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Purpose of review We describe the recent advances in rehabilitation nutrition, which is especially important for disabled or frail older individuals. Recent findings Recent evidence pertaining to rehabilitation nutrition conducted in rehabilitation wards and acute care hospitals has been accumulating. The combination of rehabilitation nutrition and rehabilitation pharmacotherapy is important for eliciting higher functions. The 2020 update of the clinical practice guidelines for rehabilitation nutrition provides a weak recommendation for enhanced nutritional care for patients with cerebrovascular disease, hip fracture, cancer, or acute illness who are undergoing rehabilitation. Rehabilitation nutritional care process and the International Classification of Functioning, Disability and Health-Dietetics are used to implement high-quality rehabilitation nutrition. Aggressive nutrition therapy incorporates the daily energy expenditure plus daily energy accumulation to increase body weight and muscle mass. Preventing and treating sarcopenic dysphagia should include iatrogenic sarcopenia prevention and aggressive nutrition therapy. The diagnosis criteria for respiratory sarcopenia and sarcopenic respiratory disability have been established. Summary The International Association of Rehabilitation Nutrition and Total Nutrition Therapy Rehabilitation program may contribute to international expansion of rehabilitation nutrition. Improving evidence-practice gaps in rehabilitation nutrition and increasing national health insurance coverage of aggressive nutrition therapy and rehabilitation nutrition teams are warranted.

Background: Because of the invasive nature of small cell lung cancer (SCLC), the effectiveness of local therapy for brain metastases (BM) from SCLC had been limited. In this article, we retrospectively evaluated the efficacy of chemotherapy against non-treated BM from SCLC (SCLC-CHT) in compared with TKI for BM from EGFR-mutated NSCLC (EGFR-TKI).Materials and Methods: Un-treated 218 BM, including 58 SCLCs and 160 EGFR-mutated NSCLCs were enrolled. The primary endpoints were maximum response of BM and the duration of effect, and the secondary endpoints were times to the first and maximum responses, patterns of progression and overall survival after the diagnosis of BM.Results: The objective response rate (69%) and disease control rate (92%) of BM after SCLC-CHT were inferior to those after EGFR-TKI (85%, 97%), but were sufficiently satisfactory. Both the times to the first response (0.8m, 95% CI:0.6–0.9) and to the maximum effect after treatment(1.6m, 0.9–1.9) with SCLC-CHT were shorter than with EGFR-TKI (0.9m,0.9–1.0, P=0.011, and 2.4m, 1.9–2.8, P=0.004), but the duration of the response was conversely shorter with SCLC-CHT (5.1m, 4.2–5.6) than with EGFR-TKI (12.3m,9.2–15.1, P

Background Neuroendovascular therapy is a common treatment for patients with acute ischemic stroke of the anterior circulation who fail to respond to recombinant tissue plasminogen activator. However, although most hospitals can provide recombinant tissue plasminogen activator therapy, many cannot perform neuroendovascular therapy. Thus, use of a drip-and-ship treatment-liaison system allowing recombinant tissue plasminogen activator-treated patients to be transferred to facilities offering neuroendovascular therapy is important. Methods We retrospectively analyzed 16 drip-and-ship patients transferred to our hospital for additional neuroendovascular therapy after they received intravenous recombinant tissue plasminogen activator at prior hospitals between June 2009 and March 2017. Results The mean patient age was 68 ± 17 years. Ten patients had cardiogenic embolism and 6 had atherothrombosis. Additional neuroendovascular therapy was performed in 14 patients. Median National Institute of Health Stroke Scale and diffusion-weighted image-Alberta Stroke Program Early Computed Tomography Scores before recombinant tissue plasminogen activator therapy were 14 and 8, respectively. Occluded or stenotic lesions of the cerebral arteries were detected by magnetic resonance angiography in the internal carotid artery (n = 4), middle cerebral artery (n = 10), and basilar artery (n = 3) (1 patient had tandem lesions). Mean intervals from onset-to-recombinant tissue plasminogen activator, recombinant tissue plasminogen activator-to-our hospital (door), door-to-puncture, and onset-to-recanalization were 166, 65, 32, and 334 minutes, respectively. No patients showed symptomatic intracranial hemorrhage. Conclusions Magnetic resonance imaging/angiography performed in previous hospitals allows initiation of reperfusion therapy immediately after transfer. Thus, drip-and-ship plus neuroendovascular therapy is a safe and useful system for treatment of patients with acute infarcts.

The management of grade 1 checkpoint inhibitor pneumonitis (CIP) is to withhold immune checkpoint inhibitors; however, the natural history of this condition is unknown. We herein report the case of a woman with squamous cell lung cancer who was a long-term survivor after CIP. After 4 rounds of treatment with nivolumab, a chest CT revealed a reticular pattern and ground-glass attenuation with shrinkage of the primary nodule. Nivolumab treatment was withheld without the administration of steroids. Although she remained asymptomatic, subsequent images revealed an increasing interstitial shadow until 2 months after the stop of nivolumab treatment. Thereafter, the interstitial shadow began to improve spontaneously without steroid treatment. Moreover, although the patient has not received additional therapy, disease control of lung cancer has been obtained within a follow-up period of more than 3 years. Although the exacerbation of CIP may appear on images for several months, asymptomatic cases can be followed without the administration of steroids. If the tumor had already responded prior to the onset of CIP, a favorable long-term prognosis can be expected.

BACKGROUND: Despite the favorable response, most brain metastases (MBs) acquire resistance to TKIs. T790M is the most common mechanism and accounts for approximately half of acquired resistance to TKIs. The aim of this study is to clarify the role of T790M in the acquired resistance of BMs, and optimal treatment for BMs progressed after TKI. METHOD: Upfront TKI was performed for BMs from EGFR-mutated NSCLC, and TKI was changed at progression. Gefitinib, erlotinib, afatinib and osimertinib were used and the selection of these TKIs were owing to the physicians’ decision. During the disease course, re-biopsies of progressed diseases were performed to verify mutations of EGFR, and the incidences of T790M were compared among the organs biopsied. The time to CNS-progression (TCP) were evaluated for each TKI. RESULTS: 141 cases were enrolled. Gefitinib was used only as the first line TKI (n=91). Erlotinib was selected for both the gefitinib-naïve patients (n=27) and after gefitinib (n=51). Afatinib (n=21) and osimertinib (n=17) were selected for only recurrent cases. TCPs after gefitnib, erlotinib, afatinib, and osimertinib were 13.4, 20.1, 19.9, and 13.8months, respectively. The history of treatment with gefitinib did not affect the TCP after erlotinib (HR:1.37, 95%CI:0.61–3.25, P=0.451). Re-evaluations of EGFR was performed using 107 samples (lung:51, serum:25, CNS:22, others:9) from 88 cases. The incidence of T790M from CNS samples was 9.1% (Tumor:1/6, CSF:1/16), and was significantly lower than that from the other organs (lung:50.1%, surum:28.0%, others:44.4%) (Odds ratio:0.130, P=0.001). The extremely low incidence of T790M and satisfied effects of TKIs even after TKI-failure suggested the different mechanism of acquired resistance of BMs to TKIs in compared with the extracranial lesions. CONCLUSIONS: T790M played only a limited role in acquired resistance of BMs to TKIs, and alterations of the types of TKIs were still recommended for the progressed BMs after TKI.

We report the case of a 46-year-old man with hemicrania continua presenting as exacerbations mimicking trigeminal neuralgia. The patient was tentatively diagnosed with trigeminal neuralgia, and treatment with various combinations of drugs was performed after the onset of pain. However, when the condition of the patient did not improve, we suspected hemicrania continua, and treatment with indomethacin was initiated. There was a marked alleviation of his pain within 24 hours. Thus, clinicians should be aware that the duration and frequency of exacerbations of hemicrania continua are variable.

We encountered two patients with sumatriptan-induced reversible cerebral vasoconstriction syndrome (RCVS). The present patients were taking sumatriptan for the first time because they had been tentatively diagnosed with a migraine. On reviewing the literature, we found nine other cases of triptan-induced RCVS, predominantly among women aged 30 to 40 years. RCVS has been precipitated by triptan at the first ever use, after daily use, and even with long-term use at a normal dose. Patients with acute onset of severe headache should be thoroughly evaluated, and triptan should be administered appropriately. If triptan-induced RCVS is suspected, vascular imaging should be repeated after several days.

Background Endothelial dysfunction plays a key role in the development of ischemic stroke. However, the relationship between endothelial function and stroke subtypes has not been thoroughly examined. Methods We measured the percentage of brachial flow-mediated vasodilatation (%FMD) in 62 patients with chronic stroke and 13 age- and sex-matched control patients. Patients with stroke included those classified into large artery atherosclerosis (LAA), cardioembolism (CE), and small vessel occlusion (SVO) according to the criteria of the Trial of ORG 10172 in Acute Stroke Treatment classification. Results %FMD was significantly lower in the patients with any of LAA, CE, and SVO than in the control patients. %FMD was also significantly lower in men than in women as well as in patients with than without hypertension or diabetes mellitus. After adjustment for confounding factors, the patients with LAA and CE but not SVO had lower %FMD compared to the controls. Conclusions Our results suggest that endothelial function in conduit artery was impaired in patients with LAA and CE regardless with or without concomitant vascular risk factors.

Background and Purpose— Paroxysmal atrial fibrillation (PAF) is often difficult to detect in patients with acute ischemic stroke. We aimed to assess the predictive value of a prolonged QT interval corrected for heart rate (QTc) in PAF detection after acute ischemic stroke. Methods— We enrolled 972 patients with acute ischemic stroke consecutively extracted from our observational stroke registry system. Exclusion criteria were as follows: (1) AF on the initial 12-lead ECG (n=171); (2) previously diagnosed PAF (n=47); and (3) the use of a cardiac pacemaker (n=10). Of the 972 patients, 744 (mean age, 67.6 years; men, 62.6%) were eligible for analysis. The clinical characteristics and 12-lead ECG findings of the patients with and without PAF were compared, and multiple logistic regression analysis was performed to identify predictors of poststroke PAF. Results— The poststroke cardiac work-up yielded 69 (9.3%) de novo PAF cases among the 744 patients. The QTc interval was significantly longer in patients with PAF than in those without PAF (436 versus 417 ms; P P Conclusions— The QTc interval prolongation is potentially a strong and useful predictor for poststroke PAF.

This study investigated the associations of mitral and aortic valve calcification with complex aortic atheroma among patients with embolic stroke of undetermined source.We included 52 consecutive patients (mean age 58.1 years; 75.0% male) with embolic stroke of undetermined source. Mitral annular calcification, aortic annular calcification, and aortic valve sclerosis were assessed by transthoracic echocardiography. Complex aortic atheroma was assessed by transesophageal echocardiography and was defined as plaque protruding greater than or equal to 4 mm into the lumen or with ulcerated or mobile components.Ten patients (19.2%) had complex aortic atheroma. Patients with and without complex aortic atheroma showed significant differences in terms of hypertension (80.0% versus 38.1%, P = .017), dyslipidemia (90.0% versus 31.0%, P .01), chronic kidney disease (60.0% versus 14.3%, P .01), previous coronary artery disease (30.0% versus 4.8%, P = .013), prior stroke (40.0% versus 7.1%, P .01), left atrial dimension (4.0 cm versus 3.6 cm, P = .023), aortic valve sclerosis (80.0% versus 26.2%, P .01), aortic valve calcification (aortic annular calcification or aortic valve sclerosis) (80.0% versus 26.0%, P .01), and left-sided valve calcification (mitral annular calcification or aortic annular calcification or aortic valve sclerosis) (80.0% versus 28.6%, P .01). In multivariate analysis, left-sided valve calcification was independently associated with complex aortic atheroma (odds ratio 4.1, 95% confidence interval 1.3-26.1, P = .049).Mitral or aortic valve calcification detected by transthoracic echocardiography can be a useful marker for predicting complex aortic atheroma in patients with embolic stroke of undetermined source.

The hypercoagulable state in patients with cancer has been shown to be closely associated with ischemic stroke. However, it is unlikely that benign tumors are related to stroke. The development of benign uterine tumors is common in middle-aged women. Previous studies have shown cases of ischemic stroke with benign uterine tumor, but the causal relationship between these 2 remain unknown. We report a case of recurrent ischemic stroke in a middle-aged woman who had a benign uterine tumor. After excision, there was no recurrence for 2 years. Microemboli detection, clinical course and histological findings support a relationship between uterine tumor and ischemic stroke.

Isolated brain infarction in the anterior cerebral artery (ACA) territory is rare, and its etiology has not yet been fully elucidated. Thus, we aimed to determine the etiologic and clinical characteristics of patients with isolated ACA territory infarction due to arterial dissection.Of 2315 patients with acute cerebral infarction admitted to our hospital between April 2007 and September 2013, 34 patients (1.5%; 28 men, 6 women; mean age, 65 ± 15 years) suffered isolated ACA territory infarction. We performed cranial magnetic resonance (MR) imaging and MR angiography for all the patients. Whenever possible, we also performed 3-dimensional computed tomography angiography, digital subtraction angiography, and MR cisternography to diagnose the stroke subtype.The stroke subtypes of the 34 patients with isolated ACA territory infarction were atherothrombotic infarction, cardioembolic infarction, arterial dissection, and unclassified in 11 patients (32%), 11 patients (32%), 11 patients (32%), and 1 patient (3%), respectively. The mean ages at onset were 48 ± 9 and 72 ± 11 years in the dissection and nondissection groups, respectively (P.001). Headaches were present at onset in 4 patients (36%) and 1 patient (4%) with and without dissection, respectively (P = .026). Blood pressure at onset was significantly higher among patients with dissection (systolic, 179 ± 34 mm Hg; diastolic, 102 ± 17 mm Hg) than among patients without dissection (systolic, 155 ± 30 mm Hg; diastolic, 86 ± 21 mm Hg; P.05), and d-dimer values were significantly lower among patients with dissection (P = .034). Favorable clinical outcome (modified Rankin Scale score, 0-2) at discharge was achieved in 9 patients (82%) and 10 patients (43%) with and without dissection, respectively (P = .035).Patients with isolated ACA territory infarction demonstrated a relatively high frequency of dissection (32%). Patients with dissection were younger, had a higher frequency of headaches, and demonstrated more favorable prognoses than patients without dissection.

Elevated serum brain natriuretic peptide (BNP) levels are associated with cardioembolic stroke mainly because of atrial fibrillation (AF). However, the mechanisms of increased serum BNP levels are hitherto unclear. We aimed to identify the factors associated with increased BNP levels in patients with acute ischemic stroke. We measured serum BNP levels in consecutive patients aged 18 years or older. Stroke subtypes were classified using the Trial of ORG 10172 in Acute Stroke Treatment criteria. Categorical variables included age, sex, smoking status, alcohol consumption status, hypertension, diabetes mellitus, dyslipidemia, coronary artery disease (CAD), AF, antiplatelet therapy, and anticoagulant therapy. Continuous variables included hemoglobin, creatinine (Cr), β-thromboglobulin, platelet factor 4, thrombin–antithrombin complex, and d-dimer levels. We further determined the relationship between serum BNP and intima–media thickness, left ventricular ejection fraction, size of infarction, National Institutes of Health Stroke Scale score on admission, and modified Rankin Scale (mRS) score at discharge. Of the 231 patients (mean age, 71 ± 12 years) with acute ischemic stroke (AIS), 36% were women. Serum BNP levels significantly correlated with CAD, AF, Cr, mRS, and cardioembolism (CE) (Dunnett method, P = .004). BNP levels were significantly higher in patients with larger infarcts, higher mRS scores, and higher CHADS 2 scores. The levels were higher in patients with larger infarcts, higher mRS scores at discharge, and higher CHADS 2 scores among AF patients.

Transient ischemic attack (TIA) is often followed by a stroke episode. Differences between early and late recurrent stroke, however, have not been elucidated.We enrolled 133 consecutive patients with acute ischemic stroke who presented to our hospital and had previously been diagnosed with TIA. They were divided into 5 groups according to the interval between TIA and subsequent stroke:48 hours (group 1); 48 hours to 1 week (group 2); 1 week to 1 month (group 3); 1 month to 3 months (group 4); and3 months (group 5). Patients who underwent recurrent stroke within and after 1 week subsequent to TIA (the early and late recurrence groups, respectively) were compared with regard to clinical findings.Of the 133 patients, 46 (34.6%) were in group 1, 29 (21.8%) in group 2, 23 (17.3%) in group 3, 18 (13.5%) in group 4, and 17 (12.8%) in group 5. Most of the noncardioembolic strokes were observed shortly after TIA, while the percentage of cardioembolic stroke remained high even after long post-TIA periods. The prevalence of atrial fibrillation (AF) was higher in the late recurrence group than in the early recurrence group (41.4% v 24.0%, P = .033). Among 42 patients with AF, 12 (28.6%) were newly diagnosed at the time of stroke.The frequency of cardioembolic stroke did not decline as time after TIA passed. More than one quarter of AF patients had been asymptomatic before stroke, suggesting the need for repeated examinations to detect AF in patients with TIA of unknown etiology.

Background Transient ischemic attacks (TIAs) greatly increase the risk of stroke, but few reports have examined subsequent stroke in patients with history of TIA. Methods This retrospective, hospital-based study included 506 consecutive patients with acute ischemic stroke who were admitted to our hospital. The clinical features and prognosis were compared between patients with and without TIA. Multiple logistic regression analysis was also performed to identify predictors for poor outcome. Results Of 506 patients, 114 (22.5%) had a history of TIA. Compared to patients without previous TIAs (non-TIA group), patients with previous TIAs (TIA group) were significantly more likely to have hypertension (76.3% vs 64.3%; P = .016), dyslipidemia (57.0% vs 41.1%; P = .003), chronic kidney disease (28.1% v 15.1%; P = .001), intracranial major artery stenosis (51.8% vs 36.2%; P = .018), and large artery atherothrombosis (43.9% vs 28.3%; P = .002). There was no difference in the previous use of antithrombotic medications between the groups (36.0% vs 35.2%; P = .881). Although stroke severity on admission was similar, poor functional outcome (modified Rankin Scale score ≥4) was significantly more frequent in the TIA group, and history of TIA was an independent determinant of unfavorable outcome on multiple logistic regression analysis (odds ratio 1.46; 95% confidence interval 1.02–2.10; P = .041). Conclusions Atherothrombotic stroke with concomitant vascular risk factors were more frequent in the stroke patients with than without previous TIA. Antithrombotic therapy was conducted only in one-third of the patients even after TIA. The stroke patients with history of TIA were at great risk of disabling stroke.

Objective Decompressive craniectomy (DC) in patients with malignant middle cerebral artery (MCA) infarction is known to decrease the mortality rate. However, the functional outcomes (communication and oral intake) of this procedure remain unclear. Most patients with malignant MCA infarction exhibit a loss of consciousness, which may be principally governed by the thalamus. We herein investigated the functional outcomes of DC at 90 days after the onset of malignant MCA infarction and their association with preoperative thalamus deformation, which can occur due to pressure and edema. Methods Twelve of 2,692 patients with acute cerebral infarction were diagnosed with malignant MCA infarction and underwent DC. We evaluated preoperative thalamus damage using brain computed tomography and its association with communication and oral intake abilities and the modified Rankin Scale (mRS) and Barthel index scores at 90 days after stroke onset. Results The mRS score at 90 days was 0-4 in five patients. Seven patients could communicate immediately after surgery, while five could do so by 90 days. Five patients were able to resume the oral intake of food at 90 days. All patients with preoperative thalamus deformation showed a poor recovery, while those with absent or slight preoperative thalamus deformation showed a good recovery. Conclusion Patients with preoperative thalamus deformation caused by pressure and edema show a poor oral intake and communication abilities after DC, suggesting that preoperative thalamus deformation is a predictor of poor functional outcomes after DC in patients with malignant MCA infarction.

Brachial-ankle pulse wave velocity (baPWV) is a good measure of arterial stiffness and is associated with risk of future vascular events. The present study aimed to examine whether baPWV can also predict 3-month functional outcome after stroke.This hospital-based study included 327 consecutive patients with acute ischemic stroke and in whom baPWV was measured during hospitalization. We defined good and poor functional outcomes as a modified Rankin Scale score of3 and ≥ 3 at 3 months, respectively, after initial stroke.Patients with poor outcomes were significantly older (73.1 versus 66.3 years, p 0.001) and more likely to have extracranial carotid arterial stenosis (29.5% versus 13.1%, p 0.001), atrial fibrillation (21.0% versus 11.3%, p = 0.020), history of coronary artery disease (20.0% versus 11.7%, p = 0.042), and high baPWV value (22.84 versus 19.48 m/s, p 0.001). Irrespective of patients' age, sex, baseline risk factors, initial stroke severity, and stroke etiology, baPWV was consistently higher in patients with poor outcome than those with good outcome. Multivariate analysis revealed that baPWV23.11 m/s, calculated from the receiver-operating characteristic curve, had an independent predictive value for poor functional outcome (odds ratio, 1.51; 95% confidence interval, 1.08-2.11; p = 0.016).BaPWV measured during the acute phase of stroke can independently predict 3-month functional prognosis. We suggest that baPWV should be performed as part of the early stroke work-up to identify patients suffering from severe stroke-related disability.

We report a patient who presented with adversive seizures associated with periodic lateralised epileptiform discharges (PLEDs), a month after head trauma. The PLEDs predominantly involving the left frontal contacts became more frequent at the onset of adversive seizures during EEG. Brain MRI demonstrated a contusion scar in the left orbital cortex with reduced diffusion, not only around this orbital lesion but also in the ipsilateral anteromedial thalamus. Single photon emission computed tomography revealed focal cerebral hyperperfusion in the left medial orbitofrontal region, basal ganglia, and thalamus. The abnormal metabolism involving the thalamus and striatum could be associated with the ipsilateral orbital contusion and might have been caused by cortical-subcortical, trans-synaptic hyperactivity. Further studies are warranted to determine the role of subcortical structures in the generation of PLEDs and adversive seizures. [Published with video sequences].

In patients with lung cancer accompanied by idiopathic pulmonary fibrosis (IPF), acute exacerbation of the IPF often occurs after pulmonary resection; however, few studies have been done to identify its preexisting risk factors. We analyzed the high-resolution computed tomography (HRCT) findings of IPF to identify the radiological characteristics of IPF susceptible to acute exacerbation after lung cancer surgery. We reviewed retrospectively 28 lung cancer patients with IPF who underwent pulmonary resection. Clinical data, respiratory function, HRCT findings, and historical features were compared between the acute exacerbation (n = 9) and nonexacerbation (n = 19) groups. The classification of radiological findings of IPF on HRCT was done using a scoring system of seven factors related to the interstitial shadow, including fibrosis, ground-glass opacity, and low-attenuation area. There were no significant differences in clinical background, respiratory function, composite physiologic index, or pathological features between the groups; however, the degree of fibrosis on preoperative HRCT was significantly higher in the exacerbation group (P < 0.003). The fibrosis score was higher on the opposite side to the lung cancer in the exacerbation group (P < 0.05). Although it is difficult to predict postoperative acute IPF exacerbation, the degree and laterality of co-existing fibrosis seem to be predictors.

Background and objective: Although lung cancer is frequently accompanied by COPD and interstitial lung disease (ILD), the precise coincidence of these diseases with lung cancer is not well understood. The objectives of this study were to determine the prevalence of abnormal CT and spirometric findings suggestive of COPD or ILD in a population of patients with untreated lung cancer, and to estimate the lung cancer risk in this population. Methods: The study population consisted of 256 patients with untreated lung cancer and 947 subjects participating in a CT screening programme for lung cancer. Semi-quantitative analysis of low attenuation area (LAA), fibrosis and ground glass attenuation (GGA) on CT was performed by scoring. Gender- and age-matched subpopulations, with stratification by smoking status, were compared using the Mantel–Haenszel projection method. Results: Inter-observer consistency was excellent for LAA, but not as good for fibrosis or GGA scores. Pooled odds ratios for lung cancer risk using LAA, fibrosis, GGA scores and reduced FEV1/FVC and %VC were 3.63, 5.10, 2.71, 7.17 and 4.73, respectively (P

BACKGROUND The purpose of this study was to evaluate the usefulness and safety of multidetector-row computed tomography (MDCT) pulmonary angiography and indirect venography management of acute pulmonary embolism (PE), including indication for inferior vena cava (IVC) filter. METHODS AND RESULTS Seventy-one consecutive patients who were clinically suspected of PE and underwent 16-slice MDCT pulmonary angiography and indirect venography were enrolled. Management included indication of IVC filter for patients with extensive deep venous thrombosis (DVT) in submassive or massive PE. A right ventricular to left ventricular short-axis diameter by MDCT>1.0 was judged as submassive PE. All patients were followed for 1 year. MDCT identified 50 patients with venous thromboembolism and 47 patients had acute PE: 4 were judged as massive, 14 as submassive, and 29 as non-massive by MDCT; 3 patients had DVT alone and 7 patients had caval or iliac DVT. Only 1 patient with massive PE and DVT near the right atrium died of recurrence. No other patients died of PE. CONCLUSION Management based on MDCT pulmonary angiography combined with indirect venography is considered to be safe and reliable in patients with suspected acute PE.

OBJECTIVE Anticoagulation therapy with warfarin is associated with a favorable prognosis in ischemic stroke. Dabigatran, a new oral anticoagulant, is widely used to prevent ischemic stroke in non-valvular atrial fibrillation (NVAF) patients. However, its association with decreased severity and a favorable prognosis once ischemic stroke has occurred remains unknown. METHODS We retrospectively reviewed all the patients with NVAF-associated ischemic stroke admitted to our hospital from April 2011 to December 2014 and included those who received dabigatran therapy. We assessed whether the patients were under regular use of the drug or discontinuance and classified them into 2 groups, the treatment and discontinuation groups. Clinical data, including the age, sex, ASCOD stroke phenotype, NVAF type, prescribed drug dose, comorbidities, CHADS2 score, renal function, National Institute of Health Stroke Scale (NIHSS) score on admission, modified Rankin scale (mRS) score at discharge, D-dimer, and brain natriuretic peptide, were investigated and compared between the groups. RESULTS Nine patients were under regular dabigatran therapy, and 6 were under discontinuance of the drug. The age, sex, ASCOD stroke phenotype, NVAF type, comorbidities, renal function, and CHADS2 scores did not differ between the 2 groups; however, the NIHSS scores were significantly lower in the treatment group. The mRS scores at discharge were additionally decreased in the treatment group. Moreover, the D-dimer scores were lower in the treatment group, thus suggesting a possible role in the decreased stroke severity. CONCLUSION Dabigatran may therefore decrease the severity of ischemic stroke, even if ischemic stroke occurs.

Chronic kidney disease (CKD) is an increased risk for the development of active tuberculosis, but few studies have analyzed the treatment outcome of pulmonary tuberculosis among CKD patients. A retrospective cohort study was conducted at Chiba-East Hospital in Chiba, Japan. Our study estimated the treatment outcomes in smear-positive pulmonary tuberculosis in relation to CKD and its stages. Total subjects were 759 patients (12-99 years) hospitalized between 2007 and 2012. Patients suffering from multi-drug-resistant tuberculosis were excluded. Patients with CKD were 19.3% aged65 years (n = 384), and 49.6% aged ≥ 65 years, respectively (P 0.001). Successful treatment was 52.7% in CKD (n = 260) and 67.3% in non-CKD (n = 499) (P 0.001). Death was 25.4% in CKD and 12.4% in non-CKD (P 0.001). Treatment outcome was especially poor in patients with low estimated glomerular filtration rate (eGFR) of30 ml/min/1.73 m(2), as successful treatment was 20.0%, and death was 50.0%, significantly lower than in other CKD and non-CKD patients. After multivariate logistic regression analysis, eGFR30 ml/min/1.73 m(2) was an independent factor affecting successful treatment and death, and its adjusted odds ratios (aOR) were 0.20 (95% confidence interval (CI) 0.07-0.50) and 2.99 (95%CI 1.20-7.51), respectively. Other factors affecting successful treatment were serum albumin3.0 mg/dl, steroid therapy for underlying disease and cardiovascular disease, with aOR (95%CI) of 0.28 (0.20-0.39), 0.32 (0.16-0.63) and 0.49 (0.28-0.86), respectively. Several factors were associated with poor treatment outcome of smear-positive pulmonary tuberculosis. Advanced stage of CKD with eGFR of30 ml/min/1.73 m(2) was a risk factor for poor treatment outcome.

The Arabidopsis CLAVATA3 ( CLV3 ) gene encodes a stem cell–specific protein presumed to be a precursor of a secreted peptide hormone. Matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) applied to in situ Arabidopsis tissues determined the structure of a modified 12–amino acid peptide (MCLV3), which was derived from a conserved motif in the CLV3 sequence. Synthetic MCLV3 induced shoot and root meristem consumption as cells differentiated into other organs, displaying the typical phenotype of transgenic plants overexpressing CLV3 . These results suggest that the functional peptide of CLV3 is MCLV3.

Amrubicin is a novel, completely synthetic 9‐aminoanthracycline derivative. Amrubicin and its C‐13 alcohol metabolite, amrubicinol, inhibited purified human DNA topoisomerase II (topo II). Compared with doxorubicin (DXR), amrubicin and amrubicinol induced extensive DNA‐protein complex formation and double‐strand DNA breaks in CCRF‐CEM cells and KU‐2 cells. In this study, we found that ICRF‐193, a topo II catalytic inhibitor, antagonized both DNA‐protein complex formation and double‐strand DNA breaks induced by amrubicin and amrubicinol. Coordinately, cell growth inhibition induced by amrubicin and amrubicinol, but not that induced by DXR, was antagonized by ICRF‐193. Taken together, these findings indicate that the cell growth‐inhibitory effects of amrubicin and amrubicinol are due to DNA‐protein complex formation followed by double‐strand DNA breaks, which are mediated by topo II.

Patients with vertebrobasilar (VB) circulation ischemia can present with nonspecific symptoms, which complicate the distinction of transient ischemic attack (TIA) from other benign disorders. According to previously accepted classifications, typical TIA does not occur with VB symptom such as vertigo, diplopia, or dysarthria in isolation. However, there is a lack of evidence to support this hypothesis.This hospital-based study included 214 consecutive patients with acute ischemic VB stroke. We defined transient neurological attacks (TNAs) as temporary (24h) episodes with neurological symptoms, and further divided them into TIA, nonspecific TNA, or other specific disorder groups. We investigated the incidence and clinical symptoms of TNAs within 3months prior to the stroke episode, and comparisons were made between patients with and without previous TNA history with respect to their background and stroke profiles.Among 214 patients with VB stroke, 56 (26.2%) had previous TNAs. Six of them were diagnosed with other specific disorders and excluded from the analysis. The remaining 33 and 17 were diagnosed with TIA and nonspecific TNA, respectively. Twenty-one (42.0%) had attacks with a nonfocal symptom in isolation, and acute infarction in neuroimaging was confirmed in 4 of these patients. Vertigo was the most frequent nonspecific TNA symptom. Patients with prior TNA had a significantly higher rate of atherothrombotic stroke than those without TNA (40.0% vs. 21.5%, P=0.009).A considerable fraction of TIAs due to VB circulation ischemia may be overlooked among clinically nonfocal TNAs.

Background The high risk of stroke after transient ischemic attack (TIA) has been widely recognized, although the differences of clinical characteristics between early and late recurrent stroke were not well-known. Materials and methods The subjects were 133 consecutive ischemic stroke patients who were admitted to our hospital within one week of onset, and had previously diagnosed as “definite TIA” by trained stroke neurologists. They were divided into five groups according to the interval between prior TIA and subsequent stroke; (1) within 48 hours, (2) 48 hours to 1 week, (3) 1 week to 1 month, (4) 1 month to 3 months, and (5) after 3 months (group 1 to 5, respectively). Then, we compared clinical characteristics and prognosis between the patients who presented recurrent stroke within and after 1 week subsequent to TIA (early recurrence group and late recurrence group, respectively). Results Of the 133 acute stroke patients (mean age 69.9 years, male 66.9%), 46 (34.9%) were in group 1, 28 (21.2%) in group 2, 23 (17.4%) in group 3, 18 (13.6%) in group 4, and 17 (12.9%) in group 5. As to stroke subtypes, most of the non-cardioembolic strokes were frequently observed shortly after TIA, while the percentage of cardioembolism remained high even the time from prior TIA passed ( Figure ). The prevalence of atrial fibrillation (Af) was higher (39.7% vs. 21.3%, P =0.034), and dyslipidemia was lower (41.4% vs. 64.0%, P =0.014) in the late recurrence group than in the early recurrence group. The percentages of patients with hypertension, diabetes mellitus, and higher ABCD 2 score (≥3 or ≥5) were similar in both groups. Among 42 patients with Af, 14 (33.3%) were premorbid, 16 (38.1%) were diagnosed when TIA presented, and 12(28.6%) were diagnosed when stroke presented. In the late recurrence group, 37/58 patients (63.8%) had a poor outcome (modified Rankin Scale ≥3) at 3 month of stroke onset, significantly higher than the 29/75 (38.7%) patients in the early recurrence group ( P =0.005). Conclusions The frequency of cardioembolic stroke dose not decline during the time course after TIA, while most of the non-cardioembolic stroke recur early after TIA. This might be responsible for the poorer functional outcome in late recurrent stroke. More than quarter of Af patients had been asymptomatic before stroke, which suggests the need for repeated examinations to detect Af in patients with TIA of unknown etiology.

症例は70歳,女性. 20歳頃より両手指の姿勢時振戦を認め,悪化傾向なく経過していた. 65歳より近医でパーキンソン病としてL-DOPAを投与されていたが,振戦以外の症状は認められず, 1999年にL-DOPA中止後も症状の増悪は認められなかったため,本態性振戦と診断された. 2000年2月よりファモチジンの内服を開始したところ, 3月頃よりパーキンソン症状が出現した.ファモチジンが薬剤性パーキンソニズムの原因になり得るかどうか,今後の臨床的観察が必要と考え,症例を報告した.

To observe the current situation of tuberculosis and its control measures in hemodialysis facilities in Chiba Prefecture, Japan.Questionnaires on medical dialysis and tuberculosis were sent to hemodialysis facilities in Chiba Prefecture.The questionnaires were answered by 55 of 127 facilities. Of the respondents, 46 (83.6%) were not aware of the recommendation of treatment for latent tuberculosis infections in Japanese patients. Moreover, 30 (54.5%) facilities did not examine patients for tuberculosis prior to the initiation of hemodialysis. Of the 21 facilities that did assess patients for tuberculosis infection, only 5 (23.8%) performed a tuberculin skin test or QuantiFERON TB-2G. Three of the five (60.0%) that were treating tuberculosis by themselves expressed fear or uncertainty about the diagnosis and treatment of latent tuberculosis infections. During January 2006 through December 2007, tuberculosis patients were detected in 11 facilities, and the proportion of extrapulmonary tuberculosis among these patients was 52.4%. Seven facilities reported that they took no control measures against tuberculosis.It is important to inform medical dialysis facilities about latent tuberculosis infections, the early diagnosis of tuberculosis, and the combination of nosocomial infection control. It is also important for experts in hemodialysis and tuberculosis to work closely together.

Stomata are composed of a pair of guard cells and a pore between them, and their density and positions are regulated by developmental and environmental signals. In a screen in which we overexpressed many genes coding for putative secretory proteins one by one in Arabidopsis, we identified a gene named STOMAGEN, which increases stomatal density when overexpressed. The STOMAGEN gene encodes a small peptide with a putative secretory signal sequence at its N-terminus and is expressed preferentially in mesophyll cells. This peptide belongs to the EPIDERMAL PATTERNING FACTOR (EPF) family of the cysteine-rich peptides superfamily. The mature form was a 45-amino-acid peptide (stomagen) with three intramolecular disulfide bonds. Stomagen treatment at very low concentrations, as low as 10 nM, increased the stomatal density of wild-type Arabidopsis plants. We propose that stomagen is a mesophyll-to-epidermis signaling molecule that positively regulates stomatal density. We also suggest that stomagen increases stomatal density by competing with negative regulators EPF1 and EPF2 for the receptor-like protein TOO MANY MOUTHS.

To examine the clinical problems of died cases with pulmonary tuberculosis.Clinical findings of 52 patients with active pulmonary tuberculosis, who had died in our hospital between April 2005 to March 2007, were analyzed.Mean age was 72.3 10.6 years old, 9 cases (17.3 %) were relapsed, and 35 cases (67.3%) had cavity on the chest X-ray. 34 cases (65.4%) were PS4 and none was PS0 or PS1 on admission. Complications were malignancy in 11 cases, diabetes mellitus in 10 cases, and respiratory diseases in 6 cases. 15 cases (28.8%) were treated with drugs including INH, RFP and PZA, 14 cases (26.9%) with drugs including INH and RFP, 16 cases (30.8%) with the other drugs, and 7 cases (13.5%) were not able to be administered any drug. 35 cases (67.3%) died of tuberculosis and 17 cases (32.7%) died of non-tuberculous conditions.Many died cases were under very poor general condition, needed frequent care, had many kind of complications and had difficulty with standard treatment on admission. Tuberculous death were observed highly, but death by complications were observed in many cases. It is necessary to control complications and enlighten society and docters about importance of early diagnosis and treatment of tuberculosis continuously.

A 79-year-old man with past history of thoracoplasty due to pulmonary tuberculosis visited a general clinic complaining of left back pain and left axillary tumor. As the pus of tumor aspirated was positive for PCR-TB, the patient was diagnosed as pericostal tuberculosis and introduced to our hospital. At first, the operation was considered, but the patient had high risk for the operation because he was old and low body weight and the lesion of tuberculosis in his thorax was very extensive. Anti-tuberculous drugs were administrated and exclusion of pus by needle aspiration was repeated. After starting the treatment, the size of tumor had reduced guradually. Pericostal tuberculosis should be taken into consideration in case of pericostal mass with past history of tuberculosis, and the method of treatment should be decided with considering patient's condition.

Recent studies on lung cancer screening with CT disclosed a discrepancy between its efficiency in detecting early lung cancer and a lack of proof for decreasing mortality from lung cancer. The present study, in a city in Japan where an X-ray screening program is provided, bi-annual CT screening was performed for X-ray screening negative subjects for 4 years. Ten patients with lung cancer were detected among 22,720 person-year subjects (0.044%) through the X-ray screening. Among the X-ray screening-negative subjects, 3305 subjects participated in a CT screening program resulting in the detection of 15 patients with lung cancer (0.454%). All 15 cases detected by CT screening and 5 of the 10 cases detected by X-ray screening were at stage IA. In respect of gender, histological type and CT findings, patients detected by CT screening had a better prognostic profile than those detected by X-ray screening. Survival was significantly better in the former than the latter, both in its entirety comparison and in a comparison limited to patients who underwent surgery. In conclusion, CT screening might have the potential to detect lung cancer with good prognostic factors not limited to early detection. Sufficiently long follow-up time, therefore, would be required to evaluate the efficacy for decreasing lung cancer mortality with CT screening.

Recently, several reports have been published on ultrasonic vascular dilation produced with relatively low-frequency ultrasound. It has been speculated that nitric oxide (NO) is an important factor for this ultrasonic vascular dilation. However, a quantitative relationship between the ultrasound intensity and NO generation was not clarified in these reports. We investigated the quantity of NO generated by various ultrasonic intensities by means of real-time measurement of NO concentration in the adductor muscles of the thigh of New Zealand white rabbits exposed to a continuous-wave ultrasound (490 kHz). In the quantitative relationship between NO generation and ultrasonic intensity, the percent increase in NO concentration was 1.25% +/- 1.25%, 10.6% +/- 2.9% and 20.1% +/- 3.5%, with the maximum muscle temperature increase 0.5 +/- 0.2 degrees C, 0.7 +/- 0.2 degrees C, and 0.8 +/- 0.3 degrees C at the ultrasonic intensity (SPTA) of 0.21, 0.35 and 0.48 W/cm(2), respectively. The effect of ultrasound on NO generation was intensity-dependent with a progressive increase from 0.21 W/cm(2) to 0.48 W/cm(2) without significant thermal effect. Ultrasonic NO generation was partially reduced by NOS inhibitor of L-NMMA, clarifying that ultrasound can activate both NOS-dependent and NOS-independent NO generation. These new findings provided scientific basis for ultrasonic vasodilatation and support the potentiality of a new ultrasonic technology for the treatment and prevention of the ischemic tissue based on the new concept of NO generated angiogenesis. (E-mail: furuhata@jikei.ac.jp).

N-Ethylacetoacetamide and acetoacetanilide were enantioselectively converted into the corresponding (S)-3-hydroxy compounds by alginate- or polyurethaneimmobilized bakers’ yeasts, while without immobilization the yield of the yeast-mediated reaction was very low.