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1.
Am J Emerg Med ; 78: 62-68, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38217899

ABSTRACT

INTRODUCTION: The role of lactate measurement in out-of-hospital cardiac arrest (OHCA) survivors remains controversial. We assessed the association between early lactate-related variables, OHCA characteristics, and long-term neurological outcome. METHODS: In OHCA patients who received targeted temperature management, lactate levels were measured at 0, 12, and 24 h after the return of spontaneous circulation. We calculated lactate clearance and time-weighted cumulative lactate (TWCL), which represent the area under the time-lactate curve. The area under the receiver operating characteristic curve (AUC) and the adjusted odds ratios (AORs) of lactate-related variables for predicting 6-month poor outcome (Cerebral Performance Category 3-5) were evaluated. Interactions between lactate variables and characteristics of OHCA were evaluated by a multivariable logistic model with interaction terms and subgroup analysis. RESULTS: A total of 347 OHCA patients were included. After adjustment, higher lactate levels at the three time points were associated with a poor outcome (AOR 1.10 [95% CI, 1.03-1.18], AOR 1.15 [95% CI, 1.02-1.29], and AOR 1.36 [95% CI, 1.15-1.60], respectively), while TWCL was the only lactate kinetics variable associated with a poor outcome (AOR 1.29 [95% CI, 1.12-1.49]). We identified several interactions between lactate-related variables and OHCA characteristics. In particular, the AUC of TWCL was excellent in cases of noncardiac etiology (AUC 0.92 [95% CI, 0.86-0.96] but only moderate in cardiac etiology (AUC 0.69 [95% CI, 0.62-0.75]). CONCLUSIONS: Early lactate levels, especially at 24 h, and TWCL were independent predictors of neurologic outcome in these patients, whereas lactate clearance was not. The prognostic ability of lactate-related variables varied depending on the OHCA characteristics.


Subject(s)
Cardiopulmonary Resuscitation , Hypothermia, Induced , Out-of-Hospital Cardiac Arrest , Humans , Lactic Acid , Out-of-Hospital Cardiac Arrest/therapy , Out-of-Hospital Cardiac Arrest/complications , Prognosis , Logistic Models
2.
Crit Care ; 27(1): 113, 2023 03 16.
Article in English | MEDLINE | ID: mdl-36927495

ABSTRACT

OBJECTIVE: To determine the clinical feasibility of novel serum biomarkers in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM). METHODS: This study was a prospective observational study conducted on OHCA patients who underwent TTM. We measured conventional biomarkers, neuron­specific enolase and S100 calcium-binding protein (S-100B), as well as novel biomarkers, including tau protein, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and ubiquitin C-terminal hydrolase-L1 (UCH-L1), at 0, 24, 48, and 72 h after the return of spontaneous circulation identified by SIMOA immunoassay. The primary outcome was poor neurological outcome at 6 months after OHCA. RESULTS: A total of 100 patients were included in this study from August 2018 to May 2020. Among the included patients, 46 patients had good neurologic outcomes at 6 months after OHCA. All conventional and novel serum biomarkers had the ability to discriminate between the good and poor neurological outcome groups (p < 0.001). The area under the curves of the novel serum biomarkers were highest at 72 h after cardiac arrest (CA) (0.906 for Tau, 0.946 for NFL, 0.875 for GFAP, and 0.935 for UCH-L1). The NFL at 72 h after CA had the highest sensitivity (77.1%, 95% CI 59.9-89.6) in predicting poor neurological outcomes while maintaining 100% specificity. CONCLUSION: Novel serum biomarkers reliably predicted poor neurological outcomes for patients with OHCA treated with TTM when life-sustaining therapy was not withdrawn. Cutoffs from two large existing studies (TTM and COMACARE substudy) were externally validated in our study. The predictive power of the novel biomarkers was the highest at 72 h after CA.


Subject(s)
Hypothermia, Induced , Out-of-Hospital Cardiac Arrest , Humans , Prognosis , Biomarkers , Out-of-Hospital Cardiac Arrest/complications , Out-of-Hospital Cardiac Arrest/therapy , S100 Proteins
3.
Am J Emerg Med ; 66: 22-30, 2023 04.
Article in English | MEDLINE | ID: mdl-36669440

ABSTRACT

INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) outcomes are unsatisfactory despite postcardiac arrest care. Early prediction of prognoses might help stratify patients and provide tailored therapy. In this study, we derived and validated a novel scoring system to predict hypoxic-ischemic brain injury (HIBI) and in-hospital death (IHD). METHODS: We retrospectively analyzed Korean Hypothermia Network prospective registry data collected from in Korea between 2015 and 2018. Patients without neuroprognostication data were excluded, and the remaining patients were randomly divided into derivation and validation cohorts. HIBI was defined when at least one prognostication predicted a poor outcome. IHD meant all deaths regardless of cause. In the derivation cohort, stepwise multivariate logistic regression was conducted for the HIBI and IHD scores, and model performance was assessed. We then classified the patients into four categories and analyzed the associations between the categories and cerebral performance categories (CPCs) at hospital discharge. Finally, we validated our models in an internal validation cohort. RESULTS: Among 1373 patients, 240 were excluded, and 1133 were randomized into the derivation (n = 754) and validation cohorts (n = 379). In the derivation cohort, 7 and 8 predictors were selected for HIBI (0-8) and IHD scores (0-11), respectively, and the area under the curves (AUC) were 0.85 (95% CI 0.82-0.87) and 0.80 (95% CI 0.77-0.82), respectively. Applying optimum cutoff values of ≥6 points for HIBI and ≥7 points for IHD, the patients were classified as follows: HIBI (-)/IHD (-), Category 1 (n = 424); HIBI (-)/IHD (+), Category 2 (n = 100); HIBI (+)/IHD (-), Category 3 (n = 21); and HIBI (+)/IHD (+), Category 4 (n = 209). The CPCs at discharge were significantly different in each category (p < 0.001). In the validation cohort, the model showed moderate discrimination (AUC 0.83, 95% CI 0.79-0.87 for HIBI and AUC 0.77, 95% CI 0.72-0.81 for IHD) with good calibration. Each category of the validation cohort showed a significant difference in discharge outcomes (p < 0.001) and a similar trend to the derivation cohort. CONCLUSIONS: We presented a novel approach for assessing illness severity after OHCA. Although external prospective studies are warranted, risk stratification for HIBI and IHD could help provide OHCA patients with appropriate treatment.


Subject(s)
Brain Injuries , Out-of-Hospital Cardiac Arrest , Humans , Hospital Mortality , Retrospective Studies , Out-of-Hospital Cardiac Arrest/therapy , Prognosis
4.
Am J Emerg Med ; 58: 100-105, 2022 08.
Article in English | MEDLINE | ID: mdl-35660366

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic situation is a state that has had a great impact on the medical system and society. To respond to the pandemic situation, various methods, such as a pre-triage system, are being implemented in the emergency medical field. However, there are insufficient studies on the effects of this pandemic situation on patients visiting the emergency department (ED), especially those with cardio/cerebrovascular diseases (CVD)1 classified as time-dependent emergencies. METHODS: We performed a retrospective analysis of a cohort of patients from April 2020 to December 2020 (April 2020 was when the pre-triage system was established) compared to a parallel comparison patient cohort from 2019. The primary outcome was in-hospital mortality. CVD was defined by the patient's final diagnosis. RESULTS: During the same period, the number of patients who had visited the ED after COVID-19 had decreased to 79.1% of the number of patients who had visited the ED before COVID-19. The overall patient mortality and the mortality in the patients cardiovascular disease had both increased, while the mortality from cerebrovascular disease did not increase. Meanwhile, the ED length of stay had increased in all patients but did not increase in the patients with cardiovascular disease. CONCLUSION: As with prior studies conducted in other regions, in our study, the total number of ED visits were decreased compared to before COVID-19. The overall mortality had increased, particularly in the patients with cardiovascular disease.


Subject(s)
COVID-19 , Cardiovascular Diseases , Cerebrovascular Disorders , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Cerebrovascular Disorders/epidemiology , Emergency Service, Hospital , Humans , Pandemics , Retrospective Studies , SARS-CoV-2
5.
Am J Emerg Med ; 40: 133-137, 2021 02.
Article in English | MEDLINE | ID: mdl-32008828

ABSTRACT

BACKGROUND: The objective of this study was to test the hypothesis that an elevated neutrophil to lymphocyte ratio (NLR) at admission is associated with and increased risk of mortality in older patients admitted to the emergency department (ED). METHODS: We performed a retrospective analysis of patients admitted to the ED between November 2016 and February 2017. We included patients who were older than 65 years who visited the ED with any medical problem. We excluded patients with hematologic malignancy. Baseline NLR values were measured at the time of admission to the ED. The primary outcome was all-cause in-hospital mortality. A multivariate logistic analysis was performed. RESULTS: A total of 2777 patients were included in this study. The median age was 75 years (IQR 70-81), and 1359 (48.9%) patients were male. The in-hospital mortality rate was 5.0% (140 patients). The NLR value was higher in nonsurvivors (median, 8.08, IQR 4.29-15.25) than in survivors (median, 3.69, IQR 2.1-6.92, P < 0.001). In the multivariate logistic regression analysis, the NLR was associated with all cause in-hospital mortality after adjusting for confounding factors (OR = 1.03, 95% CI = 1.014-1.046). CONCLUSIONS: These results show that the NLR at admission is associated with in-hospital mortality among patients older than 65 years without hematologic malignancy. Thus, NLR at admission may represent a surrogate marker of disease severity.


Subject(s)
Emergency Service, Hospital , Hospital Mortality , Lymphocytes , Neutrophils , Aged , Female , Humans , Leukocyte Count , Male , Retrospective Studies , Risk Factors
6.
Exp Dermatol ; 27(3): 285-288, 2018 03.
Article in English | MEDLINE | ID: mdl-29392819

ABSTRACT

Skin cancer is the most common type of cancer. The incidence rate of skin cancer has continuously increased over the past decades. In an effort to discover novel anticancer agents, we identified a novel tubulin inhibitor STK899704, which is structurally distinct from other microtubule-binding agents such as colchicine, vinca alkaloids and taxanes. STK899704 inhibited microtubule polymerization leading to mitotic arrest and suppressed the proliferation of various cancer cell lines as well as multidrug resistance cancer cell lines. In this study, our investigation is further extended into animal model to evaluate the effect of STK899704 on skin carcinogenesis in vivo. Surprisingly, almost 80% of the tumors treated with STK899704 were regressed with a one-fifth reduction in tumor volume. Furthermore, the efficacy of STK899704 was nearly 2 times higher than that of 5-fluorouracil, a widely used skin cancer therapeutic. Overall, our results suggest that STK899704 is a promising anticancer chemotherapeutic that may replace existing therapies, particularly for skin cancer.


Subject(s)
Benzofurans/therapeutic use , Skin Neoplasms/drug therapy , Tubulin Modulators/therapeutic use , 9,10-Dimethyl-1,2-benzanthracene , Animals , Antimetabolites, Antineoplastic/therapeutic use , Carcinogenesis , Colchicine/therapeutic use , Disease Models, Animal , Fluorouracil/therapeutic use , Male , Mice , Skin Neoplasms/chemically induced , Skin Neoplasms/pathology , Tetradecanoylphorbol Acetate , Tubulin/metabolism
7.
Am J Emerg Med ; 36(12): 2187-2191, 2018 12.
Article in English | MEDLINE | ID: mdl-29622394

ABSTRACT

INTRODUCTION: The aim of this study was to identify factors associated with absent hematuria in patients with symptomatic urinary stones. METHODS: This retrospective study analyzed the clinical and imaging findings of emergency department patients who underwent computed tomography (CT) for suspected ureteral colic over the past 2years. All patients also underwent a microscopic urinalysis, and the presence of 4 or more red blood cells/high-power field was defined as microhematuria. RESULTS: A total of 798 patients were included in this study. Of these patients, 750 (94.0%) presented with hematuria, while 48 (6.0%) urine samples did not have evidence of hematuria. The group with an absence of hematuria was more likely to have a lower stone location (located in an area from the distal ureter to the bladder) and perinephric stranding on CT than the hematuria group (75.0% vs. 54.3%, p=0.005; 47.9% vs. 30.5%, p=0.012, respectively). The degree of hematuria at each stone location was significantly different (p=0.001). In multivariate analysis, perinephric stranding (odds ratios (OR) 1.87 [95% confidence interval (CI) 1.01-3.46], p=0.047), a lower stone location (OR 2.72 [95% CI 1.37-5.36], p=0.004), and elevated serum blood urea nitrogen (BUN) levels (OR 1.06 [95% CI 1.01-1.12], p=0.026) were associated with absent hematuria. CONCLUSIONS: In this large cohort of patients with renal colic, 6% had no microhematuria. Although some CT findings and elevated BUN were independently associated with hematuria absence, there was no difference in the demographics, time of presentation and degree and location of pain between the groups.


Subject(s)
Hematuria/diagnosis , Hydronephrosis/complications , Urinary Calculi/complications , Adult , Blood Urea Nitrogen , Emergency Service, Hospital , Female , Hematuria/etiology , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Renal Colic/diagnosis , Renal Colic/etiology , Republic of Korea/epidemiology , Retrospective Studies , Tomography, X-Ray Computed , Urinalysis , Urinary Calculi/diagnostic imaging
8.
Clin Sci (Lond) ; 130(2): 105-16, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26519425

ABSTRACT

Although apolipoprotein B100 (ApoB100) plays a key role in peripheral fat deposition, it is not considered a suitable therapeutic target in obesity. In the present study we describe a novel ApoB100 mimotope, peptide pB1, and the use of pB1-based vaccine-like formulations (BVFs) against high-fat diet (HFD)-induced obesity. In HFD- compared with chow-fed adolescent mice, BVFs reduced the 3-month body-weight gains attributable to increased dietary fat by 44-65%, and prevented mesenteric fat accumulation and liver steatosis. The body-weight reductions paralleled the titres of pB1-reactive immunoglobulin G (IgG) antibodies, and pB1-reactive antibodies specifically recognized native ApoB100 and a synthetic peptide from the C-terminal half of ApoB100. In cultured 3T3L1 adipocytes, anti-pB1 antibodies increased lipolysis and inhibited low-density lipoprotein (LDL) uptake. In cultured RAW 264.7 macrophages, the same antibodies enhanced LDL uptake (without causing foam cell formation). These findings make ApoB100 a promising target for an immunization strategy against HFD-induced obesity.


Subject(s)
Anti-Obesity Agents/therapeutic use , Apolipoprotein B-100/drug effects , Hypolipidemic Agents/pharmacology , Obesity/prevention & control , Peptides/therapeutic use , Animals , Anti-Obesity Agents/immunology , Antibody Formation/drug effects , Apolipoprotein B-100/immunology , Apolipoprotein B-100/physiology , Diet, High-Fat/adverse effects , Epitopes/immunology , Fatty Liver/prevention & control , Hypolipidemic Agents/immunology , Lipolysis/drug effects , Lipolysis/immunology , Lipolysis/physiology , Lipoproteins, LDL/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred ICR , Peptides/immunology , Rats , Rats, Sprague-Dawley
9.
Bioorg Med Chem Lett ; 25(23): 5625-31, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-26508549

ABSTRACT

Somatic heterozygous mutations of isocitrate dehydrogenase-1 (IDH1) are abundantly found in several types of cancer and strongly implicate altered metabolism in carcinogenesis. In the present study, we have identified α-mangostin as a novel selective inhibitor of mutant IDH1 (IDH1-R132H). We have observed that α-mangostin competitively inhibits the binding of α-ketoglutarate (α-KG) to IDH1-R132H. The structure-relationship study reveals that α-mangostin exhibits the strongest core inhibitor structure. Finally, we have observed that α-mangostin selectively promotes demethylation of 5-methylcytosine (5mC) and histone H3 trimethylated lysine residues in IDH1 (+/R132H) MCF10A cells, presumably via restoring the activity of cellular α-KG-dependent DNA hydroxylases and histone H3 lysine demethylases. Collectively, we provide evidence that α-mangostin selectively inhibits IDH1-R132H.


Subject(s)
Drug Discovery , Isocitrate Dehydrogenase/antagonists & inhibitors , Xanthones/chemistry , Binding, Competitive , Humans , Isocitrate Dehydrogenase/genetics , MCF-7 Cells , Molecular Structure , Mutation , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Structure-Activity Relationship , Xanthones/pharmacology
10.
J Cell Biochem ; 115(6): 1147-58, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24402912

ABSTRACT

Free fatty acid-induced lipotoxicity via increased endoplasmic reticulum (ER) stress and hepatocyte apoptosis is a key pathological mechanism of non-alcoholic steatohepatitis. A role of hypoxia-inducible factor 1α (HIF-1α) in this process has been suggested, but direct evidence is lacking. Here, we used HepG2 cells as a model to study whether HIF-1α can reduce palmitic acid-induced lipotoxicity and ER stress. In HepG2 cells treated with 500 µM palmitic acid, HIF-1α expression increased transiently, the decline was associated with increased cleaved caspase-3 expression. Overexpression and knockdown of HIF-1α decreased and exacerbated, respectively, palmitic acid-induced lipoapoptosis. The overexpression also blunted upregulation of the ER stress markers, C/EBP homologous protein (CHOP) and chaperone immunoglobulin heavy chain binding protein (Bip), while the knockdown increased the level of CHOP. In line with this, CHOP promoter activity decreased following HIF-1α binding to the CHOP promoter hypoxia response element. These results indicate that hepatocyte lipotoxicity is associated with decreased HIF-1α expression. It also suggests that upregulation of HIF-1α can be a possible strategy to reduce lipotoxicity in non-alcoholic fatty liver disease.


Subject(s)
Apoptosis/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Palmitic Acid/pharmacology , Animals , Blotting, Western , Caspase 3/metabolism , Cell Hypoxia , Cell Survival/drug effects , Choline Deficiency , Diet , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress/drug effects , Endoplasmic Reticulum Stress/genetics , Gene Expression/drug effects , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Hep G2 Cells , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Liver/metabolism , Liver/pathology , Methionine/deficiency , Mice, Inbred C57BL , Promoter Regions, Genetic/genetics , Protective Factors , Protein Binding , RNA Interference , Response Elements/genetics , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factor CHOP/genetics , Transcription Factor CHOP/metabolism
11.
Nat Cell Biol ; 9(11): 1303-10, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17952061

ABSTRACT

Mitochondrial proteins function as essential regulators in apoptosis. Here, we show that mitochondrial adenylate kinase 2 (AK2) mediates mitochondrial apoptosis through the formation of an AK2-FADD-caspase-10 (AFAC10) complex. Downregulation of AK2 attenuates etoposide- or staurosporine-induced apoptosis in human cells, but not that induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) or Fas ligand (FasL). During intrinsic apoptosis, AK2 translocates to the cytoplasm, whereas this event is diminished in Apaf-1 knockdown cells and prevented by Bcl-2 or Bcl-X(L). Addition of purified AK2 protein to cell extracts first induces activation of caspase-10 via FADD and subsequently caspase-3 activation, but does not affect caspase-8. AFAC10 complexes are detected in cells undergoing intrinsic cell death and AK2 promotes the association of caspase-10 with FADD. In contrast, AFAC10 complexes are not detected in several etoposide-resistant human tumour cell lines. Taken together, these results suggest that, acting in concert with FADD and caspase-10, AK2 mediates a novel intrinsic apoptotic pathway that may be involved in tumorigenesis.


Subject(s)
Adenylate Kinase/physiology , Apoptosis/physiology , Caspase 10/metabolism , Fas-Associated Death Domain Protein/metabolism , Isoenzymes/physiology , Adenylate Kinase/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cells, Cultured , HeLa Cells , Humans , Isoenzymes/pharmacology , Multienzyme Complexes/metabolism , Subcellular Fractions/metabolism
12.
Ther Hypothermia Temp Manag ; 14(1): 24-30, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37219575

ABSTRACT

Prognostication studies of cardiac arrest patients have mainly focused on poor neurological outcomes. However, an optimistic prognosis for good outcome could provide both justification to maintain and escalate treatment and evidence-based support to persuade family members or legal surrogates after cardiac arrest. The aim of the study was to evaluate the utility of clinical examinations performed after return of spontaneous circulation (ROSC) in predicting good neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM). This retrospective study included OHCA patients treated with TTM from 2009 to 2021. Initial clinical examination findings related to the Glasgow coma scale (GCS) motor score, pupillary light reflex, corneal reflex (CR) and breathing above the set ventilator rate were assessed immediately after ROSC and before the initiation of TTM. The primary outcome was good neurological outcome at 6 months after cardiac arrest. Of 350 patients included in the analysis, 119 (34%) experienced a good neurological outcome at 6 months after cardiac arrest. Among the parameters of the initial clinical examinations, specificity was the highest for the GCS motor score, and sensitivity was the highest for breathing above the set ventilator rate. A GCS motor score of >2 had a sensitivity of 42.0% (95% confidence interval [CI] = 33.0-51.4) and a specificity of 96.5% (95% CI = 93.3-98.5). Breathing above the set ventilator rate had a sensitivity of 84.0% (95% CI = 76.2-90.1) and a specificity of 69.7% (95% CI = 63.3-75.6). As the number of positive responses increased, the proportion of patients with good outcomes increased. Consequently, 87.0% of patients for whom all four examinations were positive experienced good outcomes. As a result, the initial clinical examinations predicted good neurological outcomes with a sensitivity of 42.0-84.0% and a specificity of 69.7-96.5%. When more examinations with positive results are achieved, a good neurological outcome can be expected.


Subject(s)
Cardiopulmonary Resuscitation , Hypothermia, Induced , Out-of-Hospital Cardiac Arrest , Humans , Hypothermia, Induced/methods , Prognosis , Retrospective Studies , Out-of-Hospital Cardiac Arrest/diagnosis , Out-of-Hospital Cardiac Arrest/therapy , Glasgow Coma Scale , Cardiopulmonary Resuscitation/methods
13.
PLoS One ; 19(2): e0298632, 2024.
Article in English | MEDLINE | ID: mdl-38330019

ABSTRACT

Hyperglycemia is commonly observed in critically ill patients and postcardiac arrest patients, with higher glucose levels and variability associated with poorer outcomes. In this study, we aim to compare glucose control in diabetic and nondiabetic patients using glycated hemoglobin (HbA1c) levels, providing insights for better glucose management strategies. This retrospective observational study was conducted at Seoul St. Mary's Hospital from February 2009 to May 2022. Blood glucose levels were measured hourly for 48 h after return of spontaneous circulation (ROSC), and a glucose management protocol was followed to maintain arterial blood glucose levels between 140 and 180 mg/dL using short-acting insulin infusion. Patients were categorized into four groups based on diabetes status and glycemic control. The primary outcomes assessed were neurological outcome and mortality at 6 months after cardiac arrest. Among the 332 included patients, 83 (25.0%) had a previous diabetes diagnosis, and 114 (34.3%) had an HbA1c of 6.0% or higher. At least one hyperglycemic episode was observed in 314 patients (94.6%) and hypoglycemia was found in 63 patients (19.0%) during 48 h. After the categorization, unrecognized diabetes was noticed in 51 patients with median HbA1c of 6.3% (interquartile range [IQR] 6.1-6.6). Patients with inadequate diabetes control had the highest initial HbA1c level (7.0%, IQR 6.5-7.8) and admission glucose (314 mg/dL, IQR 257-424). Median time to target glucose in controlled diabetes was significantly shorter with the slowest glucose reducing rate. The total insulin dose required to reach the target glucose level and cumulative insulin requirement during 48 h were different among the categories (p <0.001). Poor neurological outcomes and mortality were more frequently observed in patients with diagnosed diabetes. Occurrence of a hypoglycemic episode during the 48 h after ROSC was independently associated with poor neurologic outcomes (odds ratio [OR] 3.505; 95% confidence interval [CI], 2.382-9.663). Surviving patients following cardiac arrest exhibited variations in glucose hemodynamics and outcomes according to the categories based on their preexisting diabetes status and glycemic condition. Specifically, even experiencing a single episode of hypoglycemia during the acute phase could have an influence on unfavorable neurological outcomes. While the classification did not directly affect neurological outcomes, the present results indicate the need for a customized approach to glucose control based on these categories.


Subject(s)
Diabetes Mellitus , Heart Arrest , Hypoglycemia , Hypothermia, Induced , Humans , Blood Glucose , Glycated Hemoglobin , Insulin , Hypoglycemia/drug therapy , Heart Arrest/drug therapy , Hypoglycemic Agents/therapeutic use
14.
Arch Biochem Biophys ; 533(1-2): 11-7, 2013 May.
Article in English | MEDLINE | ID: mdl-23474458

ABSTRACT

Adenylate kinase isozyme 4 (AK4) belongs to a family of nucleotide monophosphate kinases involved in energy metabolism. Recently, AK4 was reported to play a role in protection from stress: In HEK293 cells, hypoxia increases AK4 expression but does not affect proliferation or viability, while RNA interference (RNAi) directed against AK4 inhibits proliferation and promotes death. By contrast, we show here that HepG2 cells showed much higher AK4 levels, which decreased under hypoxia along with markedly reduced cell proliferation and increased cell death. Nevertheless, RNAi directed against AK4 inhibited cell proliferation and caused death in both cell types, although cell cycle parameters were affected only in HepG2 cells. Hence reductions of AK4 levels were always associated with cell death. These results extend the notion of a stress-protective function of AK4 to a novel physiological context and show that AK4-mediated stress protection is not limited to one particular death scenario. Our data also allow the hypothesis that the different basal AK4 levels reflect different basal stress levels, causing alternative responses to additional stress.


Subject(s)
Adenylate Kinase/genetics , Gene Expression Regulation, Enzymologic , Stress, Physiological/genetics , Adenylate Kinase/deficiency , Adenylate Kinase/metabolism , Cell Death/genetics , Cell Hypoxia/genetics , Cell Proliferation , HEK293 Cells , Hep G2 Cells , Humans , Myeloid Cell Leukemia Sequence 1 Protein , Proto-Oncogene Proteins c-bcl-2/genetics , RNA Interference , Up-Regulation
15.
Pain Med ; 14(1): 5-13, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23241063

ABSTRACT

BACKGROUND AND OBJECTIVES: Ultrasound-guided cervical periradicular steroid injection (US-CPSI) is an attractive alternate to conventional C-arm guided transforaminal epidural injection for treatment of cervical radicular pain. We compared the technical differences and clinical outcomes between these two techniques. METHODS: Following ultrasound-guided needle placement, the extent of contrast media spread and the degree of tissue penetration were monitored by real-time fluoroscopy at the time of cervical periradicular injection in 59 patients. The spread pattern was judged to be medial foramen (medial bisector of foramen), lateral foramen (lateral bisector of foramen), or extraforaminal. The degree of tissue penetration was classified into periradicular, pararadicular, and intramuscular based on the penetration characteristics. Ultrasonographic images were categorized into crescent, perineuronal protruding, and intramuscular types. These groups were then correlated with clinical outcomes. RESULTS: The actual distance between the ultrasound-guided needle position and fluoroscopic target point was 1.9 and 2.3 cm in the oblique and anteroposterior view, respectively. Despite a difference in ultrasound and fluoroscopic end points, contrast dye spread was found to reach lateral foramen in 53%, medial foramen in 34%, and extraforaminal in 13% of the subjects. Analysis of postprocedural pain reduction (PPPR) showed significantly the better outcomes in periradicular and pararadicular penetration, medial and lateral, and crescent and perineural protruding type without subgroup differences than intramuscular penetration, extraforaminal spread, and ultrasonographic images of intramuscular type (P < 0.001). Analysis of clinical overall outcome showed favorable outcome in the groups with better results of PPPR. CONCLUSION: Our preliminary data suggest that the technique of UP-CPSI can provide an adequate local spread pattern, tissue penetration for treatment of cervical radicular pain.


Subject(s)
Contrast Media/pharmacokinetics , Pain/prevention & control , Radiculopathy/metabolism , Radiculopathy/prevention & control , Steroids/administration & dosage , Steroids/pharmacokinetics , Ultrasonography, Interventional/methods , Female , Humans , Injections, Epidural , Male , Middle Aged , Pain/diagnosis , Pain/metabolism , Pain Measurement/drug effects , Radiculopathy/diagnosis , Tissue Distribution , Tomography, X-Ray Computed/methods , Treatment Outcome
16.
Sci Rep ; 13(1): 14885, 2023 09 09.
Article in English | MEDLINE | ID: mdl-37689768

ABSTRACT

Comprehensive prediction of urolithiasis using available factors obtained in the emergency department may aid in patient-centered diagnostic imaging decisions. This retrospective study analyzed the clinical factors, blood chemistry and urine parameters of patients who underwent nonenhanced urinary computed tomography for suspected urolithiasis. A scoring system was developed from a logistic regression model and was tested using the area under the curve (AUC). The prevalence of urolithiasis and important possible causes in the three risk subgroups were determined. Finally, the scoring model was validated. In the derivation cohort (n = 673), 566 patients were diagnosed with urolithiasis. Age > 35 years, history of urolithiasis, pain duration < 8 h, nausea/vomiting, costovertebral angle tenderness, serum creatinine ≥ 0.92 mg/dL, erythrocytes ≥ 10/high power field, no leukocytes ≤ + , and any crystalluria were retained in the final multivariable model and became part of the score. This scoring model demonstrated good discrimination (AUC 0.808 [95% CI, 0.776-0.837]). In the validation cohort (n = 336), the performance was similar (AUC 0.803 [95% CI, 0.756-0.844]), surpassing that of the STONE score (AUC 0.654 [95% CI, 0.601-0.705], P < 0.001). This scoring model successfully stratified patients according to the probability of urolithiasis. Further validation in various settings is needed.


Subject(s)
Body Fluids , Urolithiasis , Humans , Adult , Retrospective Studies , Urinalysis , Urolithiasis/diagnosis , Urolithiasis/epidemiology , Area Under Curve
17.
Heliyon ; 9(12): e22582, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38076158

ABSTRACT

Objectives: Spectrin breakdown products 145 kDa (SBDP145) and neurofilament heavy chain (Nf-H) have been identified as potential biomarkers of neuronal injury. However, their ability to predict hypoxic-ischemic brain injury following cardiac arrest in humans is not well understood. This study aimed to investigate whether SBDP145 and Nf-H could be used as biomarkers to predict neurological outcomes after cardiac arrest. Methods: This prospective study was conducted at two academic hospitals and included adults who survived after cardiac arrest. Blood samples were collected at 0, 24, and 48 h after the return of spontaneous circulation, and biomarker analyses were performed to measure SBDP145 and Nf-H. Poor neurological outcome was defined as a modified Rankin Score of 4-6, and diagnostic performance was determined by receiver-operating characteristics analysis. Results: A total of 56 patients were included in this study. There were no significant differences in levels of SBDP145 or Nf-H between the poor and good outcome groups at any time point. Areas under the receiver-operating characteristics curve of SBDP145 and Nf-H were small, ranging from 0.51 to 0.7. At 0, 24, and 48 h, SBDP145 showed very low sensitivity (18.61 %, 13.89 %, and 13.79 %, respectively) and accuracy (33.93 %, 36.74 %, and 39.02 %, respectively) at a cut-off value for 100 % specificity. Nf-H also showed very low sensitivity (9.30 %, 16.67 %, and 0 %, respectively) and accuracy (29.09 %, 36.74 %, and 30.95 %, respectively). Conclusions: SBDP145 and Nf-H were found to be poor predictors of poor neurological outcomes six months after cardiac arrest.

18.
PLoS One ; 18(1): e0279653, 2023.
Article in English | MEDLINE | ID: mdl-36608053

ABSTRACT

BACKGROUND: During cardiac arrest (CA) and after cardiopulmonary resuscitation, activation of blood coagulation and inadequate endogenous fibrinolysis occur. The aim of this study was to describe the time course of coagulation abnormalities after out-of-hospital CA (OHCA) and to examine the association with clinical outcomes in patients undergoing targeted temperature management (TTM) after OHCA. METHODS: This prospective, multicenter, observational cohort study was performed in eight emergency departments in Korea between September 2018 and September 2019. Laboratory findings from hospital admission and 24 hours after return of spontaneous circulation (ROSC) were analyzed. The primary outcome was cerebral performance category (CPC) at discharge, and the secondary outcome was in-hospital mortality. RESULTS: A total of 170 patients were included in this study. The lactic acid, prothrombin time (PT), activated partial thrombin time (aPTT), international normalized ratio (INR), and D-dimer levels were higher in patients with poor neurological outcomes at admission and 24 h after ROSC. The lactic acid and D-dimer levels decreased over time, while fibrinogen increased over time. PT, aPTT, and INR did not change over time. The PT at admission and D-dimer levels 24 h after ROSC were associated with neurological outcomes at hospital discharge. Coagulation-related factors were moderately correlated with the duration of time from collapse to ROSC. CONCLUSION: The time-dependent changes in coagulation-related factors are diverse. Among coagulation-related factors, PT at admission and D-dimer levels 24 h after ROSC were associated with poor neurological outcomes at hospital discharge in patients treated with TTM.


Subject(s)
Cardiopulmonary Resuscitation , Out-of-Hospital Cardiac Arrest , Humans , Treatment Outcome , Prospective Studies , Blood Coagulation , Lactic Acid
19.
J Cerebrovasc Endovasc Neurosurg ; 24(2): 121-128, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34695885

ABSTRACT

OBJECTIVE: The surgical method for treating spontaneous intracranial hemorrhage (ICH) is not well established despite ICH's high prevalence and poor prognosis. Minimally invasive surgery has recently received attention; however, literature on this method is scarce. In particular, the appropriate location of the catheter in the hematoma has not been described. We examined whether the catheter position affects the hematoma reduction in a hematoma >50 cc. METHODS: We investigated the prognoses of 36 patients with ICH who underwent stereotactic aspiration and hematoma drainage using urokinase from January 2010 to December 2018 and the hematoma reduction rates according to the tube position. Two methods evaluated the position of the catheter. In the first method, the hematoma was an imaginary sphere. The center point was set as the operation target. We evaluated the catheter position by determining whether it was in the deep part or the outer part of the half point from that location to the hematoma margin. In the second method, we evaluated whether the catheter was located 1 cm inside the hematoma margin. RESULTS: In both the first and second evaluations, there were no differences in age, midline shift, intraventricular hemorrhage status, hematoma volume on admission, Glasgow Coma Scale score on admission, time to operation after symptom onset, and systolic blood pressure. The rates of decrease in bleeding and the prognoses were also not significantly different. CONCLUSIONS: If the catheter is in the hematoma, the rate of hematoma reduction at any position is similar.

20.
Korean J Med Educ ; 34(4): 319-325, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36464902

ABSTRACT

PURPOSE: Using simulation in continuing professional development (CPD) courses for local practitioners is uncommon in Korea. The aim of our study was to evaluate the responses of the local practitioners for a simulation-based short CPD course. METHODS: Following the targeted needs assessment of local practitioners, we developed and implemented a 3-hour simulation-based CPD course for the first 5 minutes of cardiac arrest in the resource-limited local clinics. We evaluated the participant's responses to the course using a questionnaire. RESULTS: During the 3-year implementation period, 115 practitioners participated in 10 courses, and 113 (98%) responded to the questionnaire. The overall course satisfaction (10-point scale) was very positive (10 in 93 [82.3%], 9 in 19 [16.8%], and 8 in 1 [0.8%]). The level (5-point scale) of recommendation to the others was also high (5 in 103 [91.2%] and 4 in 10 [8.8%]). Many participants positively commented on the authentic practical experience of the uncommon crisis in their contexts. CONCLUSION: A simulation-based short CPD course for in-hospital cardiac arrest could provide an authentic practical experience for local practitioners working in resource-limited clinics.


Subject(s)
Heart Arrest , Humans , Republic of Korea , Needs Assessment
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