Arterial Thromboembolism in Japanese Patients With Cancer: Incidence, Predictors, and Survival Impact.

Background: Thromboembolism is a significant complication for patients with cancer, leading to treatment interruptions and poor outcomes. Objectives: The aim of this study was to investigate the incidence of arterial thromboembolism (ATE) within cancer populations, identify the predictors of ATE, and determine its survival impact. Methods: A retrospective multicenter study was performed using data from the Osaka Cancer Registry linked with administrative data from 2010 to 2015. Patients were monitored for 5 years after cancer diagnosis, and ATE incidence was calculated with death as a competing risk. Fine and Gray competing risk regression models and Cox proportional hazards models were used to evaluate the predictors of ATE and the survival impact. Restricted mean survival time (RMST) was used to assess whether antithrombotic therapy after ATE contributed to improved survival. Results: The cohort comprised 97,448 patients with cancer (42.3% women, median age 70 years). ATE incidence displayed an annual increase, peaking 1 year after cancer diagnosis (1-, 2-, 3-, 4-, and 5-year cumulative incidences were 1.29%, 1.77%, 2.05%, 2.22%, and 2.32%, respectively). Male sex, advanced age, advanced cancer stage, and hematologic malignancies correlated with a high risk for ATE. Patients with ATE had a 2-fold increased risk for mortality compared with those without ATE. The 90-day and 1-year RMST differences for those on antithrombotic therapy were 13.3 days (95% CI: 10.4-16.2 days; P < 0.001) and 57.8 days (95% CI: 43.1-72.5 days; P < 0.001), favoring the antithrombotic therapy group. The RMST differences varied by cancer stage. Conclusions: The risk for ATE varies according to sex, age, and cancer progression and type. Antithrombotic therapy after ATE is associated with improved survival among patients with cancer.

Von Willebrand Factor Antigen Levels Predict Poor Outcomes in Patients With Stroke and Cancer: Findings From the Multicenter, Prospective, Observational SCAN Study.

BACKGROUND: Patients with acute ischemic stroke and active cancer have more severe neurological symptoms, elevated risks of stroke recurrence, and death compared with the general population. We examined whether von Willebrand factor (vWF) antigen levels at stroke onset were associated with the poor outcomes of patients with stroke and cancer. METHODS AND RESULTS: Using data from 90 patients with acute ischemic stroke and active cancer who were registered in the SCAN (Ischemic Stroke in Patients With Cancer and Neoplasia) study, a prospective multicenter, observational study in Japan, we divided patients into 2 groups according to their median vWF antigen levels (high, n=46; or low, n=44). The high-vWF group had a significantly higher initial National Institutes of Health Stroke Scale score (median, 7 [interquartile range, 3-11.25] versus 3 [interquartile range, 1-8.5]; P<0.05) and a significantly higher incidence of cryptogenic stroke (32 [70%] versus 16 [36%]; P<0.01) and venous thromboembolism (7 [15%] versus 0 [0%]; P<0.01), as well as multiple lesions (28 [62%] versus 12 [27%]; P<0.001), than the low-vWF group. We observed no significant difference in the rate of stroke recurrence within 1 year between the groups. However, increased vWF levels were an independent predictor of death within 1 year of stroke onset, after adjusting for potential confounders (odds ratio, 6.77 [95% CI, 1.49-30.78]; P<0.05). CONCLUSIONS: Elevated vWF antigen levels were associated with adverse outcomes in patients with cancer-associated stroke and may represent a useful biomarker to guide future therapeutic interventions.

Association between the controlling nutritional status score and outcomes in ischemic stroke patients with active cancer.

BACKGROUND: The effect of nutritional status on survival in ischemic stroke patients with active cancer remains unclear. METHODS: This study retrospectively evaluated ischemic stroke patients with active cancer admitted to a university hospital in Japan between 2006 and 2016. Patients were followed for 2 years after stroke. The controlling nutritional status (CONUT) score was used to classify undernutrition degree into 4 groups: normal, light, moderate, and severe. Survival rates were compared using the Kaplan-Meier method. Hazard ratio (HR) and 95 % confidence intervals (CIs) for mortality were calculated using Cox regression models. RESULTS: A total of 158 patients (31 % women; median age: 71 years) were analyzed. Of these, 47 % had distant metastasis. The median (interquartile range) National Institute of Health Stroke Scale and CONUT scores were 4 (1-10) and 5 (3-7), respectively. Kaplan-Meier curve indicated that patients with poorer nutritional status had worse outcomes (overall log-rank test, p < 0.001). The univariable Cox regression analysis showed that the HR (95 % CI) for the light, moderate, and severe groups were 1.14 (0.45-2.86), 3.01 (1.27-7.12), and 2.94 (1.10-7.84), respectively. This statistical significance did not persist after adjustment for potential confounders (HR [95 % CI] for the light, moderate, and severe groups were 0.95 [0.36-2.49], 1.56 [0.57-4.28], and 1.34 [0.37-4.92], respectively). Past stroke, distant metastasis, and plasma D-dimer levels on admission were independent predictors of prognosis. CONCLUSIONS: This single-center, retrospective study suggests that nutritional status serves as a prognostic indicator for ischemic stroke patients with active cancer. However, the effect is not statistically independent.

Adult-onset botulism in a Japanese woman with prolonged spore excretion.

We report a case of an 80-year-old woman with botulism from 2020 in Osaka, Japan. The patient complained of dysarthria and dizziness. On the same day, the patient developed respiratory failure, and was intubated and placed on mechanical ventilation. Subsequently, ophthalmoparesis and quadriparesis progressed rapidly. Ten days after onset, the patient failed to respond to any external stimulation. Blood tests showed anemia, and computed tomography revealed undiagnosed cervical cancer. Initially, diagnosis of neuromuscular junction disorder and acute motor neuropathy, including paraneoplastic syndrome, were considered. However, intravenous immunoglobulin therapy and plasma exchange were ineffective. A fecal sample on day 30 showed a large number of C. botulinum spores. On day 34, a mouse bioassay revealed botulinum toxin type A in the patient's serum; therefore, a botulinum antitoxin was administered. Later, the patient's muscle strength was gradually improved. However, severe muscle paralysis persisted, and the patient died of cachexia owing to cervical cancer on day 196. The etiology of this case was unknown because no contaminated food was identified during an inspection of the patient's home. Fecal 16S rRNA gene sequencing revealed dysbiosis of the intestinal microbiota with abundant Enterococcus species. Long-lasting excretion of substantial botulinum spores even on day 30 indicated colonization of C. botulinum in the intestinal tract. This case suggests that C. botulinum colonization with co-existing intestinal dysbiosis may be associated with severe and prolonged symptoms of botulism.

Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study.

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82-5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.

Racial and Ethnic Differences in the Association Between Classical Cardiovascular Risk Factors and Common Carotid Intima-Media Thickness: An Individual Participant Data Meta-Analysis.

Background The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid-intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. Methods and Results Cross-sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B-mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 2-stage individual participant data meta-analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coefficient, 0.39; 95% CI, 0.09-0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01-0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06-0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High-density lipoprotein-cholesterol had significant protective effects in African American (beta coefficient, -0.31; 95% CI, -0.42 to -0.21) and African (beta coefficient, -0.26; 95% CI, -0.31 to -0.19) populations only. Conclusions The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race- ethnicity-specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations.

RNF213 p.R4810K Variant Carriers with Intracranial Arterial Stenosis Have a Low Atherosclerotic Burden.

AIM: The ring finger protein 213 gene (RNF213) p.R4810K variant is a major susceptibility gene for intracranial arterial stenosis in East Asia. We hypothesized that if intracranial arterial stenosis is induced by a non-atherosclerotic mechanism similar to moyamoya disease, the patients with RNF213 p.R4810K variant may have a lower cumulative atherosclerotic burden than the non-carriers. METHODS: A total of 112 participants with intracranial arterial stenosis were enrolled in this multicenter cross-sectional study. We compared the prevalence of atherosclerotic risk factors and three different cardiovascular risk scores (Essen Stroke Risk Score, Framingham Risk Score, and Suita Risk Score) between the RNF213 p.R4810K variant carriers and non-carriers. Patients with moyamoya disease were excluded from the study. RESULTS: The RNF213 p.R4810K variant carriers were younger than the non-carriers (P＜0.001). The prevalence of each atherosclerotic risk factor was not significant, but it tended to be lower in the variant carriers. The Essen Stroke Risk Score (carriers: 2.3±1.5 vs. non-carriers: 2.9±1.5, P=0.047), Framingham Risk Score (10.7±6.4 vs. 15.3±6.2, P=0.001), and Suita Risk Score (35.4±15.8 vs. 48.7±15.2, P＜0.001) were significantly lower in the variant carriers. Among the three risk scores, the Suita score showed the highest predictive accuracy for the variant carriers. CONCLUSIONS: RNF213 p.R4810K variant carriers have a lower cumulative atherosclerotic burden than non-carriers among patients with intracranial arterial stenosis. New therapeutic approaches beyond the standard management of atherosclerotic risk factors are required to prevent the development of intracranial arterial stenosis.

The Effect of Chemotherapy on Stroke Risk in Cancer Patients.

BACKGROUND: Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We investigated how chemotherapy affects stroke risk in cancer patients. METHODS: Of 27,932 patients in a hospital-based cancer registry (which contains clinical data on all patients treated for cancer at Osaka University Hospital) screened between 2007 and 2015, medical records of 19,006 patients with complete data were investigated. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression. RESULTS: Of 19,006 patients, 5,887 (31%) were in the chemotherapy group. Stroke occurred in 44 (0.75%) and 51 (0.39%) patients in the chemotherapy and nonchemotherapy group, respectively. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than those in the nonchemotherapy group (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.75). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03). CONCLUSION: In our study, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.

Prevalence of RNF213 p.R4810K Variant in Early-Onset Stroke With Intracranial Arterial Stenosis.

Background and Purpose- The ring finger protein 213 gene ( RNF213) is a susceptibility gene for moyamoya disease and large-artery ischemic stroke in East Asia. We examined the prevalence and correlates of the RNF213 p.R4810K variant in patients with early-onset ischemic stroke in a Japanese single-center cohort. Methods- We analyzed 70 early-onset stroke patients with intracranial arterial stenosis who developed a noncardioembolic stroke or transient ischemic attack from 20 to 60 years of age. Patients with moyamoya disease were excluded. Results- The RNF213 p.R4810K variant was found in 17 patients (24%), and more often in women than men (38% versus 16%, odds ratio 3.3; 95% CI, 1.1-10.2, P=0.04). The variant was identified in 35% of patients with stenosis in the M1 segment of the middle cerebral artery or the A1 segment of the anterior cerebral artery (odds ratio, 25.0; 95% CI, 1.4-438; P<0.01) but in only one patient (9%) with intracranial posterior circulation stenosis. Conventional atherosclerotic risk factors did not differ between variant carriers and noncarriers. Conclusions- The RNF213 p.R4810K variant is common in early-onset ischemic stroke with anterior circulation stenosis in Japan. Further investigation of the RNF213 gene will provide new insights into pathogenetic mechanisms of early-onset stroke.

Clustering of cardiovascular risk factors and carotid intima-media thickness: The USE-IMT study.

BACKGROUND: The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation. METHODS: Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group. RESULTS: Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women. CONCLUSION: Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters.

Characteristics of cryptogenic stroke in cancer patients.

OBJECTIVE: To clarify the characteristics of cryptogenic stroke in patients with active cancer. METHODS: Patients with or without cancer diagnosed with acute ischemic stroke between January 2006 and February 2015 were extracted from a prospectively collected stroke database of Osaka University Hospital. Patients were categorized according to the presence of active cancer and known stroke mechanisms. RESULTS: Among 1191 patients with acute ischemic stroke, 145 (12%) had active cancer. Patients with active cancer were diagnosed more often with cryptogenic stroke than were patients without cancer (47% vs. 12%, P < 0.001). Compared with cryptogenic stroke patients without cancer, cryptogenic stroke patients with active cancer had fewer atherosclerotic risk factors, lower nutrition status, higher plasma D-dimer levels, and multiple vascular lesions. In a multivariate logistic analysis, plasma D-dimer level (odds ratio [OR] per 1 standard deviation increase: 6.30; 95% confidence interval [CI]: 2.94-15.69; P < 0.001), and the presence of multiple vascular lesions (OR: 6.40; 95% CI: 2.35-18.35; P < 0.001) were independent predictors of active cancer. When comparing active cancer patients who had known stroke mechanisms with those who had cryptogenic stroke, high plasma D-dimer levels, multiple vascular lesions, and receiving chemotherapy and/or radiation therapy were associated with cryptogenic stroke etiology. INTERPRETATION: In cryptogenic stroke, patients with active cancer has a unique pathology characterized by high plasma D-dimer levels and multiple vascular lesions. The hypercoagulable state and malnutrition due to cancer and its treatments potentially influence the development of cryptogenic stroke in cancer patients.

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.

BACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

MRI Characteristics of the Evolution of Supratentorial Recent Small Subcortical Infarcts.

OBJECTIVE: Morphological changes of recent small subcortical infarcts are not well defined. The purpose of the present study was to describe the MRI characteristics of the evolution for this stroke subtype. METHODS: We conducted a retrospective review of patients diagnosed with definite supratentorial recent small subcortical infarcts according to the ASCO classification with baseline and follow-up MRI (≥90 days of stroke onset). We investigated the incidence of cavity formation, the infarct volume change, and the positional relationship between infarct lesions and preexisting white matter hyperintensities (WMHs) of presumed vascular origin. RESULTS: We identified 62 patients with a median age of 71 years (range: 30-87). Median follow-up period was 26 months (range: 3-99). Cavity formation was observed in 38 infarct lesions (61%). Eighteen lesions (29%) were partially adjacent to WMHs and 7 (11%) were fused into WMHs. In a multiple logistic regression analysis, age [odds ratio per 5-year increase: 1.34; 95% confidence interval (CI): 1.03-1.80; p = 0.03] and baseline infarct volume (odds ratio per 1-ml increase: 4.7; 95% CI: 1.6-19.7; p = 0.003) were independent predictors of cavity formation. There was a significant volume reduction between baseline and follow-up infarct lesions (median volume reduction rate: 44%). CONCLUSION: More than one-third of recent small subcortical infarcts do not lead to cavity formation and 40% of infarct lesions overlap with WMHs. Our data indicate the continuity between recent small subcortical infarcts and WMHs.

Anemia Is a Risk Factor of New Intraoperative Hemorrhagic Stroke During Valve Surgery for Endocarditis.

BACKGROUND: Infective endocarditis is often associated with cerebral complications, the most serious of which is intraoperative hemorrhagic stroke owing to anticoagulation for cardiopulmonary bypass. However, its prevalence and risk factors are unknown. We evaluated the prevalence and risk factors of intraoperative hemorrhagic stroke in patients with infective endocarditis. METHODS: In 246 patients who underwent valve surgery for active endocarditis between 2005 and 2012, 127 patients had both preoperative and postoperative intracranial neuroimaging. The prevalence and risk factors of intraoperative stroke were analyzed in those 127 patients. RESULTS: Valve surgery was performed in 127 patients 19.6 ± 27.1 days after infective endocarditis diagnosis. Fourteen experienced intraoperative hemorrhagic stroke, and 1 died. None of 29 patients with preoperative hemorrhagic stroke showed exacerbation of hemorrhagic lesions, whereas 1 of 57 patients with preoperative cerebral infarction showed hemorrhagic transformation of infarct lesions. Thirteen of 14 hemorrhagic complications were new ectopic intracranial hemorrhage. Multivariate analysis showed not preoperative cerebral lesions but preoperative low hemoglobin level as the only risk factor for intraoperative hemorrhagic stroke (odds ratio, 0.51; 95% confidence interval, 0.26 to 0.87; p = 0.03). A preoperative hemoglobin cutoff value of 9.2 g/dL was determined by receiver operating curve analysis. Of 41 patients with preoperative hemoglobin level less than 9.2 g/dL, 9 (22%) had intraoperative new hemorrhage, whereas 4 (5%) of 86 patients with hemoglobin level of at least 9.2 g/dL had ectopic new hemorrhage. CONCLUSIONS: Intraoperative hemorrhagic stroke was not rare, and ectopic hemorrhagic stroke, associated with preoperative anemia, was more prevalent than hemorrhagic transformation of existing cerebral lesions.

Association of interleukin-6 with the progression of carotid atherosclerosis: a 9-year follow-up study.

BACKGROUND AND PURPOSE: Limited information is available on the long-term effects of interleukin-6 (IL-6) on systemic atherosclerosis. The purpose of the present study was to clarify the relationship between chronic elevation of IL-6 and the long-term progression of carotid atherosclerosis. METHODS: We prospectively evaluated 210 patients with ≥1 vascular risk factors for 9.0±1.0 years. Carotid mean-maximal intima-media thickness (mmIMT), the serum high-sensitivity C-reactive protein (hs-CRP) level, and the serum IL-6 level were measured at baseline and every 3 years. The associations between the progression of mmIMT and the long-term average levels of hs-CRP and IL-6 were analyzed. RESULTS: Carotid mmIMT increased throughout the study period (0.031±0.026 mm/y). Baseline mmIMT was significantly associated with baseline hs-CRP (P=0.002) and baseline IL-6 (P<0.001) levels. Progression of mmIMT was positively correlated with average hs-CRP (P=0.001) and average IL-6 (P<0.001) levels. When adjusted for age, sex, traditional risk factors, and baseline mmIMT, mmIMT progression remained significantly associated only with the average IL-6 level (standardized ß=0.17; P=0.02), but not with the average hs-CRP level (standardized ß=0.10; P=0.18). CONCLUSIONS: Chronic elevation of serum IL-6 was associated with the progression of atherosclerosis in patients with vascular risk factors. IL-6 could be used as a quantitative marker and a potential therapeutic target for accelerated atherosclerosis.

Valve surgery in active endocarditis patients complicated by intracranial haemorrhage: the influence of the timing of surgery on neurological outcomes.

OBJECTIVES: The risk of neurological deterioration during valve surgery using cardiopulmonary bypass under systemic heparinization in infective endocarditis (IE) patients with intracranial haemorrhage (ICH) is unknown. The objective of this retrospective study was to investigate the stratified risk related to the timing of valve surgery on neurological outcomes in patients with active IE and preoperative ICH. METHODS: From 2004 to 2012, 246 patients underwent valve surgery for IE in hospitals enrolled in the Osaka Cardiovascular Research Group. Of these, a group of 30 patients had preoperative ICH, and they included 18 patients with cerebral haemorrhage, 8 with subarachnoid haemorrhage and 4 with haemorrhagic infarction. The preoperative characteristics, neurological statuses and postoperative results of these patients were retrospectively explored to analyse the effects of the timing of surgery on neurological outcomes. RESULTS: Twenty-one patients had symptomatic ICH, and the median modified Rankin score was 1.5 (95% confidence interval [CI] 1.2-2.8). Eight patients were diagnosed with mycotic aneurysms, and 7 of these patients underwent aneurysm resection or clipping before valve surgery. All 30 patients underwent valve surgery, and the median interval between ICH onset and surgery was 22.5 (95% CI 15.5-39.4) days. Four patients died of multiple organ dysfunction or heart failure. The interval between ICH onset and valve surgery was within 7 days for 5 cases, between 8 and 14 days for 6, between 15 and 28 days for 9 and >29 days for 10. Postoperative neuroimaging showed that neither neurological deterioration nor exacerbation of haemorrhagic lesions had occurred among the 30 patients, regardless of the timing of surgery. However, 2 cases who underwent valve surgery 8 and 81 days after the onset of ICH developed new ectopic asymptomatic haemorrhages postoperatively. CONCLUSIONS: The risk of postoperative neurological deterioration resulting from the exacerbation of haemorrhagic lesions seemed relatively low, even in IE patients who underwent valve surgery within 2 weeks of ICH onset. However, further evaluation of the sizes and aetiologies of haemorrhagic lesions is vital to establish a safe interval between the ICH onset and surgery.

Ischemic stroke in patients with solid gynecologic tract tumors and coagulopathy.

AIM: Patients with gynecological neoplasms often suffer ischemic stroke. This study aimed to clarify the underlying mechanisms of ischemic stroke in patients with gynecological tract tumors. METHODS: We retrospectively reviewed 6 patients with gynecologic tumors and hypercoagulability who were being treated for acute ischemic stroke between 2006 and 2012. Diffusion-weighted magnetic resonance imaging (DW-MRI), cardiovascular risk factors including plasma D-dimer levels, and histologic examination of the patients' solid tumors were performed. All 6 patients underwent transesophageal echocardiography (TEE) for nonbacterial thrombotic endocarditis (NBTE) and paradoxical embolism. RESULTS: All 6 patients showed elevated plasma D-dimer levels. In 1 patient, paradoxical embolism was diagnosed. In the remaining 5 patients, DW-MRI scans showed numerous lesions in multiple vascular territories, and in 4 of these 5 patients, TEE demonstrated vegetations on the mitral valve, leading to the diagnosis of NBTE. Interestingly, 2 of these 4 patients had benign uterine tumors, whereas the other 2 had ovarian cancer. CONCLUSIONS: NBTE was the main etiology for ischemic stroke in patients with gynecologic tract tumors and coagulopathy. Both malignant and benign tumors of the gynecologic tract can cause NBTE.