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1.
Neurosurg Rev ; 47(1): 549, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39237692

RESUMO

This study aims to discuss the identification of the C1 nerve root as an effective surgical approach to successfully locate the shunting point of craniocervical junction spinal dural arteriovenous fistula (CCJ-SDAVF) intraoperatively. This study included all patients with CCJ-SDAVF who underwent surgical treatment using the far-lateral transcondylar approach at a single institution from January 2017 to June 2023. Data on patient demographics, clinical and angiographic characteristics of CCJ-SDAVF, surgical details, and treatment outcomes were collected. Follow-up assessments were conducted for all patients until December 31, 2023. The study included a total of 7 patients, comprising 5 men(71.4%) and 2 women (28.6%), with an average age of 57.6 years. Among them, 4 patients (57.1%) developed diffuse subarachnoid hemorrhage(SAH), while 2 patients (28.6%) experienced progressive cervical myelopathy. The shunting points of all CCJ-SDAVFs, which exhibited engorged veins, were identified next to the C1 root. Complete obliteration of CCJ-SDAVFs was successfully achieved in all patients, as confirmed by postoperative angiography one month later. No recurrent CCJ-SDAVFs were observed two years after the operation. Among the patients, 5 (71.4%) experienced good functional recovery, as indicated by an mRS score ranging from 0 to 1, while the remaining 2 patients (28.6%) showed incomplete functional recovery. The surgical interruption of CCJ-SDAVFs is the preferred treatment option, given its high obliteration rate and favorable functional recovery outcomes. We advocate the identification of C1 spinal nerve root as a crucial surgical step to identify the shunting points of CCJ- SDAVFs.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Raízes Nervosas Espinhais , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Raízes Nervosas Espinhais/cirurgia , Idoso , Estudos Retrospectivos , Adulto , Resultado do Tratamento , Procedimentos Neurocirúrgicos/métodos , Vértebras Cervicais/cirurgia , Hemorragia Subaracnóidea/cirurgia , Doenças da Medula Espinal/cirurgia
2.
J Neurol Sci ; 466: 123216, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39255590

RESUMO

BACKGROUND: Blunt cerebrovascular injury (BCVI) accounts for 1-3 % of patients with blunt trauma, which should be promptly diagnosed and managed due to risk of cerebral infarction and death. Antithrombotic therapy had been proven to reduce risk of stroke and mortality. However, due to concern of hematoma progression, treatment suggestion is still inconclusive for patients with concurrent traumatic intracranial hemorrhage. MATERIALS AND METHODS: We performed a retrospective, observational study from 2002 to 2020 at a Level I trauma center, all patients with BCVI and concurrent traumatic intracranial hemorrhage were recruited. Patients' demographics, initial CT findings, severity of BCVI, treatment and outcomes were documented and analyzed to define possible risk factors of death and stroke. RESULTS: Among all 57 patients, 49 (86.0 %) patients had injury at ICA, 6 (10.5 %) had VA injury, and 2 (3.5 %) suffered from both. Targeted treatments for BCVI were provided to 33 (57.9 %) patient, mostly endovascular intervention (78.8 %), antithrombotic treatment was given to 11 (19.3 %) patients. At 3-month follow-up, 17 (29.8 %) patients expired, and 18 (31.6 %) patients had cerebral infarction due to BCVI. We identified more severe initial CT findings (p = 0.016), higher head Abbreviated Injury Scale (p = 0.049) and initial life-threatening events (p = 0.047) as risk factors of death, and traumatic basal cistern subarachnoid hemorrhage(SAH) (p = 0.040) as single risk factor of cerebral infarction. CONCLUSIONS: Around one-thirds of patients with concurrent BCVI and traumatic intracranial hemorrhage were death or suffered from cerebral infarction within 3 months, with severity of initial head injury and SAH at basal cistern as risk factors, respectively.

3.
Medicine (Baltimore) ; 103(38): e39764, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39312347

RESUMO

RATIONALE: Blunt traumatic arteriovenous fistula (AVF) of scalp, are uncommon and most of them can be secured by simple embolization or surgical ligation of the feeders. Our goal in writing this paper is to show patients with traumatic scalp AVFs how to prevent complications and the likelihood of recurrence. PATIENT CONCERNS: Complete treatment and reduce the recurrence rate of traumatic AVF on the scalp. DIAGNOSES: Traumatic scalp AVF. INTERVENTIONS: Transarterial embolization and surgical resection. OUTCOMES: Complete resection of the AVF and subsequent angiography showed resolution of the contralateral lesion. LESSONS: Combination of endovascular embolization with subsequent surgical removal may reduce intraoperative blood loss compared with surgery alone. In addition, a well-designed scalp flap can be performed based on the angiography findings after embolization.


Assuntos
Fístula Arteriovenosa , Embolização Terapêutica , Couro Cabeludo , Humanos , Couro Cabeludo/lesões , Couro Cabeludo/irrigação sanguínea , Fístula Arteriovenosa/etiologia , Fístula Arteriovenosa/cirurgia , Embolização Terapêutica/métodos , Masculino , Adulto
4.
Medicine (Baltimore) ; 103(31): e38620, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093775

RESUMO

This study aimed to investigate the galectin-3 and associated cytokines levels in the cerebrospinal fluid (CSF) of severe traumatic brain injury (sTBI) patients. Temporal CSF expression of galectin-3 and associated cytokines levels in sTBI patients within 1-week post-injury were studied using the multiplex bead array. STBI patient group was stratified using the Modified Rankin Score (mRS) into 3 groups: mRS 6 (died), mRS 5 (severely disabled) and mRS 1-4 (mild-to-moderately disabled) group. Analysis for bead array data using Kruskal-Wallis test with post hoc Dunn's multiple comparisons test, and temporal changes and correlation analysis using Spearman's correlation were carried out. At day 1 post-injury, CSF galectin-3 and interleukin-6 (IL-6), interleukin-10 (IL-10), cysteine-cysteine motif chemokine ligand-2 (CCL-2), and cysteine-cysteine motif chemokine ligand-20 (CCL-20), but not interleukin-1ß (IL-1ß) and tumor necrosis factor (TNF-α) levels were significantly elevated in mRS 5 group compared to non-TBI controls. Temporal correlation analysis at 1-7 days showed decreased IL-10 level in the mRS 6 group, decreased IL-10 and CCL-2 levels in mRS 5 group, and decreased IL-6, CCL-2, and CCL-20 levels in the mRS 1-4 group. Receiver operating characteristic curve analyses revealed a significant area under the curve for comparison between mRS 6 and mRS 5 groups for galectin-3 and IL-6. No significant differences in sex, age, Glasgow Coma Scale score, C-reactive protein levels and types of TBI-induced hemorrhages were observed between the groups. CSF galectin-3 and associated cytokines, especially IL-6, CCL-2 and CCL-20 levels were different within sub-groups of sTBI patients, suggesting their potential use in sTBI prognostics.


Assuntos
Lesões Encefálicas Traumáticas , Citocinas , Galectina 3 , Humanos , Lesões Encefálicas Traumáticas/líquido cefalorraquidiano , Masculino , Feminino , Pessoa de Meia-Idade , Citocinas/líquido cefalorraquidiano , Adulto , Galectina 3/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Galectinas/líquido cefalorraquidiano , Idoso , Adulto Jovem , Proteínas Sanguíneas
5.
J Immunother Cancer ; 12(8)2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142719

RESUMO

BACKGROUND: Oxylipin metabolism plays an essential role in glioma progression and immune modulation in the tumor microenvironment. Lipid metabolic reprogramming has been linked to macrophage remodeling, while the understanding of oxylipins and their catalyzed enzymes lipoxygenases in the regulation of glioma-associated microglia/macrophages (GAMs) remains largely unexplored. METHODS: To explore the pathophysiological relevance of oxylipin in human glioma, we performed Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) analysis in human glioma and non-tumor brain tissues. To comprehensively investigate the role of arachidonate lipoxygenase 5 (ALOX5) in glioma, we performed in vivo bioluminescent imaging, immunofluorescence staining and flow cytometry analysis on tumors from orthotopic glioma-bearing mice. We developed an ALOX5-targeted nanobody, and tested its anti-glioma efficacy of combination therapy with α-programmed cell death protein-1 (PD-1). RESULTS: In this study, we found that ALOX5 and its oxylipin 5-hydroxyeicosatetraenoic acid (5-HETE) are upregulated in glioma, accumulating programmed death-ligand 1 (PD-L1)+ M2-GAMs and orchestrating an immunosuppressive tumor microenvironment. Mechanistically, 5-HETE derived from ALOX5-overexpressing glioma cells, promotes GAMs migration, PD-L1 expression, and M2 polarization by facilitating nuclear translocation of nuclear factor erythroid 2-related factor 2. Additionally, a nanobody targeting ALOX5 is developed that markedly suppresses 5-HETE efflux from glioma cells, attenuates M2 polarization of GAMs, and consequently ameliorates glioma progression. Furthermore, the combination therapy of the ALOX5-targeted nanobody plus α-PD-1 exhibits superior anti-glioma efficacy. CONCLUSIONS: Our findings reveal a pivotal role of the ALOX5/5-HETE axis in regulating GAMs and highlight the ALOX5-targeted nanobody as a potential therapeutic agent, which could potentiate immune checkpoint therapy for glioma.


Assuntos
Araquidonato 5-Lipoxigenase , Antígeno B7-H1 , Glioma , Ácidos Hidroxieicosatetraenoicos , Microglia , Glioma/metabolismo , Glioma/patologia , Glioma/imunologia , Humanos , Araquidonato 5-Lipoxigenase/metabolismo , Camundongos , Animais , Antígeno B7-H1/metabolismo , Microglia/metabolismo , Ácidos Hidroxieicosatetraenoicos/metabolismo , Progressão da Doença , Macrófagos/metabolismo , Macrófagos/imunologia , Microambiente Tumoral , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Masculino , Linhagem Celular Tumoral , Feminino
6.
World Neurosurg ; 192: 9-14, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39209253

RESUMO

BACKGROUND: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition that is known to recur and that leads to unfavorable clinical outcomes. Middle meningeal artery embolization (MMAE) has emerged as an alternative treatment to prevent recurrence. This study investigated the efficacy of combined 2 therapies in a hybrid operative suite for high-risk patients. METHODS: This retrospective review provides evidence for the indications and benefits of one-stage combined therapy in a hybrid neurovascular operative suite. The procedures include burr hole craniostomy, irrigation, and drainage followed by adjuvant MMAE at the lesion site. Subsequently, routine cone beam computed tomography is conducted after the whole process. RESULTS: Five patients with symptomatic CSDH and mass effect were enrolled in this study. Among them, 3 patients had undergone burr hole surgery previously but experienced hematoma recurrence. Two patients presented with a history of recent cardiac stent placement due to coronary artery disease, precluding the cessation of antiplatelet or anticoagulant therapy. All patients experienced symptom resolution and demonstrated no evidence of CSDH recurrence during the follow-up period. CONCLUSIONS: In our initial case experiences, one-stage burr hole surgery and adjuvant MMAE for treating chronic subdural hematoma in a hybrid operative angiography suite could be a feasible and effective treatment modality.

7.
Molecules ; 29(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731479

RESUMO

Manganese molybdate has garnered considerable interest in supercapacitor research owing to its outstanding electrochemical properties and nanostructural stability but still suffers from the common problems of transition metal oxides not being able to reach the theoretical specific capacitance and lower electrical conductivity. Doping phosphorus elements is an effective approach to further enhance the electrochemical characteristics of transition metal oxides. In this study, MnMoO4·H2O nanosheets were synthesized on nickel foam via a hydrothermal route, and the MnMoO4·H2O nanosheet structure was successfully doped with a phosphorus element using a gas-solid reaction method. Phosphorus element doping forms phosphorus-metal bonds and oxygen vacancies, thereby increasing the charge storage and conductivity of the electrode material. The specific capacitance value is as high as 2.112 F cm-2 (1760 F g-1) at 1 mA cm-2, which is 3.2 times higher than that of the MnMoO4·H2O electrode (0.657 F cm-2). The P-MnMoO4//AC ASC device provides a high energy density of 41.9 Wh kg-1 at 666.8 W kg-1, with an 84.5% capacity retention after 10,000 charge/discharge cycles. The outstanding performance suggests that P-MnMoO4 holds promise as an electrode material for supercapacitors.

8.
J Clin Neurosci ; 119: 93-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992420

RESUMO

Minimally invasive surgeries have shown potential to improve mortality and clinical outcomes of spontaneous intracerebral hemorrhage (ICH). The present study assessed the first-in-human outcomes of a novel, portable neuroendoscopic system for ICH evacuation at our single center. This neuroendoscopic system integrates real-time visualization into a handpiece which has controllable suction, irrigation, and coagulation to allow a neurosurgeon to conduct minimally invasive ICH evacuation independently with bimanual dexterity. Pre- and postoperative data of ten patients who had spontaneous basal ganglia hemorrhage (mean: 46.5 ± 12.2 mL) and underwent evacuation with the specified neuroendoscopic system were collected prospectively. The mean time to receive surgery was 12.1 ± 7.6 h. Mean operative time was 3.4 ± 0.9 h. The mean hematoma volume decreased to 6.0 ± 3.9 mL at postoperative 6 h, resulting in a mean volume reduction of 86.0 ± 11.2% (P = 0.005). The median length of intensive care unit stay was 3 days (IQR, 3-4 days). At discharge, the median Glasgow Coma Scale (GCS) score significantly improved to 11.5 (IQR, 11-15; P = 0.016), and the median modified Rankin Scale (mRS) score was 4 (IQR, 4-5). Six patients (60%) showed a favorable mRS score of ≤ 3 on their last return visit. Neither death nor rebleeding occurred during the follow-up periods. Integrated design of the innovative device is valuable to optimize minimally invasive endoscopic ICH evacuation procedure. Further studies are needed to clarify long-term benefits from such type of the innovative device to early intervention of ICH.


Assuntos
Hemorragia dos Gânglios da Base , Neuroendoscopia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Neuroendoscopia/métodos , Hemorragia dos Gânglios da Base/diagnóstico por imagem , Hemorragia dos Gânglios da Base/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Hematoma/cirurgia
10.
Acta Neurochir (Wien) ; 165(9): 2551-2560, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37553445

RESUMO

BACKGROUND: Programmable valve (PV) has been shown as a solution to the high revision rate in pediatric hydrocephalus patients, but it remains controversial among adults. This study is to compare the overall revision rate, revision cause, and revision-free survival between PV and non-programmable valve (NPV) in adult patients with different hydrocephalus etiologies. METHOD: We reviewed the chart of all patients with hydrocephalus receiving index ventricular cerebrospinal fluid (CSF) shunt operations conducted at a single institution from January 2017 to December 2017. Patients included in the study were followed up for at least 5 years. Statistical tests including independent t-test, chi-square test, and Fisher's exact test were used for comparative analysis, and Kaplan-Meier curve using log-rank test was performed to compare the revision-free survival between the PV and NPV groups. RESULTS: A total of 325 patients were included in the study, of which 181 patients were receiving PVs and 144 patients receiving NPV. There were 23 patients (12.8%) with PV and 22 patients (15.3%) with NPV receiving initial revision. No significant statistical difference in the initial revision rate was observed between the two groups (p = 0.52). No survival difference was found between the PV and NPV groups. However, better revision-free survival was noted in the PV group among idiopathic normal pressure hydrocephalus (iNPH) (p = 0.0274) and post-traumatic hydrocephalus (p = 0.017). CONCLUSIONS: The combination of the different etiologies of hydrocephalus and the features of PV and NPV results in different outcomes-revision rate and revision-free survival. PV use might be superior to NPV in iNPH and post-traumatic hydrocephalus patients. Further studies are needed to clarify the indications of PV use in adult hydrocephalus patients.


Assuntos
Hidrocefalia , Adulto , Humanos , Derivações do Líquido Cefalorraquidiano/métodos , Seguimentos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Próteses e Implantes , Estudos Retrospectivos , Derivação Ventriculoperitoneal/métodos
11.
Front Neurol ; 14: 1096970, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456647

RESUMO

Objective: Superior hypophyseal artery (SHA) aneurysms are intradural, and their rupture can result in subarachnoid hemorrhage. Considering the related surgical difficulty and anatomical restrictions, endovascular treatment (EVT) is considered the most favorable modality for SHA aneurysms; however, the long-term outcomes of EVT have rarely been reported. The study assessed the incidence of and risk factors for recurrence of SHA aneurysms after EVT as well as the correlation factors for SHA aneurysm rupture. Methods: We included 112 patients with SHA aneurysms treated with EVT at our facility between 2009 and 2020. Here, EVT included non-stent-assisted (simple or balloon-assisted) or stent-assisted coiling. Flow diverter was not included because it was barely used due to its high cost under our national insurance's limitation, and a high proportion of ruptured aneurysms in our series. Univariate and multivariate logistic regression was performed to evaluate the correlation factors for SHA aneurysm rupture, along with the incidence of and risk factors for post-EVT SHA aneurysm recurrence and re-treatment. Results: In our patients, the mean angiographic follow-up period was 3.12 years. The presence of type IA or IB cavernous internal carotid artery (cICA) was strongly correlated with SHA aneurysm rupture. Recurrence occurred in 17 (13.4%) patients, of which only 1 (1.4%) patient had received stent-assisted coiling. All cases of recurrence were observed within 2 years after EVT. The multivariate logistic regression results showed that ruptured aneurysm and non-stent-assisted coiling were independent risk factors for aneurysm recurrence. Of the 17 cases of aneurysm recurrence, 9 (52.9%) received re-treatment. Moreover, aneurysm rupture was the only factor significantly correlated with re-treatment in multivariate logistic regression. No re-recurrence was observed when a recurrent aneurysm was treated with stent-assisted coiling. Conclusion: Type I cICA was common factor for aneurysm rupture. Although flow-diverter treatment serves as another suitable technique that was not compared with, coils embolization was effective treatment modality for SHA aneurysms, leading to low recurrence and complication rates, especially with stent use. All cases of recurrence occurred within 2 years after EVT; they were strongly associated with prior aneurysm rupture. Further stent-assisted coiling was noticed to prevent re-recurrence.

12.
Front Surg ; 10: 1083833, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36874457

RESUMO

Background: This report presents the first case of intracranial cryptococcoma arising from the right frontal lobe causing right middle cerebral artery infarction. Intracranial cryptococcomas usually occur in the cerebral parenchyma, basal ganglia, cerebellum, pons, thalamus, and choroid plexus; they may mimic intracranial tumors, but seldom cause infarction. Of the 15 cases of pathology-confirmed intracranial cryptococcomas in the literature, no case has been complicated by middle cerebral artery (MCA) infarction. Here, we discuss a case of intracranial cryptococcoma with an ipsilateral middle cerebral artery infarction. Case Description: A 40-year-old man was referred to our emergency room due to progressive headaches and acute left hemiplegia. The patient was a construction worker with no history of avian contact, recent travel, or human immunodeficiency virus (HIV) infection. Brain computed tomography (CT) showed an intra-axial mass, and subsequent magnetic resonance imaging (MRI) delineated a large mass of 53 mm in the right middle frontal lobe and a small lesion of 18 mm in the right caudate head, with marginal enhancement and central necrosis. A neurosurgeon was consulted in view of the intracranial lesion, and the patient underwent en-bloc excision of the solid mass. The pathology report later identified a Cryptococcus infection rather than malignancy. The patient underwent 4 weeks of postoperative treatment with amphotericin B plus flucytosine; he then received subsequent oral antifungal treatment for 6 months, and had neurologic sequelae that manifested as left side hemiplegia. Conclusion: Diagnosis of fungal infections in the CNS remains challenging. This is especially true of Cryptococcus CNS infections that present as a space-occupying lesion in an immunocompetent patient. A Cryptococcus infection should be considered in the differential diagnoses in patients with brain mass lesions, as this infection can be misdiagnosed as a brain tumor.

13.
Clin Neurol Neurosurg ; 228: 107687, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36963286

RESUMO

OBJECTIVE: Continuous cardiac monitoring on patients with aneurysmal subarachnoid hemorrhage (aSAH) is difficult out of intensive care unit (ICU) in the subacute stage. Therefore, we verified the feasibility of a novel electrocardiography (ECG) patch device to record long-term heart rhythm. METHODS: The ECG patches were applied on aSAH patients during their stay in general ward. Any types of significant arrythmia were identified, and heart rate variability (HRV) measures were calculated in time and frequency domains. We analyzed the correlation between heart rhythm with Hunt and Hess scale and modified Fisher scale as well as the occurrence of secondary complications. RESULTS: Twenty-six patients used the devices on median day 6 after aSAH onset, with put on and take down time average as 137 s and 45 s, respectively. Mean record time was 221.7 h, and no adverse event presented within the period. Hunt and Hess II/III subgroup had higher percentage of HRV high frequency band than IV/V subgroup (9.1 % vs 3.5 %, p = 0.043), whereas ultra low frequency band presented more in the later subgroup (50.4 % vs 61.4 %, p = 0.035). The very low frequency percentage significantly decreased (p = 0.025) at an average of 3 days prior to the occurrence of secondary complications compared to the days without complications. CONCLUSION: For aSAH patients in general ward during subacute stage, the ECG patch is a safe and feasible tool. The correlation of long-term heart rhythm with prognosis is worthy to be investigated on larger sample size using this device in the future.


Assuntos
Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Estudos de Viabilidade , Prognóstico , Eletrocardiografia
14.
J Transl Med ; 21(1): 40, 2023 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681849

RESUMO

BACKGROUND: Current diagnosis tools for prostate cancer (PCa) such as serum PSA detection and prostate biopsy cannot distinguish dormant tumors from invasive malignancies, either be used as prognosis marker for castration resistant prostate cancer (CRPC), the lethal stage of PCa patients. Exosomes have been widely investigated as promising biomarkers for various diseases. We aim to characterize the proteomic and metabolomic profile of exosomes and to evaluate their potential value for the diagnosis of PCa, especially CRPC. We also investigate the functions of some specific exosome biomarkers in the progression of CRPC. METHODS: Integrated proteomics and metabolomics analysis were performed for plasma-derived exosomes collected from tumor-free controls (TFC), PCa and CRPC patients. Expression of specific exosomal proteins were further validated by targeted 4D-parallel reaction monitoring (PRM) mass spectrometry among the three cohorts. Tissue distribution and functional role of exosomal protein LRG1 was studied in clinical PCa tissue samples and cell line models. RESULTS: Three potential exosomal protein markers were identified. The apolipoprotein E level in PCa samples was 1.7-fold higher than that in TFC (receiver operating characteristic value, 0.74). Similarly, the levels of exosome-derived leucine-rich alpha2-glycoprotein 1 (LRG1) and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) in the CRPC group were 1.7 and 2.04 times, respectively, higher than those in the PCa group (ROC values, 0.84 and 0.85, respectively), indicating that LRG1 and ITIH3 could serve as predictive markers for CRPC. For metabolomic evaluation of exosomes, a series of differentially expressed metabolites were identified, and a combined metabolite panel showed ROC value of 0.94 for distinguishing PCa from TFC and 0.97 for distinguishing CRPC from PCa. Immunohistochemistry of tissue microarray showed that LRG1 protein was significantly upregulated in advanced prostate cancer and functional assay revealed that ectopic expression of LRG1 can significantly enhance the malignant phenotype of prostate cancer cells. More importantly, PCa cell derived LRG1-overexpressed exosomes remarkably promoted angiogenesis. CONCLUSION: Integration of proteomics and metabolomics data generated proteomic and metabolic signatures of plasma exosomes that may facilitate discrimination of CRPC from PCa and TFC patients, suggesting the potential of exosomal proteins and metabolites as CRPC markers. The study also confirmed the important role of exosomal protein LRG1 in PCa malignant progression.


Assuntos
Exossomos , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Proteômica , Próstata/metabolismo , Exossomos/metabolismo
15.
Mol Cancer ; 22(1): 3, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36617554

RESUMO

BACKGROUND: This study aimed to validate whether infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells is safe and whether CAR-T cells exert anti-glioblastoma (GBM) activity. METHODS: A total of eight patients with GD2-positive GBM were enrolled and infused with autologous GD2-specific 4SCAR-T cells, either through intravenous administration alone or intravenous combined with intracavitary administration. RESULTS: 4SCAR-T cells expanded for 1-3 weeks and persisted at a low frequency in peripheral blood. Of the eight evaluable patients, four showed a partial response for 3 to 24 months, three had progressive disease for 6 to 23 months, and one had stable disease for 4 months after infusion. For the entire cohort, the median overall survival was 10 months from the infusion. GD2 antigen loss and infiltrated T cells were observed in the tumor resected after infusion. CONCLUSION: Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events. In addition, GD2-specific 4SCAR-T cells partially mediate antigen loss and activate immune responses in the tumor microenvironment. Validation of our findings in a larger prospective trial is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03170141 . Registered 30 May 2017.


Assuntos
Glioblastoma , Receptores de Antígenos Quiméricos , Humanos , Glioblastoma/tratamento farmacológico , Imunoterapia Adotiva/efeitos adversos , Estudos Prospectivos , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos/genética , Linfócitos T , Microambiente Tumoral
16.
Turk Neurosurg ; 33(4): 548-555, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34542899

RESUMO

AIM: To identify the effect of patients with diabetes mellitus (DM) with traumatic brain injury (TBI) in Taiwan. MATERIAL AND METHODS: Data from the trauma registry in Chang Gung Memorial Hospital, Linkou, Taiwan were collected and reviewed. Several clinical characteristics and outcomes were extracted and analyzed. The trauma databank includes 3090 patient medical records, of which 475 patients were identified as having DM. Because several baseline characteristics of patients with TBI in the DM group differed from those in the non-DM group, we performed propensity score matching to eliminate confounding factors. RESULTS: After propensity score matching, 895 patients with TBI comprised the non-DM group, and no significant differences were noted in the baseline characteristics between groups. Patients in the DM group had more craniotomies, longer hospital stays, and longer ICU stays. We also segmented the DM group into two subgroups based on survival status. Compared with the survivor group, the nonsurvivor group had a significantly higher serum glucose level. Furthermore, patients with DM were divided into four subgroups according to their serum glucose level. The in-hospital mortality rate was higher in the subgroup with glucose levels greater than 200mg/dL than in the other subgroups. A receiver-operating-characteristic analysis revealed that the ability of serum glucose level to predict in-hospital mortality was modest, with an area under the curve of 0.641 and an associated optimal cutoff of 206 mg/dl. CONCLUSION: DM should be considered a risk factor for patients with TBI receiving neurosurgical intervention and a predictor of longer hospitalization and stay in an intensive care unit. Moreover, in patients with TBI with DM, higher admission serum glucose levels are associated with a higher in-hospital mortality rate.


Assuntos
Lesões Encefálicas Traumáticas , Diabetes Mellitus , Hiperglicemia , Humanos , Diabetes Mellitus/epidemiologia , Hiperglicemia/etiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/cirurgia , Fatores de Risco , Glucose , Estudos Retrospectivos
17.
Mol Cancer Res ; 21(3): 189-198, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36469009

RESUMO

Our previous study illustrated that nuclear factor IX (NFIX) promotes glioblastoma (GBM) progression by inducing migration and proliferation of GBM cells. However, the underlying mechanism of how NFIX regulates GBM cell proliferation remains obscure. In this study, we uncovered that Go-Ichi-Ni-San 1 (GINS1) is upregulated and positively correlated with NFIX in human GBM specimen. NFIX silencing downregulates the expression of GINS1, which is pivotal for cell-cycle progression and proliferation of GBM cells. Replenishment of GINS1 largely rescues the NFIX-null effect on GBM cell proliferation. Mechanistic investigation revealed that NFIX transcriptionally actives GINS1 expression by directly binding to promoter region (-1779 to -1793bp) of the GINS1 gene. Furthermore, knockdown of NFIX sensitizes GBM cells to DNA damage-inducing agents including doxorubicin and temozolomide, in a GINS1-dependent manner. IMPLICATIONS: Our study highlights that targeting NFIX-GINS1 axis could be a novel and potential therapeutic approach for GBM treatment.


Assuntos
Neoplasias Encefálicas , Proteínas de Ligação a DNA , Glioblastoma , Fatores de Transcrição NFI , Humanos , Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/metabolismo , Temozolomida/farmacologia , Ativação Transcricional , Fatores de Transcrição NFI/metabolismo
18.
Strahlenther Onkol ; 199(8): 718-726, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36326857

RESUMO

BACKGROUND: Initial tumor enlargement (or pseudoprogression) instead of true tumor progression is a common phenomenon in patients with acoustic neuromas who are treated with stereotactic radiosurgery (SRS). This phenomenon can affect clinical decision-making and patient management. This study assessed the correlation between initial tumor enlargement and magnetic resonance imaging characteristics in patients with acoustic neuromas who were treated with linear accelerator (LINAC)-based SRS. The long-term tumor control outcomes were also analyzed. MATERIALS AND METHODS: In total, 330 patients with sporadic acoustic neuromas who were treated with LINAC SRS between March 2006 and March 2020 were retrospectively evaluated to assess their initial tumor enlargement. The tumors were divided into homogeneously enhanced, heterogeneously enhanced, and cystic types based on the morphological characteristics noted on magnetic resonance images. Tumor control was assessed in 275 patients with a follow-up duration of more than 2 years. RESULTS: Initial enlargement was observed in 137 of 330 (41.5%) tumors as early as 3 months after LINAC SRS. Data analysis revealed that postoperative tumors with a residual volume lower than 2.5 cm3 had a lower incidence of initial enlargement (p = 0.039). No correlation was noted between the initial enlargement and morphological characteristics of tumors. In patients with a mean follow-up duration of 82.8 ± 37.2 months, heterogeneously enhanced tumors exhibited a lower control rate than homogeneously enhanced and cystic tumors (p = 0.045). No correlation was noted between initial enlargement and tumor control. CONCLUSION: Initial enlargement can occur as early as 3 months after SRS. Postoperative residual tumors with a volume lower than 2.5 cm3 exhibit a lower incidence of initial enlargement. Heterogeneously enhanced tumors have a lower local control rate.


Assuntos
Neuroma Acústico , Radiocirurgia , Humanos , Radiocirurgia/métodos , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Imageamento por Ressonância Magnética , Aceleradores de Partículas , Seguimentos , Resultado do Tratamento
19.
World Neurosurg ; 167: e685-e693, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36007771

RESUMO

OBJECTIVE: Laparoscopic ventriculoperitoneal shunt surgery has been reported to have several advantages in selected patients. However, the prognostic factors have been understudied specifically for this surgery. We sought to investigate the factors influencing the complications after the laparoscopic ventriculoperitoneal shunt placement. METHODS: All surgeries in this prospective study were performed by the same team of neurosurgeons and general surgeons. Clinical parameters as well as potential risk factors for postoperative complications were analyzed. The endpoint was overall complications requiring surgical revision within the follow-up period after surgery. RESULTS: Ninety-nine patients (51 male and 48 female) scheduled for laparoscopic-assisted ventriculoperitoneal shunt surgery between 2019 and 2021 were included. Overall shunt complication rate was 9% (9 of 99 cases), and there was 1 patient (1%) who had distal dysfunction among them. Body mass index ≥27 kg/m2 (hazard ratio 4.87; 95% confidence interval 1.05-22.57; P = 0.043), and nonprogrammable shunts (hazard ratio 7.91; 95% confidence interval 1.51-41.50; P = 0.014) were significantly associated with an increased risk of complications. Among 75 patients who received programmable shunts, the vertical distance from the distal tip to the presumed bottom of peritoneal cavity was significant positively associated with the number of pressure adjustments (R2 0.511, adjusted R2 0.504, and P < 0.001). CONCLUSIONS: Ventriculoperitoneal shunt surgery provided benefits with little complication rate, whereas patients treated with nonprogrammable shunts and obese patients had less favorable outcome. A positive correlation between the vertical distance from the distal tip to the bottom of peritoneal cavity and pressure adjustments inferred to the advantage of the laparoscopic method.


Assuntos
Hidrocefalia , Laparoscopia , Humanos , Masculino , Feminino , Derivação Ventriculoperitoneal/efeitos adversos , Derivação Ventriculoperitoneal/métodos , Prognóstico , Estudos Prospectivos , Índice de Massa Corporal , Resultado do Tratamento , Hidrocefalia/cirurgia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Estudos Retrospectivos
20.
Int J Infect Dis ; 122: 537-542, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35788418

RESUMO

OBJECTIVES: Interferon-γ release assays (IGRAs) are widely used in public health practice to diagnose latent tuberculosis. During the COVID-19 pandemic and rollout of COVID-19 vaccination, it has remained unclear whether COVID-19 vaccines interfere with IGRA readouts. METHODS: We prospectively recruited healthcare workers during their annual occupational health examinations in 2021. Baseline IGRA readouts were compared with follow-up data after the participants had received two doses of COVID-19 vaccination. RESULTS: A total of 134 baseline IGRA-negative cases (92 with ChAdOx1 vaccine, 27 with mRNA-1273 vaccine, and 15 with heterologous vaccination) and seven baseline IGRA-positive cases were analyzed. Among the baseline IGRA-negative cases, there were decreased interferon-γ concentrations over the Nil (P = 0.005) and increased Mitogen-Nil (P < 0.001) values after vaccination. For TB2-Nil value, a similar trend (P = 0.057) of increase was observed. Compared with the 0.35 IU/ml threshold, the baseline and follow-up readout differences were less than |± 0.10| IU/ml over the TB1-Nil and TB2-Nil values in >90% baseline IGRA-negative cases. No significant readout difference was observed among baseline IGRA-positive cases. CONCLUSION: COVID-19 vaccination did not change IGRA interpretation in most cases. Cases showing conversion/borderline IGRA readouts should be given special consideration.


Assuntos
COVID-19 , Tuberculose Latente , Vacina de mRNA-1273 contra 2019-nCoV , COVID-19/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Pandemias , Estudos Prospectivos , Teste Tuberculínico , Vacinação
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