Better performance of deep learning pulmonary nodule detection using chest radiography with pixel level labels in reference to computed tomography: data quality matters.

Labeling errors can significantly impact the performance of deep learning models used for screening chest radiographs. The deep learning model for detecting pulmonary nodules is particularly vulnerable to such errors, mainly because normal chest radiographs and those with nodules obscured by ribs appear similar. Thus, high-quality datasets referred to chest computed tomography (CT) are required to prevent the misclassification of nodular chest radiographs as normal. From this perspective, a deep learning strategy employing chest radiography data with pixel-level annotations referencing chest CT scans may improve nodule detection and localization compared to image-level labels. We trained models using a National Institute of Health chest radiograph-based labeling dataset and an AI-HUB CT-based labeling dataset, employing DenseNet architecture with squeeze-and-excitation blocks. We developed four models to assess whether CT versus chest radiography and pixel-level versus image-level labeling would improve the deep learning model's performance to detect nodules. The models' performance was evaluated using two external validation datasets. The AI-HUB dataset with image-level labeling outperformed the NIH dataset (AUC 0.88 vs 0.71 and 0.78 vs. 0.73 in two external datasets, respectively; both p < 0.001). However, the AI-HUB data annotated at the pixel level produced the best model (AUC 0.91 and 0.86 in external datasets), and in terms of nodule localization, it significantly outperformed models trained with image-level annotation data, with a Dice coefficient ranging from 0.36 to 0.58. Our findings underscore the importance of accurately labeled data in developing reliable deep learning algorithms for nodule detection in chest radiography.

Improvement in Delivery of Ischemic Stroke Treatments but Stagnation of Clinical Outcomes in Young Adults in South Korea.

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.

Densely Convolutional Spatial Attention Network for nuclei segmentation of histological images for computational pathology.

Introduction: Automatic nuclear segmentation in digital microscopic tissue images can aid pathologists to extract high-quality features for nuclear morphometrics and other analyses. However, image segmentation is a challenging task in medical image processing and analysis. This study aimed to develop a deep learning-based method for nuclei segmentation of histological images for computational pathology. Methods: The original U-Net model sometime has a caveat in exploring significant features. Herein, we present the Densely Convolutional Spatial Attention Network (DCSA-Net) model based on U-Net to perform the segmentation task. Furthermore, the developed model was tested on external multi-tissue dataset - MoNuSeg. To develop deep learning algorithms for well-segmenting nuclei, a large quantity of data are mandatory, which is expensive and less feasible. We collected hematoxylin and eosin-stained image data sets from two hospitals to train the model with a variety of nuclear appearances. Because of the limited number of annotated pathology images, we introduced a small publicly accessible data set of prostate cancer (PCa) with more than 16,000 labeled nuclei. Nevertheless, to construct our proposed model, we developed the DCSA module, an attention mechanism for capturing useful information from raw images. We also used several other artificial intelligence-based segmentation methods and tools to compare their results to our proposed technique. Results: To prioritize the performance of nuclei segmentation, we evaluated the model's outputs based on the Accuracy, Dice coefficient (DC), and Jaccard coefficient (JC) scores. The proposed technique outperformed the other methods and achieved superior nuclei segmentation with accuracy, DC, and JC of 96.4% (95% confidence interval [CI]: 96.2 - 96.6), 81.8 (95% CI: 80.8 - 83.0), and 69.3 (95% CI: 68.2 - 70.0), respectively, on the internal test data set. Conclusion: Our proposed method demonstrates superior performance in segmenting cell nuclei of histological images from internal and external datasets, and outperforms many standard segmentation algorithms used for comparative analysis.

Development and validation of a convolutional neural network model for diagnosing Helicobacter pylori infections with endoscopic images: a multicenter study.

BACKGROUND AND AIMS: Insufficient validation limits the generalizability of deep learning in diagnosing Helicobacter pylori infection with endoscopic images. The aim of this study was to develop a deep learning model for the diagnosis of H pylori infection using endoscopic images and validate the model with internal and external datasets. METHODS: A convolutional neural network (CNN) model was developed based on a training dataset comprising 13,403 endoscopic images from 952 patients who underwent endoscopy at Seoul National University Hospital Gangnam Center. Internal validation was performed using a separate dataset comprised of images of 411 individuals of Korean descent and 131 of non-Korean descent. External validation was performed with the images of 160 patients in Gangnam Severance Hospital. Gradient-weighted class activation mapping was performed to visually explain the model. RESULTS: In predicting H pylori ever-infected status, the sensitivity, specificity, and accuracy of internal validation for people of Korean descent were .96 (95% confidence interval [CI], .93-.98), .90 (95% CI, .85-.95), and .94 (95% CI, .91-.96), respectively. In the internal validation for people of non-Korean descent, the sensitivity, specificity, and accuracy in predicting H pylori ever-infected status were .92 (95% CI, .86-.98), .79 (95% CI, .67-.91), and .88 (95% CI, .82-.93), respectively. In the external validation cohort, sensitivity, specificity, and accuracy were .86 (95% CI, .80-.93), .88 (95% CI, .79-.96), and .87 (95% CI, .82-.92), respectively, when performing 2-group categorization. Gradient-weighted class activation mapping showed that the CNN model captured the characteristic findings of each group. CONCLUSIONS: This CNN model for diagnosing H pylori infection showed good overall performance in internal and external validation datasets, particularly in categorizing patients into the never- versus ever-infected groups.

Frequency, management, and outcomes of early neurologic deterioration due to stroke progression or recurrence.

OBJECTIVE: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated. MATERIALS AND METHODS: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed. RESULTS: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months. CONCLUSION: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.

Prevalence of Mutations in Mendelian Stroke Genes in Early Onset Stroke Patients.

OBJECTIVE: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population. METHODS: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel. RESULTS: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients. INTERPRETATION: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782.

Stroke of Other Determined Etiology: Results From the Nationwide Multicenter Stroke Registry.

BACKGROUND: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups. METHODS: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups. RESULTS: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively. CONCLUSIONS: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.

Association of ischemic stroke onset time with presenting severity, acute progression, and long-term outcome: A cohort study.

BACKGROUND: Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke. METHODS AND FINDINGS: In a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules. CONCLUSIONS: Night-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.

Platelet-Derived Growth Factor Is Associated with Progression of Symptomatic Intracranial Atherosclerotic Stenosis.

BACKGROUND AND PURPOSE: We aimed to determine the relationships of 33 biomarkers of inflammation, oxidation, and adipokines with the risk of progression of symptomatic intracranial atherosclerotic stenosis (ICAS). METHODS: Fifty-two of 409 patients who participated in the TOSS-2 (Trial of Cilostazol in Symptomatic Intracranial Stenosis-2) showed progression of symptomatic ICAS in magnetic resonance angiography at 7 months after an index stroke. We randomly selected 20 patients with progression as well as 40 age- and sex-matched control patients. We serially collected blood samples at baseline, 1 month, and 7 months after an index stroke. Multiplex analysis of biomarkers was then performed. RESULTS: Demographic features and risk factors such as hypertension, diabetes, and smoking history were comparable between the two groups. Univariate analyses revealed that the levels of platelet-derived growth factor (PDGF)-AA [median (interquartile range)=1.64 (0.76-4.57) vs. 0.77 (0.51-1.71) ng/mL], PDGF-AB/BB [10.31 (2.60-25.90) vs. 2.35 (0.74-6.70) ng/mL], and myeloperoxidase [10.5 (7.5-22.3) vs. 7.8 (5.5-12.2) ng/mL] at 7 months were higher in the progression group. In the multivariate analysis using logistic regression, the PDGF AB/BB level at 7 months was independently associated with the progression of ICAS (p=0.02). CONCLUSIONS: The PDGF-AB/BB level is associated with the progression of ICAS, and so may play a significant role in the progression of human ICAS.

Effects of Carotid Calcification on Restenosis After Carotid Artery Stenting: A Follow-Up Study with Computed Tomography Angiography.

BACKGROUND: Carotid Doppler sonography has been used routinely in the screening for restenosis after carotid artery stenting (CAS) by applying the criteria of flow velocity; however, computed tomography angiography (CTA) enables us to detect restenosis directly and has some advantages that help to overcome the limitations of Carotid Doppler sonography. We aimed to investigate the incidence of restenosis with CTA and to identify factors related to restenosis after CAS. METHODS: We conducted a retrospective study of 225 patients (235 arteries, mean age of 71.9 ± 7.7 years) who had undergone CTA of the neck for the evaluation of restenosis after CAS between July 2002 and June 2012. We assessed the cumulative incidence of restenosis (>50%) and the predictors of restenosis after CAS. RESULTS: During 1064.4 patient-years of follow-up (mean 4.5 years; range 1-9.7 years), the incidence of restenosis was 10.2% (24/235). The cumulative rate of freedom from restenosis was 94.1%, 88.8%, and 86.7% at 1, 3, and 5 years, respectively. The statistically significant factors associated with restenosis after CAS were residual stenosis (adjusted odds ratio 1.07, 95% confidence interval 1.03-1.11, P < 0.01) and high-grade (>50%) calcification (adjusted odds ratio 6.04, 95% confidence interval 1.29-28.36, P = 0.02) on multivariate analysis. CONCLUSIONS: This study revealed that carotid arteries with high-grade calcification were prone to develop restenosis after CAS. Regular follow-up should be performed for the monitoring of restenosis after CAS in patients with highly calcified carotid plaques.

Cytokine Response to Diet and Exercise Affects Atheromatous Matrix Metalloproteinase-2/9 Activity in Mice.

BACKGROUND: The aim of this study is to identify the principal circulating factors that modulate atheromatous matrix metalloproteinase (MMP) activity in response to diet and exercise.Methods and Results:Apolipoprotein-E knock-out (ApoE-/-) mice (n=56) with pre-existing plaque, fed either a Western diet (WD) or normal diet (ND), underwent either 10 weeks of treadmill exercise or had no treatment. Atheromatous MMP activity was visualized using molecular imaging with a MMP-2/9 activatable near-infrared fluorescent (NIRF) probe. Exercise did not significantly reduce body weight, visceral fat, and plaque size in either WD-fed animals or ND-fed animals. However, atheromatous MMP-activity was different; ND animals that did or did not exercise had similarly low MMP activities, WD animals that did not exercise had high MMP activity, and WD animals that did exercise had reduced levels of MMP activity, close to the levels of ND animals. Factor analysis and path analysis showed that soluble vascular cell adhesion molecule (sVCAM)-1 was directly positively correlated to atheromatous MMP activity. Adiponectin was indirectly negatively related to atheromatous MMP activity by way of sVCAM-1. Resistin was indirectly positively related to atheromatous MMP activity by way of sVCAM-1. Visceral fat amount was indirectly positively associated with atheromatous MMP activity, by way of adiponectin reduction and resistin elevation. MMP-2/9 imaging of additional mice (n=18) supported the diet/exercise-related anti-atherosclerotic roles for sVCAM-1. CONCLUSIONS: Diet and exercise affect atheromatous MMP activity by modulating the systemic inflammatory milieu, with sVCAM-1, resistin, and adiponectin closely interacting with each other and with visceral fat.

Cystatin C, a novel indicator of renal function, reflects severity of cerebral microbleeds.

BACKGROUND: Chronic renal insufficiency, diagnosed using creatinine based estimated glomerular filtration rate (GFR) or microalbumiuria, has been associated with the presence of cerebral microbleeds (CMBs). Cystatin C has been shown to be a more sensitive renal indicator than conventional renal markers. Under the assumption that similar pathologic mechanisms of the small vessel exist in the brain and kidney, we hypothesized that the levels of cystatin C may delineate the relationship between CMBs and renal insufficiency by detecting subclinical kidney dysfunction, which may be underestimated by other indicators, and thus reflect the severity of CMBs more accurately. METHODS: Data was prospectively collected for 683 patients with ischemic stroke. The severity of CMBs was categorized by the number of lesions. Patients were divided into quartiles of cystatin C, estimated GFR and microalbumin/creatinine ratios. Ordinal logistic regression analysis was used to examine the association of each renal indicator with CMBs. RESULTS: In models including both quartiles of cystatin C and estimated GFR, only cystatin C quartiles were significant (the highest vs. the lowest, adjusted OR, 1.88; 95% CI 1.05-3.38; p = 0.03) in contrast to estimated GFR (the highest vs. the lowest, adjusted OR, 1.28; 95% CI 0.38-4.36; p = 0.70). A model including both quartiles of cystatin C and microalbumin/creatinine ratio also showed that only cystatin C quartiles was associated with CMBs (the highest vs. the lowest, adjusted OR, 2.06; 95% CI 1.07-3.94; p = 0.03). These associations were also observed in the logistic models using log transformed-cystatin C, albumin/creatinine ratio and estimated GFR as continuous variables. Cystatin C was a significant indicator of deep or infratenorial CMBs, but not strictly lobar CMBs. In addition, cystatin C showed the greatest significance in c-statistics for the presence of CMBs (AUC = 0.73 ± 0.03; 95% CI 0.66-0.76; p = 0.02). CONCLUSION: Cystatin C may be the most sensitive indicator of CMB severity among the renal disease markers.

Hydrogen sulfide treatment induces angiogenesis after cerebral ischemia.

Hydrogen sulfide (H2 S) is a potent vasodilator and regulates cardiovascular homeostasis. Furthermore, H2 S has a crucial role in ischemia-reperfusion injuries, especially of the heart, liver, and kidneys. This study indicates that treatment with hydrogen sulfide is able to restore neurological function after ischemic stroke by promoting angiogenesis. Treatment with H2 S augments angiogenesis in the peri-infarct area, and it significantly improves functional outcomes after 2 weeks in a rat MCAO model. H2 S promotes the phosphorylation of AKT and ERK and increases the expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1). H2 S-treated rats showed more newly synthesized endothelial cells in the ischemic lesion (2.31-fold, P < 0.01). H2 S-treated astrocytes increased VEGF and Ang-1 expression, and the inhibition of phosphatidylinositide 3-kinase (PI3K)/AKT signaling by LY294002 significantly reduced H2 S-induced VEGF and Ang-1 expression in astrocytes. Finally, H2 S stimulated endothelial cell migration (3.92-fold increase in wound healing assay) and tube formation (3.69-fold increase, P < 0.001) through PI3K/AKT signaling. In conclusion, treatment with H2 S promotes angiogenesis and thereby contributes to improvement of functional outcome after cerebral ischemia. Our findings strongly suggest that H2 S may be of value in regenerative recovery after stroke.

High serum alkaline phosphatase in relation to cerebral small vessel disease.

OBJECTIVES: Vascular calcification is related with cerebral small vessel disease. We investigated whether alkaline phosphatase (ALP), a marker of vascular calcificiation, is related to cerebral small vessel disease. METHODS: We included 1082 neurologically healthy subjects who underwent brain magnetic resonance image for a routine health checkup. ALP levels were divided into quartiles. We used quantile regression and logistic regression to evaluate the associations of ALP with white matter hyperintensities (WMH), cerebral infarct and cerebral microbleeds. RESULTS: Subjects with higher ALP were more likely to have a large WMH volume. The adjusted difference of WMH volume between the highest and the lowest quartiles was 0.27 mL (95% confidence interval [CI]; 0.22-0.31 mL). In addition, cerebral infarct was more prevalent in subjects with higher ALP. Compared to the lowest quartile, adjusted odds ratios of having cerebral infarct for the highest quartile was 2.60 (95% CI, 1.10-6.10). No association was found between ALP and cerebral microbleeds. In addition, we found a conjoint effect of ALP and C-reactive protein(CRP) on cerebral small vessel disease. Compared with subjects with low ALP (≤63 IU/L) and low CRP (≤0.5 mg/dl), those with high ALP (>63 IU/L) and high CRP (>0.5 mg/dl) had larger WMH volume (adjusted difference 0.39 mL; 95% CI 0.37-0.42 mL) and a 3-fold (adjusted OR. 3.37; 95% CI, 1.61-7.03) risk of cerebral infarct. CONCLUSION: We found that higher serum levels of ALP are independently associated with WMH and cerebral infarct, but not with cerebral microbleeds.

Impact of smoking cessation on the risk of subarachnoid haemorrhage: a nationwide multicentre case control study.

BACKGROUND AND PURPOSE: Subarachnoid haemorrhage (SAH) is the most devastating cerebrovascular disease. Cigarette smoking is one of the established risk factors for SAH, but the risk of SAH has not been properly elucidated in relation to smoking cessation. METHODS: We performed a nationwide multicentre case control study involving 33 hospitals in Korea. A total of 426 SAH cases and 426 age and sex matched controls were enrolled. We obtained detailed information on lifestyle, medical history and, in particular, smoking habits from participants using structured questionnaires. RESULTS: 148 SAH patients (37.4%) were current smokers compared with 103 (24.2%) controls, giving an adjusted OR of 2.84 (95% CI, 1.63 to 4.97) after controlling for possible confounders. Based on cumulative dose of smoking (pack years), the risk of SAH was found to increase in a dose-responsive fashion. Smoking cessation (≥5 years) caused a reduction in SAH to 59% (p<0.05). However, participants with a history of heavy smoking (≥20 cigarettes per day) had a 2.3 times increased risk of SAH compared with participants who had never smoked (p<0.05). CONCLUSIONS: We have demonstrated that cigarette smoking increases the risk of SAH, but smoking cessation decreases the risk in a time dependent manner, although this beneficial effect may be diminished in previous heavy smokers. To forestall tragic SAH events, our results call for more global and vigorous efforts for people to stop smoking.

Advanced coronary artery calcification and cerebral small vessel diseases in the healthy elderly.

BACKGROUND: Coronary artery calcification (CAC) scores are widely accepted to predict risk of coronary heart diseases and are associated with atherosclerosis in other vasculatures. Cerebral small vessel diseases (SVDs), including white matter lesions (WML), silent lacunar infarction (SLI) and cerebral microbleeds (CMB), are considered to develop in conjunction with pro-atherogenic conditions, measured by CAC scores. METHODS AND RESULTS: Of 672 individuals aged ≥65 years that underwent health screening, 312 subjects with brain magnetic resonance imagings (MRIs) were enrolled in this study. The distribution of baseline characteristics among individuals with or without MRIs was not different. Clinical and laboratory information was collected and CAC scores were measured using multi-detector computed tomography. Cerebral SVD were independently assessed by 2 raters who were unaware of the CAC scores. The prevalence of CAC (CAC>0) was 71.7% in men and 50.0% in women. The associations between moderate-to-extensive CAC (CAC score ≥100) and WML (adjusted odds ratio and 95% confidence interval, 4.99 and 1.33-18.73), SLI (5.04 and 1.86-13.63) and CMB (6.07 and 1.54-23.94) remained significant after adjusting for relevant confounders. CONCLUSIONS: This study documents significant associations between CAC and cerebral SVDs. The findings suggest that SVDs in the brain and CAC in the heart may develop under similar systemic pathogenic processes.

Advanced coronary artery calcification is associated with ischemic stroke.

BACKGROUND: Coronary artery calcification (CAC) is widely accepted as a quantitative index of subclinical atherosclerosis in the coronary artery, and is utilized as a valuable tool for the global risk assessment of cardiovascular events in individuals at intermediate risk. However, the association between CAC and ischemic stroke has not been evaluated. METHODS: CAC scores were measured in 401 consecutive first-ever acute ischemic stroke patients and in 5,420 healthy subjects who underwent detailed medical health screening. The authors randomly matched case:referent sets (1:2) for gender, age, hypertension, diabetes and hyperlipidemia. Accordingly, 290 stroke cases were matched with 580 referent controls. RESULTS: Moderate-to-extensive CAC (CAC > or =100) was detected in 78 (26.9%) of the ischemic stroke cases and in 120 (20.7%) of the referent controls. Conditional logistic regression analysis, which was conducted to investigate the association between categorized CAC scores and ischemic stroke, and adjusted for other relevant confounders, revealed that moderate-to-extensive CAC was associated with the occurrence of ischemic stroke (OR 1.72, 95% CI 1.05-2.80, compared to the subjects with no CAC). The mean +/- SE of the AUC-ROC curve for Framingham risk score (FRS) plus CAC score (0.760 +/- 0.018) was significantly greater than that of FRS alone (0.748 +/- 0.018; p = 0.005). CONCLUSIONS: Our results demonstrate that moderate-to-extensive CAC is associated with an increased occurrence of ischemic stroke. In view of the contribution made by CAC to the risk assessment of cardiovascular diseases, the CAC score may be utilized to evaluate the risk of ischemic stroke.