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Aims Elevated serum alkaline phosphatase (ALP) levels are associated with an increased risk of cerebrocardiovascular diseases. However, the associations of ALP with peripheral arterial disease (PAD) and outcomes in patients with acute ischemic stroke (AIS) are not well-known. Methods We examined the association between ALP levels and the ankle-brachial index (ABI) in 2111 consecutive patients with AIS. A poor functional outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 3 months after stroke. A low ABI was defined as a value of ≤ 0.9. Results Of the total cohort, 482 patients (22.8%) had a low ABI. ALP levels were higher in patients with a low ABI than in those without (p＜0.001). The multivariable logistic analysis revealed that quartiles of ALP levels were significantly associated with a low ABI (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.08-1.33). Of the 1322 patients with a premorbid mRS score of 0-2, 434 patients (32.8%) had a poor outcome. The multivariable analysis revealed that elevated serum ALP levels and a low ABI were independently associated with poor stroke outcomes after adjustment for baseline characteristics (OR: 1.21, 95% CI: 1.07-1.38, and OR: 2.00, 95% CI: 1.40-2.84, respectively). Conclusions Increased serum ALP levels are significantly associated with a low ABI. These indicators are independent prognostic factors for poor stroke outcomes at 3 months.

Histone acetylation is a post-translational modification of histones that is catalyzed by histone acetyltransferases (HATs) and plays an essential role in cellular processes. The HAT domain of EP300/CBP has recently emerged as a potential drug target for cancer therapy. Here, we describe the identification of the novel, highly potent, and selective EP300/CBP HAT inhibitor DS-9300. Our optimization efforts using a structure-based drug design approach based on the cocrystal structures of the EP300 HAT domain in complex with compounds

Associated factors of the Myasthenia Gravis Activities of Daily Living (MG-ADL) score were investigated in 55 patients who had had generalized MG for more than 5 years. In multivariate analysis, correlates of the MG-ADL score at the last follow-up were the total number of fast-acting treatments (FTs) (standardized regression coefficient 0.617，P0.001) and Myasthenia Gravis Foundation of America (MGFA) classification (standardized regression coefficient 0.227，P = 0.032) (F = 32.7，P0.001). In patients with a score of 5 or more on MG-ADL at the last follow-up, tendency as follows were seen: 1) early-onset (P = 0.002), 2) longer duration (P = 0.014), 3) high frequency of MGFA classification V (P = 0.017), 4) high frequency of the total number of FTs (P0.001), and 5) higher dose of prednisolone at the last follow-up (P = 0.003). MGFA V, early-onset without depending on E-L-T classification, or difficulty of reduction for high doses of prednisolone can be the target of novel treatment for MG, and future prospective study will be expected.

The investigation of asteroids near the Sun is important for understanding the final evolutionary stage of primitive solar system objects. A near-Sun asteroid, (155140) 2005 UD, has orbital elements similar to those of (3200) Phaethon (the target asteroid for the JAXA's $DESTINY^+$ mission). We conducted photometric and polarimetric observations of 2005 UD and found that this asteroid exhibits a polarization phase curve similar to that of Phaethon over a wide range of observed solar phase angles ($ \alpha = 20 - 105^\circ $) but different from those of (101955) Bennu and (162173) Ryugu (asteroids composed of hydrated carbonaceous materials). At a low phase angle ($\alpha \lesssim 30^\circ$), the polarimetric properties of these near-Sun asteroids (2005 UD and Phaethon) are consistent with anhydrous carbonaceous chondrites, while the properties of Bennu are consistent with hydrous carbonaceous chondrites. We derived the geometric albedo, $ p_\mathrm{V} \sim 0.1 $ (in the range of 0.088-0.109); mean $ V $-band absolute magnitude, $ H_\mathrm{V} = 17.54 \pm 0.02 $; synodic rotational period, $ T_\mathrm{rot} = 5.2388 \pm 0.0022 $ hours (the two-peaked solution is assumed); and effective mean diameter, $ D_\mathrm{eff} = 1.32 \pm 0.06 $ km. At large phase angles ($ \alpha \gtrsim 80^\circ$), the polarization phase curve are likely explained by the dominance of large grains and the paucity of small micron-sized grains. We conclude that the polarimetric similarity of these near-Sun asteroids can be attributed to the intense solar heating of carbonaceous materials around their perihelia, where large anhydrous particles with small porosity could be produced by sintering., Comment: 15 pages, 9 figures, accepted for publication in Monthly Notices of Royal Astronomical Society (MNRAS)

Cancer-associated ischemic stroke (CAS) refers to a hypercoagulation disorder related to malignant tumors, especially adenocarcinoma. Carbohydrate antigen (CA) 125 is a mucinous serum marker that might reflect hypercoagulation status, but the association between CA 125 and CAS is unclear across various types of cancer. The aim of this study was to investigate the associations among tumor markers, coagulation markers, and clinical factors in acute ischemic stroke (AIS) patients with active cancer. Consecutive AIS patients with active cancer (a diagnosis or ongoing active therapy for cancer within 6 months) were prospectively enrolled at four hospitals. D-dimer, C-reactive protein (CRP), carcinoembryonic antigen (CEA), CA19-9, and CA 125 levels were measured. Of 120 AIS patients with active cancer, 47 were diagnosed with CAS. CA 125 had the strongest correlations with D-dimer and CRP (ρ = 0.543, p

Although associations between malnutrition status at stroke admission and poor stroke outcomes have been established, the effect of nutritional intake during the acute phase remains unclear. We aimed to evaluate the associations between nutritional intake one week after admission and the outcome at three months among acute ischemic stroke (AIS) patients.Consecutive AIS patients were investigated. Nutritional status at admission was evaluated using the Controlling Nutritional Status score, calculated from the serum albumin, lymphocyte count, and total cholesterol. We retrospectively evaluated nutritional intake (energy and protein) one week after admission, and the cutoff value of each nutritional intake level for good outcome was defined as the modified Rankin Scale 0-2 at three months after stroke onset using the receiver operating characteristic curve.Of the 205 patients, 146 patients had good outcomes. Mild initial neurological symptoms and good nutritional status at admission were associated with good outcome. The cutoff value of good outcome for protein intake was 0.812 g/kg/day (sensitivity: 0.884, specificity: 0.509) and that for energy intake was 19.0 kcal/kg/day (sensitivity: 0.918, specificity: 0.424). Those nutritional intake indicators were independently associated with good outcome after adjusting for baseline confounders, including stroke severity and nutritional status at admission (protein intake: odds ratio (OR), 4.04; 95% confidence intervals (CIs), 1.14-13.1, and energy intake: OR, 5.00; 95% CIs, 1.41-17.8, respectively).Adequate nutritional intake at one week after admission was independently associated with good outcome regardless of the nutritional status at admission or stroke severity.

Primary head and neck osteosarcomas (HNOS) arising from skull base are rare. It may be difficult to detect in the early stage. We discuss the symptoms that should be noted in daily clinical practice. We aimed to present a case of an osteosarcoma (OS) arising from the mandibular fossa of the temporal bone that was initially misinterpreted as temporomandibular disorder (TMD). Since TMD is a common disease, other rare serious diseases can be misinterpreted as TMD at an early stage. Spontaneous pain, swelling, maximal diameter of mouth opening of less than 20 mm, long-term trismus, and neurological symptoms, may be useful in the differential diagnosis of TMD. If there is a possibility that it is not TMD, it may be better to employ other diagnostic modalities such as CT or MRI to investigate the possibility of HNOS.

Necrotizing lymphadenitis (NEL) is a self-limited systemic disease exhibiting characteristic clinical features. The pathogenesis of the disease remains unclear, but it may be associated with viral infection. In lymph nodes affected by this disease, innumerable plasmacytoid dendritic cells produce interferon-α when triggered by certain viral stimuli. IFN-α presents antigens causing the transformation of CD8+ cells into immunoblasts and apoptosis of CD4+ cells. From the perspective of innate immunity, UNC93B1, an endoplasmic reticulum (ER)-resident protein, associates more strongly with TLR9 than TLR7. Homeostasis is maintained under normal conditions. However, in NEL, TLR 7 was observed more than TLR 9, possibly because mutant type UNC93B1 associates more tightly with TLR7. The inhibitory effects against TLR7 by TLR9 were reported to disappear. It is likely that more TLR7 than TLR9 is transported from the ER to endolysosomes. In conclusion, overexpression of TLR7, an innate immune sensor of microbial single-stranded RNA, is inferred. Consequently, NEL may be induced.

A 76-year-old man with renal cell carcinoma exhibited consciousness disturbance and high fever after two cycles of combination therapy with ipilimumab and nivolumab. His cerebrospinal fluid (CSF) showed a protein concentration of 385 mg/dl, a cell count of 147/mm3, an interleukin-6 concentration of 1,280 pg/ml, and an adenosine deaminase concentration of 24.8 U/l. Contrast-enhanced FLAIR images were notable for diffuse meningeal enhancement. He was diagnosed with meningoencephalitis caused by an immune-related adverse event from immune checkpoint inhibitors (ICIs). His symptoms improved after repeated intravenous methylprednisolone pulse therapy and oral prednisolone. The meningeal enhancement disappeared, and the CSF findings became almost normal. As consciousness levels improved, we observed quadriplegia and peripheral neuropathy with antiganglioside antibodies, which led to a diagnosis of polyradiculoneuropathy. This is a rare case of a patient with overlapping meningoencephalitis and polyradiculo-neuropathy induced by ICIs.

Central nervous system methotrexate-associated lymphoproliferative disorder (CNS-MTX-LPD) is rare, but its spontaneous regression has been observed in some patients after withdrawal of agents. We herein report three cases of primary CNS-MTX-LPD that received oral MTX for rheumatoid arthritis. Epstein-Barr virus and oligoclonal bands (OCBs) were positive, while proton magnetic resonance spectroscopy (

Morphology of nova ejecta is essential for fully understanding the physical processes involved in nova eruptions. We studied the 3D morphology of the expanding ejecta of the extremely slow nova V1280 Sco with a unique light curve. Synthetic line profile spectra were compared to the observed [O III] 4959, 5007 and [N II] 5755 emission line profiles in order to find the best-fit morphology, inclination angle, and maximum expansion velocity of the ejected shell. We derive the best fitting expansion velocity, inclination, and squeeze as $V_{\rm exp} = 2100^{+100}_{-100}$ \,km\,s$^{-1}$, $i = 80^{+1}_{-3}$ deg, and $squ = 1.0^{+0.0}_{-0.1}$ using [O III] line profiles, and $V_{\rm exp} = 1600^{+100}_{-100}$ \,km\,s$^{-1}$, $i = 81^{+2}_{-4}$ deg, and $squ = 1.0^{+0.0}_{-0.1}$ using [N II] 5755 line profile. A high inclination angle is consistent with the observational results showing multiple absorption lines originating from clumpy gases which are produced in dense and slow equatorially focused outflows. Based on additional observational features such as optical flares near the maximum light and dust formation on V1280 Sco, a model of internal shock interaction between slow ejecta and fast wind proposed for the $\gamma$-ray emission detected in other novae seems to be applicable to this extremely slow and peculiar nova. Increasing the sample size of novae whose morphology is studied will be helpful in addressing long-standing mysteries in novae such as the dominant energy source to power the optical light at the maximum, optical flares near the maximum, clumpiness of the ejecta, and dust formation., Comment: 21 pages, 8 figures, accepted for publication in ApJ

Objective Onco-cardiology services are expanding rapidly in Japan. To provide a better service, it is important to consider the needs of oncologists. However, little is known regarding specific needs for which oncologists should consult cardiologists to manage cardiovascular problems of their patients. We analysed cardiology consultations sought by oncologists to evaluate the role of cardiologists in cancer treatment. Method We retrospectively investigated consecutive 2064 cardiology consultations of cancer patients in the University of Tsukuba Hospital, Tsukuba, Japan, between January 2014 and December 2018. Results The most common timing of cardiology consultation was before the commencement of cancer treatment (n = 1355; 65.7%), followed by after the commencement of cancer treatment (n = 686; 33.2%). Among the 361 consultations before the administration of anticancer drugs, 235 (65.1%) were for anthracycline-based regimens. There were 506 (24.5%) consultations for the management of cardiovascular emergencies developing after the commencement of cancer treatment; venous thromboembolism was the most frequent (n = 125; 24.7%), followed by atrial fibrillation (n = 110; 21.7%) and heart failure (n = 74; 14.6%). There were marked differences in the types of cardiovascular emergencies depending on the type of cancer. Conclusions This survey revealed the various cardiovascular problems for which oncologists sought interventions by cardiologists. A multidisciplinary approach in an onco-cardiology service is essential to achieve optimal long-term outcomes.

Although hypercoagulability using D-dimer levels may be a useful marker for predicting outcomes in ischemic stroke patients with cancer, other biological markers for predicting outcomes are unclear. We aimed to investigate the associations between several biological markers and short-term or long-term outcomes among ischemic stroke patients with cancer.Consecutive acute ischemic stroke patients with cancer (n = 309) were registered. Biological markers such as hemoglobin, albumin, C-reactive protein and D-dimer levels were assessed. Stroke outcomes, namely, a 3-month modified Rankin Scale score indicating poor functional outcome (mRS score of 3-6) and 1-year survival, were assessed.Of the 277 patients who could be assessed for 3 months outcome, 131 patients (47.3%) had a poor outcome at 3 months. Multivariable analysis revealed that increased D-dimer levels and decreased albumin levels were independently associated with poor stroke outcomes (adjusted odds ratio [aOR]: 1.04, 95% confidence interval [CI]: 1.00-1.08, and aOR: 0.50, 95% CI: 0.31-0.80, respectively). Of 309 patients, 70 patients (22.7%) died during the follow-up period (median, 241 days). Multivariate Cox proportional hazard analyses showed that high D-dimer levels and hypoalbuminemia were independently associated with mortality (adjusted hazard ratio [aHR]: 2.65, 95% CI: 1.37-5.12, and aHR: 2.29, 95% CI: 1.21-4.49, respectively). The effect of each biological marker on mortality was notably observed among patients with active cancer but not among those with nonactive cancer.Low albumin levels were independently associated with short- and long-term outcomes, as were D-dimer levels, in acute ischemic stroke patients with cancer.

We present our spectroscopic observations of V455 Andromedae during the 2007 superoutburst. Our observations cover this superoutburst from around the optical peak of the outburst to the post-superoutburst stage. During the early superhump phase, the emission lines of Balmer series, He I, He II, Bowen blend, and C IV / N IV blend were detected. He II 4686 line exhibited a double-peaked emission profile, where Balmer emission lines were single-peaked, which is unexpected from its high inclination. In the ordinary superhump phase, Balmer series transitioned to double-peaked emission profiles, and high-ionization lines were significantly weakened. These transitions of the line profiles should be related to the structural transformation of the accretion disk, as expected between the early and ordinary superhump transition in the thermal-tidal instability model. The Doppler map of H$\alpha$ during the early superhump phase exhibits a compact blob centered at the primary white dwarf. In analogy to SW Sex-type cataclysmic variables, this feature could emerge from the disk wind and/or the mass accretion column onto the magnetized white dwarf. The Doppler map of He II 4686 \AA~ is dominated by the ring-like structure and imposed two flaring regions with the velocity of $\sim$300 km/s, which is too slow for a Keplerian accretion disk. The phase of the flaring regions was coincident with the inner spiral arm structure identified during the early superhump phase. Our disk wind model with the enhanced emission from the inner arm structure successfully reproduced the observed properties of He II 4686 \AA. Therefore, V455 And is the first case in dwarf nova outbursts that the presence of the disk wind is inferred from an optical spectrum., Comment: 19 pages, 11 figures, 3 tables, accepted for publication in PASJ

A 36-year-old man experienced severely impaired consciousness twice after drinking because of hyperammonemia. No abnormal blood tests were found other than ammonia levels. However, magnetic resonance imaging (MRI) showed atrophy of the brain parenchyma. One the second occasion, the patient suffered severe impairment of consciousness, and because of seizures and glossoptosis, mechanical ventilation was started. Urea cycle disorders (UCDs) were assumed to be involved. Genetic testing revealed a monoallelic mutation of the carbamoyl phosphate synthase 1 (CPS1) gene. When transient hyperammonemia of unknown cause occurs repeatedly in adults, an active investigation for UCDs should be conducted.

The mainstay of treatment for idiopathic normal-pressure hydrocephalus (iNPH) is spinal fluid shunting. A tap test (TT) is recommended as an indication of shunting. Patients with iNPH are often elderly and have multiple comorbidities affecting the shunting outcome. We investigated the factors affecting TT in patients with iNPH.Seventy-five patients with iNPH were admitted to our department for a TT from April 2010 to May 2021. The patients were divided into a responsive group and an unresponsive group according to the clinical outcomes after TT on the Timed Up and Go Test (TUG), Mini-Mental State Examination (MMSE), or iNPH grading scale. Factors affecting the TT were compared between the responders and nonresponders.There were 38 patients (50.7%) in the TT responder group, and the prevalence of improvement was 82.9% in the TUG, 27.6% in the MMSE, and 76.3% in the iNPH grading scale. There were no significant differences in the vascular risk factors between the two groups. The prevalence of lumbar spondylosis, compression fracture, severe periventricular hyperintensity, deep and subcortical white matter hyperintensity (DSWMH), and old cerebral infarcts was significantly higher among the TT nonresponders. The logistic regression analysis showed that severe DSWMH and lumbar spondylosis were associated with a TT nonresponse (p 0.001 and p = 0.003, respectively). Shunting was performed in 22 patients, 19 of whom were TT responders.Severe DSWMH and lumbar spondylosis were associated with a poor response to the TT in iNPH patients. We should consider risk factors when selecting candidates for shunt surgery.

Background This multicenter retrospective study aimed to determine whether elective neck dissection (END) can be performed for T1-2N0M0 tongue cancer. Methods Patients with T1-2N0M0 tongue squamous cell carcinoma who received treatment between January 2000 and December 2012 were enrolled at 14 multicenter study sites. The 5-year overall survival (OS) and 5-year disease-specific survival (DSS) were compared between the propensity score-matched END and observation (OBS) groups. Results The results showed that the OS rates among the 1234 enrolled patients were 85.5% in the END group and 90.2% in the OBS group (P = 0.182). The DSS rates were 87.0% in the END group and 94.3% in the OBS group (P = 0.003). Among the matched patients, the OS rates were 87.1% in the END group and 76.2% in the OBS group (P = 0.0051), and the respective DSS rates were 89.2% and 82.2% (P = 0.0335). Conclusion This study showed that END is beneficial for T1-2N0M0 tongue cancer. However, END should be performed for patients with a tumor depth of 4–5 mm or more, which is the depth associated with a high rate of lymph node metastasis. The use of END should be carefully considered for both elderly and young patients.

EP300 and its paralog CBP play an important role in post-translational modification as histone acetyltransferases (HATs). EP300/CBP inhibition has been gaining attention as an anticancer treatment target in recent years. Herein, we describe the identification of a novel, highly selective EP300/CBP inhibitor, compound 11 (DS17701585), by scaffold hopping and structure-based optimization of a high-throughput screening hit 1. Compound 11 (DS17701585) shows dose-dependent inhibition of SRY-box transcription factor 2 (SOX2) mRNA expression in a human lung squamous cell carcinoma cell line LK2-xenografted mouse model.

As the number of cancer survivors increases, cardiac management in anthracycline-treated patients has become more important. We planned to conduct a prospective multicenter registry study for comprehensive echocardiographic and biomarker data collection and an evaluation of the current practice in terms of diagnosis and management of anthracycline-induced cardiotoxicity (AIC registry). To examine the feasibility of this registry study, we analyzed the 1-year follow-up data of 97 patients registered during the first year of this registry. The AIC registry was launched in July 2016. Data on echocardiographic parameters (e.g., two-and three-dimensional [(2- and 3-D) left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and biomarkers (e.g., troponin T and brain natriuretic peptide) were collected before anthracycline treatment, every 3 months during the first year after starting anthracycline, and every 6 months during the second year. Eighty-three patients (86%) completed a 1-year follow-up. The measurable rates of 2D LVEF, 3D LVEF, and GLS on each visit were nearly optimal (100%, 86–93%, and 84–94%, respectively). During the 1-year follow-up, 5 patients (6.0%) developed cardiotoxicity (a reduction in LVEF ≥ 10 percentage points from baseline and &lt, 55%). The AIC registry study is feasible and will be the first study to collect sizable echocardiographic and biomarker data on cardiotoxicity in Japanese patients treated with anthracycline in a real-world setting.

The asteroid exploration project "Hayabusa2" has successfully returned samples from the asteroid (162173) Ryugu. In this study, we measured the linear polarization degrees of Ryugu using four ground-based telescopes from 2020 September 27 to December 25, covering a wide-phase angle (Sun-target-observer's angle) range from 28$^\circ$ to 104$^\circ$. We found that the polarization degree of Ryugu reached 53$\%$ around a phase angle of 100$^\circ$, the highest value among all asteroids and comets thus far reported. The high polarization degree of Ryugu can be attributed to the scattering properties of its surface layers, in particular the relatively small contribution of multiply-scattered light. Our polarimetric results indicate that Ryugu's surface is covered with large grains. On the basis of a comparison with polarimetric measurements of pulverized meteorites, we can infer the presence of submillimeter-sized grains on the surface layer of Ryugu. We also conjecture that this size boundary represents the grains that compose the aggregate. It is likely that a very brittle structure has been lost in the recovered samples, although they may hold a record of its evolution. Our data will be invaluable for future experiments aimed at reproducing the surface structure of Ryugu., Comment: 8 pages, 3 figures, 2 tables, Accepted for publication in ApJ Letters

Background: There is an unmet need for treatment options for generalised myasthenia gravis that are effective, targeted, well tolerated, and can be used in a broad population of patients. We aimed to assess the safety and efficacy of efgartigimod (ARGX-113), a human IgG1 antibody Fc fragment engineered to reduce pathogenic IgG autoantibody levels, in patients with generalised myasthenia gravis. Methods: ADAPT was a randomised, double-blind, placebo-controlled, phase 3 trial done at 56 neuromuscular academic and community centres in 15 countries in North America, Europe, and Japan. Patients aged at least 18 years with generalised myasthenia gravis were eligible to participate in the study, regardless of anti-acetylcholine receptor antibody status, if they had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 (>50% non-ocular), and were on a stable dose of at least one treatment for generalised myasthenia gravis. Patients were randomly assigned by interactive response technology (1:1) to efgartigimod (10 mg/kg) or matching placebo, administered as four infusions per cycle (one infusion per week), repeated as needed depending on clinical response no sooner than 8 weeks after initiation of the previous cycle. Patients, investigators, and clinical site staff were all masked to treatment allocation. The primary endpoint was proportion of acetylcholine receptor antibody-positive patients who were MG-ADL responders (≥2-point MG-ADL improvement sustained for ≥4 weeks) in the first treatment cycle. The primary analysis was done in the modified intention-to-treat population of all acetylcholine receptor antibody-positive patients who had a valid baseline MG-ADL assessment and at least one post-baseline MG-ADL assessment. The safety analysis included all randomly assigned patients who received at least one dose or part dose of efgartigimod or placebo. This trial is registered at ClinicalTrials.gov (NCT03669588); an open-label extension is ongoing (ADAPT+, NCT03770403). Findings: Between Sept 5, 2018, and Nov 26, 2019, 167 patients (84 in the efgartigimod group and 83 in the placebo group) were enrolled, randomly assigned, and treated. 129 (77%) were acetylcholine receptor antibody-positive. Of these patients, more of those in the efgartigimod group were MG-ADL responders (44 [68%] of 65) in cycle 1 than in the placebo group (19 [30%] of 64), with an odds ratio of 4·95 (95% CI 2·21–11·53, p

Aim The prediction of functional outcome is essential in the management of acute ischemic stroke patients. We aimed to explore the various prognostic factors with multivariate linear discriminant analysis or neural network analysis and evaluate the associations between candidate factors, baseline characteristics, and outcome. Methods Acute ischemic stroke patients (n=1,916) with premorbid modified Rankin Scale (mRS) scores of 0-2 were analyzed. The prediction models with multivariate linear discriminant analysis (quantification theory type II) and neural network analysis (log-linearized Gaussian mixture network) were used to predict poor functional outcome (mRS 3-6 at 3 months) with various prognostic factors added to age, sex, and initial neurological severity at admission. Results Both models revealed that several nutritional statuses and serum alkaline phosphatase (ALP) levels at admission improved the predictive ability. Of the 1,484 patients without missing data, 560 patients (37.7%) had poor outcomes. The patients with poor outcomes had higher ALP levels than those without (294.3±259.5 vs. 246.3±92.5 U/l, P＜0.001). Multivariable logistic analyses revealed that higher ALP levels (1-SD increase) were independently associated with poor stroke outcomes after adjusting for several confounding factors, including the neurological severity, malnutrition status, and inflammation (odds ratio 1.21, 95% confidence interval 1.02- 1.49). Several nutritional indicators extracted from prediction models were also associated with poor outcome. Conclusion Both the multivariate linear discriminant and neural network analyses identified the same indicators, such as nutritional status and serum ALP levels. These indicators were independently associated with functional stroke outcome.

Backgrounds Vascular compression of the rostral ventrolateral medulla (RVLM) has been associated with hypertension or blood pressure (BP) variability. For acute ischemic stroke patients, increased BP variability may cause poor functional outcomes. We tested the hypothesis that RVLM compression was associated with increased BP variability or stroke outcome in acute ischemic stroke patients. Methods Acute ischemic stroke patients (n = 622) with 24-h ambulatory BP monitoring during the subacute phase of stroke (median 9 days from onset) were retrospectively studied. Variability in BP was evaluated with the SD and coefficient of variation of SBP and DBP. The morning surge was also evaluated. The presence of RVLM compression was evaluated using time-of-flight three-dimensional MRI. A poor outcome was defined as a modified Rankin Scale score of 3-6 at 3 months. Results Patients with RVLM compression (n = 213) had significantly higher 24-h SBP mean, 24-h SBP SD, 24-h SBP coefficient of variation, 24-h DBP mean, 24-h DBP SD, and 24-h DBP coefficient of variation values and a higher prevalence of morning surge than those without (n = 409). Multiple regression analysis revealed that RVLM compression was associated with increased SBP variability, DBP variability, and morning surge. Despite the significant association between RVLM compression and BP variability, RVLM compression was not associated with poor stroke outcome. Conclusion Although RVLM compression was closely associated with BP variability in the subacute ischemic stroke phase, an effect of RVLM compression on stroke outcome was not observed.

Clear cell carcinoma is an extremely rare low-grade malignancies occurring in less than 1% of salivary gland tumors. We report a case of clear cell carcinoma of the hard palate in a 15-year-old adolescent patient. She first noticed a palatal tumor at age 9, but the tumor was left untreated for 6 years. We performed incisional biopsy, but no definitive diagnosis was obtained. Excisional biopsy was then performed, and the histopathological diagnosis was clear cell carcinoma of the salivary gland. However, the tumor was exposed at the margin of the surgical specimen; thus, additional excision was performed. Five years after the treatment, no local recurrence or metastasis has been observed.

Introduction The association of malnutrition on stroke subtypes has not been well established. We investigated the relationship between malnutrition and functional outcome according to stroke subtypes. Methods Acute consecutive ischemic stroke patients (n = 1915, 73 ± 12 years) were analysed. The nutritional status was evaluated using the Controlling Nutritional Status (CONUT) score, which was calculated from the serum albumin level, lymphocyte count, and total cholesterol level; malnutrition was defined as a CONUT score of 5 to 12. A poor outcome was defined as a modified Rankin Scale score ≥ 3 at 3 months. Results Of the 1518 patients, 113 (7.4%) had malnutrition, and 533 (33.1%) had a poor outcome. Among the patients with cardioembolic stroke and stroke of other etiologies, those with malnutrition had higher rates of poor outcomes than those without. After adjusting for age, sex, and baseline stroke severity, malnutrition was independently associated with poor outcomes in patients with cardioembolic stroke and other stroke etiologies (odds ratio 3.25, 95% confidence interval 1.02–10.4, p = .044; 6.22, 2.71–14.3, p Conclusions Considering stroke subtype, malnutrition determined using the CONUT score was independently associated with poor outcomes in the patients with cardioembolic stroke or stroke of other etiologies.

Background Malnutrition is an independent risk factor for poor outcomes in patients with acute ischemic stroke. However, the indicator of malnutrition has not yet been established. We investigated the relationship between the Controlling Nutritional Status score, a useful prognostic measure of malnutrition in patients with cardiovascular diseases and malignant tumors, and functional outcomes in patients with acute ischemic stroke. Methods Patients with acute ischemic stroke (n = 264, 71 ± 12 y old) were consecutively evaluated within 7 d of stroke onset. The Controlling Nutritional Status score was calculated from the serum albumin, total peripheral lymphocyte count, and total cholesterol; a Controlling Nutritional Status score of 5 to 12 was defined as malnutrition. Poor functional outcome was defined as a modified Rankin Scale score of 3 to 6 at 3 mo. Results Of the total cohort, 230 patients (87.1%) were assessed. The patients with poor functional outcome (n = 85) were older; had a lower body mass index; had a higher frequency of atrial fibrillation, chronic heart failure, and anemia; and had a lower frequency of dyslipidemia and a current smoking status. In addition, the Controlling Nutritional Status score and National Institutes of Health Stroke Scale score at admission were significantly higher for the patients with poor functional outcome. After multivariate analysis, adjusted for baseline characteristics, a Controlling Nutritional Status score of 5 to 12 was found to be independently associated with poor outcome (odds ratio: 4.15, 95% confidence interval: 1.52–11.67, P = 0.005). Conclusions The Controlling Nutritional Status score at admission could be a useful prognostic marker of 3-mo functional outcomes in patients with acute ischemic stroke.

Background The risk of complications from thromboembolism is increased for patients with malignancy. Cancer-associated stroke is also a serious issue with regard to the management of patients with cancer because stroke incidence often causes disabilities that affect daily life and cancer treatment strategy. Methods Between March 2011 and September 2017, 328 patients with acute ischemic stroke were registered to our hospital. Results Of these patients, 26 (7.9%) had a cancer-associated stroke diagnosis, namely, Trousseau syndrome. After ischemic stroke onset, malignancy treatment was changed to palliative treatment for 11 patients. Eighteen patients died 1 year after ischemic stroke onset, and 15 of these patients underwent cancer treatment according to the best supportive care policy. Of those who died, 8 underwent anticoagulation therapy. We described the clinical courses of 3 cases among 26 cases with Trousseau syndrome. Two cases took direct oral anticoagulants (DOACs) due to cancer-associated venous thromboembolism before stroke onset, and there has been no stroke recurrence with subcutaneous unfractionated heparin. In the third case, when cancer activity was suppressed, we changed DOACs from subcutaneous unfractionated heparin and continued DOACs without thromboembolic events. Conclusions There is insufficient evidence regarding cases for which DOACs would be suitable for the prevention of thromboembolism and regarding its long-term efficacy and safety in patients with cancer. As it stands, heparin treatment, which has multifaceted antithrombotic actions, may be suitable for cancer-associated stroke prevention.

Histone acetyltransferases (HATs) play a crucial role in post-translational modification. Among them, overexpression, mutation, or hyperfunction of EP300/CBP has been associated with various cancers. In this study, we identified the novel compound 2-chloro-5-[5-[(E)-[1-(3-chlorophenyl)-3-methyl-5-oxo-pyrazol-4-ylidene]methyl]-2-furyl]benzoic acid (1) as an EP300 HAT inhibitor via virtual screening. Further research has been focused on the design, synthesis, and in vitro biological evaluation of virtual hit derivatives. The studies revealed that 4-pyridone-3-carboxylic acid derivatives exhibited bioisosterism of benzoic acid. Replacement proved effective, providing compounds with similar EP300 HAT-inhibitory activity and improved cell growth-inhibitory activity compared to the benzoic acid analogs. Through these studies, we identified a potent and selective EP300/CBP HAT inhibitor.