Serum anti­KIAA0513 antibody as a common biomarker for mortal atherosclerotic and cancerous diseases.

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

Stage-Specific Alteration and Prognostic Relationship of Serum Fumarate Hydratase Autoantibodies in Gastric Cancer.

The relationship between energy production and cancer is attracting attention. This study aimed to investigate the clinicopathological significance of fumarate hydratase (FH), a tricarboxylic acid cycle enzyme, in gastric cancer using autoantibodies as biomarkers. The study analyzed 116 patients who underwent gastric cancer surgery and 96 healthy controls. Preoperative serum FH autoantibody (s-FH-Ab) titers were analyzed using an immunosorbent assay with an amplified luminescent proximity homogeneous assay. Receiver operating characteristic analysis was used to determine the cutoff s-FH-Ab titer. Clinicopathological factors and prognosis were compared between the high and low s-FH-Ab groups. The s-FH-Ab levels were significantly higher in the gastric cancer group than in the control group (p = 0.01). Levels were elevated even in patients with stage I gastric cancer compared with healthy controls (p = 0.02). A low s-FH-Ab level was significantly associated with distant metastasis (p = 0.01), peritoneal dissemination (p < 0.05), and poor overall survival (p < 0.01). Multivariate analysis revealed that low s-FH-Ab levels were an independent risk factor for poor prognosis (p < 0.01). Therefore, s-FH-Ab levels may be a useful biomarker for early diagnosis and the prediction of prognosis in patients with gastric cancer.

JMJD6 Autoantibodies as a Potential Biomarker for Inflammation-Related Diseases.

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

Combination of high anti-SKI and low anti-TMED5 antibody levels is preferable prognostic factor in esophageal carcinoma.

Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto-oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti-SKI antibody (s-SKI-Ab) and anti-TMED5 antibody (s-TMED5-Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s-SKI-Abs and s-TMED5-Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s-SKI-Ab-positive and s-TMED5-Ab-negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s-SKI-Ab-positive and s-TMED5-Ab-negative cases showed an even clearer difference in overall survival as compared with that of s-SKI-Ab-negative and s-TMED5-Ab-positive cases. The s-SKI-Ab and s-TMED5-Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses.

Toward an application of automatic evaluation system for central facial palsy using two simple evaluation indices in emergency medicine.

A stroke is a medical emergency and thus requires immediate treatment. Paramedics should accurately assess suspected stroke patients and promptly transport them to a hospital with stroke care facilities; however, current assessment procedures rely on subjective visual assessment. We aim to develop an automatic evaluation system for central facial palsy (CFP) that uses RGB cameras installed in an ambulance. This paper presents two evaluation indices, namely the symmetry of mouth movement and the difference in mouth shape, respectively, extracted from video frames. These evaluation indices allow us to quantitatively evaluate the degree of facial palsy. A classification model based on these indices can discriminate patients with CFP. The results of experiments using our dataset show that the values of the two evaluation indices are significantly different between healthy subjects and CFP patients. Furthermore, our classification model achieved an area under the curve of 0.847. This study demonstrates that the proposed automatic evaluation system has great potential for quantitatively assessing CFP patients based on two evaluation indices.

Effect of admission in the stroke care unit versus intensive care unit on in-hospital mortality in patients with acute ischemic stroke.

BACKGROUND/OBJECTIVE: Few reports have directly compared the outcomes of patients with acute ischemic stroke (AIS) who are managed in a stroke care unit (SCU) with those who are managed in an intensive care units (ICU). This large database study in Japan aimed to compare in-hospital mortality between patients with AIS admitted into SCU and those admitted into ICU. METHODS: Patients with AIS who were admitted between April 1, 2014, and March 31, 2019, were selected from the administrative database and divided into the SCU and ICU groups. We calculated the propensity score to match groups for which the admission unit assignment was independent of confounding factors, including the modified Rankin scale (mRS) score. The primary outcome was in-hospital mortality, and secondary outcomes were the mRS score at discharge, length of stay (LOS), and total hospitalization cost. RESULTS: Overall, 8,683 patients were included, and 960 pairs were matched. After matching, the in-hospital mortality rates of the SCU and ICU groups were not significantly different (5.9% vs. 7.9%, P = 0.106). LOS was significantly shorter (SCU = 20.9 vs. ICU = 26.2 days, P < 0.001) and expenses were significantly lower in the SCU group than in the ICU group (SCU = 1,686,588 vs. ICU = 1,998,260 yen, P < 0.001). mRS scores (score of 1-3 or 4-6) at discharge were not significantly different after matching. Stratified analysis showed that the in-hospital mortality rate was lower in the ICU group than in the SCU group among patients who underwent thrombectomy. CONCLUSIONS: In-hospital mortality was not significantly different between the ICU and SCU groups, with significantly lower costs and shorter LOS in the SCU group than in the ICU group.

Serum anti-PCK1 antibody levels are a prognostic factor for patients with diabetes mellitus.

BACKGROUND: Autoantibodies develop in autoimmune diseases, cancer, diabetes mellitus (DM), and atherosclerosis-related diseases. However, autoantibody biomarkers have not been successfully examined for diagnosis and therapy. METHODS: Serological identification of antigens through recombinant cDNA expression cloning (SEREX) was used for primary screening of antigens. The cDNA product was expressed in bacteria and purified. Amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) was used to evaluate antibody levels in serum samples. RESULTS: Phosphoenolpyruvate carboxykinase 1 (PCK1) was recognized as an antigen by serum IgG antibodies in the sera of patients with atherosclerosis. AlphaLISA showed significantly higher serum antibody levels against recombinant PCK1 protein in patients with DM and cardiovascular disease than in healthy donors, but not in those with acute ischemic stroke, transient ischemic attack, or obstructive sleep apnea syndrome. The area under the receiver operating characteristic curve for anti-PCK1 antibodies was 0.7024 for DM. The serum anti-PCK1 antibody levels were associated with age, platelet count, and blood pressure. Anti-PCK1-antibody-positive patients showed significantly lower overall survival than the negative patients. CONCLUSIONS: Serum anti-PCK1 antibody levels were found to be associated with DM. The anti-PCK1 antibody marker is useful for predicting the overall survival of patients with DM.

Prehospital stroke-scale machine-learning model predicts the need for surgical intervention.

While the development of prehospital diagnosis scales has been reported in various regions, we have also developed a scale to predict stroke type using machine learning. In the present study, we aimed to assess for the first time a scale that predicts the need for surgical intervention across stroke types, including subarachnoid haemorrhage and intracerebral haemorrhage. A multicentre retrospective study was conducted within a secondary medical care area. Twenty-three items, including vitals and neurological symptoms, were analysed in adult patients suspected of having a stroke by paramedics. The primary outcome was a binary classification model for predicting surgical intervention based on eXtreme Gradient Boosting (XGBoost). Of the 1143 patients enrolled, 765 (70%) were used as the training cohort, and 378 (30%) were used as the test cohort. The XGBoost model predicted stroke requiring surgical intervention with high accuracy in the test cohort, with an area under the receiver operating characteristic curve of 0.802 (sensitivity 0.748, specificity 0.853). We found that simple survey items, such as the level of consciousness, vital signs, sudden headache, and speech abnormalities were the most significant variables for accurate prediction. This algorithm can be useful for prehospital stroke management, which is crucial for better patient outcomes.

GADD34 activates p53 and may have utility as a marker of atherosclerosis.

We previously identified growth arrest and DNA-damage-inducible gene 34 (GADD34) as a marker of ischemic stroke. In the present study, serum levels of anti-GADD34 antibodies were found to be significantly higher in patients with acute ischemic stroke or chronic kidney disease compared to healthy donors. We then examined the biological function of GADD34 by transfection into U2OS human osteosarcoma and U87 human glioblastoma cells. Knockdown of GADD34 by siRNA resulted in enhanced cell proliferation, which was reversed by co-knockdown of MDM2. Luciferase reporter assays revealed that the transactivation ability of p53 enhanced by genotoxic anticancer drugs such as camptothecin and etoposide was further potentiated by enforced expression of GADD34 but attenuated by co-transfection with p53 shRNA expression plasmids. Western blotting demonstrated increased p53 protein levels after treatment with camptothecin, which was also potentiated by GADD34 but suppressed by GADD34 siRNA, ATM siRNA, and ATM inhibitor wortmannin. GADD34 levels also increased in response to treatment with camptothecin or adriamycin, and this increase was attenuated by MDM2 siRNA. Immunoprecipitation with anti-GADD34 antibody followed by Western blotting with anti-MDM2 antibodies indicated ubiquitination of GADD34 is mediated by MDM2. Accordingly, GADD34 may function as a ubiquitination decoy to reduce p53 ubiquitination and increase p53 protein levels. Increased neuronal cell death due to activation of p53 by GADD34 may account for the elevated serum levels of anti-GADD34 antibodies observed in patients with acute ischemic stroke.

Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer.

Introduction: Autoantibodies against inflammatory cytokines may be used for the prevention of atherosclerosis. Preclinical studies consider colony-stimulating factor 2 (CSF2) as an essential cytokine with a causal relationship to atherosclerosis and cancer. We examined the serum anti-CSF2 antibody levels in patients with atherosclerosis or solid cancer. Methods: We measured the serum anti-CSF2 antibody levels via amplified luminescent proximity homogeneous assay-linked immunosorbent assay based on the recognition of recombinant glutathione S-transferase-fused CSF2 protein or a CSF2-derived peptide as the antigen. Results: The serum anti-CSF2 antibody (s-CSF2-Ab) levels were significantly higher in patients with acute ischemic stroke (AIS), acute myocardial infarction (AMI), diabetes mellitus (DM), and chronic kidney disease (CKD) compared with healthy donors (HDs). In addition, the s-CSF2-Ab levels were associated with intima-media thickness and hypertension. The analyzes of samples obtained from a Japan Public Health Center-based prospective study suggested the utility of s-CSF2-Ab as a risk factor for AIS. Furthermore, the s-CSF2-Ab levels were higher in patients with esophageal, colorectal, gastric, and lung cancer than in HDs but not in those with mammary cancer. In addition, the s-CSF2-Ab levels were associated with unfavorable postoperative prognosis in colorectal cancer (CRC). In CRC, the s-CSF2-Ab levels were more closely associated with poor prognosis in patients with p53-Ab-negative CRC despite the lack of significant association of the anti-p53 antibody (p53-Ab) levels with the overall survival. Conclusion: S-CSF2-Ab was useful for the diagnosis of atherosclerosis-related AIS, AMI, DM, and CKD and could discriminate poor prognosis, especially in p53-Ab-negative CRC.

Serum anti­TSTD2 antibody as a biomarker for atherosclerosis­induced ischemic stroke and chronic kidney disease.

Autoantibodies can be used in the early diagnosis and treatment of atherosclerosis-related diseases. Using ProtoArray® screening of samples from patients with atherosclerosis, the present study identified thiosulfate sulfurtransferase-like domain-containing 2 (TSTD2) as a novel atherosclerosis antigen. The serum TSTD2 antibody levels were then quantified using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay. This demonstrated the levels of TSTD2 antibodies (TSTD2-Abs) to be significantly higher in patients with acute cerebral infarction or chronic kidney disease than in healthy donors. The TSTD2-Ab levels were also found to be higher in males, older adults, smokers, in those who consumed alcohol regularly, and in those with hypertension. Furthermore, Spearman's rank correlation analysis revealed TSTD2-Ab levels to be strongly associated with measures of atherosclerosis severity, including plaque scores, intima-media thickness of the carotid artery and the cardio-ankle vascular index. Thus, TSTD2-Abs may thus be a promising novel biomarker for atherosclerosis-related cerebral infarction and kidney disease.

Primary results of mechanical thrombectomy for acute ischemic stroke: The K-NET registry in the Japanese metropolitan area.

BACKGROUND: Endovascular treatment (EVT) for acute large vessel occlusion has proven to be effective in randomized controlled trials. We conducted a prospective cohort study to evaluate the real-world efficacy of EVT in a metropolitan area with a large number of comprehensive stroke centers and to compare it with the results of other registries and randomized controlled trials (RCTs). METHODS: We analyzed the Kanagawa Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry, a prospective, multicenter observational study of patients treated by EVT and/or intravenous tissue-type plasminogen activator (tPA). Of the 2488 patients enrolled from January 2018 to June 2020, 1764 patients treated with EVT were included. The primary outcome was a good outcome, which was defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Secondary analysis included predicting a good outcome using multivariate logistic regression analysis. RESULTS: The median age was 77 years, and the median National Institute of Health Stroke Scale (NIHSS) score was 18. Pretreatment mRS score 0-2 was 87%, and direct transport was 92%. The rate of occlusion in anterior circulation was 90.3%. Successful recanalization was observed in 88.7%. The median time from onset to recanalization was 193 min. Good outcomes at 90 days were 43.3% in anterior circulation and 41.9% in posterior circulation. Overall mortality was 12.6%. Significant predictors for a good outcome were as follows: age, male, direct transfer, NIHSS score, Alberta Stroke Program Early Computed Tomography Score, intravenous tPA, and successful recanalization. CONCLUSION: EVT in routine clinical use in a metropolitan area showed comparable good outcomes and lower mortality compared to previous studies, despite the high proportion of patients with older age, pretreatment mRS score of >2, posterior circulation occlusion, and higher NIHSS. Those results may have been associated with more direct transport and faster onset-to-recanalization times.

Ruptured bilateral middle cerebral artery aneurysms diagnosed based on cerebral vasospasm-associated ischemic symptoms: A case report.

We report a case of subarachnoid hemorrhage presenting with ischemic symptoms due to cerebral vasospasm. A 64-year-old woman with right facial paralysis was referred to our hospital for treatment because of bilateral middle cerebral artery aneurysms observed using magnetic resonance imaging. She had no headache episodes; however, contrast-enhanced magnetic resonance imaging showed contrast enhancement of the aneurysmal wall only on the left side. Therefore, she was considered to have a ruptured aneurysm and underwent craniotomy and aneurysmal neck clipping. The postoperative course was uneventful; however, she developed aphasia and dysphagia 9 months after the surgery and was readmitted. New cerebral infarction and subarachnoid hemorrhage were observed on the right side, and the patient exhibited marked vasospasm. Because of a headache episode one week earlier, coil embolization was performed after the vasospasm. She was discharged home with a modified Rankin scale score of 2 and planned rehabilitation. Aneurysms that enlarge and rupture in a short time period should be treated with caution. Vessel wall imaging was useful in identifying the ruptured aneurysm in the current case.

Transarterial embolization for falx dural arteriovenous fistula through the artery of Davidoff and Schechter: A case report.

Endovascular transarterial embolization is the standard treatment for the nonsinus-type of dural arteriovenous fistulae. Here, we report a rare case of successful transarterial embolization from the artery of Davidoff and Schechter for falx dural arteriovenous fistulae. A 74-year-old-man was incidentally diagnosed with falx dural arteriovenous fistulae during head magnetic resonance imaging. Results revealed dilatation of the cortical veins in the right occipital lobe. Angiographically, falx dural arteriovenous fistula was observed to be fed by the right middle meningeal artery, right occipital artery, right posterior meningeal artery, and the artery of Davidoff and Schechter (Borden type III). However, due to the tortuosity, the first transarterial embolization surgery through the middle meningeal artery, occipital artery, and posterior meningeal artery was unsuccessful. Therefore, the second transarterial embolization was performed through the artery of Davidoff and Schechter. Arteriovenous fistulae disappeared after administering Onyx injections through the artery of Davidoff and Schechter. Based on our findings, the artery of Davidoff and Schechter can be an approach route to treat dural arteriovenous fistulae. Moreover, the most important point of transarterial embolization procedures through the artery of Davidoff and Schechter is to navigate the microcatheter along the falx.

Two Patients with Reversible Cerebral Vasoconstriction after Carotid Artery Stenting.

Objective: We herein report two cases of transient cerebral vasoconstriction after carotid artery stenting (CAS). Case Presentation: An 81-year-old man presented with asymptomatic severe stenosis in the right carotid artery accompanied by a slight reduction in cerebrovascular reactivity. CAS was performed, but the patient had a generalized seizure because of transient cerebral ischemia caused by intolerance to carotid artery occlusion with balloon protection. Confusion and left hemiparesis persisted. DSA suggested cerebral ischemia due to vasoconstriction as the cause of these prolonged symptoms. A 66-year-old man presented with asymptomatic severe stenosis in the right carotid artery with slight hypoperfusion. CAS was performed. The patient developed left hemispatial neglect, dysarthria, and left hemiparesis 12 hours after the procedure. DSA revealed cerebral vasoconstriction in the responsible territory. The conditions of both patients improved within several days with medical treatment and they were discharged without neurological deficits. Conclusion: The cases presented herein show that transient ischemic complications caused by cerebral vasoconstriction may develop after CAS.

Carotid Artery Stenting for Patients with Radiation-Induced Carotid Artery Stenosis.

Objective: In radiation-induced carotid artery stenosis (RIS), morphological characteristics, such as bilateral and long lesion distances and in-stent stenosis, have been reported as common after carotid artery stenting (CAS). Here, we present 25 cases at our hospital wherein CAS was performed for RIS and compare the morphological characteristics and the safety of the treatment with cases of atherosclerotic carotid artery stenosis (AS). Methods: Twenty-five lesions from 21 patients underwent CAS for RIS at our hospital between March 2002 and July 2020. The procedure was performed at a mean of 10.0 ± 5.2 years after radiation therapy with 60-72 Gy, with a median follow-up of 45 months. We retrospectively selected consecutive patients with AS with comparable follow-up times from the beginning of the study as controls. We compared the patients' background, stenosis findings including plaque MRI, perioperative period, and postoperative course. Results: All patients in both groups completed the procedure, and the median follow-up time for the RIS and AS groups was 45 and 40 months, respectively (p = 0.1479). Patients in the RIS group had a lower mean age (69.9 ± 6.9 vs. 75.3 ± 7.04, p = 0.0075), a higher stenosis rate (79.1 ± 8.7% vs. 68.6 ± 11.7%, p = 0.0032), and longer stenosis greater than one vertebra (long lesions) (10 vs. 1, p = 0.0046) compared with the patients in the AS group. Although there was no significant difference in outcomes between the two groups, restenosis tended to be more common in the RIS group. Plaque MRI was characterized by a significantly higher T2WI signal (p = 0.0381) in the RIS group, which was attributable to the fact that a necrotic core has been reported commonly in the plaque tissue of RIS. Conclusion: RIS has a high likelihood of restenosis both morphologically and in terms of plaque characteristics. Thus, close follow-up is crucial.

Serum anti-SERPINE1 antibody as a potential biomarker of acute cerebral infarction.

The presence of disease-specific antigens and autoantibodies in the sera of patients with atherosclerosis-related diseases has been widely reported and is considered to result from inflammation of the arterial wall and the involvement of immune factors. The aim of this study was to identify a novel antibody in patients with ischemic stroke by serological identification of antigens using recombinant cDNA expression cloning from patients who had a transient ischemic attack (TIA). We identified the serpin peptidase inhibitor, clade E member 1 (SERPINE1), as a candidate antigen. The serum anti-SERPINE1 antibody levels quantified using amplified luminescent proximity homogeneous assay-linked immunosorbent assay were significantly higher in patients with ischemic stroke, including those with acute cerebral infarction (aCI), TIA, and chronic cerebral infarction, than in healthy donors. The antibody levels were strongly associated with old age, female sex, and presence of hypertension, diabetes mellitus, and cardiovascular disease. Age and intima-media thickness of the carotid artery were positively correlated with antibody levels, which suggests that SERPINE1 may reflect the progression of atherosclerosis. In a multivariate analysis, SERPINE1 antibody level was an independent predictor of aCI. Thus, the serum levels of anti-SERPINE1 antibody could potentially serve as a biomarker of atherothrombotic infarction.

A prehospital diagnostic algorithm for strokes using machine learning: a prospective observational study.

High precision is optimal in prehospital diagnostic algorithms for strokes and large vessel occlusions. We hypothesized that prehospital diagnostic algorithms for strokes and their subcategories using machine learning could have high predictive value. Consecutive adult patients with suspected stroke as per emergency medical service personnel were enrolled in a prospective multicenter observational study in 12 hospitals in Japan. Five diagnostic algorithms using machine learning, including logistic regression, random forest, support vector machine, and eXtreme Gradient Boosting, were evaluated for stroke and subcategories including acute ischemic stroke with/without large vessel occlusions, intracranial hemorrhage, and subarachnoid hemorrhage. Of the 1446 patients in the analysis, 1156 (80%) were randomly included in the training (derivation) cohort and cohorts, and 290 (20%) were included in the test (validation) cohort. In the diagnostic algorithms for strokes using eXtreme Gradient Boosting had the highest diagnostic value (test data, area under the receiver operating curve 0.980). In the diagnostic algorithms for the subcategories using eXtreme Gradient Boosting had a high predictive value (test data, area under the receiver operating curve, acute ischemic stroke with/without large vessel occlusions 0.898/0.882, intracranial hemorrhage 0.866, subarachnoid hemorrhage 0.926). Prehospital diagnostic algorithms using machine learning had high predictive value for strokes and their subcategories.

Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction.

BACKGROUND: Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers. METHODS: In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991-1993) were also examined. RESULTS: The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case-control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima-media thickness, which reflects atherosclerotic stenosis. CONCLUSIONS: ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.