Hyperattenuating lesions after mechanical thrombectomy in acute ischaemic stroke: factors predicting symptomatic haemorrhage and clinical outcomes.

AIM: To evaluate the clinical significance of hyperattenuating lesions on CT after mechanical thrombectomy for acute ischaemic stroke, and to identify imaging factors that predict symptomatic haemorrhage and unfavourable outcomes. MATERIALS AND METHODS: Seventy-eight patients with acute ischaemic stroke in the anterior circulation who underwent mechanical thrombectomy were evaluated. All patients underwent post-interventional unenhanced computed tomography (CT) within 24 h and follow-up CT or magnetic resonance imaging (MRI) within 7 days. Baseline characteristics and clinical outcomes were compared between patients with and without hyperattenuating lesions. In patients with hyperattenuating lesions, clinical and imaging factors that predict symptomatic haemorrhage and unfavourable outcomes were determined. RESULTS: Fifty-six of 78 patients (71.8%) demonstrated hyperattenuating lesions on post-interventional CT. Patients with hyperattenuating lesions showed lower Alberta Stroke Program Early CT score (ASPECTS), persistent/symptomatic haemorrhage, and unfavourable outcomes than those without. In patients with hyperattenuating lesions, larger hyperattenuating lesion volume (>21.3 ml; OR, 55.60, p<0.001) and perilesional oedema (OR, 46.04, p=0.015) were independent factors predicting symptomatic haemorrhage. Older age (OR, 1.2, p=0.006) and lower ASPECTS (OR, 0.45, p=0.046) were independent factors predicting unfavourable outcomes in patients with hyperattenuating lesions. Adding the volume of the hyperattenuating lesion to age and ASPECTS increased the predictive performance of unfavourable outcomes (area under the curve 0.874 versus 0.934, p=0.043). CONCLUSIONS: Hyperattenuating lesions on post-interventional CT are associated with increased risk of symptomatic haemorrhage and unfavourable outcomes. Larger hyperattenuating lesion volume is an independent factor of symptomatic haemorrhage and it has added predictive value for unfavourable outcomes.

Association between body mass index and stroke severity in acute ischaemic stroke with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after acute ischaemic stroke (AIS) in patients with non-valvular atrial fibrillation (NVAF). METHODS: Patients were categorized on the basis of their BMI into underweight (BMI <18.5, n = 111), normal (18.5 ≤ BMI <25, n = 1036) and overweight to obese (BMI ≥25, n = 472) groups. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score and functional outcomes were assessed using the modified Rankin Scale score at discharge. The differences in stroke severity and functional outcomes were compared between groups using robust log-linear regression with a Poisson distribution and binary logistic regression analysis. RESULTS: A total of 1619 AIS patients with NVAF from six hospitals were included. Compared with the NIHSS scores [median 5, interquartile range (IQR) 2-14] of normal-weight patients, the NIHSS scores (median 9, IQR 4-19) of underweight patients were more likely to be higher, whereas those of overweight to obese patients were lower (median 4, IQR 1-12) (P < 0.001). In terms of functional outcomes after stroke, underweight patients had a higher risk of poor functional outcomes (odds ratio 1.78, 95% confidence interval 1.09-2.56, P = 0.01) but overweight to obese patients had no significant difference in functional outcomes compared with normal-weight patients. CONCLUSION: An inverse association was found between BMI and stroke severity in AIS patients with NVAF. This suggests the presence of an obesity paradox for short-term outcomes in patients with NVAF.

Nonlinear association between bone mineral density and all-cause mortality: the Dong-gu study.

There was a U-shaped association between hip BMD and all-cause mortality, with the lowest mortality in the 90th percentile in males. However, there was an inverse linear relationship in females. In contrast, the association between lumbar spine BMD and mortality was less evident in males, with no association in females. INTRODUCTION: Bone mineral density (BMD) is reported inversely associated with mortality. Although some previous studies provided evidence for nonlinear associations, these were not adequately assessed in most previous works. METHODS: We evaluated the nonlinear relationship between BMD and mortality in Asians. Our study involved 8629 participants in the Dong-gu study from 2007 to 2010. Cox proportional hazard regression was used to calculate hazard ratios (HRs) according to BMD categories after adjusting for potential confounders. During a follow-up of 6.7 ± 1.4 years, 712 participants died. RESULTS: There was a U-shaped association between hip BMD and all-cause mortality, with the lowest mortality in the 90th percentile in males. However, there was an inverse linear relationship in females. In males, compared with the 75th to 95th percentile group, the < 2.5th percentile group had a 3.89 (95% CI 2.41-6.28)-fold higher risk and the 2.5th to 5th percentile group had a 2.51 (95% CI 1.25-5.04)-fold higher risk. The HR was 2.51 (95% CI 1.25, 5.04) in the > 97.5th percentile group. In females, compared with that in the 75th to 95th percentile group, the HR was 2.33 (95% CI 1.24, 4.39) in the < 2.5th percentile group. In contrast, the association between lumbar spine BMD and mortality was less evident in males, with no association in females. CONCLUSION: In conclusion, this study shows that the association between BMD and mortality varies by gender and that high and low BMD are predictors of all-cause mortality in males.

Increased protein oxidation and decreased expression of nuclear factor E2-related factor 2 protein in skin tissue of patients with diabetes.

BACKGROUND: Reactive oxygen species (ROS) contribute to the cell dysfunction and tissue damage that result from glucolipotoxicity in diabetes. ROS formation in cells causes oxidative stress, thereby activating oxidative damage-inducing genes. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to play an essential role in the vital defence mechanisms that help cells cope with oxidative stress. AIM: To compare Nrf2 protein expression in nondiabetic skin tissue with that in diabetic skin tissue. METHODS: Nrf2 expression was evaluated by Western blotting, reverse transcription (RT)-PCR, and immunohistochemical staining in diabetic and nondiabetic skin tissues. Dinitrophenylhydrazone derivatives of protein carbonyls in the oxidized proteins were measured by oxyblotting analysis. Cytoplasmic and nuclear Nrf2 protein expression was determined to identify the activity and level of Nrf2. RESULTS: Protein oxidation, a marker of oxidative stress, was found to be increased in diabetic skin tissue. In subcellular fraction analysis, Nrf2 protein was detected in the nuclei and cytoplasm of nondiabetic skin tissues, and the Nrf2 protein band was identified from among the multiple bands detected, using small interfering RNA-mediated Nrf2 gene silencing. Compared with nondiabetic tissue, diabetic skin tissue showed simultaneous downregulation of Nrf2 at both the mRNA and protein levels. Nuclear condensation, loss of nuclei, and vacuolization were seen in some parts of the specimen by haematoxylin and eosin staining of diabetic skin tissue. Immunohistochemical staining of Nrf2 confirmed the RT-PCR and Western blotting results. CONCLUSIONS: Collectively, our data show that expression of Nrf2 is clearly downregulated in diabetic skin tissue, and suggest that Nrf2 may be necessary for protection against glucose-induced oxidative stress.

Differential impact of unrecognised brain infarction on stroke outcome in non-valvular atrial fibrillation.

There has been little information regarding the impact of unrecognised brain infarctions (UBIs) on stroke outcome in patients with non-valvular atrial fibrillation (NVAF). By using volumetric analysis of ischaemic lesions, we evaluated the potential impact of UBIs on clinical outcome according to their presence and categorised type. This study enrolled 631 patients with NVAF having no clinical stroke history. UBIs were categorised into three types as territorial, lacunar, or subcortical. We collected stroke severity, functional outcome at three months, and the total volume of UBIs and acute infarction lesions. We investigated the association between clinical outcome and the type or volume of UBI, using a linear mixed model and logistic regression analysis. UBIs were detected in 285 (45.2 %) patients; territorial UBIs were observed in 24.4 % of patients (154/631), lacunar UBIs in 25 % (158/631), and subcortical UBIs in 15.7 % (99/631). Although initial stroke severity was not different between patients with UBIs and those without, those with UBIs had less improvement during hospitalisation, leading to poorer outcome at three months. Among the three types of UBIs, only territorial UBIs were associated with poor outcome, especially in patients with relatively smaller acute infarction volume. UBIs, in particular, territorial UBIs, may be considered as predictors for poor outcome after ischaemic stroke in patients with NVAF. Our results suggest that the impact of UBIs on clinical outcome differs according to the type of UBIs and the acute stroke severity.

Comparison of stent retriever and intra-arterial fibrinolysis in patients with acute ischaemic stroke.

BACKGROUND AND PURPOSE: Although the stent retriever (SR) has shown a better reperfusion rate and clinical outcome than the older generation mechanical clot retrieval device, it is uncertain whether the SR is superior to intra-arterial fibrinolysis (IAF). METHODS: Ischaemic stroke patients who were treated with SR or IAF as initial endovascular treatment modality for unilateral arterial occlusion in the anterior circulation were included. Successful reperfusion was defined as Thrombolysis in Cerebral Infarction grade ≥2b. A favourable clinical outcome was defined as a modified Rankin Score ≤2 at 3 months. RESULTS: Between January 2009 and May 2012, 55 patients were treated with SR and 50 patients were treated with IAF. The baseline characteristics were similar between the two groups except for the occlusion site and rescue treatment. In binary logistic regression analysis adjusted for the occlusion site and rescue treatment, SR was independently associated with increased successful reperfusion [82.0% vs. 47.3%; odds ratio (OR) 5.21; 95% confidence interval (CI) 1.92-14.14) and a more favourable clinical outcome at 3 months (54.0% vs. 43.6%; OR 3.40; 95% CI 1.31-8.84). The frequency of symptomatic intracranial haemorrhage and mortality at 3 months was not different between the two groups. CONCLUSIONS: Stent retriever was as safe as and more effective than IAF. Our findings suggest that SR may be considered as an initial modality rather than IAF in acute stroke patients who undergo endovascular treatment.

The distribution of cerebral microbleeds determines their association with arterial stiffness in non-cardioembolic acute stroke patients.

BACKGROUND AND PURPOSE: Increased arterial stiffness causes vessel damage in the end-organs. Therefore small vessels in the brain may be susceptible to increased arterial stiffness. Cerebral microbleeds (CMBs) are topographically or pathophysiologically categorized as deep or infratentorial type and strictly lobar type. Whether the presence and location of CMBs are associated with brachial-ankle pulse wave velocity (baPWV) which represents a measure of arterial stiffness was investigated. METHODS: Between June 2006 and January 2012, 1137 consecutive patients diagnosed with non-cardioembolic acute ischaemic stroke and who underwent baPWV measurement and brain gradient-echo imaging were enrolled. CMBs were classified as deep or infratentorial or strictly lobar according to their location. Severity of leukoaraiosis was determined using the Fazekas scoring system. RESULTS: CMBs were found in 30.7% of the included patients. These patients were older than those without CMBs. Mean baPWV was higher in patients with CMBs than in those without (20 ± 5 m/s vs. 19 ± 5 m/s; P = 0.001). When comparing baPWV according to the location of the CMB, it was higher in the deep or infratentorial CMB group than in the strictly lobar CMB group (22 ± 5 m/s vs. 20 ± 5 m/s; P = 0.001). In univariate and multivariate multinomial logistic regression analyses, baPWV was found to be independently associated with deep or infratentorial CMBs. CONCLUSIONS: Arterial stiffness was independently associated with deep or infratentorial CMBs but not lobar CMBs. These findings suggest a pathophysiological association between arterial stiffness and CMBs in the deep or infratentorial region.

Race/ethnic differences in associations between bone mineral density and fracture history in older men.

SUMMARY: To determine whether there are race/ethnic differences in bone mineral density (BMD) by fracture history in men aged 65 years and older, we performed cross-sectional analysis in five large independent cohorts. Low BMD was associated with a higher prevalence of fracture in all cohorts, and the magnitude of the BMD differences by fracture status was similar across groups. INTRODUCTION: We aimed to determine whether there are race/ethnic and geographic differences in bone mineral density by fracture history in men aged 65 years and older. METHOD: The datasets included the Osteoporotic Fractures in Men (MrOS) Study (5,342 White, 243 African-American, 190 Asian, and 126 Hispanic), MrOS Hong Kong (1,968 Hong Kong Chinese), Tobago Bone Health Study (641 Afro-Caribbean), Namwon Study (1,834 Korean), and Dong-gu Study (2,057 Korean). The two Korean cohorts were combined. RESULTS: The prevalence of self-reported non-traumatic fracture was US white, 17.1 %; Afro-Caribbean, 5.5 %; US African-American, 15.1 %; US Hispanic, 13.7 %; US Asian, 10.5 %; Hong Kong Chinese, 5.6 %, and Korean, 5.1 %. The mean differences in hip and lumbar spine BMD between subjects with fracture and without fracture were statistically significant in all cohorts except US African American and US Asian men. There was a significant race/ethnic interaction for lumbar spine BMD by fracture status (p for interaction = 0.02), which was driven by the small number of Hispanic men. There was no interaction for femoral neck or total hip BMD. There were no significant race/ethnic differences in the odds ratio of fracture by BMD. CONCLUSIONS: Low BMD was associated with a higher prevalence of fracture in all cohorts and the magnitude of the BMD differences by fracture status was similar across groups suggesting homogeneity in the BMD-fracture relationship among older men.

Suicidal ideation in Korean persons with spinal cord injury.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To investigate the prevalence of suicidal ideation and attempt in Korean persons with spinal cord injury (SCI) and the factors related with suicidal ideation in comparison with a control group (CG). SETTINGS: Community-dwelling persons with chronic SCI in Korea. METHODS: A total of 382 persons with chronic SCI and 1104 able-bodied persons randomly selected from the general population and matched for age, sex and education level were compared. Suicidal ideation and attempt were recorded positive if the subjects had that experience during the past year. Psychosocial variables and injury-related factors were also evaluated. RESULTS: Suicidal ideation was found in 34.8% (127/365) of SCI persons and 10.4% (115/1104) in the CG (P<0.001). The rate of suicidal attempt among those with suicidal ideation was 17.3% (22/127) in SCI and 8.7% (10/115) in CG (P=0.048). Multiple logistic regression revealed that SCI itself (odds ratio (OR) 2.865) was a significant risk factor of suicidal ideation. However, completeness of injury and injury level were not significantly associated with suicidal ideation. Depressive mood (OR 11.194, P<0.001) and female gender (OR 3.706, P<0.001) were significant risk factors of suicidal ideation in the SCI group with a predictive percentage of 77.5%. CONCLUSION: Suicidal ideation was more frequent among Korean persons with SCI compared with able-bodied peers and closely related to psychosocial adjustment. The results support the need for active intervention to prevent suicide regardless of injury severity.

Disparate hypervariable region-1 of mitochondrial DNA did not induce skin allograft rejection in cloned porcine models.

INTRODUCTION: Alloantigen recognition in skin transplantation is the bane for surgeons. Several studies have mainly focused on the immunogenicity of major histocompatibility (MHC) antigens and H-Y minor histocompatibility antigens. However, the roles of the mitochondrial DNA (mtDNA) encorded miHA have not been identified. Therefore, we sought to address the antigenicity of the hypervariable region 1 (HV-1) of mtDNA in skin transplantation using cloned pig models. METHODS: Swine leukocyte antigen and HV-1 of mtDNA were analyzed using sequencing methods. Skin transplantation was performed between MHC-matched, mtDNA-mismatched cloned miniature pigs. Full-thickness skin was grafted between cloned pigs without any immunosuppressants. The grafted tissues were observed for 3 months and evaluated histologically. RESULTS: The cloned pigs shared identical MHC but mtDNA mismatched at 9 positions. Skin grafts between the cloned pigs were accepted and hair growth maintained, whereas MHC-mismatched grafts showed acute rejection within 7 days after transplantation and were replaced by hairless scar tissue. CONCLUSIONS: HV-1 disparate skin grafts were not recognized as alloantigenic by MHC-matched cloned pigs.

The association between asymptomatic coronary artery disease and CHADS2 and CHA2 DS2 -VASc scores in patients with stroke.

BACKGROUND AND PURPOSE: CHADS2 and CHA2 DS2 -VASc scores are measurement tools that stratify thromboembolic risk in patients with non-valvular atrial fibrillation, and are predictive of cerebral atherosclerosis, fatal stroke and ischaemic heart disease. Patients with higher CHADS2 and CHA2 DS2 -VASc scores are more likely to have had an akinetic/hypokinetic left ventricular segment or a recent myocardial infarction, all of which are associated with coronary artery disease (CAD). Most of the CHADS2 score components are also risk factors for atherosclerosis. Thus, CHADS2 and CHA2 DS2 -VASc scores may be predictive of CAD. METHODS: In all, 1733 consecutive patients with acute ischaemic stroke who underwent multi-slice computed tomography coronary angiography were enrolled. The association of CHADS2 and CHA2 DS2 -VASc scores with the presence and severity of CAD was investigated. RESULTS: Of the 1733 patients, 1220 patients (70.4%) had any degree of CAD and 576 (33.3%) had significant CAD (≥ 50% stenosis in at least one coronary artery). As the CHADS2 and CHA2 DS2 -VASc scores increased, the presence of CAD also increased (P < 0.001). The severity of CAD was correlated with CHADS2 score (Spearman coefficient 0.229, P < 0.001) and CHA2 DS2 -VASc score (Spearman coefficient 0.261, P < 0.001). In multivariate analysis, after adjusting for confounding factors, CHADS2 and CHA2 DS2 -VASc scores ≥2 were independently associated with CAD. The CHA2 DS2 -VASc score was a better predictor of the presence of CAD than the CHADS2 score on area under the curve analysis. CONCLUSION: CHADS2 and CHA2 DS2 -VASc scores were predictive of the presence and severity of CAD in patients with stroke. When a patient has high CHADS2 or CHA2 DS2 -VASc scores, physicians should consider coronary artery evaluation.

The frequency of cerebral microbleeds increases with CHADS(2) scores in stroke patients with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are extravasations of blood from lipohyalinized or amyloid angiopathic cerebral arterioles, and the presence and numbers of CMBs are significantly associated with the development of oral anticoagulation (OA)-related intracranial haemorrhage (ICH). The aim of this study was to investigate whether there is a difference in CMBs burden according to CHADS(2) scores or CHA(2) DS(2) -VASc scores in non-valvular atrial fibrillation (NVAF) patients. METHODS: We included 550 ischaemic stroke patients who had NVAF and who had undergone brain magnetic resonance imaging (MRI) with gradient-recalled echo (GRE) T2 sequences from our prospective stroke registry between January 2005 and November 2011. We calculated CHADS(2) scores and CHA(2) DS(2) -VASc scores for all patients based on their underlying cardiovascular diseases. The presence, location and number of CMBs were assessed in each patient. We also investigated whether the CMBs were actually associated with the development of ICH during follow-up. RESULTS: The mean patient age was 70.4 ± 10.5 years, and 324 (58.9%) patients were men. One-hundred and seventy-three patients (31.5%) had CMBs detected on GRE MRI. Higher CHADS(2) scores or CHA(2) DS(2) -VASc scores were strongly associated with the presence and number of CMBs. During follow-up of median 3.1 ± 1.6 years, the presence of CMBs was independently associated with the development of ICH, whilst the CHADS(2) scores or CHA(2) DS(2) -VASc scores were not. CONCLUSIONS: Considering the positive association between the presence of CMBs and OA-related ICH, our results suggest that the increase in ICH in high-risk groups during OA may be related to an increased burden of CMBs.

Low ankle-brachial index is a predictive factor for initial severity of acute ischaemic stroke.

BACKGROUND: A low ankle-brachial index (ABI) is predictive of peripheral arterial disease (PAD). For unknown reasons, patients with PAD demonstrate higher vascular mortality during follow-up than do those without. Initial stroke severity is a strong predictor of long-term outcome and may be different between patients with and without PAD. Thus, we investigated whether a low ABI was associated with severe stroke presentation. METHODS: We enrolled 1147 first-ever ischaemic stroke patients who underwent ABI measurements during hospitalization. Patients were categorized into the normal (≥ 0.90) or the abnormal (<0.90) ABI group. Baseline characteristics and initial National Institutes of Health Stroke Scale (NIHSS) scores were compared between the groups. We further analysed components of the NIHSS subscales in these groups. RESULTS: Ankle-brachial index was abnormal in 85 (7.4%) patients. Mean initial NIHSS score was higher in the abnormal ABI group (6.61 ± 6.56) than in the normal ABI group (4.36 ± 4.90) (P = 0.003). A low ABI was independently associated with higher NIHSS score in a multivariate analysis. In the abnormal ABI group, leg weakness was more severe than it was in the normal ABI group, and the contribution of leg weakness to the initial NIHSS score was higher. CONCLUSIONS: Patients with low ABI values presented with more severe ischaemic stroke. Contribution of pre-existing PAD to leg weakness may play a role in the initial severity of stroke in patients with PAD. Our findings suggest that poor clinical outcomes in patients with PAD may be partially explained by their increased likelihood for severe stroke.

Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients.

BACKGROUND: Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS: Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS: Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS: The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.

Prediction of thrombus resolution after intravenous thrombolysis assessed by CT-based thrombus imaging.

The degree of thrombus resolution directly indicates the effectiveness of a thrombolytic drug. We investigated the degree of thrombus resolution and factors associated with thrombus resolution after intravenous (IV) recombinant tissue plasminogen activator (rt-PA) using thin-section noncontrast computed tomography (NCT). Thin-section NCTs were performed before and immediately after IV rt-PA infusion in acute stroke patients. The thrombus volume and Hounsfield unit were measured using three-dimensional imaging software. Immediate recanalisation was assessed immediately after IV rt-PA infusion using CT angiography. During a three-year study period, 130 patients were prospectively enrolled. On baseline thin-section NCT, no thrombi were found in 30 patients (23%). Among the 100 patients with confirmed thrombus, the median volume decreased by 20% on the follow-up NCT. The thrombus was completely resolved in 8%. Of note, an increase in thrombus volume was observed in 20 patients. Independent predictors of thrombus resolution were total rt-PA dose, thrombus location in the M2 segment of the middle cerebral artery, and time from baseline to follow-up NCT. Thrombus resolution increased by 9% per each 10-mg increase in rt-PA (p = 0.045). Immediate complete recanalisation was achieved in 12% of patients. Total dose of rt-PA was independently associated with complete recanalisation [odds ratio [OR] 4.52, 95% confidence interval [CI] 1.345-15.184) and good functional outcome at three months (modified Rankin scale score <3, OR 2.34, 95% CI 1.104-4.962). In conclusion, rt-PA dose was associated with the degree of thrombus resolution, immediate complete recanalisation, and good outcome at three months. CT-based thrombus imaging may be helpful in determining thrombolysis effectiveness.

Cardiac markers of EIH athletes in ultramarathon.

This study aimed to investigate effects of a 100-km ultramarathon on cardiac markers of exercise-induced-hypertensive marathoners. 10 marathoners with exercise-induced hypertension and 10 normal marathoners participated in the study. Their blood samples were collected before starting, at 50 km, and after finishing the course (100 km). Creatinine kinase was more significantly increased in the exercise-induced-hypertensive group than in the normal group at 100 km (P<0.05). N-terminal pro-brain nutriuretic peptide was significantly increased in the exercise-induced-hypertensive group at 50 km and 10 km (P<0.05) which was significant being doubled compared to the normal group (P<0.05). Exercise-induced-hypertensive marathoners showed a significant triple-increase in C-Reactive protein at 100 km (P<0.05). In conclusion, although the exercise-induced-hypertensive runners did not have myocardial damage during the 100 km ultramarathon, they had higher myocardial stress and more damage in active muscles due to a bloodstream disability.

Use of a handheld, computerized device as a decision support tool for stroke classification.

BACKGROUND: The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification has been widely used to determine etiology of ischemic stroke. However, interrater reliability is known to be modest. The complexity of abstraction and the interpretation of various clinical and laboratory data might limit the accuracy of the TOAST classification. In this study, we developed a computerized clinical decision support system for stroke classification that can be used in a handheld device and tested whether this system can improve diagnostic accuracy and reliability. METHODS: Based on the TOAST classification, a logical algorithm was developed and implemented on a handheld device, named iTOAST. After answering six questions using the touch interface, the stroke subtype result is displayed on the screen. Four neurology residents were randomly assigned to classify stroke subtypes using iTOAST or the conventional method (cTOAST). Using a crossover design, they classified the stroke subtypes of 70 patients. The standard subtypes were determined by three stroke experts. Correlated kappa coefficients using iTOAST compared with cTOAST were determined. RESULTS: The kappa (SE) value of iTOAST [0.790 (0.041), 95% CI: 0.707-0.870] was higher than that of cTOAST [0.692 (0.046), 95% CI: 0.600-0.782] (P<0.001). Neither sequence (P=0.857) nor period effect (P=0.999) was observed. CONCLUSIONS: The stroke classification tool using a handheld, computerized device was easy, accurate, and reliable over the conventional method. It may have additional benefit because a handheld, computerized device is accessible anytime and anywhere.

Stroke mechanism in patients with non-valvular atrial fibrillation according to the CHADS2 and CHA2 DS2 -VASc scores.

BACKGROUND AND PURPOSE: The CHADS(2) and CHA(2) DS(2) -VASc scores are useful to stratify embolic risks in patients with non-valvular atrial fibrillation (NVAF) and to identify patients eligible for anticoagulation. Although the risk of stoke increases in patients with higher CHADS(2) or CHA(2) DS(2) -VASc scores, it is uncertain why the stroke rate increases in them. Concomitant potential cardiac sources of embolism (PCSE) may be more frequent in patients with higher CHADS(2) or CHA(2) DS(2) -VASc scores because stroke risks increase when concomitant PCSE is present in Atrial fibrillation (AF). On the other hand, atherothrombosis may be the cause when considering that most components of the CHADS(2) and CHA(2) DS(2) -VASc scores are risk factors for atherosclerosis. METHODS: Amongst 5493 stroke patients who were prospectively registered with the stroke registry for 11years, 860 consecutive patients with NVAF were included for this study. We investigated the mechanisms of stroke according to the CHADS(2) /CHA(2) DS(2) -VASc score in stroke patients with NVAF. RESULTS: Amongst 860 patients, concomitant PCSE were found in 334 patients (38.8%). The number of PCSE increased as the CHADS(2) /CHA(2) DS(2) -VASc score increased (P<0.001). Of individual PCSE, akinetic left ventricular segment, hypokinetic left ventricular segment and myocardial infarction <4weeks were associated with the CHADS(2) /CHA(2) DS(2) -VASc score. The presence of possible atherothrombotic mechanism, in addition to AF, was suggested in 27.3%. The proportion of patients with concomitant presence of possible atherothrombosis was increased as the CHADS(2) /CHA(2) DS(2) -VASc score increased (P<0.001). CONCLUSIONS: Increased frequency of concomitant PCSE and that of the atherothrombotic mechanism may explain the high risk of stroke in patients with higher CHADS(2) /CHA(2) DS(2) -VASc score.

Early neurological outcomes according to CHADS2 score in stroke patients with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: A higher CHADS(2) score or CHA(2)DS(2)-VASc score is associated with an increased risk of ischaemic stroke in patients with non-valvular atrial fibrillation (NVAF). However, there are no data regarding early neurological outcomes after stroke according to the risk levels. METHODS: In this study, a total of 649 stroke patients with NVAF were enrolled and categorized into three groups: low-risk (CHADS(2) score of 0-1), moderate-risk (CHADS(2) score 2-3), or high-risk group (CHADS(2) score ≥4). CHA(2)DS(2)-VASc score was divided into four groups including 0-1, 2-3, 4-5, and ≥6. We investigated whether there were differences in initial stroke severity, early neurological outcome, and infarct size according to CHADS(2) score or CHA(2)DS(2)-VASc score in stroke patients with NVAF. RESULTS: The initial National Institutes of Health Stroke Scale (NIHSS) score was highest in high-risk group [9.5, interquartile range (IQR) 4-18], followed by moderate-risk (8, IQR 2-17) and low-risk group (6, IQR 2-15) (P=0.012). Likewise, initial stroke severity increased in a positive fashion with increasing the CHA(2)DS(2)-VASc score. During hospitalization, those in the high-risk group or higher CHA(2)DS(2)-VASc score had less improvement in their NIHSS score. Furthermore, early neurological deterioration (END) developed more frequently as CHADS(2) score or CHA(2)DS(2)-VASc score increased. Multivariate analysis showed being in the high-risk group was independently associated with END (OR 2.129, 95% CI 1.013-4.477). CONCLUSIONS: Our data indicate that patients with NVAF and higher CHADS(2) score or CHA(2)DS(2)-VASc score are more likely to develop severe stroke and a worse clinical course is expected in these patients after stroke presentation.

Expression of RUNX3 in skin cancers.

BACKGROUND: Expression of Runt-related transcription factor 3 (RUNX3) is reduced in a large number of cancers. However, a few studies have reported higher expression of RUNX3 in several cancers, including basal cell carcinoma (BCC). In light of this, we explored the expression of RUNX3 in skin cancers generally, to determine whether it acts as an oncogene or a tumour-suppressor gene in skin tumours. AIM: To investigate the expression of RUNX3 in normal skin and malignant skin tumours. METHODS: RUNX3 expression was evaluated by western blotting in 24 specimens, comprising 6 malignant melanoma (MM), 6 squamous cell carcinoma (SCC), 6 BCC and 6 normal skin specimens. Immunohistochemical staining was carried out to analyse RUNX3 expression in 16 MM, 16 SCC and 16 BCC specimens. To identify where the protein was expressed, the cytoplasmic and nuclear protein expression of RUNX3 in skin cancer tissues was determined. A cell-proliferation study was performed on an MM line (G361) by small interfering (si)RNA transfection. RESULTS: The western blotting experiments showed that RUNX3 was not expressed in normal skin tissues, but it was overexpressed in all MM and SCC samples, and in five of the six BCC samples. Using immunochemistry, RUNX3 was found to be overexpressed in all cancer tissues analysed. Subcellular fraction analysis revealed that RUNX3 was expressed in the nuclei but not the cytoplasm of all the skin cancer tissues analysed, and RUNX3 silencing by siRNA in G361 cells resulted in a decrease in proliferation. CONCLUSIONS: Based on these results, we suggest that RUNX3 has an oncogenic potential and does not act as a tumour suppressor in skin cancers.