An autopsy case of progressive multifocal leukoencephalopathy after rituximab therapy for malignant lymphoma.

Progressive multifocal leukoencephalopathy (PML) is a rare fatal demyelinating disease of the central nervous system caused by reactivation of the JC virus (JCV), which is named after the initials of the patient from whom the virus was first isolated. JCV is highly prevalent worldwide, infects humans in early childhood, and the infection persists throughout the course of life in latent form. The present paper deals with the second autopsy case report of rituximab-associated PML in Japan. A 63-year-old woman who had undergone chemotherapy for non-Hodgkin lymphoma developed progressive dysarthria and cerebellar ataxia. Head magnetic resonance imaging (MRI) revealed small, scattered, hyperintense areas in the midbrain, pons and thalamus, and the patient was first diagnosed as having cerebral infarction. Follow-up MRI showed tendency toward cerebellar atrophy and multiple system atrophy cerebellar type was suggested, which we concluded must have coincidentally occurred. It was challenging to perform biopsy due to the location of the foci and the patient's condition. Twelve months later she died of aspiration pneumonia caused by the bulbar lesion. At autopsy, the histological examination suggested the presence of demyelinating foci with numerous foamy macrophages. In the foci, oligodendrocytes with enlarged ground-glass like nuclei were found in a scattered manner and astrocytes with bizarre nuclei were also detected. These findings verified the case as PML. The first diagnosis of cerebral infarction was later withdrawn, although appropriate disorders were not recalled even after testing with various antibodies. The rate of PML development tends to increase after treatment with molecular-targeted therapies, which directly or indirectly attenuate the cellular-mediated immune system. Various novel molecular-targeted and immunosuppressive drugs have been released on the market; the cases of PML have consequently increased. Accordingly, pathologists should keep this disease in mind in the differential diagnosis when neural symptoms newly emerge in patients who are treated with these drugs.

Impact of Metformin on the Severity and Outcomes of Acute Ischemic Stroke in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for cardiovascular disease. Metformin therapy reportedly decreases the risk of stroke, but the associations between metformin treatment and neurological severity or patient prognosis have not been investigated in clinical studies. This study evaluated the effects of metformin on stroke severity and outcomes in acute ischemic stroke patients with type 2 DM. METHODS: We examined 355 stroke patients with type 2 DM without severe renal impairment or prestroke impairment of activities of daily living who were admitted to Kyushu Medical Center between April 2010 and September 2014. Neurological severity was assessed according to the National Institutes of Health Stroke Scale (NIHSS) score on admission. Mild neurological severity was defined as an NIHSS score lower than 3 on admission, and favorable functional outcome was defined as a modified Rankin Scale score of 2 or lower at discharge. RESULTS: On logistic regression analysis with adjustments for multiple confounding factors, pretreatment with metformin was independently associated with mild neurological symptoms (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.09-4.10; P = .026). In contrast, functional outcomes showed no significant associations. Nevertheless, a benefit of prior metformin use was observed in patients with a prior history of stroke (OR, 11.3; P = .046) and in patients after excluding those with mild stroke severity (OR, 5.64; P = .042). CONCLUSIONS: Administration of metformin in DM patients prior to stroke onset may be associated with reduced neurological severity and improved acute-phase therapy outcomes.

Features of brain magnetic resonance imaging diffusion-weighted images of aortogenic embolic stroke.

BACKGROUND: The features of acute aortogenic embolic stroke on magnetic resonance diffusion-weighted imaging (DWI) have not been fully elucidated, so we compared patients with acute aortogenic embolic stroke and those with acute cardioembolic stroke. METHODS AND RESULTS: This study included 40 consecutive patients with acute aortogenic embolic stroke, and 40 age- and sex-matched patients with acute cardioembolic stroke. The diagnosis of aortogenic embolic stroke was made when patients met 5 criteria: (1)acute neurologic event lasting >24h; (2) positive signals on DWI; (3) atherosclerotic lesions ≥3.5-mm thick at the aortic arch on transesophageal echocardiography; (4) neuroradiologic features suggesting embolic stroke, such as lesions involving the brain cortex or the re-opening phenomenon of previously occluded vessels on Magnetic Resonance Angiography (MRA); and (5) absence of other embolic sources, including heart disease and carotid stenosis. The number, site, and maximal diameter of the infarct lesions on DWI were compared between the aortogenic and cardiogenic groups. The aortogenic patients more frequently had ≥3 lesions (25.0% vs. 2.5%, P<0.01), lesions with a maximal diameter <30mm (77.5% vs. 20.0%, P< 0.001), and vertebrobasilar system lesions (55.0% vs. 10.0%, P< 0.001) than the cardiogenic patients. CONCLUSIONS: Acute aortogenic embolic stroke is characterized by multiple (≥3) and small lesions, and involvement of the vertebrobasilar system.

Association of deep venous thrombosis with calf vein diameter in acute hemorrhagic stroke.

We investigated the association between the development of deep venous thrombosis (DVT) and calf vein diameter in patients with acute hemorrhagic stroke. We measured the maximum diameter of paralytic side posttibial veins (PTVs) and peroneal veins (PVs) in 49 patients with intracerebral hemorrhage on admission and at 2 weeks after stroke onset by ultrasonography. We also examined for the presence or absence of DVT, and then analyzed the association of DVT with the maximum vein diameter. At 2 weeks after stroke, DVTs were detected in PTVs in 7 patients and in PVs in 6 patients. The maximum calf vein diameters at 2 weeks were significantly greater in patients with DVT compared with those without DVT (PTV, P = .033; PV, P = .015). Although calf vein diameter at admission did not influence the future incidence of DVT in patients with intracerebral hemorrhage, the presence of DVT was associated with calf vein dilatation.

Antegrade internal carotid artery collateral flow and cerebral blood flow in patients with common carotid artery occlusion.

OBJECTIVES: To determine the incidence of antegrade internal carotid artery collateral flow in patients with common carotid artery occlusion, which artery supplies blood to the internal carotid artery, and whether the flow affects regional cerebral blood flow in the middle cerebral artery territory. METHODS: We determined the incidence of antegrade internal carotid artery collateral flow and identified its arterial origins using carotid sonography in 10 patients with common carotid artery occlusion and evaluated middle cerebral artery territory regional cerebral blood flow by single-photon emission computed tomography in these patients and 30 age- and sex-matched patients with internal carotid artery occlusion. RESULTS: Six (60%) of the 10 patients with common carotid artery occlusion had antegrade internal carotid artery collateral flow, which was supplied through the carotid bifurcation from retrograde flow of the external carotid artery in 5 and by a small artery directly into the internal carotid artery in 1. The regional cerebral blood flow ipsilateral to the occlusion at rest was higher in patients with common carotid artery occlusion than those with internal carotid artery occlusion (mean ± SD, 40.4 ± 8.5 versus 34.3 ± 6.2 mL/100 g/min; P = .02). The regional cerebral blood flow was significantly higher in the 6 patients with antegrade internal carotid artery flow than those with internal carotid artery occlusion at rest (42.2 ± 7.2 versus 34.3 ± 6.2 mL/100 g/min; P = .02) but not in the other 4 patients without antegrade internal carotid artery flow. CONCLUSIONS: Antegrade collateral internal carotid artery flow was found in 60% of patients with common carotid artery occlusion and was mainly supplied by retrograde external carotid artery flow. It contributes to maintenance of middle cerebral artery territory regional cerebral blood flow.

Long-term results of medical and surgical therapy for Japanese patients with moderate carotid stenosis.

To clarify the efficacy of medication versus carotid endarterectomy (CEA), we investigated cardiovascular events and outcomes in Japanese patients with moderate carotid stenosis. We consecutively registered patients with significant carotid stenosis (50%-79%) measured by digital subtraction angiography (DSA) over 10 years and compared the incidences of stroke, myocardial infarction, and death between treatment groups (surgical group vs medical group). Of 406 registered patients, 163 (108 treated surgically and 55 treated medically) with moderate carotid stenosis were analyzed. Complete follow-up data (mean, 4.2 years) were available for 105 patients in the surgical group (97.2%) and 54 patients in the medical group (98.2%). Surgical treatment was associated with lower incidences of any stroke, myocardial infarction, and death compared with medication. Although the incidence rates differed significantly between CEA and medication in the 66 symptomatic patients, there were no significant differences in the 93 asymptomatic patients. The results of this single-center study in Japanese patients suggest that CEA is an acceptable treatment for patients with symptomatic moderate carotid stenosis, but that CEA for asymptomatic moderate carotid stenosis seems to be less effective in Japanese patients.

Outcomes associated with carotid pseudo-occlusion.

PURPOSE: We tested the hypothesis that patients with carotid pseudo-occlusion (PO) have a different prognosis from those with carotid artery stenosis (CS) without PO. MATERIALS AND METHODS: 500 patients were examined for CS by cerebral angiography; those with severe CS ≥ 70% (CS group) or with PO (PO group) were enrolled in this study. The primary endpoint was defined as the combined endpoint of the occurrence of stroke, myocardial infarction, or death. Patients without any events were censored at 60 months. We followed patients for the occurrence and date of primary endpoints and compared clinical characteristics and outcomes between the PO group and the CS group. RESULTS: We enrolled 337 patients (281 men, 56 women, mean age: 70.4 years, mean follow-up period: 32.0 months), of whom 303 (89.9%) were allocated to the CS group while 34 (10.1%) were allocated to the PO group. The rate of diabetes mellitus in the PO group (55.9%) tended to be higher than in the CS group (39.9%). According to Kaplan-Meier analysis, the PO group suffered from the primary outcome more frequently than the CS group. The occurrence of the primary outcome was also associated with older age, peripheral arterial disease and a history of myocardial infarction. Multivariate analysis indicated that patients in the PO group had a significantly poorer outcome compared with those in the CS group (p = 0.013). CONCLUSION: Patients in the PO group more frequently had neurological and cardiac events or died compared with those in the CS group.

Correlation between the degree of left subclavian artery stenosis and the left vertebral artery waveform by pulse Doppler ultrasonography.

BACKGROUND: Development of retrograde blood flow may be observed in the vertebral artery and is associated with progressive ipsilateral proximal subclavian or innominate artery stenosis. The subclavian steal phenomenon is more prevalent in the left subclavian artery (LSA). The purpose of this study was to analyze the correlation between the degree of LSA stenosis and pulse Doppler waveforms of the left vertebral artery (LVA). METHODS: A retrospective analysis of LVA waveforms was performed in 22 cases with LSA proximal stenosis before the origin of the LVA in conventional angiograms. The degree of LSA stenosis was classified into 5 groups (<50, 50-59, 60-69, 70-89, 90-100%). Pulse Doppler waveforms of the LVA were also classified into 5 subtypes depending on the depth of the mid-systolic notch representing retrograde blood flow (normal, mid-systolic notch, retrograde flow smaller than antegrade flow, retrograde flow larger than antegrade flow, retrograde flow without antegrade flow). RESULTS: A statistically significant correlation (R(2) = 0.646, p < 0.0001) was found between the degree of LSA stenosis and the LVA waveform. CONCLUSIONS: The pattern analysis of LVA pulse Doppler waveforms seems to be useful in determining the degree of LSA stenosis.

[Left to right ratio of transcranial color-coded sonography for monitoring hyperperfusion syndrome after carotid artery stenting: a case report].

Hyperperfusion syndrome is a significant complication after carotid endarterectomy (CEA) or carotid artery stenting (CAS). A few reports have shown that an increase in the ratio of mean flow velocity (MFV) of the middle cerebral artery (MCA) of the affected side by transcranial color-coded sonography (TCCS) is useful for the evaluation of hyperperfusion after CEA or CAS. We report a case of hyperperfusion syndrome after CAS in which not only the increased ratio of the affected side based on preoperative mean flow velocity, but also the left to right ratio (L/R ratio) was useful for monitoring hyperperfusion. A 48-year-old man was admitted to our hospital because of cerebral infarction of the right internal carotid artery (ICA) due to stenosis of the right ICA at origin. The preoperative L/R ratio of MFV of the MCA by TCCS was 0.58. We performed CAS and the patient then developed hyperperfusion syndrome with epilepsy and was intubated under the management of strict blood control. We performed TCCS daily and the patient was extubated when the L/R ratio of MFV of the MCA decreased to 1.1 from a maximum of 2.6, although the increased ratio of MFV of the MCA of the affected side was still higher than 1.4. The patient went home without any complications from hyperperfusion. When there is preoperative laterality of cerebral blood flow, the L/R ratio of MFV by TCCS can be useful for monitoring hyperperfusion after CEA or CAS.

[Association of location of deep venous thrombosis and d-dimer value in acute intracerebral hemorrhage].

AIM: We investigated the association of the presence and the location of deep venous thrombosis (DVT) with D-dimer value in acute intracerebral hemorrhage (ICH). METHODS: We analyzed the data regarding DVT in patients with ICH. Based on an ultrasonographic examination 2 weeks after the occurrence of ICH, the patients were divided according to the presence/absence and the location of DVT, i.e. no evidence of DVT (n-DVT), calf DVT (c-DVT), and proximal DVT (p-DVT). D-dimer value was measured 2 weeks later and compared among the groups. RESULTS: The numbers of patients with n-DVT, c-DVT and p-DVT were 27, 19, and 2, respectively. Univariate analysis indicated that D-dimer values were significantly different between patients with n-DVT and c-DVT and between patients with n-DVT and p-DVT (p<0.05, respectively). The cut-off value for estimating the presence of DVT and p-DVT was 3.9 µg/mL and 18.5 µg/mL, respectively. CONCLUSION: D-dimer value assessment after 2 weeks may be associated with the presence and the location of DVT in patients with ICH.

Morphological classification of mobile plaques and their association with early recurrence of stroke.

BACKGROUND: The present study investigated the frequency and morphological characteristics of carotid mobile plaques and examined the relationship between carotid mobile plaques and recurrent strokes. METHODS: The study included 94 consecutive acute stroke patients with large-artery atherosclerosis associated with extracranial carotid stenosis. We investigated the presence of mobile plaques by carotid ultrasonography and classified patients into two groups (mobile group and non-mobile group). We compared backgrounds, MRI and ultrasonographic findings, neurological severity on admission and at discharge, and the rate of early recurrent stroke between both groups. RESULTS: Mobile plaques were detected in 12 patients (12.8%). There were four types of mobile plaques: (1) the jellyfish-type plaque, in which the fibrous cap fluctuated like a jellyfish; (2) the streaming-band-type plaque, in which the string attached to the plaque was swaying; (3) the mobile-thrombus-type plaque, in which a mobile mass was attached to the plaque surface, and (4) the fluctuating-ulcer-type plaque, which contained a mobile substance in the plaque ulcer. Although National Institutes of Health Stroke Scale (NIHSS) scores on admission were less severe in the mobile group than in the non-mobile group (median 1 vs. 4, respectively; p = 0.004), the rate of early recurrent stroke was significantly higher in the mobile group than in the non-mobile group (33.3 vs. 7.3%, respectively; p = 0.022). There were no significant differences in NIHSS scores at discharge between groups. CONCLUSIONS: Morphologically, several types of mobile plaques were detected in consecutive patients with acute stroke associated with carotid stenosis. Mobile plaques are strongly associated with an early recurrence of stroke.

[A case of brain infarction and thoracic aortic dissection without chest nor back pain diagnosed by carotid duplex ultrasonography].

A 63-year-old man was admitted because of sudden transient consciousness disturbance and left-side hemiparesis 110 minutes after the onset. Typical symptoms of aortic dissection, such as chest pain, back pain, neck pain, laterality of blood pressure or hypotension were not found. Brain magnetic resonance imaging (MRI) showed multiple acute brain infarction of the right middle cerebral artery territory. Carotid duplex ultrasonography demonstrated a subintimal dissection with a false channel of the right common carotid artery (CCA) and the right internal carotid artery (ICA). Thoracoabdominal computed tomographic (CT) scan demonstrated the false lumen in ascending and descending thoracic aorta. Cervical CT scan showed a dissection with a false channel of the right CCA. Intravenous administration of recombinant tissue plasminogen activator (rt-PA) is a contraindicant therapy in patients of brain infarction with aortic dissection. Thus our patient showed thoracic aortic dissection with extension of the dissection toward the right internal carotid artery. And the patient complained of neither the pain in the chest, the back nor the neck. So we emphasize the necessity of carotid duplex ultrasonography examination before intravenous administration of rt-PA in the treatment of the cerebral infarction, regardless of having chest pain, back pain, neck pain or not.

Deep venous thrombosis after acute intracerebral hemorrhage.

BACKGROUND: We evaluated the incidence of deep venous thrombosis (DVT) and the characteristics of patients with acute ICH who developed DVT. METHODS: We enrolled 52 patients with acute ICH between June 2005 and September 2006. We recorded their stroke risk factors, neurological deficit, hemorrhage size and laboratory data, and performed ultrasonography to detect DVT within 72 h of onset of ICH and after two weeks. RESULTS: DVT was detected a total of 21 patients (40.4%) after two weeks. Patients with DVT tended to be older, and had significantly more severe disturbance of consciousness (p=0.020) and paralysis (p=0.035) on admission than those without DVT. The National Institutes of Health Stroke Scale (NIHSS) score was significantly higher in patients with DVT than those without (p=0.002). Patients with a larger diameter of ICH were more likely to develop DVT (p=0.021). D-dimer value on admission was significantly higher in patients with DVT than those without (p=0.002). Logistic regression analysis indicated that both NIHSS score and D-dimer value were independent risk factors for the occurrence of DVT. CONCLUSIONS: We need be aware that acute ICH patients with severe neurological deficit and high D-dimer value are at increased risk of developing DVT.

Polymorphisms in the lymphotoxin alpha gene and the risk of ischemic stroke in the Japanese population. The Fukuoka Stroke Registry and the Hisayama Study.

BACKGROUND AND PURPOSE: Lymphotoxin alpha (LTA), one of the tumor necrosis factor family proteins, is an important proinflammatory cytokine and appears to play a putative role in the inflammatory process of atherosclerosis. Recent genetic studies have suggested that variations in the gene encoding LTA, which affect its expression and biological function, may contribute to the development of vascular diseases. We conducted a case-control study to clarify the association of LTA gene polymorphisms with ischemic stroke in a large Japanese population. METHODS: Genotyping for LTA A252G and C804A polymorphisms was achieved by a rapid-cycle polymerase chain reaction and melting curve analysis using fluorescent probes in 1,044 incident cases of ischemic stroke recruited from the Fukuoka Stroke Registry and 1,044 age- and sex-matched control subjects recruited from the Hisayama Study. RESULTS: The overall distribution of allele and genotype for each polymorphism was similar between stroke patients and control subjects. The allele frequencies of 252G and 804A were slightly lower in stroke patients than in control subjects; however, conditional logistic regression analysis adjusted for potential risk factors found no association between the risk of ischemic stroke and either polymorphism. In terms of stroke subtype, we also found no association of these polymorphisms with any subtypes of ischemic stroke. CONCLUSIONS: Neither the A252G nor C804A polymorphism of the LTA gene was associated with stroke overall and any subtypes of ischemic stroke in the Japanese population.

[A case of the spontaneous dissection of the bilateral internal carotid arteries diagnosed by the transoral carotid ultrasonography (TOCU)].

A 56-year-old-man was admitted to our hospital because of acute brain infarction with symptoms of consciousness disturbance and left hemiparesis. After admission, the symptoms disappeared rapidly. MRI diffusion-weighted image on day one revealed high intensity area at the right insular cortex and MRA showed stenosis of the right middle cerebral artery. MRA on the next day demonstrated that the stenotic lesion improved, but another stenosis appeared at the petrous portion of the right internal carotid artery (ICA). Brain angiography on day eight showed improvement of the stenosis of the right ICA petrous portion and stenosis of bilateral ICAs extracranial distal portion. The transoral carotid ultrasonography (TOCU) on day nine showed clearly true lumen and false lumen at the bilateral extracranial distal ICAs, which indicated spontaneous dissection of the bilateral extracranial distal ICAs. TOCU seems very useful in evaluating the extracranial carotid arterial dissection.

Improvement and Aggravation of Spontaneous Unruptured Vertebral Artery Dissection.

BACKGROUND: Intracranial vertebral artery dissection (VAD) is a well-recognized cause of stroke in young and middle-aged individuals, especially in Asian populations. However, a long-term natural course remains unclear. We investigated the long-term time course of VAD using imaging findings to examine the rate and predisposing factors for improvement. METHODS: We registered 56 consecutive patients (40 males; mean age, 51.8 ± 10.7 years) with acute spontaneous VAD and retrospectively investigated neuroimaging and clinical course within 1 month and at 3 months ± 2 weeks, 6 months ± 2 weeks, and 12 months ± 2 weeks after onset to ascertain predisposing factors and time course for improvement. RESULTS: The most common presenting symptoms were headache and/or posterior neck pain, seen in 41 patients (73%). Magnetic resonance imaging showed brainstem and/or cerebellum infarction in only 32 patients (57%). Of the 56 VADs, 16 (28%) presented with pearl and string sign, 5 (9%) with pearl sign, 15 (27%) with string sign, and 20 (36%) with occlusion sign. VAD occurred on the dominant side in 20 patients and on the nondominant side in the other 36 patients. The pearl and string sign was more frequently noted on the dominant side than on the nondominant side (50 vs. 17%, p = 0.008). On the other hand, occlusion occurred more often on the nondominant side than on the dominant side (47 vs. 15%, p = 0.016). Furthermore, the pearl and string sign was more frequently seen in the improvement group (41 vs. 15%, p = 0.028), whereas the occlusion sign was evident more frequently in the nonimprovement group (21 vs. 52%, p = 0.015). Follow-up neuroimaging evaluation was performed at 1 and 3 months in 91% each, and at 6 and 12 months in 82% each. VAD aggravation was identified within 1 month after onset in 14%, while VAD improvement was seen in 14, 38, 50, and 52% at each period, mainly within 6 months after onset. Older patients and current smoking were negatively associated with VAD improvement. CONCLUSIONS: VAD improvement primarily occurs within 6 months after onset, and VAD aggravation within 1 month. It seems that older patients and current smoking are negative predictors of VAD improvement as risk factors, and as image findings, the pearl and string sign is a positive predictor and occlusion a negative predictor.

C-reactive protein and risk of first-ever ischemic and hemorrhagic stroke in a general Japanese population: the Hisayama Study.

BACKGROUND AND PURPOSE: The role of high-sensitivity C-reactive protein (hsCRP) in the development of stroke is not clearly understood. We investigated the relationship between serum hsCRP levels and stroke occurrence in a general Japanese population. METHODS: We followed 2692 subjects > or =40 years of age for 12 years. The relative risks and 95% CIs for ischemic and hemorrhagic stroke occurrence were calculated according to the hsCRP quintiles. RESULTS: During the follow-up, 129 first-ever ischemic and 59 hemorrhagic strokes occurred. In men, the age-adjusted incidence of ischemic stroke significantly increased with elevated serum hsCRP levels; the difference between the first and fifth quintiles was statistically significant (1.4 versus 6.6 per 1000 person-years; P=0.02). This association remained significant even after adjustment for other confounding factors, such as age, systolic blood pressure, ECG abnormalities, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol, smoking habits, alcohol intake, and regular exercise (adjusted relative risks, 3.11; 95% CI, 1.04 to 9.32; P=0.04). However, such associations were not observed for ischemic stroke in women or in hemorrhagic stroke in either sex. Among male subjects who were both in the fifth hsCRP level and had hypertension, diabetes, obesity, hypercholesterolemia, or a smoking habit, the risk of ischemic stroke was extremely increased, even after adjustment for other risk factors. CONCLUSIONS: Our findings suggest that elevated serum hsCRP levels are an independent risk factor for future ischemic stroke in Japanese men and that the coexistence of a high hsCRP level with another risk factor extremely increases the risk of ischemic stroke.

Elevated C-reactive protein is a predictor of the development of diabetes in a general Japanese population: the Hisayama Study.

OBJECTIVE: We examined the association between high-sensitivity C-reactive protein (CRP) levels and the development of diabetes in a general Japanese population. RESEARCH DESIGN AND METHODS: A total of 1,759 Japanese subjects, aged 40-79 years and without diabetes (according to American Diabetes Association fasting criteria), were stratified into three groups according to CRP tertiles by sex and followed up prospectively for a mean of 9.0 years. RESULTS: During the follow-up, 131 subjects (67 men and 64 women) developed diabetes. In both sexes, the age-adjusted cumulative incidence of diabetes increased significantly as the tertiles of CRP levels increased. In multivariate analyses, the risk of developing diabetes was significantly higher in the highest CRP tertile than in the lowest after adjustment for a number of confounding factors (odds ratio 2.63 [95% CI 1.23-5.65] for men and 2.25 [1.01-5.01] for women). In stratified analyses, this CRP-diabetes association was stronger in subjects without obesity or other risk factors related to insulin resistance and in nondrinking subjects. CONCLUSIONS: Our findings suggest that elevated CRP concentration is a significant predictor of diabetes in the general Japanese population, independent of obesity and insulin resistance.

[Repeated Cerebellar Hemorrhage Related to Rivaroxaban and Apixaban: A Case Report].

We report a case of repeated cerebral hemorrhage associated with administration of rivaroxaban and apixaban. A 74-year-old man had undergone catheter ablation for non-valvular paroxysmal atrial fibrillation in 2 years prior. Warfarin treatment was continued after successful catheter ablation, and was then changed to rivaroxaban in 1 year prior. Three months later, he developed subcortical cerebral hemorrhage in the right occipital lobe and pharmacotherapy was changed to apixaban. At the current presentation, he complained of headache and left visual field defect, and was admitted to our hospital. Computed tomography of the head revealed recurrent hematoma at the same site as the previous hemorrhagic lesion. Administration of apixaban was subsequently stopped. Magnetic resonance imaging of the head revealed no vascular anomalies around the hemorrhagic lesion, except for two microbleeds in the left cerebral cortex, suggesting amyloid angiopathy. We report the current case from the perspective of whether anticoagulation should be continued after successful catheter ablation, and whether anticoagulation is appropriate in patients with microbleed signals in the cerebral cortex.

Safety and Management of Antithrombotic Therapy with Intra-Arterial Catheter Procedures.

OBJECTIVE: Intravascular catheter procedures are often performed in patients undergoing antithrombotic therapy. However, methods for the management of antithrombotic agents in the perioperative period are currently unclear. Therefore, the safety and management of antithrombotic agents in these patients were investigated. METHODS: A prospective, multicenter, observational study [Management of Antithrombotic Agents During Surgery or Medical Procedures with Bleeding (MARK study)] at 58 National Hospital Organization institutions in Japan was performed. 1,040 patients were enrolled in the MARK study and underwent an intravascular catheter procedure. For all participants, the details of the procedure, method of perioperative management of antithrombotic agents, and occurrence of thrombosis, embolism, and bleeding complications during the study period were investigated. RESULTS: The use of antithrombotic agents was continued in 1,017 patients (98%, continuation group) and discontinued in the other 23 (2%, discontinuation group). Continuation of the antithrombotic agents did not have a significant effect on the overall occurrence of thromboembolism [hazard ratio (HR), 0.15; p=0.08] or bleeding events (HR, 0.19; p=0.12). However, the overall adverse event risk was significantly lower in the continuation group than in the discontinuation group (HR, 0.18; p=0.03). CONCLUSION: It is both safe and appropriate to perform intravascular catheter procedures in patients continuing with antithrombotic therapy.