the accurate monitoring of treatment responses in MM patients receiving daratumumab. This assay represents a significant advancement in overcoming the diagnostic challenges posed by daratumumab interference.

Therapeutic Drug Monitoring of 6 New-Generation Antiseizure Medications Using a Mass Spectrometry Method: Analysis of 2-Year Experience in a Large Cohort of Korean Epilepsy Patients.

CONTEXT.­: New-generation antiseizure medications (ASMs) are increasingly prescribed, and therapeutic drug monitoring (TDM) has been proposed to improve clinical outcome. However, clinical TDM data on new-generation ASMs are scarce. OBJECTIVE.­: To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of 6 new-generation ASMs in serum and analyze the clinical TDM data from a large cohort of Korean patients with epilepsy. DESIGN.­: Stable isotope-labeled internal standards were added to protein precipitations of serum. One microliter of sample was separated on Agilent Poroshell EC-C18 column, and lacosamide, perampanel, gabapentin, pregabalin, vigabatrin, and rufinamide were simultaneously quantified by Agilent 6460 triple-quad mass spectrometer in multiple-reaction monitoring mode. Linearity, sensitivity, precision, accuracy, specificity, carryover, extraction recovery, and matrix effect were evaluated. TDM data of 458 samples from 363 Korean epilepsy patients were analyzed. RESULTS.­: The method was linear with limit of detection less than 0.05 µg/mL in all analytes. Intraassay and interassay imprecisions were less than 5% coefficient of variation. Accuracy was within ±15% bias. Extraction recovery ranged from 85.9% to 98.8%. A total of 88% (403 of 458) were on polypharmacy, with 29% (118 of 403) using concomitant enzyme inducers. Only 38% (175 of 458) of the concentrations were therapeutic, with 53% (244 of 458) being subtherapeutic. Drug concentration and concentration-to-dose ratio were highly variable among individuals in all 6 ASMs. CONCLUSIONS.­: A simple and rapid LC-MS/MS method for TDM of 6 ASMs was developed and successfully applied to clinical practice. This large-scale TDM data could help establish an effective monitoring strategy for these drugs.

Clinical feature, GALC variant spectrum, and genotype-phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years.

Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by deficiency of the galactocerebrosidase (GALC) due to variants in the GALC gene. Here, we provide the first and the largest comprehensive analysis of clinical and genetic characteristics, and genotype-phenotype correlations of KD in Korean in comparison with other ethnic groups. From June 2010 to June 2023, 10 patients were diagnosed with KD through sequencing of GALC. Clinical features, and results of GALC sequencing, biochemical test, neuroimaging, and neurophysiologic test were obtained from medical records. An additional nine previously reported Korean KD patients were included for review. In Korean KD patients, the median age of onset was 2 years (3 months-34 years) and the most common phenotype was adult-onset (33%, 6/18) KD, followed by infantile KD (28%, 5/18). The most frequent variants were c.683_694delinsCTC (23%) and c.1901T>C (23%), while the 30-kb deletion was absent. Having two heterozygous pathogenic missense variants was associated with later-onset phenotype. Clinical features were similar to those of other ethnic groups. In Korean KD patients, the most common phenotype was the adult-onset type and the GALC variant spectrum was different from that of the Caucasian population. This study would further our understanding of KD.

Mental health of South Korean adolescents in the COVID-19 Era: Web-based survey focused on suicide-related factors.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has negatively impacted many aspects of life. Measures for preventing the spread of COVID-19 (e.g., school lockdowns, remote and hybrid classes, group and outdoor activity restrictions, and social distancing in the classroom and meal time) could have led to adolescents to experience anxiety and depressive symptoms. Such mental health impacts could increase the risk of suicidal ideation in this population. Moreover, according to a report by the Organization for Economic Co-operation and Development, although the total number of suicide deaths in South Korea decreased in 2021, the suicide rate of those aged 10-29 years increased. One factor affecting the result is adolescent mental health by COVID-19. This study examines the mental health status of South Korean adolescents amid the prolonged COVID-19 pandemic, and identifies and analyzes predictors of suicidal ideation, suicide planning, and suicide attempts. METHODS: The study used data from 54,948 adolescents who participated in the 2020 Korea Youth Risk Behavior Web-based Survey. Based on their responses to suicide-related questions, the sample was divided into a healthy group, suicide-ideation group, suicide-planning group, and suicide-attempt group. The descriptive statistics of these groups were then analyzed. An analysis of covariance, post-hoc tests, and multiple logistic regression analysis were performed on the four groups. RESULTS: Overall, 6.9% of the participants reported suicidal ideation, 2.2% reported planning suicide, and 1.9% reported attempting suicide in the previous 12 months. CONCLUSIONS: During the prolonged COVID-19 pandemic, there is a strong need for various individualized programs that identify and intervene to support adolescents at risk of suicide by accurately assessing their mental health risk factors, such as stress, sadness and despair, loneliness, and generalized anxiety disorder. Accordingly, it is necessary to develop and distribute a mental health and well-being curriculum, strengthen suicide prevention programs and support services, expand mental health diagnostic tests, and school-based mental health programs.

Analysis of MicroRNA Signature Differentially Expressed in Pancreatic Islet Cells Treated with Pancreatic Cancer-Derived Exosomes.

Since the majority of patients with pancreatic cancer (PC) develop insulin resistance and/or diabetes mellitus (DM) prior to PC diagnosis, PC-induced diabetes mellitus (PC-DM) has been a focus for a potential platform for PC detection. In previous studies, the PC-derived exosomes were shown to contain the mediators of PC-DM. In the present study, the response of normal pancreatic islet cells to the PC-derived exosomes was investigated to determine the potential biomarkers for PC-DM, and consequently, for PC. Specifically, changes in microRNA (miRNA) expression were evaluated. The miRNA specimens were prepared from the untreated islet cells as well as the islet cells treated with the PC-derived exosomes (from 50 patients) and the healthy-derived exosomes (from 50 individuals). The specimens were subjected to next-generation sequencing and bioinformatic analysis to determine the differentially expressed miRNAs (DEmiRNAs) only in the specimens treated with the PC-derived exosomes. Consequently, 24 candidate miRNA markers, including IRS1-modulating miRNAs such as hsa-miR-144-5p, hsa-miR-3148, and hsa-miR-3133, were proposed. The proposed miRNAs showed relevance to DM and/or insulin resistance in a literature review and pathway analysis, indicating a potential association with PC-DM. Due to the novel approach used in this study, additional evidence from future studies could corroborate the value of the miRNA markers discovered.

Factors associated with the download and use of mobile personal health record applications in Korean hospitals.

The use of mobile personal health records (m-PHR) has been little studied at the organizational level. This study was to investigate the relationships of various hospital-related factors with m-PHR use in Korean hospitals. Downloads of m-PHR applications for 101 hospitals were examined from May 26 to 30 June 2022. The dependent variable was the number of m-PHR downloads, and the major independent variables included six technological, organizational, and environmental factors. As technological factors, the number of computed tomography and magnetic resonance imagery devices were significantly associated with downloads (RR = 1.119, CI = 1.022-1.226, p = 0.016; and RR = 1.155; 95% CI = 1.024-1.302, p = 0.019, respectively). At the organizational level, the number of physicians, adjusting for the number of beds, and the number of medical information management staff showed significant associations (RR = 1.059, CI = 1.019-1.100, p = 0.004; and RR = 1.026, CI = 1.002-1.050, p = 0.033, respectively). From an environmental standpoint, downloads were positively associated with the proportion of the local population of working age (20-59 years) (RR = 1.102, CI 1.022-1.189, p = 0.012). Healthcare policymakers should pay close attention to these factors to advocate for the widespread use of m-PHR applications.

Assessing the Fear Factor of Coronavirus Disease 2019 (COVID-19) in Korea Using the COVID-19 Phobia Scale: A Cross-Sectional Study.

BACKGROUND: A study on coronavirus disease 2019 (COVID-19) phobia among students revealed that fear of contracting COVID-19 was associated with commuting to school and spending time with others at school. Therefore, it is the need-of-the-hour for the Korean government to identify factors affecting COVID-19 phobia among university students and to consider these factors while framing the policy direction for the process of returning to normalcy in university education. Consequently, we aimed to identify the current state of COVID-19 phobia among Korean undergraduate and graduate students and the factors affecting COVID-19 phobia. METHODS: This cross-sectional survey was conducted to identify the factors affecting COVID-19 phobia among Korean undergraduate and graduate students. The survey collected 460 responses from April 5 to April 16, 2022. The questionnaire was developed based on the COVID-19 Phobia Scale (C19P-S). Multiple linear regression was performed on the C19P-S scores using five models with the following dependent variables: Model 1, total C19P-S score; Model 2, psychological subscale score; Model 3, psychosomatic subscale score; Model 4, social subscale score; and Model 5, economic subscale score. The fit of these five models was established, and a P-value of less than 0.05 (F test) was considered statistically significant. RESULTS: An analysis of the factors affecting the total C19P-S score led to the following findings: women significantly outscored men (difference: 4.826 points, P = 0.003); the group that favored the government's COVID-19 mitigation policy scored significantly lower than those who did not favor it (difference: 3.161 points, P = 0.037); the group that avoided crowded places scored significantly higher than the group that did not avoid crowded places (difference: 7.200 points, P < 0.001); and those living with family/friends scored significantly higher than those in other living situations (difference: 4.606 points, P = 0.021). Those in favor of the COVID-19 mitigation policy had significantly lower psychological fear than those who were against it (difference: -1.686 points, P = 0.004). Psychological fear was also significantly higher for those who avoided crowded places compared to those who did not difference: 2.641 points, P < 0.001). Fear was significantly higher in people cohabitating than those living alone (difference: 1.543 points, P = 0.043). CONCLUSION: The Korean government, in their pursuit of a policy that eases COVID-19-related restrictions, will also have to spare no efforts in providing correct information to prevent the escalation of COVID-19 phobia among people with a high fear of contracting the disease. This should be done through trustworthy information sources, such as the media, public agencies, and COVID-19 professionals.

Efficient Generation of Dopaminergic Neurons from Mouse Ventral Midbrain Astrocytes.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a wellknown neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

Reduced Cytotoxicity by Repetitive mRNA Transfection in Differentiated Neurons.

Background and Objectives: mRNA-based protein expression technology has been used to express functional proteins. We have previously generated dopamine neurons from rat-embryo derived neural precursor cells (NPCs) through repeated transfection of synthetic transcription factor mRNA encoding dopamine-inducible genes. However, NPCs began to die approximately 10 d post-transfection. In this study, we examined a long-term transfection protocol that did not affect cell viability. Methods and Results: Experiments were performed in eight groups sorted according to the start date of mRNA transfection. mRNA was transfected into NPCs daily for 21 d and live cell images of each group were recorded. NPCs which were differentiated for more than five days showed sustained gene expression and appreciable viability despite daily mRNA transfection for 21 d. Conclusions: Repeated mRNA transfection requires cells with a sufficient differentiation period.

Identification of Mutations in the Thyroxine-Binding Globulin (TBG) Gene in Patients with TBG Deficiency in Korea.

BACKGRUOUND: Thyroxine-binding globulin (TBG) is a major transporter protein for thyroid hormones. The serpin family A member 7 (SERPINA7) gene codes for TBG, and mutations of the SERPINA7 gene result in TBG deficiency. Although more than 40 mutations have been reported in several countries, only a few studies of TBG deficiency and SERPINA7 gene mutation have been performed in Korea. The aim of this study is to review the clinical presentations and laboratory findings of patients with TBG deficiency and to investigate the types of SERPINA7 gene mutation. METHODS: Five unrelated Korean adults with TBG deficiency attending endocrinology clinic underwent SERPINA7 gene sequencing. Four patients harbored a SERPINA7 gene mutation. Serum thyroid hormones, anti-microsomal antibodies, and TBG were measured. Genomic DNA was extracted from whole blood. All exons and intron-exon boundaries of the TBG gene were amplified and sequencing was performed. RESULTS: Two patients were heterozygous females, and the other two were hemizygous males. One heterozygous female had coexisting hypothyroidism. The other heterozygous female was erroneously prescribed levothyroxine at a local clinic. One hemizygous male harbored a novel mutation, p.Phe269Cysfs*18, which caused TBG partial deficiency. Three patients had the p.Leu372Phefs*23 mutation, which is known as TBG-complete deficiency Japan (TBG-CDJ) and was also presented in previous mutation analyses in Korea. CONCLUSION: This study presents four patients diagnosed with TBG deficiency and provides the results of SERPINA7 gene sequencing. One novel mutation, p.Phe269Cysfs*18, causing TBD-partial deficiency and three cases of TBG-CDJ were demonstrated. It is necessary to identify TBG deficiency to prevent improper treatment. Also, sequencing of the SERPINA7 gene would provide valuable information about the TBG variants in Korea.

A novel splicing variant in GALNS in mucopolysaccharidosis IVA and the necessity of re-evaluating primer sequences.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome type A) is an autosomal recessive disorder caused by defects in the lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (GALNS) gene, leading to progressive systemic skeletal dysplasia. Early diagnosis and early intervention with enzyme replacement therapy are crucial for improving outcomes in these patients. However, a relatively high number of patients are genetically undiagnosed due to high allelic heterogeneity and the absence of robust functional evidence for most variants of the GALNS gene. Herein, we report a novel intronic variant identified with RNA analysis and an allele dropout (ADO) event caused by a common benign variant in the primer-binding site in a Korean boy with MPS IVA. A 28-month-old boy presented with pectus carinatum, kyphoscoliosis, and joint hypermobility with multiple skeletal dysplasia involving the vertebrae and hip joint. Total urinary glycosaminoglycans were elevated with a predominant keratan sulfate fraction, and GALNS (EC 3.1.6.4) activity was significantly decreased in leukocytes. Sanger sequencing was performed; however, only one heterozygous intronic variant with uncertain clinical significance, c.566+3A > T (p.(?)), was identified. As the patient exhibited clinical and biochemical features of MPS IVA, we conducted whole genome sequencing (WGS) of the patient and his family to clarify the molecular diagnosis. WGS revealed a compound heterozygous genotype, c.1019G > A (p.(Gly340Asp)) and c.566+3A > T (p.(?)), in the GALNS gene. On mRNA sequencing, c.566+3A > T, was confirmed to cause exon 5 skipping and a premature stop codon. With subsequent investigation, we discovered that the variant, c.1019G > A, was undetected on initial sequencing because of ADO due to a common benign variant (rs3859024:G > C) at the primer annealing location. We present a novel intronic variant with a splicing defect in the GALNS gene and suggest that clinicians review primer sequences in cases not diagnosed on Sanger sequencing before progressing to diagnostic steps such as WGS.

Clinical Characteristics of Adolescents Hospitalized Through Emergency Room for Intentional Self-Harm or Suicide Attempts.

Objectives: This study aimed to investigate the clinical characteristics of adolescents hospitalized through the emergency room for intentional self-harm or suicide attempts. Methods: This retrospective study used data from the Korean National Hospital Discharge In-depth Injury Survey conducted between 2006 and 2018 for individuals aged 10-24 years. The clinical characteristics of the patients were analyzed and compared across sex and age groups using the Rao-Scott chi-square tests and multiple logistic regression analysis for complex survey data. Results: The most common psychiatric diagnosis was mood disorder (22.0%), and more female patients were diagnosed with it than male patients (p=0.010). The 19-24 years age group was diagnosed with mood disorder the most compared to other younger groups (p=0.012). Male patients used lethal methods more than female patients (p=0.008), and the 19-24 years age group used more drug poisoning and cutting or piercing (p<0.001) for intentional self-harm or suicide attempts than younger groups. Conclusion: Adolescents hospitalized for intentional self-harm or suicide attempts showed significant differences in clinical characteristics across sex and age groups. These findings suggest that measures for preventing self-harm or suicide attempts need to be differentiated according to the sex and age of adolescents.

Correction: Kim et al. Diagnostic Value of Multiple Serum Biomarkers for Vancomycin-Induced Kidney Injury. J. Clin. Med. 2021, 10, 5005.

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Performance Evaluation of the i-SmartCare 10 Analyzer and Method Comparison of Six Point-of-Care Blood Gas Analyzers.

Blood gas, electrolyte, glucose, and lactate level measurement have an immediate and critical impact on patient care. We evaluated the performance of i-SmartCare 10 (i-SENS Inc., Seoul, Korea) and conducted a method comparison study of five point-of-care (POC) analyzers with i-SmartCare 10 as the comparator, according to the CLSI guidelines. Ten analytes (pH, pCO2, pO2, Na+, K+, Cl-, iCa2+, glucose, lactate, and Hct) were tested on six analyzers: i-SmartCare 10, ABL90 FLEX PLUS (Radiometer Medical ApS, Copenhagen, Denmark), i-Stat (Abbott Point of Care Inc., Princeton, NJ, USA), RapidLab 1265 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA), Stat Profile pHOx Ultra (Nova Biomedical, Waltham, MA, USA), and Gem Premier 5000 (Instrumentation Laboratory, Bedford, MA, USA). The total imprecision and linearity (r2>0.99) were excellent, except for a few analytes that narrowly escaped the preset criteria. Interference was noted for Na+ in the presence of a high K+ level and for iCa2+ in the presence of high K+ and Mg2+ levels. Forty of 48 items demonstrated either a proportional or systematic difference in regression analysis; the relative mean difference (%) of 14/48 items escaped the allowable total error in the difference plot analysis. i-SmartCare 10 shows acceptable performance, and using a single POC blood gas analyzer is recommended for monitoring.

Patient Factors Associated with Different Hospice Programs in Korea: Analyzing Healthcare Big Data.

The Korean government has implemented a pilot project that introduces a new type of hospice care program called "Consultative Hospice Care" (COHC) since August 2017. The COHC is a new type of hospice program for terminally ill patients in acute care wards, which is different from the Independent Hospice Unit (IHU) care. This study aimed to compare the characteristics of two groups of hospice patients: COHC care only and both IHU care and COHC groups. Healthcare claim data from 1 April 2018 to 31 March 2020 were retrieved from the HIRA data warehouse system. The main outcome variable was patients receiving COHC only or both COHC and IHU care. The total number of hospice patients was 6482. A multivariate logistic regression analysis was used. Of 6482 hospice care recipients, 3789 (58.5%) received both COHC and IHU care. Those who received both COHC and IHU care were significantly associated with several factors: period from the first evaluation to death (adjusted odds ratio (aOR), 1.026; 95% confidence internal (CI), 1.024-1.029; p < 0.0001), disease severity measured by the Charlson Comorbidity Index (aOR, 1.032; CI, 1.017-1.047; p < 0.0001), consciousness (aOR, 3.654; CI, 3.269-4.085; p < 0.0001), and awareness of end-stage disease (aOR, 1.422; CI, 1.226-1.650; p < 0.0001). The COHC program had a critical role in hospice delivery to terminally ill patients. Policymakers on hospice care need to establish plans that promote efficient hospice care delivery systems.

The influence of cohabitation type on the psychological vulnerability of family caregivers of people with dementia: Results from a community health survey of 324,078 people in Korea.

PURPOSE: The purpose of this study was to identify the mental health problems and quality of life of family caregivers of people with dementia, depending on whether they live with people with dementia. METHODS: The sample was divided into three groups: those without a family member with dementia, those with a family member with dementia but not living with them, and those living with a family member with dementia. Descriptive statistics, ANCOVA, and post-hoc tests were performed on key variables. We included a total of 324,078 people with at least one family member older than 60 years, whose data were extracted from the Korean Community Health Survey. Dependent variables: depressive symptoms, stress recognition, subjective health, happiness, and quality of life. INDEPENDENT VARIABLES: family member with dementia (yes/no), cohabitation type. Control variables: Sex, age, region (urban/rural), household income, and education level. RESULTS: Depressive symptoms and stress recognition were higher in people who live with a family member with dementia. Their subjective health, happiness, and quality of life were the lowest of the three groups. Overall, the indicators for people who lived with a family member with dementia were the most negative, followed by those who did not live with their family member with dementia, and then those who did not have such a family member. CONCLUSIONS: Family caregivers living with people with dementia must be prioritized in policies regarding dementia; a program that can provide emotional support and reduce the burden of care is needed.

Diagnostic Value of Multiple Serum Biomarkers for Vancomycin-Induced Kidney Injury.

Acute kidney injury (AKI) is a major contributor to in-hospital morbidity and mortality. Vancomycin, one of the most commonly used antibiotics in a clinical setting, is associated with AKI, with its incidence ranging up to 43%. Despite the high demand, few studies have investigated serum biomarkers to detect vancomycin-induced kidney injury (VIKI). Here, we evaluated the diagnostic value of nine candidate serum biomarkers for VIKI. A total of 23,182 cases referred for vancomycin concentration measurement from January 2018 to December 2019 were screened and 28 subjects with confirmed VIKI were enrolled (VIKI group). Age- and sex- matched control group consisted of 21 subjects who underwent vancomycin therapy without developing VIKI (non-VIKI group), and 23 healthy controls (HC group). The serum concentrations of clusterin, retinol binding protein 4 (RBP4), interleukin-18 (IL-18), tumor necrosis factor receptor 1 (TNF-R1), C-X-C motif chemokine ligand 10 (CXCL10), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, trefoil factor-3 (TFF3), and cystatin C were compared among the three groups, and their correlations with estimated glomerular filtration rate (eGFR) and diagnostic values for VIKI were assessed. All of the biomarkers except clusterin and RBP4 exhibited significant elevation in the VIKI group. Serum TFF3, cystatin C, TNF-R1, and osteopontin demonstrated an excellent diagnostic value for VIKI (TFF3, area under the curve (AUC) 0.932; cystatin C, AUC 0.917; TNF-R1, AUC 0.866; osteopontin, AUC 0.787); and except osteopontin, a strong negative correlation with eGFR (TFF3, r = -0.71; cystatin C, r = -0.70; TNF-R1, r = -0.60). IL-18, CXCL10, and NGAL showed weak correlation with eGFR and moderate diagnostic value for VIKI. This study tested multiple serum biomarkers for VIKI and showed that serum TFF3, cystatin C, TNF-R1, and osteopontin could efficiently discriminate VIKI patients. Further studies are warranted to clarify the diagnostic value of these biomarkers in VIKI.

Serum 5-Hydroxyindoleacetic Acid and Ratio of 5-Hydroxyindoleacetic Acid to Serotonin as Metabolomics Indicators for Acute Oxidative Stress and Inflammation in Vancomycin-Associated Acute Kidney Injury.

The incidence of vancomycin-associated acute kidney injury (VAKI) varies from 5-43%, and early detection of VAKI is important in deciding whether to discontinue nephrotoxic agents. Oxidative stress is the main mechanism of VAKI, and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been examined with respect to their involvement in ischemia/reperfusion damage in experimental animal models. In the current study, we assessed 5-HT and 5-HIAA as novel biomarkers for detecting VAKI in patients who have infections or compromised renal function, using a mass spectrometry-based metabolomics approach. We conducted amino acid profiling analysis and measurements of 5-HT and 5-HIAA using serum from subjects with VAKI (n = 28) and non-VAKI control subjects (n = 69), consisting of the infection subgroup (n = 23), CKD subgroup (n = 23), and healthy controls (HCs, n = 23). 5-HT was significantly lower in the VAKI group than in the non-VAKI groups, and the concentration of 5-HIAA and the ratio of 5-HIAA to 5-HT (5-HIAA/5-HT) showed higher values in the VAKI group. The infection subgroup presented a significantly greater 5-HIAA/5-HT ratio compared with the HC subgroup. Our study revealed that increased 5-HIAA/5-HT ratio has the potential to act as a VAKI surrogate marker, reflecting acute oxidative stress and inflammation.

Correlation between peripheral blood automated hematopoietic progenitor cell counts and flow cytometric CD34+ cell counts differs according to diagnosis in patients undergoing autologous peripheral blood stem cell transplantation.

BACKGROUND: An automated hematopoietic progenitor cell count measurement in Sysmex XN analyzer (XN-HPC) has been developed to assist flow cytometry CD34+ cell count measurement, which requires technical expertise and a long turnaround time. Here, we evaluated the correlation between XN-HPC count and flow cytometric CD34+ cell count in pre-harvest peripheral blood (PB) samples from patients undergoing autologous peripheral blood stem cell (PBSC) transplantation according to diagnosis and investigated the possible cause of the decreased correlation in plasma cell neoplasm patients. MATERIALS AND METHODS: We retrospectively included 399 patient data that had matched PB XN-HPC count and CD34+ cell count of PB and apheresis product from Samsung Medical Center (SMC) and the Hematopoietic Stem Cell (HSC) registry. We assessed the diagnostic accuracy and the potential cutoff values of XN-HPC count for predicting adequate PBSC collection. RESULTS: The PB XN-HPC count was 1.6 and 1.3-fold higher than the CD34+ cell count in SMC (25.0 vs 15.9/µl) and the HSC registry (20.0 vs 15.2/µl), respectively. Overall the correlation between the PB XN-HPC and CD34+ cell count was moderate (SMC, r = 0.71; HSC registry, r = 0.66). A significant proportional and systemic bias with overestimation of XN-HPC count were noted in the plasma cell neoplasm patients in both SMC and the HSC registry. However, no significant difference in correlation was observed according to myeloma-related laboratory parameters in plasma cell neoplasm patients. CONCLUSION: Our results suggest that XN-HPC count should be interpreted cautiously in cancer patients undergoing autologous PBSC transplantation, especially in those with plasma cell neoplasm.