Different Metabolomic and Proteomic Profiles of Cerebrospinal Fluid in Ventricular and Lumbar Compartments in Relation to Leptomeningeal Metastases.

The different molecular profiles of cerebrospinal fluid (CSF) between ventricular and lumbar compartments remain elusive, especially in the context of leptomeningeal metastasis (LM), which affects CSF flow. We evaluated CSF metabolomic and proteomic profiles based on the compartments and the diagnosis of spinal LM, proved by MRI from 20 paired ventricular and lumbar CSF samples of LM patients, including 12 spinal LM (+) samples. In metabolome analysis, 9512 low-mass ions (LMIs) were identified-7 LMIs were abundant in all lumbar versus paired ventricular CSF samples, and 3 LMIs were significantly abundant in all ventricular CSF. In comparisons between spinal LM (+) CSF and LM (-) CSF, 105 LMIs were discriminative for spinal LM (+) CSF. In proteome analysis, a total of 1536 proteins were measured. A total of 18 proteins, including complement C3, were more highly expressed in all lumbar CSF, compared with paired ventricular CSF, while 82 proteins, including coagulation factor V, were higher in the ventricular CSF. Of 37 discriminative proteins, including uteroglobin and complement component C8 gamma chain, 4 were higher in all spinal LM (+) CSF versus spinal LM (-) CSF. We further evaluated metabolic pathways associated with these discriminative proteins using the Gene Ontology database. We found that 16/17 spinal LM (+) pathways, including complement activation, were associated with lumbar discriminative proteins, whereas only 2 pathways were associated with ventricular-discriminative proteins. In conclusion, we determined that metabolite and protein profiles differed between paired lumbar and ventricular CSF samples. The protein profiles of spinal LM (+) CSF showed more similarity with the lumbar CSF than the ventricular CSF. Thus, we suggest that CSF LMIs and proteins could reflect LM disease activity and that LM-associated differences in CSF are more likely to be present in the lumbar compartment.

Defects in aminoacyl-tRNA synthetase cause partial B and T cell immunodeficiency.

Aminoacyl-tRNA synthetases (ARSs) are emerging as important regulators in various immune diseases; however, their roles in immune cells remain unclear. In this study, using alanyl-tRNA synthetase (AARS) mutant (sti) mice with neurodegenerative disorder, we investigated the effect of translational fidelity in immune cells. Dysfunctional AARS caused disorders in immune cell responses and cellularity. The impairment was caused by dampened TCR signaling than cytokine signaling. Therefore, sti mutant inhibits TCR signaling, impeding T cell survival and responses. B cell numbers were decreased in sti mice. Despite low B cell cellularity, serum IgM, IgA, and IgE levels were higher in sti mice than in wild-type mice. Misacylation of ARS and the consequent translational infidelity induce disturbances in signaling pathways critical for immune cell survival and responses. Our findings provide a novel mechanism by which translational fidelity might play a critical role in cellular and humoral immune responses.

Experimental Assessment of Leptomeningeal Metastasis Diagnosis in Medulloblastoma Using Cerebrospinal Fluid Metabolomic Profiles.

Diagnosing leptomeningeal metastasis (LM) in medulloblastoma is currently based on positive cerebrospinal fluid (CSF) cytology or magnetic resonance imaging (MRI) finding. However, the relevance of discordant results has not been established. We evaluated the diagnostic potential of CSF metabolomic profiles in the medulloblastoma LM assessment. A total of 83 CSF samples from medulloblastoma patients with documented MRI and CSF cytology results at the time of sampling for LM underwent low-mass ions (LMIs) analysis using liquid chromatography-mass spectrometry. Discriminating LMIs were selected by a summed sensitivity and specificity (>160%) and LMI discriminant equation (LOME) algorithms, evaluated by measuring diagnostic accuracy for verifying LM groups of different MRI/cytology results. Diagnostic accuracy of LM in medulloblastoma was 0.722 for cytology and 0.889 for MRI. Among 6572 LMIs identified in all sample, we identified 27 discriminative LMIs differentiating MRI (+)/cytology (+) from MRI (-)/cytology (-). Using LMI discriminant equation (LOME) analysis, we selected 9 LMIs with a sensitivity of 100% and a specificity of 93.6% for differentiating MRI (+)/cytology (+) from MRI (-)/cytology (-). Another LOME of 20 LMIs significantly differentiated sampling time relative to treatment (p = 0.007) and the presence or absence of LM-related symptoms (p = 0.03) in the MRI (+)/cytology (-) group. CSF metabolomics of medulloblastoma patients revealed significantly different profiles among LM diagnosed with different test results. We suggest that LM patients could be screened by appropriately selected LOME-generated LMIs to support LM diagnosis by either MRI or cytology alone.

Plasma complement C7 as a target in non-small cell lung cancer patients to implement 3P medicine strategies.

BACKGROUND: Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) significantly affect outcomes in non-small cell lung cancer (NSCLC) patients. However, differences in reactions toward PD-1/PD-L1 ICI among patients impose inefficient treatment. Therefore, developing a reliable biomarker to predict PD-1/PD-L1 ICI reaction is highly necessary for predictive, preventive, and personalized (3P) medicine. MATERIALS AND METHODS: We recruited 63 patients from the National Cancer Center (NCC) and classified them into the training and validation sets. Next, 99 patients were recruited for inclusion into the external validation set at the Samsung Medical Center (SMC). Proteomic analysis enabled us to identify plasma C7 levels, which were significantly different among groups classified by their overall response to the RECIST V 1.1-based assessment. Analytical performance was evaluated to predict the PD-1/PD-L1 ICI response for each type of immunotherapy, and NSCLC histology was evaluated by determining the C7 levels via ELISA. RESULTS: Plasma C7 levels were significantly different between patients with and without clinical benefits (PFS ≥ 6 months). Among the groups sorted by histology and PD-1/PD-L1 immunotherapy type, only the predicted accuracy for pembrolizumab-treated patients from both NCC and SMC was greater than 73%. In patients treated with pembrolizumab, C7 levels were superior to those of the companion diagnostics 22C3 (70.3%) and SP263 (62.1%). Moreover, for pembrolizumab-treated patients for whom the PD-L1 tumor proportion score (TPS) was < 50%, the predictive accuracy of C7 was nearly 20% higher than that of 22C3 and SP263. CONCLUSION: Evaluation of plasma C7 levels shows an accurate prediction of NSCLC patient reactions on pembrolizumab. It demonstrates plasma C7 is an alternative and supportive biomarker to overcome the predictive limitation of previous 22C3 and SP263. Thus, it is clear that clinical use of plasma C7 allows predictive diagnosis on lung cancer patients who have not been successfully treated with current CDx and targeted prevention on metastatic diseases in secondary care caused by a misdiagnosis of current CDx. Reduction of patients' financial burden and increased efficacy of cancer treatment would also enable prediction, prevention, and personalization of medical service on NSCLC patients. In other words, plasma C7 provides efficient medical service and an optimized medical economy followed which finally promotes the prosperity of 3P medicine. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00266-x.

Influenza-associated Neurologic Complications in Hospitalized Pediatric Patients: A Multicenter Retrospective Study in Republic of Korea.

BACKGROUND: The rates of influenza-associated neurologic complications are variable among studies, and a difference has been observed between the Western and Asian countries. The study aims to evaluate the frequency and characteristics of influenza-associated neurologic complications. METHODS: We performed a retrospective review of hospitalized cases of influenza infection from October 2010 to April 2017 from 3 referral hospitals. RESULTS: A total of 1988 influenza cases were identified. Influenza-associated neurologic complications were 161 cases (8.1%); influenza virus A was detected in 113 (70.2%) cases, B in 47 (29.2%) cases and both A and B in 1 case (0.6%). Twenty-four patients (15%) had underlying neurologic diseases. The most common diagnosis was a simple febrile convulsion (44%), followed by complex febrile convulsion (29%), fever-provoked seizure under pre-existing neurologic disease or afebrile seizure (14%), encephalopathy/encephalitis (8%) and meningitis (5%). Most of the patients fully recovered (96%). Three patients (1.9%) died of myocarditis (n = 1), encephalopathy (n = 1), and simultaneous encephalitis and myocarditis (n = 1). Pre-existing neurologic disease, age groups of 6 months to 6 years and 6-12 years were a risk factor of influenza-associated neurologic complications with an adjusted odds ratio of 5.41 (95% confidence interval [CI] 3.23-9.06, P < 0.001), 12.99 (95% CI 1.77-95.19, P = 0.01) and 8.54 (95% CI 1.14-64.79, P = 0.04), respectively. There was no association between neuropsychiatric adverse events and oseltamivir prescription (P = 0.17). CONCLUSIONS: Influenza-associated neurologic complications are not uncommon, and most patients fully recovered. The frequency of influenza-associated neurologic complications in Korean children was not significantly different from that of children in Western countries.

Evaluation of changing trend in depression, suicidal ideation, and suicide attempts among adolescents with asthma and identification of associated factors: 11-year national data analysis in 788,411 participants.

OBJECTIVES: We identified associated factors for depression and suicidality in adolescents with asthma. METHODS: We obtained data from the annual Korea Youth Risk Behavior Web-based Surveys, completed from 2007 to 2017, as a stratified, multistage, clustered sample. Using self-reported questionnaires, students provided yes-or-no answers to questions addressing doctor-diagnosed asthma and self-experienced depression and suicidality. Associated factors for depression and suicidality were tested by logistic regression models after controlling for potential confounding factors. A total of 788,411 adolescents completed the survey. RESULTS: The prevalence of asthma was similar every year during the survey with 8.9% overall rate. Among them, the prevalence of depression (45.8-29.9%), suicidal ideation (28.6-15.5%), and suicide attempts (9.3-3.9%) decreased. Participants with asthma perceived themselves as unhealthier and unhappier, had more stress, sleep dissatisfaction, depression, suicidal ideation and suicide attempts than did subjects without asthma. In the multivariate model, perception of stress was most strongly associated with depression (adjusted Odds ratio: 4.78, 95% confidence intervals; 4.17-5.06) and suicide attempts (2.51; 1.67-2.93), whereas, perceived unhappiness was most strongly associated with suicidal ideation (4.81; 3.87-5.46) among adolescents with asthma. Asthma itself was also associated with depression, suicidal ideation and suicide attempts (1.12; 1.09-1.22, 1.18; 1.07-1.24, and 1.15; 1.04-1.19, respectively). CONCLUSION: Although the prevalence of asthma was similar every year, the prevalence of depression and suicidality among adolescents with asthma decreased. Nevertheless, clinical physicians should pay more attention to screen for depression and suicidality among adolescents with asthma, especially having associated factors.

Associated factors for depression, suicidal ideation and suicide attempt among asthmatic adolescents with experience of electronic cigarette use.

INTRODUCTION: While electronic cigarette (EC) use is rapidly increasing among asthmatic adolescents, little is known about the links between EC use and depression or suicidality. We assessed associated factors for depression and suicidality in asthmatic adolescents with experience of EC use. METHODS: We analyzed the data from the 11th to 13th Korea Youth Risk Behavior Web-based Surveys, which were completed from 2015 to 2017. Data were obtained from a stratified, multistage, clustered sample. Students supplied 'yes or no' answers to questions about previous asthma diagnosis by a doctor. Associated factors for depression and suicidality were evaluated by logistic regression models after controlling for potential confounding factors. We targeted 203336 adolescents, and 195847 completed the survey. RESULTS: The proportion of asthma among the respondents was 8.9%. The rate of experience of EC use was higher among asthmatic respondents than non-asthmatic respondents (10.3% vs 8.6%). Asthmatic respondents with experience of EC use had a much higher proportion of negative mental health states including depression and suicidality than subjects without EC experience. In our adjusted models, perception of stress was most strongly associated with depression (adjusted odds ratio, AOR=4.79; 95% CI: 4.12-5.58), and perception of unhappiness was most strongly associated with suicidal ideation (AOR=5.24; 95% CI: 4.51-6.09) and suicide attempt (AOR=4.37; 95% CI: 3.36-5.69). CONCLUSIONS: Many Korean asthmatic adolescents with experience of EC use report relatively high depression and suicidal behaviors. A multidisciplinary approach, including psychological help, may be required to prevent suicide among this population, especially those who report associated factors.

Comparative cerebrospinal fluid metabolites profiling in glioma patients to predict malignant transformation and leptomeningeal metastasis with a potential for preventive personalized medicine.

Glioma shows progression presenting as malignant transformation or leptomeningeal metastasis (LM). However, longitudinal biopsy of brain parenchyma is difficult due to its critical location, whereas cerebrospinal fluid (CSF) can be obtained serially with a little invasiveness of puncture. Thus, if we could find a biomarker for glioma progression, we could predict such event and determine therapeutic interventions as early as possible. In this study, we examined whether cerebrospinal fluid (CSF) metabolome profiles can reflect glioma grade, difference with non-glial tumor, and LM status. We selected 32 CSF samples from glioma patients, and compared them with 10 non-tumor control and seven non-glial brain tumor (medulloblastoma) samples. A total of 10,408 low-mass ions (LMIs) were detected as a candidate of metabolites using mass spectrometry, and representative LMIs were identified via the Human Metabolome Database. Grade IV gliomas showed eight LMIs, including acetic acid, of higher levels (summed sensitivity and specificity > 180%) than grade III gliomas. Grade IV gliomas demonstrated more abundant 30 LMIs, including glycerophosphate, compared with medulloblastoma, but none was mutually exclusive. Phospholipid derivatives were significantly more abundant in LM (-) than LM (+) gliomas regardless of glioma grade. LMIs representative of LM (+) gliomas were derivatives of glycolysis. We also verified discriminative LMIs based on mean expression level of each LMI (Student t test, p < 0.05) and evaluated the differences of the above analyses. Over 90% of metabolite pathways indicated from two analytical models were common to each other. Non-targeted mass spectrometry of CSF metabolites revealed significantly different profiles across gliomas that possibly permitted differentiation between glioma grades, LM, and non-glial brain tumors.

Associations between dietary habits, emotional state and subjective oral symptoms in 62,276 South Korean adolescents.

OBJECTIVE: The purpose of this study was to investigate the associations between dietary habits, emotional states, and subjective oral symptoms in Korean adolescents. METHODS: Data from 62,276 adolescents were derived from the 13th Korean Youth Risk Behavior Web-based Survey, conducting from June 1, 2017 to June 30, 2017. Oral symptoms were assessed by asking students whether they had experienced any of following symptoms within the last 12 months: (i) have you had a crack in your teeth or had any broken teeth not caused by exercise or other accidents?, (ii) have you experienced any toothaches while drinking or eating cold or hot beverages or foods?, (iii) have you ever felt throbbing in your teeth?, and (iv) have you experienced any gum pain or gum bleeding? A multivariable Poisson regression model for prevalence ratio (PR) was conducted. RESULTS: Of the participants, 53.1% experienced subjective oral symptoms. After adjusting for confounders, participants with consumption of sweet drinks more than five times weekly in dietary behaviors (PR: 1.17 [95% confidence interval (CI); 1.13-1.21]), feeling stress in the emotional state (PR: 1.27 [95% CI; 1.24-1.31]), and never brushing teeth (PR: 1.22 [95% CI; 1.14-1.30]) in the frequency of toothbrushing had higher risks of having oral symptoms compared to the reference group. CONCLUSION: Many adolescents in Korea experienced oral symptoms. The consumption of sweet drinks, infrequent toothbrushing, and a negative emotional state adversely affected perceived oral symptoms. Public concern about the oral health of adolescents is warranted.

Identification of influencing factors for suicidal ideation and suicide attempts among adolescents: 11-year national data analysis for 788,411 participants.

Suicide is one of the most common causes of death in adolescents. This study identified trends in the prevalence of and factors influencing suicidal ideation and attempts among Korean adolescents. Data were drawn from the third through the thirteenth (2007-2017) annual Korean Youth Risk Behavior Web-based Surveys. Participants included stratified, multistage clustered samples selected from 400 middle schools and 400 high schools annually. Depression, suicidal ideation, and suicide attempts were binary dependent variables (requiring answers of yes or no). A total of 818,684 adolescents were targeted and 788,411 adolescents completed the survey. The prevalence rates of both suicidal ideation and attempts gradually decreased from 23.7% and 5.8%, respectively, in 2007 to 12.1% and 2.6%, respectively, in 2017. Overall, 16.8% of participants had suicidal ideation and 3.9% had suicide attempts during the survey period. During logistic regression analysis, depression was most strongly associated with suicidal ideation (adjusted odds ratio: 5.78 [95% confidence interval: 5.64-5.88]) and suicide attempts (adjusted odds ratio: 5.56, [95% confidence interval: 5.22-5.83]). Despite decreasing trends, the high rate of suicidal behaviors remains a critical public health problem. Depression most strongly predicts suicidal behaviors. Early interventions are essential to treat depression and reduce or prevent suicide.

Evaluation of a possible association between allergic rhinitis and depression, suicidal ideation, and suicide attempts among adolescents based on a nationwide cross-sectional study.

OBJECTIVE: We assessed associated factors for depression and suicidality among adolescents with allergic rhinitis (AR) by analyzing data from annual Korea Youth Risk Behavior Web-based Surveys (KYRBSs) completed from 2007 to 2017. METHODS: Data from the KYRBS were obtained from a stratified, multistage, clustered sample. Using self-reported questionnaires, students provided yes-or-no answers to questions addressing their doctor-diagnosed AR and self-experienced depression, suicidal ideation and suicide attempts. Associated factors for depression and suicidality were identified by logistic regression models after controlling for potential confounding factors. A total of 818,684 adolescents were targeted, and 788,411 adolescents completed the survey. RESULTS: An AR diagnosis was reported in 30.8% of respondents. Among respondents with AR, 34.5%, 18.4%, and 4.2% reported depression, suicidal ideation, and suicide attempts, respectively. Adolescents with AR were significantly more likely to have negative mental health status, including suicidality than adolescents without AR. After multiple logistic regression analyses, perception of stress was most strongly associated with depression and suicidal ideation (adjusted odds ratio: 5.16 [95% confidence interval; 5.04-5.28], 4.81 [4.65-4.98], respectively). For suicide attempts, subjective unhappiness was most strongly associated (3.63 [3.47-3.79]) among adolescents with AR. Presence of AR itself was also associated with depression and suicidality (1.10 [1.08-1.11], 1.08 [1.06-1.10], 1.05 [1.01-1.08], respectively). CONCLUSION: Adolescents with AR had significantly greater prevalence of depression and suicidality. Multidisciplinary team approaches, including psychological support, may be needed to prevent suicide among adolescents with AR, especially those with identifiable risk factors.

Health-related behaviors and mental health states of South Korean adolescents with atopic dermatitis.

Atopic dermatitis (AD) is a common chronic skin disease with a negative influence on adolescent mental health state. We aimed to identify the influencing factors for mental health in adolescents with AD. We used data from the 13th Korean Youth Risk Behavior Web-based Survey (KYRBS) conducted in 2017. KYRBS data were obtained from a stratified, multistage, clustered sample. Participants responded to the question "have you ever been diagnosed with AD by a doctor?" and several yes/no questions about stress, depressive symptoms and suicidal ideation. Among 62 276 participants, the proportion of adolescents with AD was 25.0%. Compared with adolescents without AD, those with AD were significantly more likely to experience stress, depressive symptoms and suicidal ideation (P < 0.001) at rates of 59.1%, 27.8% and 13.9%, respectively. In the multivariate logistic regression model, subjective unhappiness was most strongly associated with stress in subjects with AD (adjusted odds ratio [aOR], 7.34; 95% confidence interval [CI], 5.87-9.18), while depression (aOR, 9.83; 95% CI, 7.85-11.32) and suicidal ideation (aOR, 5.70; 95% CI, 5.01-6.48) were reciprocally the most important risk factors in adolescents with AD. AD in adolescents is associated with a higher prevalence of stress, depressive symptoms and suicidal ideation. It is important for pediatricians to watch for these risks and to screen for suicidality in adolescents with AD.

Association of atopic dermatitis with suicide risk among 788,411 adolescents: A Korean cross-sectional study.

BACKGROUND: Atopic dermatitis (AD) is known to negatively influence the mental health of patients. However, only a few studies have explored the influencing factors for psychiatric problems among adolescents with AD. OBJECTIVE: To assess the association of AD and suicidal behaviors among adolescents by analyzing data from the 3rd through the 13th annual Korean Youth Risk Behavior Web-based Surveys (completed from 2007 to 2017). METHODS: Survey data were obtained from a stratified, multistage, clustered sample. Students self-reported AD if they had received a diagnosis of AD by a physician. Influencing factors for suicidal behaviors were tested by logistic regression models. RESULTS: A total of 788,411 adolescents completed the survey. The proportion of participants with AD was 22.2%. Those reporting suicide ideation and suicide attempts were 19.0%, and 4.5%, respectively. Compared with adolescents without AD, those with AD were more likely to be female, to skip breakfast less frequently, to exercise less frequently, to drink less alcohol, and to not be current smokers and were statistically significantly more likely to have negative mental health states. In the multivariable model, perceived unhappiness and suicidal ideation were the strongest influencing factors for suicidal ideation (adjusted odds ratio, 4.90; 95% CI, 4.31-5.57) and for suicidal attempts (adjusted odds ratio, 48.01; 95% CI, 42.69-53.09), respectively. CONCLUSION: Adolescents with AD had a meaningful prevalence of suicidal behaviors. Although further research is needed to clarify this association, adolescents with AD with influencing factors for negative mental health state may need intervention from practitioners who use a multidisciplinary team approach to prevent suicide.

Influencing Factors for Influenza Vaccination among South Korean Adolescents with Asthma Based on a Nationwide Cross-Sectional Study.

BACKGROUND: Influenza viral infection is a major public health problem with significant morbidity and mortality.Asthma is a risk factor for developing serious complications related to influenza infection. OBJECTIVE: We explored factors associated with influenza vaccination coverage among adolescents with asthma. METHODS: Data were obtained from 62,276 participants in the 13th Korean Youth Risk Behavior Web-Based Survey (KYRBS) conducted in 2017. KYRBS data were obtained from a stratified, multistage, clustered sample. We used multiple logistic regression analyses to identify variables potentially related to influenza vaccination in adolescents with asthma. RESULTS: The proportion of asthma was 8.8%, and the influenza vaccination rate overall was 37.9%. It was 41.8% in the asthma group and 37.5% in the nonasthma group (p < 0.001). After regression, male sex (odds ratio (OR) = 1.45; 95% CI 1.35-1.55), a high socioeconomic status (OR = 1.12; 95% CI 1.05-1.19), residence at an orphanage (OR = 1.93; 95% CI 1.38-2.29), regular breakfast consumption (OR = 1.09; 95% CI 1.02-1.17), and subjective good health (OR = 2.39; 95% CI 1.69-3.39) were associated with increased influenza vaccination, whereas current smoking (OR = 0.87; 95% CI 0.67-0.96) and a depressive mood (OR = 0.77; 95% CI 0.64-0.95) were inversely associated in adolescents with asthma. CONCLUSION: It is important to improve influenza vaccination in adolescents with asthma, especially females, those with a low socioeconomic status, independent residents, breakfast skippers, current smokers, and those who consider themselves unhealthy and have depressive moods.

Are there effects of lunar cycle on pediatric febrile seizure?: A single-center retrospective study (2005-2018).

BACKGROUND: Several studies have reported an association between seizure and the lunar cycle; however, results are conflicting. Thus, we investigated whether emergency department (ED) visits due to febrile seizure (FS) or FS plus were affected by lunar cycle. METHODS: We reviewed the medical records of patients who were admitted to the ED with a main diagnosis of FS or FS plus from January 1, 2005 to August 31, 2018 (13 years 8 months), a period of 4991 days with 169 lunar cycles. During that period, we collected weather data such as mean temperature, average atmospheric pressure (AP), and humidity according to lunar phase (new moon, first quarter, full moon, and third or last quarter). RESULTS: A total of 1979 patients were identified. We found male predominant with a mean age of 2.62 ±â€¯2.09 years. Acute pharyngotonsillitis was the most common cause of fever, generalized tonic-clonic seizure was the most common type of seizure, and the mean peak body temperature was 38.77 ±â€¯0.81 °C. The lunar cycle did not affect the onset or frequency of FS after adjustment; however, several factors, including season, O3 and NO2 concentrations, and holidays, were associated with FS. CONCLUSION: We did not find an association between lunar cycle and FS or FS plus. However, several factors, including season, O3, NO2, and holidays were associated with FS or FS plus.

Hyperammonemia in a case of herpes simplex and anti-N-methyl-d-aspartate receptor encephalitis.

Herpes simplex encephalitis (HSE) is a widely accepted risk factor for anti N-methyl-d-aspartate receptor (NMDAR) encephalitis. Association of inherited metabolic disease has never been reported in a patient with HSE and anti-NMDAR encephalitis. Herein, we report a case of pediatric HSE complicated by development of anti-NMDAR encephalitis; this patient showed subsequent recurrent, unexplained episodes of encephalopathy associated with hyperammonemia. The patient was diagnosed with lysinuric protein intolerance (LPI), a rare inborn metabolic disorder. Although it would be difficult to make conclusions regarding the casual link of HSE and anti-NMDAR encephalitis with LPI from a single case, there have been many reports that autoimmune diseases and immunologic abnormalities are frequently associated with LPI. Thus, we speculate that LPI may contribute to the development of anti-NMDAR encephalitis following HSE.

Usefulness of the procalcitonin test in young febrile infants between 1 and 3 months of age.

PURPOSE: To study the usefulness of the procalcitonin (PCT) test in young febrile infants between 1 and 3 months of age. METHODS: We evaluated the medical records of 336 febrile infants between 1 and 3 months of age who visited the Emergency Department or outpatient department of Samsung Changwon Hospital from May 2015 to February 2017, and analyzed the clinical characteristics between infants in the serious bacterial infection (SBI) group and non-SBI group. RESULTS: Among the 336 infants, 38 (11.3%) had definitive SBI (bacteremia, n=3; meningitis, n=1; urinary tract infection, n=34). The mean PCT (6.4±11.9 ng/mL) and C-reactive protein (CRP) level (3.8±2.6 mg/dL), and the absolute neutrophil count (ANC) (6,984±4,675) for patients in the SBI group were significantly higher than those for patients in the non-SBI group (PCT, 0.3±1.2 ng/mL; CRP, 1.3±1.6 mg/dL; ANC, 4,888±3,661). PCT had lower sensitivity (43.6%), but higher specificity (92.6%) and accuracy (86.9%) than CRP (92.3%, 25.3%, and 33.0%) for identifying SBI. The area under the receiver operating characteristic curves (AUCs) for definitive SBI were PCT 77.0%, CRP 80.8%, WBC 56.8%, ANC 67.8%, and PLT 48.1%. The AUCs for definitive SBI were PCT+CRP 85.4%, PCT+WBC 77.2%, PCT+ANC 81.3%, CRP+WBC 80.1%, and CRP+ANC 81.6%. CONCLUSION: Our results suggest that the PCT test or a combination of PCT and CRP tests is a more accurate and specific biomarker to detect and rule out SBIs.

Individualized metabolic profiling stratifies pancreatic and biliary tract cancer: a useful tool for innovative screening programs and predictive strategies in healthcare.

BACKGROUND: Pancreatic cancer (PC) and biliary tract cancer (BTC) are highly aggressive cancers, characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. Diagnosis of PC and BTC is complex and is made using a combination of appropriate clinical suspicion, imaging and endoscopic techniques, and cytopathological examination. However, the late-stage detection and poor prognosis of this tumor have led to an urgent need for biomarkers for early and/or predictive diagnosis and improved personalized treatments. WORKING HYPOTHESIS: There are two hypotheses for focusing on low-mass metabolites in the blood. First, valuable information can be obtained from the masses and relative amounts of such metabolites, which present as low-mass ions (LMIs) in mass spectra. Second, metabolic profiling of individuals may provide important information regarding biological changes in disease states that is useful for the early diagnosis of PC and BTC. MATERIALS AND METHODS: To assess whether profiling metabolites in serum can serve as a non-invasive screening tool for PC and BTC, 320 serum samples were obtained from patients with PC (n = 51), BTC (n = 39), colorectal cancer (CRC) (n = 100), and ovarian cancer (OVC) (n = 30), and from healthy control subjects (control) (n = 100). We obtained information on the relative amounts of metabolites, as LMIs, via triple time-of-flight mass spectrometry. All data were analyzed according to the peak area ratios of discriminative LMIs. RESULTS AND CONCLUSIONS: The levels of the 14 discriminative LMIs were higher in the PC and BTC groups than in the control, CRC and OVC groups, but only two LMIs discriminated between PC and BTC: lysophosphatidylcholine (LysoPC) (16:0) and LysoPC(20:4). The levels of these two LysoPCs were also slightly lower in the PC/BTC/CRC/OVC groups compared with the control group. Taken together, the data showed that metabolic profiling can precisely denote the status of cancer, and, thus, could be useful for screening. This study not only details efficient methods to identify discriminative LMIs for cancer screening but also provides an example of metabolic profiling for distinguishing PC from BTC. Furthermore, the two metabolites [LysoPC(16:0), LysoPC(20:4)] shown to discriminate these diseases are potentially useful when combined with other, previously identified protein or metabolic biomarkers for predictive, preventive and personalized medical approach.

Effect of Statins on Survival Following Stroke in Patients With Cancer.

The objective of this study was to investigate the potential benefits of statin therapy initiation in acute stroke in patients with active cancer. This study was conducted in two parts. First, data from patients who are presented with stroke and active cancer were obtained from prospectively collected multicenter hospital-based stroke registries. Patients were classified into statin user and non-user groups; the statin group was further divided into low-potency and high-potency statin subgroups. The primary outcome was time to mortality. Second, we obtained data from the Korean National Health Information Service-National Sample Cohort (NHIS-NSC) database for external validation and analyzed the effect of statins on mortality, taking compliance into consideration. For the stroke registry cohort, statin use was independently associated with reduced mortality in a multivariable model [hazard ratio (HR) = 0.675, 95% confidence interval (CI) = 0.457-0.996]. There was no interaction between statin use and cancer characteristics, vascular risk factors, or laboratory findings. A dose-dependent relationship between statin use and survival was also demonstrated. Analysis of the NHIS-NSC database found a similar association between statin therapy and reduced mortality (adjusted HR = 0.64, 95% CI = 0.45-0.90) and this effect persisted even after controlling for the adherence of statin use (HR = 0.60, 95% CI = 0.41-0.89). Statin therapy could be associated with reduced mortality in patients with acute stroke and active cancer.

Profiling of Serum Metabolites Using MALDI-TOF and Triple-TOF Mass Spectrometry to Develop a Screen for Ovarian Cancer.

PURPOSE: We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers. MATERIALS AND METHODS: A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis. An OVC LOME was constructed by reference to the peak intensity ratios of discriminatory low-mass ion (LMI) pairs. Triple-TOF analysiswas used to select and identify metabolic biomarkers for OVC screening. RESULTS: Three OVC LOMEs were finally constructed using discriminatory LMI pairs (137.1690 and 84.4119 m/z; 496.5022 and 709.7642 m/z; and 524.5614 and 709.7642 m/z); all afforded accuracies of > 90%. The LMIs at 496.5022 m/z and 524.5614 m/z were those of lysophosphatidylcholine (LPC) 16:0 and LPC 18:0. Triple-TOF analysis selected seven discriminative LMIs; each LMI had a specificity > 90%. Of the seven LMIs, fourwith a 137.0455 m/z ion atretention times of 2.04-3.14 minuteswere upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine. CONCLUSION: MALDI-TOF-based OVC LOMEs combined with triple-TOF-based OVC metabolic biomarkers allow reliable OVC screening; the techniques are mutually complementary both quantitatively and qualitatively.