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.

Transarterial embolization of radicular arteriovenous fistula at the craniocervical junction.

Craniocervical junction arteriovenous fistula (CCJ AVF) is a rare vascular disorder. Direct surgery for CCJ AVF is generally reported to have better outcome compared to endovascular treatment. However, no certain consensus has been obtained so far. We report a case of radicular CCJ AVF treated by transarterial embolization that resulted in a good outcome. A 69-year-old man presented with subarachnoid hemorrhage primarily in the posterior cranial fossa. Based on digital subtraction angiography showed radicular CCJ AVF with varix. Transarterial embolization was performed with n-butyl-2-cyanoacrylate on day 17 after onset and successfully cured. The neurovascular anatomy of CCJ AVF is complicated, but endovascular treatment may be a treatment option with detailed understanding of angioarchitecture and selective endovascular procedure.

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.

In-stent stenosis after stenting the PulseRider for a middle cerebral artery aneurysm: A case report.

PulseRider is a self-expanding stent implant used to treat wide-necked aneurysms. As this device has a lower metal mass than conventional stents, it is expected to have a lower rate of ischemic complications and a shorter period with antiplatelet drugs. We experienced in-stent stenosis after endovascular treatment with the PulseRider for a middle cerebral artery aneurysm. A 40-year-old woman with an unruptured aneurysm in the middle cerebral artery bifurcation underwent coil embolization using a PulseRider. The periprocedural course was not problematic, and postoperative angiography showed contrast filling in the aneurysm. The patient was discharged from our hospital on postembolization day 3. However, follow-up angiography after 6 months showed in-stent stenosis. Fortunately, no ischemic complications occurred after treatment. Although the PulseRider is characterized by a low metal mass, it should be noted that this device has some metal markers that can induce in-stent stenosis.

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.

Dual additive of lithium titanate and sulfurized pyrolyzed polyacrylonitrile in sulfur cathode for high rate performance in lithium-sulfur battery.

Lithium-Sulfur (Li-S) batteries have attracted much attention as next-generation batteries due to their high theoretical energy density. However, lithium polysulfide generated during the discharge loses intimate electrical contact with the carbon matrix due to its high solubility in the electrolyte, causing a high charge transfer resistance and slow redox kinetics for the discharge reactions, resulting in a low rate capability. A cathode additive having a strong chemical adsorbing site toward the polysulfide can effectively inhibit their dissolution. We now report a dual additive of lithium titanium oxide (LTO) and sulfurized polyacrylonitrile (SPAN). LTO provides a rapid charge transfer and a fast Li+ ion transfer in the cathode. On the other hand, SPAN helps to enhance the polysulfide adsorption capability. This dual additive system synergistically supplies the cathode with a strong polysulfide adsorption capability and fast redox kinetics. As a result, the dual additive exhibits high discharge capacities of 1430 mA h g-1 at 0.1C and 1200 mA h g-1 at 0.5C at the high-sulfur-loading cathode of 5.0 mg cm-2. Our findings demonstrated the manufacturing of the cathode with a strong polysulfide adsorption capability and a fast redox reaction which could then effectively improve the rate performance of the Li-S batteries.

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.

Serum anti-AP3D1 antibodies are risk factors for acute ischemic stroke related with atherosclerosis.

Atherosclerosis has been considered as the main cause of morbidity, mortality, and disability worldwide. The first screening for antigen markers was conducted using the serological identification of antigens by recombinant cDNA expression cloning, which has identified adaptor-related protein complex 3 subunit delta 1 (AP3D1) as an antigen recognized by serum IgG antibodies of patients with atherosclerosis. Serum antibody levels were examined using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) using a recombinant protein as an antigen. It was determined that the serum antibody levels against AP3D1 were higher in patients with acute ischemic stroke (AIS), transient ischemic attack, diabetes mellitus (DM), cardiovascular disease, chronic kidney disease (CKD), esophageal squamous cell carcinoma (ESCC), and colorectal carcinoma than those in the healthy donors. The area under the curve values of DM, nephrosclerosis type of CKD, and ESCC calculated using receiver operating characteristic curve analysis were higher than those of other diseases. Correlation analysis showed that the anti-AP3D1 antibody levels were highly associated with maximum intima-media thickness, which indicates that this marker reflected the development of atherosclerosis. The results of the Japan Public Health Center-based Prospective Study indicated that this antibody marker is deemed useful as risk factors for AIS.

Metastasis of Renal Cell Carcinoma to Spinal Hemangioblastoma in a Patient with von Hippel-Lindau Disease: A Case Report.

von Hippel-Lindau (VHL) disease is characterized by neoplastic and cystic lesions, such as central nervous system (CNS) hemangioblastoma and clear cell renal cell carcinoma (RCC), arising in multiple organs. Here, we report a case of an RCC that metastasized to a spinal hemangioblastoma in a patient diagnosed with VHL disease. This is a unique case study because visceral neoplasms rarely metastasize to the CNS. The patient had undergone posterior fossa surgery for the removal of hemangioblastomas in the right cerebellar hemisphere as a child. He was diagnosed with RCC at the age of 20 years, and he underwent partial nephrectomy at the age of 35 years. The patient underwent surgical removal of a spinal tumor from Th8, which was also diagnosed as a hemangioblastoma at the age of 40. However, the residual spinal tumor rapidly regrew within 1.5 years. A second surgery was performed due to progressive leg motor weakness. The resected tumor from the second surgery had two distinct components between the tumor center and the margin. Immunohistochemistry of CD10, PAX 8, and inhibin A demonstrated the predominant region of the tumor was RCC. Pathological findings confirmed tumor-to-tumor metastasis of the RCC migrating into residual spinal hemangioblastoma. It can be challenging to distinguish hemangioblastoma from RCC in neuroimaging. We suggest that tumor-to-tumor metastasis should be considered as a differential diagnosis if benign tumors grow rapidly, even if the pathological diagnosis does not initially confirm malignancy. The biological mechanisms of RCC migrating into residual hemangioblastoma are discussed.

Mechanical Thrombectomy for Acute Ischemic Stroke Complicated by Bacterial Meningitis and Infective Endocarditis.

Objective: We report a case of cerebral embolism from a bacterial embolus due to infective endocarditis (IE) during treatment of bacterial meningitis. Case Presentation: During treatment of bacterial meningitis, an 82-year-old woman developed left middle cerebral artery embolism. Mechanical thrombectomy was performed, and the yellowish-white emboli were retrieved. From the culture and pathological findings of the embolus, the same bacteria as the meningitis, Streptococcus gordonii, was identified and was considered to originate from IE. She was treated by postoperative antibiotics, but was transferred to the rehabilitation hospital on the 37th postoperative day due to slight right hemiparesis. Conclusion: We should always consider bacterial embolism in acute ischemic stroke combined with bacterial meningitis.

Long-Term Stable Lithium Metal Anode in Highly Concentrated Sulfolane-Based Electrolytes with Ultrafine Porous Polyimide Separator.

Highly concentrated solutions composed of lithium bis(fluorosulfonyl)imide (LiFSI) and sulfolane (SL) are promising liquid electrolytes for lithium metal batteries because of their high anodic stability, low flammability, and high compatibility with lithium metal anodes. However, it is still challenging to obtain the stable lithium metal anodes in the concentrated electrolytes due to their poor wettability to the conventional polyolefin separators. Here, we report that the highly concentrated 1:2.5 LiFSI/SL electrolyte coupled with a three-dimensionally ordered macroporous polyimide (3DOM PI) separator enables the stable lithium plating/stripping cycling with an average Coulombic efficiency of ca. 98% for over 400 cycles at 1.0 mA cm-2. The 3DOM PI separator shows good electrolyte wettability and large electrolyte uptake due to its high porosity and polar constituent of the imide structure, allowing superior cycling performance in the highly concentrated solution, compared with the polyolefin separators. Electrochemical and spectroscopic analyses reveal that the superior cycling stability in the concentrated electrolyte is attributed to the formation of highly stable and Li+ ion conductive solid electrolyte interphase (SEI) layer derived from FSI- anions, which reduces the side reactions of SL with lithium metal, prevents the growth of lithium dendrites, and suppresses the increase in cell impedance over long-term cycling. Our findings demonstrate that polar and porous separators could effectively improve the affinity to the concentrated electrolytes and allow the formation of the anion-derived SEI layer by increasing the salt concentration of the electrolytes, achieving the long-term stable lithium metal anode.

De Novo Vestibular Schwannoma: A Report of Three Cases.

The reported growth rate of vestibular schwannoma varied widely in the literature. However, emergence of vestibular schwannoma remains unsolved. We presented three patients who had undergone previous magnetic resonance imaging (MRI) confirming the absence of tumor and were diagnosed with a unilateral vestibular schwannoma with a diameter of 18-30 mm, 6-9 years after the initial MRI. One patient had solid tumor and experienced stereotactic radiosurgery. Following stereotactic radiosurgery, continuous tumor growth led to hydrocephalus and trigeminal dysfunction, resolved by surgical removal. Other two patients had the tumor with cystic component and experienced surgical removal as first treatment. All tumors were pathologically diagnosed as schwannomas without evidence of high potential of proliferation. This is the first report of three patients with de novo vestibular schwannoma, showing tumor emergence and rapid growth in a short period. Considering a de novo aspect, the "wait and scan" policy may not be appropriate for the subset of VS such as de novo VS.

Effectiveness of Low-Dose Intravenous Tissue Plasminogen Activator before Stent Retriever or Aspiration Mechanical Thrombectomy.

PURPOSE: To determine whether thrombolysis with a lower dose of intravenous recombinant tissue plasminogen activator before mechanical thrombectomy is beneficial for functional outcomes compared with mechanical thrombectomy alone. MATERIALS AND METHODS: Data for 100 Japanese patients who underwent mechanical thrombectomy between July 2014 and November 2017 were retrospectively reviewed. These patients were divided into groups according to whether they received intravenous thrombolysis before mechanical thrombectomy, and outcomes were compared. Favorable outcome was defined as a modified Rankin scale score ≤ 2 at 3 months after treatment. RESULTS: Thirty-four patients for the thrombolysis group and 66 patients for the thrombectomy-only group were identified. The thrombolysis and nonthrombolysis groups did not differ significantly in baseline characteristics (mean age, 74.3 y vs 75.7 y [P = .485]; mean preoperative National Institute Health Stroke Scale score, 19.8 vs 19.6 [P = .825]). There were no significant differences in the times required for, or the rates of, successful recanalization. However, the thrombolysis group had a higher rate of complete recanalization (67.6% vs 43.9%; P = .041). Postoperative symptomatic intracranial hemorrhage was not significantly different between groups. Favorable outcomes were observed in 73.5% of patients in the thrombolysis group and 51.5% in the nonthrombolysis group (P = .028). CONCLUSIONS: This single-center retrospective study shows that lower-dose intravenous thrombolysis improves the outcomes of mechanical thrombectomy for Japanese patients with acute anterior-circulation stroke treated within 4.5 hours of onset.

Severe Vasospasm of the Middle Cerebral Artery after Mechanical Thrombectomy Due to Infective Endocarditis: An Autopsy Case.

Untreated infective endocarditis (IE) often produces infective emboli in major cerebral arteries. We describe a case of middle cerebral artery occlusion due to IE, which caused severe vasospasm and reocclusion after mechanical thrombectomy (MT). We present the pathologic findings of the occluded middle cerebral artery and investigate the precautions to be taken while performing MT due to IE. A 72-year-old man with atrial fibrillation treated with dabigatran presented with right hemiparesis and aphasia. A diffusion-weighted image showed a high-intensity area in the left temporoparietal junction, and magnetic resonance angiography revealed a left M2 occlusion. Because of an elevated activated partial thromboplastin time, the thrombolytic therapy was contraindicated; instead, MT was performed. Just after the withdrawal of a stent retriever, the left M2 segment showed severe vasospasm. The next day, the left M2 segment reoccluded. Transthoracic echocardiogram and blood culture findings revealed IE. On the ninth day, the patient died. According to the autopsy report, the cause of death was pulmonary embolism. Pathologic analysis of the occluded M2 segment revealed fibrin thrombi containing vast amounts of neutrophils and invasion of neutrophils into the internal elastic lamina. Severe vasospasm was thought to have occurred because the vascular injury caused by the stent retriever in the vessel had a marked inflammation background. Our findings suggest that devices that are less invasive to the vascular wall are required for performing MT due to IE. The Penumbra aspiration system is thought to be a suitable device.

[Antifungal activity of the novel adduct, GX-95, of silver with nanometer-scale particles to peptidic hydrolysates from collagen].

Silver has long been known to have an antimicrobial activity against bacteria and other microorganisms, and has been used as eating utensils, as dental fillings and so on. We developed a novel adduct, GX-95, of silver with nanometer-scale particles to peptidic hydrolysates from collagen. Antifungal activity of the adduct against pathogenic yeasts and filamentous fungi was examined in terms of minimal inhibitory concentrations (MICs). GX-95 was found to possess strong and broad antifungal activities against all fungi examined in the following MICs: 0.25 to 0.31 microg/ml for Candida albicans including resistant strains to fluconazole, itraconazole and flucytosine, 0.05 to 0.2 microg/ml for Cryptococcus neoformans strains, 0.025 to 0.4 microg/ml for Aspergillus fumigatus strains, 0.4 microg/ml for Trichophyton rubrum, and 0.05 microg/ml for Cladophialophora carrionii.