α7 nicotinic acetylcholine receptor agonist attenuates allergen-induced immediate nasal response in murine model of allergic rhinitis.

The expression of nicotinic acetylcholine receptor (nAChR) subunits on various immune cells suggests their involvement in allergic rhinitis. However, how exactly they contribute to this pathogenesis is not yet confirmed. Our present study examined the therapeutic potential of GTS-21, an α7 nAChR agonist, for treating allergic rhinitis by employing its mouse models. GTS-21 treatment reduced allergen-induced immediate nasal response in ovalbumin (OVA)-sensitized model. However, nasal hyperresponsiveness or eosinophil infiltration elicited in either the OVA-sensitized or T helper 2 cell-transplanted model was not affected by GTS-21. GTS-21 did not alter allergen-induced passive cutaneous anaphylaxis response in anti-dinitrophenyl IgE-sensitized mice. This evidence implies GTS-21's potential to alleviate allergic rhinitis without perturbing T cells or mast cells.

[Clinical features of acyclovir encephalopathy without acute kidney injury].

INTRODUCTION: Few reports have described acyclovir (ACV) encephalopathy without acute kidney injury (AKI). OBJECTIVE: This study clarified the clinical features of ACV encephalopathy without AKI compared to that with AKI. METHODS: Creatinine (Cre) levels were measured on admission. After admission, Cre was measured in a timely manner for the first seven hospital days. The minimum Cre level in these measurements was then determined. ACV encephalopathy was defined when two criteria were met: 1) neurological symptoms appeared after valacyclovir (VACV) administration, and 2) neurological symptoms improved after VACV discontinuation. AKI was defined when the Cre level on admission was >1.5 times higher than the minimum Cre level. The subjects were divided into AKI and non-AKI groups based on these findings. RESULTS: Eighteen patients had ACV encephalopathy (5 males, mean age 81.3±5.5 years old). All patients were prescribed VACV 3,000 mg/day. The minimum Cre was 1.93±1.76 mg/dL. AKI occurred in 10 (56.6%) patients. VACV was discontinued in all patients, and emergency hemodialysis treatment was administered in 10 (55.6%) patients. All patients recovered. Compared to the AKI group, the non-AKI group had a lower history of taking a Ca-blocker (33.3% vs 80.0%, p=0.092), a lower rate of emergency dialysis (16.9% vs 70.0%, p=0.059) and a longer time to clinical improvement (3.67±1.86 vs 2.20±0.63 days, p=0.073). CONCLUSION: ACV encephalopathy without AKI is characterized by a low rate of emergency dialysis, which may be linked to a prolonged duration of symptoms.

[Analysis of factors leading to brain MRI lesions in Wernicke's encephalopathy].

[Objective] To investigate association between Wernicke encephalopathy (WE) and brain MRI. [Subjects] 26 patients (7 females, mean age 63.9 ± 12.7 years) with WE admitted to our department between May 2008 and September 2022. [Methods] Wernicke's encephalopathy in patients with MRI lesions was defined as "MRI-positive group" (MPG), and those without MRI lesions as "MRI-negative group" (MNG). The following parameters were assessed between the two groups: age, sex, alcoholism, neurological symptoms, vitamin B1, lymphocyte, total cholesterol, albumin, and outcome at discharge. [Results] There were 17 patients in MPG. Compared to MNG, MPG had lower rates of alcohol abuse (10.0% vs 77.8%, P = 0.025), lower vitamin B1 (median 10.0 |ng/ml vs 29.0 |ng/ml, P < 0.001), and more vitamin B1 treatment dose (median 1900 |mg vs 600 |mg, P = 0.016). [Conclusion] Alcoholic WE may be overlooked if the focus is solely on brain MRI findings.

[A case of bilateral middle cerebellar peduncle infarction with hot cross bun sign].

A 71-year-old man with hypertension and diabetes mellitus presented to our hospital because he felt lightheaded. Diffusion-weighted images (DWI) on brain MRI showed high signal lesions in the left cerebellar hemisphere and the right pons. The diagnosis of cerebellar infarction was made, but he refused treatment. One month later, he came to our hospital because his body leaned to the left. Neurological examination revealed dysarthria and cerebellar truncal ataxia. An electrocardiogram showed atrial fibrillation. DWI on brain MRI showed high signal lesions in the bilateral cerebellar hemispheres and middle cerebellar peduncles (MCP). Dabigatran 300 |mg/day was administered for cardiogenic cerebral embolism. On the 12th day of onset, he was transferred to a rehabilitation hospital. At 72 years old, T2*-weighted images on brain MRI showed hot cross bun sign (HCBs) in the pons. We considered that HCBs were caused by antegrade or retrograde degeneration (or both) of pontine infarcts and bilateral MCP infarcts in the pontine cerebellar tract. It seemed preferable to use T2*-weighted images or proton density-weighted images rather than T2-weighted images to detect HCBs. When HCBs is detected, it should be noted that HCBs can be caused by bilateral MCP infarcts in addition to multiple system atrophy.

Prospective Observational Study for the Comparison of Screening Methods Including Tongue Pressure and Repetitive Saliva Swallowing With Detailed Videofluoroscopic Swallowing Study Findings in Patients With Acute Stroke.

BACKGROUND: Simple, noninvasive, and repeatable screening methods are essential for assessing swallowing disorders. We focused on patients with acute stroke and aimed to assess the characteristics of swallowing screening tests, including the modified Mann Assessment of Swallowing Ability score, tongue pressure, and repetitive saliva swallowing test (RSST), compared with detailed videofluoroscopic swallowing study (VFSS) findings to contribute as a helpful resource for their comprehensive and complementary use. METHODS AND RESULTS: We enrolled first-ever patients with acute stroke conducting simultaneous assessments, including VFSS, modified Mann Assessment of Swallowing Ability score, tongue pressure measurement, and RSST. VFSS assessed aspiration, laryngeal penetration, oral cavity residue, vallecular residue, pharyngeal residue, and swallowing reflex delay. Screening tests were compared with VFSS findings, and multiple logistic analysis determined variable importance. Cutoff values for each abnormal VFSS finding were assessed using receiver operating characteristic analyses. We evaluated 346 patients (70.5±12.6 years of age, 143 women). The modified Mann Assessment of Swallowing Ability score was significantly associated with all findings except aspiration. Tongue pressure was significantly associated with oral cavity and pharyngeal residue. The RSST was significantly associated with all findings except oral cavity residue. Receiver operating characteristic analyses revealed that the minimum cutoff value for all VFSS abnormal findings was RSST ≤2. CONCLUSIONS: The modified Mann Assessment of Swallowing Ability is useful for broadly detecting swallowing disorders but may miss mild issues and aspiration. The RSST, with a score of ≤2, is valuable for indicating abnormal VFSS findings. Tongue pressure, especially in oral and pharyngeal residues, is useful. Combining these tests might enhance accuracy of the swallowing evaluation.

Liver fibrosis index is associated with functional outcome among acute ischemic stroke patients.

INTRODUCTION: The fibrosis-4 (FIB-4) index and the fibrosis-5 (FIB-5) index are noninvasive markers of liver fibrosis in patients with nonalcoholic fatty liver disease. Although liver fibrosis a potential risk factor for stroke development, it is uncertain whether liver fibrosis influences stroke outcomes. We investigated the associations between these two indices and stroke patient outcomes and compared their predictive accuracy. METHODS: We conducted a double-center, hospital-based, retrospective study. Consecutive acute ischemic stroke patients (n=2399) were analyzed. We calculated the FIB-4 index and the FIB-5 index and evaluated their relationships with poor stroke outcome, which was defined as a modified Rankin Scale score of 3-6 at three months after stroke. We evaluated the ability of each index to predict stroke outcome according to cutoff values calculated from receiver operating characteristic (ROC) curves. RESULTS: Of 2399 recruited patients, 1549 patients (mean age, 73 years) were analyzed. The FIB-4 index and FIB-5 index had similar areas under their ROC curves for predicting stroke outcome (FIB-4 index, 0.675 and FIB-5 index, 0.683, P=0.334). The cutoff points of the FIB-4 index and FIB-5 index according to the ROC analysis were associated with poor stroke outcome in the multivariable analyses (odds ratio [OR] 2.23, 95 % confidence interval [CI] 1.72-2.89, OR 1.93, 95 % CI 1.47-2.54, respectively). CONCLUSIONS: Liver fibrosis scores may be useful for predicting outcomes in patients with acute stroke. The FIB-4 and FIB-5 indices should be considered comprehensive tools for assessing the outcome risk after ischemic stroke.

Generation of reporter mice for detecting the transcriptional activity of nuclear factor of activated T cells.

Nuclear factor of activated T cells (NFAT) is a transcription factor essential for immunological and other biological responses. To develop analyzing system for NFAT activity in vitro and in vivo, we generated reporter mouse lines introduced with NFAT-driven enhanced green fluorescent protein (EGFP) expressing gene construct. Six tandem repeats of -286 to -265 of the human IL2 gene to which NFAT binds in association with its co-transcription factor, activator protein (AP)-1, was conjunct with thymidine kinase minimum promoter and following EGFP coding sequence. Upon introduction of the resulting reporter cassette into C57BL/6 fertilized eggs, the transgenic mice were obtained. Among 7 transgene-positive mice in 110 mice bone, 2 mice showed the designated reporter mouse character. Thus, the EGFP fluorescence of CD4+ and CD8+ T cells in these mice was enhanced by stimulation through CD3 and CD28. Each of phorbol 12-myristate 13-acetate (PMA) and ionomycin (IOM) stimulation weakly but their combined stimulation strongly enhanced EGFP expression. The stimulation-induced EGFP upregulation was also observed following T cell subset differentiation in a different manner. The EGFP induction by PMA + IOM stimulation was more potent than that by CD3/CD28 stimulation in helper T (Th)1, Th2, Th9, and regulatory T cells, while both stimulation conditions displayed the equivalent EGFP induction in Th17 cells. Our NFAT reporter mouse lines are useful for analyzing stimulation-induced transcriptional activation mediated by NFAT in cooperation with AP-1 in T cells.

Peak expiratory flow, but not tongue pressure, can predict pneumonia development in older adults.

PURPOSE: Pneumonia is the leading cause of mortality and morbidity in aging populations. Major causes of pneumonia in older adults are swallowing dysfunction and decreased airway clearance capacity, including an impaired cough reflex. Maximal tongue pressure is useful for evaluating swallowing function, and peak expiratory flow indirectly reflects cough strength. However, it is unclear whether they can predict pneumonia development in older adults. In this study, we investigated whether tongue pressure and peak expiratory flow could predict pneumonia development in older adults. METHODS: This two-center prospective observational study included older adults aged 65 years or older without respiratory disease or head and neck cancer. We enrolled 383 consenting participants, many of whom had a history of stroke, and followed them for 2 years. The association between time to pneumonia development and tongue pressure or peak expiratory flow at enrollment was examined in a Cox proportional hazards model. RESULTS: The mean age of the participants was 77.1 ± 6.2 years, and 36.0% of them were women. The mean tongue pressure was 35.4 ± 10.5 kPa and median peak expiratory flow was 218 L/min at enrollment. Six patients developed pneumonia during the study period. A low peak expiratory flow at enrollment was significantly associated with pneumonia development in the multivariate Cox proportional hazards model, but this association was not observed for tongue pressure. CONCLUSION: Decreased peak expiratory flow may predict pneumonia development in older adults. Future studies should investigate interventions for peak expiratory flow improvement.

[Diagnostic predictive factors in listeria meningitis].

PURPOSE: The purpose of this study was to elucidate the diagnostic predictive factors of listeria meningitis. SUBJECTS AND METHOD: Twenty-eight patients with bacterial meningitis (age; 65.9 ± 14.8 years, 11 female) who were admitted to Chikamori Hospital from October 1, 2006 to December 31, 2021 were included. Bacterial meningitis was defined as cerebrospinal fluids (CSF) pleocytosis with evidence of bacterial infection in CSF or blood. The blood and CSF data were reviewed for analysis. RESULTS: 9 patients were diagnosed as listeria meningitis, 19 patients were in non-listeria meningitis. Multiple logistic regression analysis showed that higher CSF lymphocyte ratio was significantly associated with listeria meningitis (Odds ratio 1.123, 95% Confidence interval 1.006-1.2155, P = 0.039). CSF lymphocyte ratio of 30% or more was found to predict listeria meningitis with a sensitivity of 55.6% and a specificity of 100%. CONCLUSION: CSF lymphocyte ratio may be useful for differentiating between listeria meningitis and non-listeria meningitis.

Re-evaluation of over-the-counter histamine H1-receptor antagonists based on their effects on murine models of allergen-induced nasal hyperresponsiveness.

T cells play an essential role in the development of allergen-induced nasal hyperresponsiveness (NHR), a pathophysiological response in allergic rhinitis. The effects of histamine H1-receptor antagonists (antihistamines) on murine NHR models were investigated. Intragastric epinastine, fexofenadine, and loratadine administration suppressed allergen-induced immediate nasal response but not NHR in immunized mice. Regardless of the alleviation of stimulation-induced Th2 cytokine expression by loratadine and desloratadine in vitro, allergen-induced NHR and nasal eosinophil infiltration in Th2 cell-transferred mice were unaffected by loratadine in vivo. This influence on T cell-mediated NHR was excluded from the pharmacological effects of antihistamines.

The association between nutritional intake one week after admission and outcome in acute ischemic stroke patients.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: Adequate nutritional intake at one week after admission was independently associated with good outcome regardless of the nutritional status at admission or stroke severity.

[Wernicke encephalopathy with lesions in the bilateral abducens nuclei: a case report].

A 35-year-old Japanese man had been treated for alcoholism until 6 months before coming to our hospital, after which he discontinued treatment for alcoholism. He noticed dizziness from two weeks ago. He visited our hospital because his dizziness was worsened and he noticed diplopia from two days ago. Physical examination revealed bilateral abducens nerve palsy, decreased limb tendon reflex, and ataxia. His blood vitamin B1 level was 16 ng/ml (normal range 24-66 ng/ml). FLAIR images on brain MRI showed high signal intensity lesions in the bilateral abducens nuclei and mammillary body. We diagnosed him as Wernicke encephalopathy (WE) with lesions in the bilateral abducens nuclei. Treatment with thiamine rapidly resulted in improvement of his neurological symptoms and MRI findings. He was discharged from our department on the 10th hospitalization day. Previous reports have shown that abducens nerve palsy and horizontal gaze evoked nystagmus may occur in the early state of WE. This case report highlights the importance to comprehend the atypical MRI findings of WE to treat a patient at the early stage.

Risk Assessment of Cnm-Positive Streptococcus mutans in Stroke Survivors (RAMESSES): Protocol for a Multicenter Prospective Cohort Study.

Introduction: The role of commensal microbiota in systemic diseases, including brain diseases, has attracted increasing attention. Oral infectious diseases, such as dental caries and periodontitis, are also involved in cerebrovascular diseases and cognitive impairment. Cerebral microbleeds (CMBs) and intracerebral hemorrhage due to small vessel disease (SVD), are presumably associated with a high risk of vascular cognitive impairment and stroke. We previously reported that Streptococcus mutans (S. mutans, the main pathogen of dental caries), harboring the cnm gene that encodes the collagen-binding protein Cnm, is associated with the development of hypertensive intracerebral hemorrhage and aggravation of CMBs. We also proposed a mechanism by which the circulating Cnm-expressing S. mutans causes intracerebral hemorrhage or CMBs; it binds to denuded basement membranes mainly composed of collagen IV through damaged tight junctions or it directly invades endothelial cells, resulting in blood-brain barrier injury. In November 2018, we initiated a multicenter, prospective cohort study (RAMESSES: Risk Assessment of Cnm-positive S. mutans in Stroke Survivors; UMIN Clinical Trials Registry: UMIN000045559) to explore the longitudinal association between Cnm-positive S. mutans and CMBs with comprehensive dental findings, which should determine the effect of Cnm-positive S. mutans in the oral cavity on the risk of CMB development and cognitive decline. Methods: Fifteen domestic institutes will be enlisted to enroll 230 patients who have at least one CMB in the deep brain area and develop a stroke within the past year. The prevalence of Cnm-positive S. mutans based on oral specimens and dental hygiene will be examined. The primary outcome is the number of newly developed deep CMBs. The secondary outcomes include the new development of lobar, subtentorial, or any type of CMBs; symptomatic intracerebral hemorrhage or ischemic stroke; changes in cognitive function or frailty; major bleeding; all-cause mortality; and antibody titers against periodontal pathogens. The observation period will be 2 years. Discussion: The 2-year longitudinal prospective cohort study is expected to establish the role of Cnm-positive S. mutans in SVD including CMBs and intracerebral hemorrhage from the perspective of the "brain-oral axis" and provide guidance for novel prophylactic strategies against Cnm-positive S. mutans-induced SVD.

Short-term or long-term outcomes for stroke patients with cancer according to biological markers.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Low albumin levels were independently associated with short- and long-term outcomes, as were D-dimer levels, in acute ischemic stroke patients with cancer.

Expression and Function of Nicotinic Acetylcholine Receptors in Induced Regulatory T Cells.

A contribution of the cholinergic system to immune cell function has been suggested, though the role of nicotine and its receptors in T cells, especially regulatory T (Treg) cells, is unclear. We herein investigated the expression and function of nicotinic acetylcholine receptors (nAChRs) in murine-induced Treg (iTreg) cells. Upon differentiation of naive BALB/c T cells into iTreg cells and other T-cell subsets, the effect of nicotine on cytokine production and proliferation of iTreg cells was examined. The expression of nAChRs and its regulatory mechanisms were comparatively analyzed among T-cell subsets. Stimulation-induced transforming growth factor-ß1 (TGF-ß1) production of iTreg cells was suppressed by nicotine, whereas interleukin (IL)-10 production and proliferation was not affected. α2-, α5-, α9-, and ß2-nAChRs were differentially expressed in naive, Th1, Th2, Th9, Th17, and iTreg cells. Among these cell types, the α9-nAChR was particularly upregulated in iTreg cells via its gene promoter, but not through tri-methylation at the 4th lysine residue of the histone H3-dependent mechanisms. We conclude that the immunoregulatory role of Treg cells is modified by the cholinergic system, probably through the characteristic expression of nAChRs.

Assessment of Serum IgG Titers to Various Periodontal Pathogens Associated with Atrial Fibrillation in Acute Stroke Patients.

OBJECTIVES: There is accumulating evidence that periodontal disease is associated with atrial fibrillation (AF) or stroke, but it is unclear which causative species of periodontal disease are present in stroke patients with AF. We aimed to investigate the associations between AF and specific periodontal pathogens using serum titers of IgG antibodies of bacteria in acute stroke patients. MATERIALS AND METHODS: Acute stroke patients were registered at two hospitals. Serum samples were evaluated for titers of antibodies against 9 periodontal pathogens (16 genotypes) using ELISAs. We identified AF in patients according to the following criteria: (1) a history of sustained or paroxysmal AF or (2) AF detection upon arrival or during admission. We carried out propensity score matching to categorize the patients as those with AF and those without. RESULTS: Of the 664 acute stroke patients, 123 (18.5%) had AF. After propensity score matching, 234 patients were selected. Patients with AF had a higher prevalence of positive serum titers of antibodies against Porphyromonas gingivalis (FimA type III) and Porphyromonas gingivalis (FimA type V) than those without AF (59.0% vs. 39.3%, p=0.004 and 58.2% vs. 40.2%, p=0.009, respectively). CONCLUSIONS: Porphyromonas gingivalis, especially FimA type III and type V, might be associated with AF in stroke patients.

Increased Serum Alkaline Phosphatase and Functional Outcome in Patients with Acute Ischemic Stroke Presenting a Low Ankle-Brachial Index.

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.

Predictors of Stroke Outcome Extracted from Multivariate Linear Discriminant Analysis or Neural Network Analysis.

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.

Various effects of nutritional status on clinical outcomes after intracerebral hemorrhage.

Although the assessment of nutrition is essential for stroke patients, detailed associations between nutritional status at admission, subsequent complications, and clinical outcomes in patients with acute intracerebral hemorrhage (ICH) are unclear. We aimed to elucidate these associations using the Controlling Nutritional Status (CONUT) score. Consecutive patients with acute ICH were investigated. Nutritional status was evaluated using the CONUT score, calculated from the serum albumin level, lymphocyte count, and total cholesterol level. Subsequent complications, such as hemorrhage expansion (HE) during the acute stage and aspiration pneumonia during hospitalization, were evaluated. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. Of the 721 patients, 49 had HE, 111 had aspiration pneumonia, and 409 had poor outcomes. Patients with HE had significantly lower total cholesterol levels than those without HE. Patients with aspiration pneumonia had significantly lower albumin levels, lower lymphocyte counts, and higher CONUT scores than those without aspiration pneumonia. Patients with poor outcomes had significantly lower albumin levels, lower lymphocyte counts, lower total cholesterol levels, and higher CONUT scores than those with good outcomes. Multivariable logistic analysis showed that higher CONUT scores were independently associated with poor outcome (odds ratio, 1.28; 95% confidence interval, 1.09-1.49; P = 0.002) after adjusting for baseline characteristics, HE, and aspiration pneumonia. Each component of CONUT was a useful predictor of subsequent complications. Malnutrition, determined using the CONUT score, was independently associated with poor outcomes in patients with ICH after adjusting for these complications.

Clinical characteristics and tumor markers in ischemic stroke patients with active cancer.

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 < 0.001 and ρ = 0.452, p < 0.001, respectively). The areas under the receiver-operating characteristic curves for the diagnosis of CAS were 0.812 (95% CI 0.718-0.878) for CA 125, 0.714 (95% CI 0.602-0.801) for CEA, and 0.663 (95% CI 0.552-0.759) for CA 19-9. Multivariable analysis revealed that CA 125 levels in the highest quartile (OR 2.91, 95% CI 1.68-5.53), multiple lesions in multiple vascular territories observed on diffusion-weighted imaging, the absence of dyslipidemia, and the absence of atrial fibrillation were independently associated with CAS. Increased CA 125 levels, which indicate hypercoagulability, were useful for diagnosing CAS in AIS patients with active cancer.