Background: and Purpose We investigated the impact of comorbidity burden on troponin elevation, with separate consideration of neurological conditions, in patients with acute ischemic stroke (AIS). Methods: This prospective, observational cohort study consecutively enrolled patients with AIS for 2 years. Serum cardiac troponin I was repeatedly measured, and disease-related biomarkers were collected for diagnosis of preassigned comorbidities, including atrial fibrillation (AF), ischemic heart disease (IHD), myocardial hypertrophy (MH), heart failure (HF), renal insufficiency (RI), and active cancer. The severity of neurological deficits and insular cortical ischemic lesions were assessed as neurological conditions. Adjusted associations between these factors and troponin elevation were determined using a multivariate ordinal logistic regression model and area under the receiver operating characteristic curve (AUC). Cox proportional hazards model was used to determine the prognostic significance of comorbidity beyond neurological conditions. Results: Among 1,092 patients (66.5±12.4 years, 63.3% male), 145 (13.3%) and 335 (30.7%) had elevated (≥0.040 ng/mL) and minimally-elevated (0.040–0.010 ng/mL) troponin, respectively. In the adjusted analysis, AF, MH, HF, RI, active cancer, and neurological deficits were associated with troponin elevation. The multivariate model with six comorbidities and two neurological conditions exhibited an AUC of 0.729 (95% confidence interval [CI], 0.698–0.759). In Cox regression, AF, IHD, and HF were associated with adverse cardio-cerebrovascular events, whereas HF and active cancer were associated with mortality. Conclusion Troponin elevation in patients with AIS can be explained by the burden of comorbidities in combination with neurological status, which explains the prognostic significance of troponin assay.

Fear of cancer recurrence (FCR) is one of the most prevalent unmet psychosocial needs. This study aimed to confirm the cultural equivalence, reliability, and validity of the Korean version of Fear of Cancer Recurrence Inventory (K-FCRI). We conducted a forward–backward translation of the English version FCRI to Korean version through meticulous process including transcultural equivalence test. The psychometric property of the K-FCRI was then validated in 444 survivors from cancers at various sites. The Korean translation was accepted well by participants. There was a good cultural equivalence between the Korean version and the English version of FCRI. Confirmatory factor analysis supported the original seven-factor structure with slightly insufficient level of goodness-of-fit indices (comparative fit index = 0.900, non-normed fit index = 0.893, root mean square error of approximation = 0.060). The K-FCRI had high internal consistency (α = 0.85 for total scale and α = 0.77–0.87 for subscales) and test-retest reliability (r = 0.90 for total scale and r = 0.54–0.84 for subscales). The K-FCRI had significant correlations with the Korean version of Fear of Progression Questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0, Hospital Anxiety and Depression Scale, and Fatigue Severity Score, supporting the good construct validity and psychometric properties of K-FCRI. The K-FCRI was confirmed as a valid and reliable psychometric test for measuring FCR of Korean survivors from cancers at various sites.
Anxiety ; Depression ; Fatigue ; Humans ; Psychometrics ; Quality of Life ; Recurrence* ; Reproducibility of Results ; Survivors

BACKGROUND AND PURPOSE: Decreasing the time delay for thrombolysis, including intravenous thrombolysis (IVT) with tissue plasminogen activator and intra-arterial thrombectomy (IAT), is critical for decreasing the morbidity and mortality of patients experiencing acute stroke. We aimed to decrease the in-hospital delay for both IVT and IAT through a multidisciplinary approach that is feasible 24 h/day. METHODS: We implemented the Stroke Alert Team (SAT) on May 2, 2016, which introduced hospital-initiated ambulance prenotification and reorganized in-hospital processes. We compared the patient characteristics, time for each step of the evaluation and thrombolysis, thrombolysis rate, and post-thrombolysis intracranial hemorrhage from January 2014 to August 2016. RESULTS: A total of 245 patients received thrombolysis (198 before SAT; 47 after SAT). The median door-to-CT, door-to-MRI, and door-to-laboratory times decreased to 13 min, 37.5 min, and 8 min, respectively, after SAT implementation (P<0.001). The median door-to-IVT time decreased from 46 min (interquartile range [IQR] 36–57 min) to 20.5 min (IQR 15.8–32.5 min; P<0.001). The median door-to-IAT time decreased from 156 min (IQR 124.5–212.5 min) to 86.5 min (IQR 67.5–102.3 min; P<0.001). The thrombolysis rate increased from 9.8% (198/2,012) to 15.8% (47/297; P=0.002), and the post-thrombolysis radiological intracranial hemorrhage rate decreased from 12.6% (25/198) to 2.1% (1/47; P=0.035). CONCLUSIONS: SAT significantly decreased the in-hospital delay for thrombolysis, increased thrombolysis rate, and decreased post-thrombolysis intracranial hemorrhage. Time benefits of SAT were observed for both IVT and IAT and during office hours and after-hours.
Ambulances ; Cerebral Infarction ; Humans ; Intracranial Hemorrhages ; Mortality ; Stroke* ; Thrombectomy ; Thrombolytic Therapy ; Tissue Plasminogen Activator

BACKGROUND AND PURPOSE: Little is known about the relationships between provoking risk factors, prognosis, and optimal duration of anticoagulation in patients with cerebral venous thrombosis (CVT), especially in Asians. We aimed to investigate whether the prognosis and required duration of anticoagulation in CVT patients differ according to the provoking risk factors. METHODS: Prospectively recorded data from a tertiary medical center in South Korea were retrospectively reviewed. CVTs were categorized into three groups: unprovoked, those with possibly resolved provoking factors (PR), and those with persistent provoking factors (PP). The baseline characteristics, treatment, and prognosis of patients in these three groups were analyzed. RESULTS: From 2000 to 2015, 61 patients presented with CVT: 19 (31.1%) unprovoked, 11 (18.0%) with PR, and 31 (50.9%) with PP. The patients in our cohort had a slight female predominance and lower frequency of oral contraceptive use compared to Western cohorts. Median follow-up and duration of anticoagulation were 35 and 8 months, respectively. Despite the similarities in baseline characteristics, deaths (n=3; P=0.256) and recurrences (n=7; P=0.020) were observed only in the PP group. The median intervals to death and recurrence were 9 and 13 months, respectively. Death was associated with underlying disease activity, not with CVT progression. Recurrences in the PP group were associated with lack of anticoagulation (P=0.012). CONCLUSIONS: Although the prognosis of CVT is generally benign in Koreans, recurrence and death were observed in patients with persistent risk factors, suggesting their need for long-term treatment with anticoagulants.
Anticoagulants ; Asian Continental Ancestry Group ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Korea ; Prognosis* ; Prospective Studies ; Recurrence ; Retrospective Studies ; Risk Factors* ; Venous Thrombosis*

BACKGROUND AND PURPOSE: Variant alleles of CYP2C9 and VKORC1 account for differences in anticoagulation response. We sought to establish a warfarin dosing formula for individualized target International Normalization Ratio of Prothrombin Times (INRs) using data from single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 in Korean patients. METHODS: Ischemic stroke patients displaying stable target INR for at least 3 months before enrollment were analyzed. Warfarin and vitamin K levels were measured to adjust for confounders. Phenotypes were defined using the 'warfarin response index' (WRI) defined as INR divided by the daily maintenance warfarin dose. We tested SNPs in CYP2C9 (3 sites: 430C>T (rs1799853), 1075A>C (rs1057910), 1076T>C) and VKORC1 (14 sites: 381C>T, 861C>A (rs17880887), 2653G>C, 3673A>G, 5496G>T, 5808T>G (r17882154), 6009C>T, 6484T>C (rs9934438), 6853C>T (rs17886369), 7566T>C, 8767G>C, 8814T>C, 9041G>A (rs17880624), and 9071G>T) using a standard sequencing method. Multivariate linear regression analysis was applied to establish the formula for warfarin dosage. RESULTS: All 204 patients had excellent drug compliance. The mean INR was 2.22 (+0.56) and mean daily maintenance dose of warfarin was 3.92 mg (+1.54). Patients with low WRI were younger (P<0.001) with high body mass index (P=0.003), high prevalence of wild-type CYP2C9 polymorphism (1075A>C, P<0.001), and six heterozygote SNPs in VRORC1 (P<0.001), which were tightly interlinked (381T>C, 3673G>A, 6484T>C, 6853C>G. 7566C>T, 9041G>A) (r2=1). Based on these data, a warfarin dosing formula was established. CONCLUSIONS: WRI is influenced by age, body mass index and SNPs in VKORC1 and CYP2C9 in Korean stroke patients. The obtained warfarin dosing formula may be clinically applicable.
Alleles ; Body Mass Index ; Compliance ; Genotype ; Heterozygote ; Humans ; International Normalized Ratio ; Linear Models ; Phenotype ; Polymorphism, Single Nucleotide ; Prevalence ; Prothrombin Time ; Stroke ; Vitamin K ; Warfarin

OBJECTIVES: An efficient clinical process guideline (CPG) modeling service was designed that uses an enhanced intelligent search protocol. The need for a search system arises from the requirement for CPG models to be able to adapt to dynamic patient contexts, allowing them to be updated based on new evidence that arises from medical guidelines and papers. METHODS: A sentence category classifier combined with the AdaBoost.M1 algorithm was used to evaluate the contribution of the CPG to the quality of the search mechanism. Three annotators each tagged 340 sentences hand-chosen from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) clinical guideline. The three annotators then carried out cross-validations of the tagged corpus. A transformation function is also used that extracts a predefined set of structural feature vectors determined by analyzing the sentential instance in terms of the underlying syntactic structures and phrase-level co-occurrences that lie beneath the surface of the lexical generation event. RESULTS: The additional sub-filtering using a combination of multi-classifiers was found to be more effective than a single conventional Term Frequency-Inverse Document Frequency (TF-IDF)-based search system in pinpointing the page containing or adjacent to the guideline information. CONCLUSIONS: We found that transformation has the advantage of exploiting the structural and underlying features which go unseen by the bag-of-words (BOW) model. We also realized that integrating a sentential classifier with a TF-IDF-based search engine enhances the search process by maximizing the probability of the automatically presented relevant information required in the context generated by the guideline authoring environment.
Data Mining ; Humans ; Hypertension ; Imidazoles ; Joints ; Knowledge Bases ; Natural Language Processing ; Nitro Compounds ; Search Engine

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells while sparing normal cells. However, many cancer cells are resistant to TRAIL-induced cell death. Here, we report that paxilline, an indole alkaloid from Penicillium paxilli, can sensitize various glioma cells to TRAIL-mediated apoptosis. While treatment with TRAIL alone caused partial processing of caspase-3 to its p20 intermediate in TRAIL-resistant glioma cell lines, co-treatment with TRAIL and subtoxic doses of paxilline caused complete processing of caspase-3 into its active subunits. Paxilline treatment markedly upregulated DR5, a receptor of TRAIL, through a CHOP/GADD153-mediated process. In addition, paxilline treatment markedly downregulated the protein levels of the short form of the cellular FLICE-inhibitory protein (c-FLIPS) and the caspase inhibitor, survivin, through proteasome-mediated degradation. Taken together, these results show that paxilline effectively sensitizes glioma cells to TRAIL-mediated apoptosis by modulating multiple components of the death receptor-mediated apoptotic pathway. Interestingly, paxilline/TRAIL co-treatment did not induce apoptosis in normal astrocytes, nor did it affect the protein levels of CHOP, DR5 or survivin in these cells. Thus, combined treatment regimens involving paxilline and TRAIL may offer an attractive strategy for safely treating resistant gliomas.
Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Astrocytes/metabolism ; CASP8 and FADD-Like Apoptosis Regulating Protein/genetics/*metabolism ; Caspase 3/metabolism ; Cell Line, Tumor ; Drug Discovery ; Flow Cytometry ; Glioma/*metabolism/pathology ; Humans ; Indoles/*pharmacology ; Inhibitor of Apoptosis Proteins/metabolism ; RNA, Small Interfering ; Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; TNF-Related Apoptosis-Inducing Ligand/metabolism/*pharmacology ; Transcription Factor CHOP/analysis

A 56-year-old male presented with resting dyspnea and chest discomfort for several years. During transthoracic and transesophageal echocardiography, a spontaneously healed membranous type ventricular septal defect (VSD) with malaligned interventricular septal wall, aneurysmal changes, a subaortic ridge and a double-chambered right ventricle (DCRV) was observed. When combined with DCRV, VSD with malalignment between the outlet and trabecular septa was associated with tetralogy of Fallot. The subaortic ridge was due to turbulent flow caused by the malalignment-type VSD. The VSD with malaligned interventricular septal wall can be developed after aneurismal changes of a perimembranous VSD. We report here in the unusual case of a 56-year-old patient who had a pathology complex comprising DCRV, subaortic ridge, spontaneously healed membranous type VSD with malaligned interventricular septal wall, and survived with surgical treatment.
Aneurysm ; Dyspnea ; Echocardiography, Transesophageal ; Heart Septal Defects, Ventricular ; Heart Ventricles ; Humans ; Male ; Middle Aged ; Tetralogy of Fallot ; Thorax

BACKGROUND: The overexpression of transforming growth factor-beta 1 receptor II (TGF-beta1RII) and transforming growth factor-beta 1 (TGF-beta1) ligand may be involved in the formation of a bulla. In this study, we tested if serum TGF-beta1 ligand levels correlated with the expression level of TGF-beta1RII and TGF-beta1 in bullous tissues from patients with spontaneous pneumothorax. MATERIAL AND METHOD: Bullous lung tissues and blood samples were obtained from 19 patients with spontaneous pneumothorax, 18 males and 1 female, aged 17 to 35 years old. The bullous tissues were obtained by video-assisted thoracic surgery (VATS), fixed in formalin, embedded in paraffin, and cut into 5~6micrometer thick slices. Sections were immunohistochemically stained with primary antibodies against TGF-beta1 or TGF-beta1RII, and serum levels of TGF-beta1 in patients and normal controls was measured by enzyme-linked immunosorbent assay (ELISA). RESULT: Of the 19 patients, 16 were TGF-beta1 positive and 10 were TGF-beta1RII positive. Among the 16 TGF-beta1 positives, 9 were also TGF-beta1RII positive. As seen previously, strong immunohistochemical staining of TGF-beta1RII and TGF-beta was detected in the boundary region between the bullous and normal lung tissues. Average TGF-beta1 blood levels of both TGF-beta1 and TGF-beta1RII positive patients was 38.36+/-16.2 ng/mL, and that of five controls was 54.06+/-15 ng/mL. CONCLUSION: These results suggest that overexpression of TGF-beta1 and TGF-beta1RII expression may be involved in the formation of bullae. TGF-beta1 blood levels in patients with primary spontaneous pneumothorax is lower than normal people, suggesting that the high level of local TGF-beta1 expression in the bullous tissue region, but not in the whole blood, may contribute more in the formation of bullae.
Aged ; Antibodies ; Blister ; Enzyme-Linked Immunosorbent Assay ; Female ; Formaldehyde ; Humans ; Lung ; Male ; Paraffin ; Pneumothorax ; Thoracic Surgery, Video-Assisted ; Transforming Growth Factor beta ; Transforming Growth Factor beta1