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OBJECTIVE: In symptomatic low-grade stenosis, most of the reports did not clarify the long-term outcome. This study aims to clarify the clinical features and long-term outcomes of symptomatic low-grade stenosis cases. MATERIALS AND METHODS: We included 123 symptomatic patients with low-grade (<50%) carotid stenosis. The relative plaque signal intensity (rSI) and expansive remodeling rate (ERR) were measured using carotid magnetic resonance imaging (MRI). Antiplatelet therapy and treatment for atherosclerosis risk factors were administered in all cases. Carotid endarterectomy (CEA) was performed when ischemic symptoms appeared, or the percent stenosis progressed despite medical treatment. RESULTS: The mean percent stenosis, rSI, and ERR on admission were 22.3, 1.70, and 2.01, respectively. The mean volume of the hyperintense plaque on carotid MRI was 641.4± 540 mm3. Sixty percent of cases involved intraplaque hemorrhage and expansive remodeling. During a mean follow-up of 52 months, recurrence of ischemic events was confirmed in 45 cases (36.6%). Of the 67 cases performed follow-up MRI, 34 cases (50%) had an increased volume of T1-hyperintense plaque. CEA or carotid artery stenting was performed in 49 cases. During a mean follow-up of 57.8 months after CEA, two cases of death (fatal intracerebral hemorrhage and asphyxia) and one case of brain stem lacunar infarction were observed, but ipsilateral ischemic events were not. CONCLUSION: Most of the symptomatic patients with low-grade stenosis had both intraplaque hemorrhage and expansive remodeling and presented a high risk of recurrence and stenosis progression. CEA may have preventive effects against ischemic events in low-grade stenosis.
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Estenose das Carótidas , Placa Aterosclerótica , Humanos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Constrição Patológica , Stents , Placa Aterosclerótica/diagnóstico , Hemorragia CerebralRESUMO
Free fatty acid receptor 1 (FFAR1 or GPR40) has attracted attention for the treatment of type 2 diabetes mellitus, and various small-molecule agonists have been developed. However, most FFAR1 agonists as well as endogenous ligands, such as linoleic acids, have high lipophilicity, and their high lipophilicity is related to off-target toxicity. Therefore, we need to focus on new ligand candidates with less toxicity. In this study, we screened peptides with FFAR1 agonist activity as new ligand candidates. First, we used phage display to identify peptides with high affinity to FFAR1. Next, the agonist activities of peptides determined by the phage display were evaluated by the TGF-α shedding assay. Finally, to improve the FFAR1 agonist activity of the peptide, we performed an inclusive single amino acid substitution and sequence analysis. Logistic regression (LR) analysis using 120 physiochemical properties was performed to predict peptides with high FFAR1 agonist activity. STTGTQY determined by phage display promoted glucose-stimulated insulin secretion in pancreatic MIN6 cells. Furthermore, STKGTF predicted by the LR analysis showed high insulin secretion at low concentrations compared to STTGTQY. The results of this study suggest that peptides could be new candidates as FFAR1 agonists.
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Substituição de Aminoácidos , Avaliação Pré-Clínica de Medicamentos/métodos , Aprendizado de Máquina , Biblioteca de Peptídeos , Peptídeos/química , Peptídeos/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Sequência de Aminoácidos , Linhagem Celular , Clonagem Molecular , Glucose/farmacologia , Células HEK293 , Humanos , Insulina/metabolismo , Peptídeos/efeitos adversos , Peptídeos/genética , Ligação Proteica , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Análise de Regressão , Fator de Crescimento Transformador alfa/metabolismoRESUMO
BACKGROUND: In mechanical thrombectomy for acute large vessel occlusion, a combined technique of using both a stent retriever and an aspiration catheter has been widely used. The authors report a case in which a stent retriever's pushwire and a microcatheter were caught and disconnected by an accordion-like deformed aspiration catheter. OBSERVATIONS: A 74-year-old man underwent mechanical thrombectomy for a left M1 occlusion. A stent retriever was deployed from the left M2 to the left distal M1, and an aspiration catheter was advanced to the left distal M1. When the stent retriever and microcatheter were pulled into the aspiration catheter at the distal M1 without releasing the deflection, traction resistance of the stent retriever occurred, and the aspiration catheter contracted and deformed like an accordion distal to the tip of the guiding catheter. The stent retriever's pushwire and the microcatheter were caught and disconnected. LESSONS: When a stent retriever is pulled into a flexible aspiration catheter in a case with vascular tortuosity, it may be caught by an accordion-like deformed aspiration catheter and disconnected. It is necessary to release the deflection of the aspiration catheter once traction resistance of the stent retriever and deflection of the aspiration catheter occur.
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An 80-year-old woman presented with impaired consciousness after malignant melanoma resection. Magnetic resonance angiography showed basilar artery occlusion, which was subjected to mechanical thrombectomy for recanalization. A pathological analysis of the retrieved embolus revealed that it was derived from a metastasis of malignant melanoma. Contrast-enhanced chest computed tomography showed multiple pulmonary metastases, one of which was in the right upper lobe and invaded the pulmonary vein. To our knowledge, this is the first case of white embolus-induced cerebral embolism due to pulmonary vein invasion of a metastasis of a pathologically diagnosed malignant melanoma.
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Embolia , Melanoma , Veias Pulmonares , Feminino , Humanos , Idoso de 80 Anos ou mais , Artéria Basilar , Trombectomia/métodos , Melanoma/complicações , Melanoma Maligno CutâneoRESUMO
OBJECTIVES: Thrombi in cerebral large vessel occlusion associated with active cancer are often fibrin and platelet-rich white thrombi. However, evaluating the thrombus composition in a short time before thrombectomy is often ineffective. We sought to determine factors related to white thrombi in acute ischemic stroke due to large vessel occlusion in cancer patients. METHODS: Consecutive cancer patients undergoing thrombectomy for acute ischemic stroke due to large vessel occlusion between January 2018 and May 2022 were retrospectively reviewed. The patients were classified into white thrombus and red thrombus groups on the basis of the pathological findings of retrieved thrombi. Patient characteristics and laboratory findings were compared between the two groups. RESULTS: There were 12 patients in the white thrombus group and 11 patients in the red thrombus group. Active cancer was significantly more in the white thrombus group than in the red thrombus group (91.7% vs. 36.3%, p = 0.0094). Internal carotid artery occlusion was significantly less in the white thrombus group than in the red thrombus group (0% vs. 36.4%, p = 0.037). Among laboratory findings, D-dimer levels were an independent factor associated with white thrombi (odds ratio 8.97 [95% confidence interval 1.71-368.99], p < 0.0001). The cutoff value of D-dimer levels for predicting white thrombi was 3.5 µg/mL (83.3% sensitivity and 100% specificity). CONCLUSIONS: In acute ischemic stroke in cancer patients, active cancer, no internal carotid artery occlusion, and higher D-dimer levels (≥3.5 µg/mL) may be associated with occlusion with fibrin and platelet-rich white thrombi.
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Arteriopatias Oclusivas , Isquemia Encefálica , AVC Isquêmico , Neoplasias , Acidente Vascular Cerebral , Trombose , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/complicações , Estudos Retrospectivos , Trombectomia , Fibrina , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/complicações , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/patologiaRESUMO
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare pediatric brain tumor with abnormalities in SMARCB1 located in 22q11.2. We report a case of AT/RT associated with Phelan-McDermid syndrome (PMS) characterized by congenital developmental disorder, mental retardation, and ring chromosome 22 with 22q13.3-qter depletion, for which we performed whole-genome sequencing (WGS). A 4-year-old girl with a developmental disability was referred to our hospital due to dysphoria. Brain magnetic resonance imaging showed a 5-cm well-demarcated mass that extended bilaterally in the frontal lobes. G-banding was performed preoperatively due to a history of developmental retardation. Ring chromosome 22 and deletion of 22q13.3-qter were observed, and she was diagnosed with PMS. She underwent gross total resection of the tumor, and the pathological diagnosis was AT/RT. WGS showed somatic SMARCB1 mutation (p.R201X) and somatic loss of the entire chromosome 22 in the tumor, but not in the blood sample. WGS confirmed previously unreported BRCA2 mutations, 6q loss, and 14q acquisition during tumor progression, but no other significant findings associated with tumor progression. The present case is discussed with reference to a systematic review of previous reports of AT/RT associated with PMS. PMS patients with ring chromosome 22 should be carefully followed up for AT/RT occurrence.
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Transtornos Cromossômicos , Tumor Rabdoide , Cromossomos em Anel , Criança , Pré-Escolar , Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Cromossomos Humanos Par 22/genética , Feminino , Humanos , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/genéticaRESUMO
We present a 69-year-old woman with colorectal cancer and a left frontal lobe tumor that was diagnosed as a cerebral amyloidoma after surgical resection. Further postoperative systemic evaluation revealed another amyloidoma in her hip as well as Sjögren's syndrome. Systemic amyloidosis was not present. To the best of our knowledge, this is the first case of cerebral amyloidoma presenting as one of the multiple localized amyloidomas accompanied by Sjögren's syndrome. We also present a systematic review of 65 cerebral amyloidoma cases reported in the literature over the past 40 years and discuss patient characteristics and pathological and imaging findings associated with prognosis.
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BACKGROUND: Tumors in the pineal region consist of various histological types, and correct diagnosis from biopsy specimens is sometimes difficult. The authors report the case of a patient with a mixed germ cell tumor infiltrating into the pineal gland despite showing no elevation of tumor markers. OBSERVATIONS: An 18-year-old man complained of headache and nausea and showed disturbance of consciousness. Magnetic resonance imaging showed hydrocephalus associated with a cystic pineal tumor. The patient underwent tumor biopsy followed by endoscopic third ventriculostomy for hydrocephalus in a local hospital. A pineocytoma was diagnosed, and the patient was referred to the authors' hospital for treatment. Concentrations of placental alkaline phosphatase, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin in cerebrospinal fluid were not elevated. However, the authors' review of the tumor specimen revealed some immature cells infiltrating the pineal gland. These cells were positive for AFP, Sal-like protein 4, and octamer-binding transcription factor 3/4; and the diagnosis was changed to mixed germ cell tumor. Chemoradiotherapy was initiated, followed by surgical removal of the residual tumor. LESSONS: Careful examination of all tumor specimens and immunohistochemical analyses are important for accurate diagnosis of pineal tumors.
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We developed a method for efficiently activating functional peptides with a large structural contribution using the peptide-searching method with machine learning. The physicochemical properties of the amino acids were employed as variables. As a model peptide, we used GHWYYRCW, which is a functional peptide that inhibits α-amylase derived from human pancreatic juice. First, training data were acquired. A total of 153 peptides were prepared in which 1 amino acid in GHWYYRCW was replaced to construct a 1-amino acid substitution coverage peptide library. The inhibitory activity of each peptide against α-amylase and α-glucosidase was evaluated. Second, random forest (RF) regression analysis was performed using 120 variables, and the enzyme inhibitory activity of the peptide was related to the physicochemical properties. The constructed model had many features describing the charge of the amino acid (isoelectric point and pK2). Then, high inhibitory (HI) peptides were predicted using a library of peptides with 2- or 3-amino acid substitution as test data, which were called HI2 and HI3 peptides. As results, the first or seventh amino acid of the HI2 peptide was replaced with Arg, Trp, or Tyr. We found that all 30 HI2 peptides had significantly higher activity than the original sequence (100%) and 26 of the 30 HI3 peptides were significantly active (86.7%). However, the actual inhibitory activity of the HI3 peptides was improved to a lesser extent. The docking simulation clarified that the CDOCKER energy decrease was roughly correlated with the inhibitory activity. The machine learning-based predictive model was a promising tool for design of substituted peptides with high activity values, and it was assumed that the advanced model that forecasts the interaction index such as the CDOCKER energy substituting for the inhibitory activity would be used to design HI peptides, even in the case of the HI3 peptides.