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The purpose of this study was to investigate the anti-inflammatory effect of tegoprazan (TEGO) in lipopolysaccharide (LPS)-stimulated bone-marrow-derived macrophages (BMMs). To this end, compared to methylprednisolone (MP; positive control), we evaluated whether TEGO effectively differentiates LPS-stimulated BMMs into M2-phenotype macrophages. Moreover, the expression of pro- and anti-inflammatory cytokines genes influenced by TEGO was measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. TEGO was found to reduce nitric oxide (NO) production in BMMs significantly. In addition, TEGO significantly decreased and increased the gene expression levels of pro-inflammatory and anti-inflammatory cytokines, respectively. In addition, we evaluated the phosphorylated values of the extracellular signal-regulatory kinase (ERK) and p38 in the mitogen-activated protein (MAP) kinase signaling pathway through Western blotting. TEGO significantly reduced the phosphorylated values of the ERK and p38. In other words, TEGO suppressed the various pro-inflammatory responses in LPS-induced BMMs. These results show that TEGO has the potential to be used as an anti-inflammatory agent.
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Medula Óssea , Lipopolissacarídeos , Humanos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Medula Óssea/metabolismo , Macrófagos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Citocinas/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Inflamação/metabolismoRESUMO
PURPOSE: Cerebrospinal fluid (CSF) leakage is one of the major complications after endoscopic endonasal surgery. The reconstructive nasoseptal flap is widely used to repair CSF leakage. However, it could not be utilized in all cases; thus, there was a need for an alternative. We developed a pericranial rescue flap that could cover both sellar and anterior skull base defects via the endonasal approach. A modified surgical technique that did not violate the frontal sinus and cause cosmetic problems was designed using the pericranial rescue flap. METHODS: We performed 12 cadaveric dissections to investigate the applicability of the lateral pericranial rescue flap. An incision was made, extending from the middle to the lateral part of the eyebrow. The pericranium layer was dissected away from the galea layer, from the supraorbital region towards the frontoparietal region. With endoscopic assistance, the periosteal flap was raised, the flap base was the pericranium layer at the eyebrow incision. After a burr-hole was made in the supraorbital bone, the pericranial flap was inserted via the intradural or extradural pathway. RESULTS: The mean size of the pericranial flap was 11.5 cm × 3.2 cm. It was large enough to cross the midline and cover the dural defects of the anterior skull base, including the sellar region. CONCLUSION: We demonstrated a modified endoscopic technique to repair the anterior skull base defects. This minimally invasive pericranial flap may resolve neurosurgical complications, such as CSF leakage.
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Procedimentos de Cirurgia Plástica , Ferida Cirúrgica , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Sobrancelhas , Humanos , Procedimentos de Cirurgia Plástica/métodos , Base do Crânio/cirurgia , Retalhos Cirúrgicos/cirurgia , Ferida Cirúrgica/cirurgiaRESUMO
In this study, we created a hydrogel composed of glycol chitosan (gC) and oxidized hyaluronate (oHA). Gold nanoparticles (GNPs) were conjugated with ursodeoxycholic acid (UDCA). The GNP-UDCA complex was embedded into gC-oHA (CHA) hydrogels to form a CHA-GNP-UDCA gel. This CHA-GNP-UDCA gel was injected once into an epicenter of an injured region in SCI rats. Near-infrared (NIR) irradiation was then applied to the lesion as a means of local therapy. To optimize the viscosity for injection into a lesion, several volume ratios of gC and oHA were investigated using scanning electron microscopy and a rotating rheometer. The optimally synthesized CHA-GNP-UDCA gel under NIR irradiation suppressed the production of inflammatory cytokines in vitro. In addition, the optimized CHA-GNP-UDCA gel under NIR irradiation inhibited the cystic cavity of the lesion and significantly improved the hindlimb function. The production of inflammatory cytokines following SCI was significantly inhibited in the CHA-GNP-UDCA gel + NIR group. CHA-GNP-UDCA gels with NIR irradiation can therefore have therapeutic effects for those with spinal cord injuries.
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Nanopartículas Metálicas , Traumatismos da Medula Espinal , Animais , Ouro , Hidrogéis/uso terapêutico , Injeções , Ratos , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológicoRESUMO
BACKGROUND: Increased use of the transorbital approach (TOA) warrants greater understanding of the risk of increased intraocular pressure (IOP) and intraorbital pressure (IORP) due to orbital compression. We aimed to investigate the changes in IOP and IORP in response to orbital retraction in TOA and establish a method for the continuous measurement of intraoperative IORP. METHODS: We assessed nine patients who underwent TOA surgery from January 2017 to December 2019, in addition to five cadavers. IORP and IOP were measured using a cannula needle monitor, tonometer, cuff manometer, and micro strain gauge monitor. RESULTS: In all nine clinical cases and five cadavers, increased physical compression of the orbit increased the IOP and IORP in a curvilinear pattern. In clinical cases, when the orbit was compressed 1.5 cm from the lateral margin in the sagittal plane, the mean IOP and IORP were 25.4 ± 5.2 mmHg and 14 ± 9.2 mmH2O, respectively. The IORP satisfactorily reflected the IOP (Pearson correlation coefficient = 0.824, p < 0.001). CONCLUSION: We measured IOP and IORP simultaneously during orbital compression to gain basic information on pressure changes. In clinical cases, the change in the IOP could be conveniently and noninvasively monitored using continuous IORP measurements.
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Glaucoma , Pressão Intraocular , Endoscopia , Humanos , Órbita/diagnóstico por imagem , Órbita/cirurgia , Tonometria OcularRESUMO
AIM: This study aimed to investigate the survival and prognostic factors for anaplastic glioma, and whether the updated 2016 WHO classification had superior ability to predict survival. MATERIALS AND METHODS: Between January 2001 and December 2013, 113 consecutive patients were diagnosed with anaplastic glioma based on the 2007 WHO classification. We re-classified their diagnoses in accordance with the 2016 WHO classification. The Kaplan-Meier method, multivariate Cox proportional regression analysis, and a time-dependent receiver operating characteristic curve were used for the analysis. RESULTS: The median overall survival was 48.4 months among all patients, and 21.5 months for the anaplastic astrocytoma, IDH wild-type (AAw) group. The median progression-free survival was 31.8 months among all patients and 16.4 in the AAw group. Age, MGMT promoter methylation status, deep tumor location, and resection extent were associated with overall survival and progression-free survival. CONCLUSION: We found that the 2016 WHO classification of central nervous system tumors had superior ability to predict survival in cases of anaplastic glioma, as compared to the 2007 WHO classification.
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Neoplasias Encefálicas/classificação , Neoplasias Encefálicas/mortalidade , Glioma/classificação , Glioma/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Feminino , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Organização Mundial da Saúde , Adulto JovemRESUMO
BACKGROUND: We devised a biportal endoscopic transorbital approach (BiETOA) to gain surgical freedom by making a port for the endoscope and investigated the benefits and limitations of BiETOA. METHODS: A cylindrical port was designed and 3-D printed using biocompatible material. The port was inserted through a keyhole between the superolateral side of the orbital rim and the temporal muscle. An endoscope was inserted through the port, and other instruments were inserted through the conventional transorbital route. BiETOA was used to dissect eight cadaveric heads, and the angle of attack and surgical freedom were assessed. RESULTS: The mean maximal angle of attack was significantly different in BiETOA and endoscopic transorbital approach (ETOA) (P < 0.01) but not in BiETOA and ETOA lateral orbital rim (LOR) osteotomy (P = 0.207, P = 0.21). The mean surgical freedom was significantly different in BiETOA and ETOA (P < 0.01) and in BiETOA and ETOA LOR osteotomy (P < 0.01). In the clinical cases, tumors were removed successfully without any complications. CONCLUSIONS: BiETOA provided increased surgical freedom and better visibility of deep target lesion and resulted in good surgical and cosmetic outcomes.
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Cirurgia Endoscópica por Orifício Natural/métodos , Órbita/cirurgia , Cadáver , Endoscópios , Humanos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/instrumentação , Órbita/anatomia & histologia , Complicações Pós-Operatórias/prevenção & controle , Impressão TridimensionalRESUMO
PURPOSE: To determine whether radiological phenotype can improve the predictive performance of the risk model based on molecular subtype and clinical risk factors in anaplastic glioma patients. METHODS: This retrospective study was approved by our institutional review board with waiver of informed consent. MR images of 86 patients with pathologically diagnosed anaplastic glioma (WHO grade III) between January 2007 and February 2016 were analyzed according to the Visually Accessible Rembrandt Images (VASARI) features set. Significant imaging findings were selected to generate a radiological risk score (RRS) for overall survival (OS) and progression-free survival (PFS) using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The prognostic value of RRS was evaluated with multivariate Cox regression including molecular subtype and clinical risk factors. The C-indices of multivariate models with and without RRS were compared by bootstrapping. RESULTS: Eight VASARI features contributed to RRS for OS and six contributed to PFS. Multifocality or multicentricity was the most influential feature, followed by restricted diffusion. RRS was significantly associated with OS and PFS (P < .001), as well as age and molecular subtype. The multivariate model with RRS demonstrated a significantly higher predictive performance than the model without (C-index difference: 0.074, 95% confidence interval [CI]: 0.031, 0.148 for OS; C-index difference: 0.054, 95% CI: 0.014, 0.123 for PFS). CONCLUSION: RRS derived from VASARI features was an independent predictor of survival in patients with anaplastic gliomas. The addition of RRS significantly improved the predictive performance of the molecular feature based model.
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Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Isocitrato Desidrogenase/genética , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Feminino , Glioma/diagnóstico por imagem , Glioma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Prognóstico , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
The authors regret to state that an incorrect image was uploaded in Fig. 2. Please see a newly updated Fig. 2. All statements including Figure Legends are correct.
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BACKGROUND: The purpose of this nationwide age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in ankylosing spondylitis (AS). METHODS: The data in this study, spanning from January 1, 2010 to December 31, 2014, was obtained from a database maintained by the Korean National Health Insurance Service. A total of 12,988 patients with a diagnosis of AS were enrolled. The control group consisted of 64,940 age-sex-stratified matching subjects without AS. The 6year ischemic stroke incidence rate for each group was calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke. RESULTS: During the follow-up period, 73 patients (0.56%) in the AS group and 250 patients (0.38%) in the control group developed ischemic stroke (p = 0.0041). The hazard ratio of ischemic stroke in the AS group was 1.46 (95% confidence interval [95% CI], 1.13-1.90) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the AS group was 1.35 (95% CI, 1.04-1.75) after controlling for demographics and comorbid medical disorders. According to subgroup analysis, in female and diabetes and non-hypertension and dyslipidemia subgroups, ischemic stroke incidence rates were significantly higher in AS patients than those in control group. CONCLUSION: Our nationwide longitudinal study suggests an increased risk of ischemic stroke in AS patients.
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Isquemia Encefálica/epidemiologia , Espondilite Anquilosante/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
Objectives: The aim of this nationwide longitudinal cohort study is to determine the risk of congestive heart failure (CHF) associated with a seropositive rheumatoid arthritis (RA) population in Korea. Methods: In this study, National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data from 2002 to 2003 were used. The cohort was followed up with for 12 years until December of 2015. Seropositive RA was defined as a patient prescribed with a disease-modifying anti-rheumatic drug (DMARD) among patients with the International Classification of Diseases code M05 (seropositive RA). Patients who were diagnosed before 2004 were excluded. The seropositive RA group consisted of 2765 patients, and a total of 13,825 patients were in the control group. The Kaplan-Meier method was used to calculate the 12-year CHF incidence rate for each group. A Cox proportional hazards regression analysis was used to estimate the hazard ratio of CHF. Results: The hazard ratio of CHF in the seropositive RA group was 2.41 (95% confidence interval (CI): 1.40-4.14) after adjusting for age and sex. The adjusted hazard ratio of CHF in the seropositive RA group was 2.50 (95% CI: 1.45-4.30) after adjusting for age, sex, income, and comorbidities. In females aged ≥65 and aged <65, the incidence rates in the non-hypertension, non-diabetes mellitus, and non-dyslipidemia subgroups were significantly higher in the seropositive RA group than in the control group. Conclusions: This nationwide longitudinal cohort study shows an increased risk of CHF in patients with seropositive RA.
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Ependymoma is a rare adult tumor that originates from ependymal cells of the central nervous system, primarily occurring in the cerebral ventricles or the central canal of the spinal cord. In this paper, we report a case of extensive leptomeningeal seeding of ependymoma of a 39-year-old male patient, in whom the tumor was found incidentally after head trauma. The MRI exhibited diffuse leptomeningeal infiltrative lesions along with bilateral multiple cerebral sulci, basal cisterns, cerebellopontine angle, cerebellar folia. It also showed multinodular enhancing T1 low T2 high signal intensity lesions along the whole spinal cord. After the tumor biopsy at right temporal lesion, pathologic diagnosis was classic ependymoma (WHO grade 2). The patient has undergone radiation therapy and chemotherapy, and is currently maintaining a stable condition two years after surgery. This report suggests that when considering the differential diagnosis of extensive lesions both in the intracranial and intraspinal space, ependymoma should also be considered.
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OBJECTIVE: The purpose of this nationwide age- and sex- matched longitudinal study was to determine the pyogenic spondylitis (PS) increases the incidence of ischemic stroke (IS) in Korea. METHODS: From the National Health Insurance Service (NHIS), we collected the patient data for the period from January 1, 2004 to December 31, 2015. PS was classified according to the International Classification of Disease codes M46.2-M46.8, M49.2, and M49.3. By using a 1:5 age- and sex- stratified matching, a total of 628 patients and 3140 control subjects were included in the study. The IS incidence rates in PS and control group was calculated by using the Kaplan-Meier method. The outcome of hazard ratio of IS was estimated by Cox proportional hazards regression analyses. This study did not exclude PS as a result of postoperative complications. RESULTS: According to the study, 51 patients (8.12%) in the PS group and 201 patients (6.4%) in the control group experienced IS. The adjusted hazard ratio of IS in the PS group was 3.419 (95% CI: 2.473-4.729) after adjusting individual medical condition and demographics. Following the results of subgroup analysis, the risk ratio of IS was greater in most of the subgroup categories (male, female, age <65, age >65, non-diabetic, hypertensive, non-hypertensive, dyslipidemic and non-dyslipidemic subgroup). However, the risk of IS did not differ significantly in diabetic subgroup (95% CI: 0.953-4.360). CONCLUSIONS: The risk rate of IS increased in patient with pyogenic spondylitis.
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The purpose of this nationwide longitudinal follow-up study is to investigate the relationship between Parkinson's disease (PD) and congestive heart failure (CHF) patients in Korea. Patient data were collected using the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. The International Classification of Diseases 10-CM code G-20 distinguished 6475 PD patients who were enrolled in the PD group. After removing 1039 patients who were not hospitalized or attended an outpatient clinic less than twice, the total number of participants was reduced to 5436 individuals. Then, 177 patients diagnosed before 1 January 2004 were removed for relevancy, leaving us with 5259 PD patients. After case-control matching was completed using 1:5 age- and gender-coordinated matching, 26,295 people were chosen as part of the control group. The Cox proportional hazards regression analysis and the Kaplan-Meier technique were used to assess the risk of CHF in patients with Parkinson's disease. After controlling for age and gender, the hazard ratio of CHF in the PD group was 5.607 (95% confidence interval (CI), 4.496-6.993). After that, the hazard ratio of CHF in the PD group was modified against for comorbid medical disorders, resulting in a value of 5.696 (95% CI, 4.566-7.107). In subgroup analysis, CHF incidence rates were significantly increased in the PD group compared to the control group (males and females; aged ≥ 65 and <65; the non-diabetes and diabetes, hypertension and non-hypertension, and dyslipidemia and non-dyslipidemia subgroups). This nationwide longitudinal study shows a higher incidence rate of CHF in PD patients.
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BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. METHODS: The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. RESULTS: All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient's prognosis unless immediate intervention is given within 24-48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4-6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. CONCLUSION: It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.
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BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. METHODS: The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. RESULTS: The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. CONCLUSION: It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.
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OBJECTIVE: The goal of the following statewide age and gender-coordinated cohort study in Korea is to find out if there is a link between acute myocardial infarction (AMI) and Parkinson's disease (PD). METHODS: Utilizing the National Health Insurance Sharing Service cohort, patient data were collected. Six thousand four hundred seventy-five individuals with PD were distinguished by utilizing the International Classification of Diseases 10 code G20 and have enrolled in the PD group. The number of participants decreased to 5259 after excluding 1039 patients who were hospitalized less than one time or who visited an outpatient clinic less than twice. Then, 26295 individuals were selected as part of the control group after case control matching was conducted through 1 : 5 age- and gender-coordinated matching. The Cox proportional hazard regression analysis and Kaplan-Meier method were utilized to analyze the likelihood of AMI in PD. RESULTS: After controlling for age and gender, the hazard ratio of AMI in the PD group was 3.603 (95% confidence interval [CI], 2.837-4.577). After that, the following hazard ratio of AMI in the PD group was modified against for co-morbid medical disorders, resulting in 3.551 (95% CI, 2.795-4.511). According to a subgroup analysis, in males and females aged <65 and aged ≥65 and in the non-diabetes and diabetes, hypertension and non-hypertension, dyslipidemia and non-dyslipidemia subgroups, the AMI incidence rates were dramatically higher in the PD group compared to that of the control. CONCLUSION: Individuals with PD have a greater chance of AMI, according to this cross-national study.
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Multiple primary tumors at adjacent site are rare. We report a rare case of coincidentally found nasopharyngeal cancer and ventral foramen magnum meningioma. The 68-year-old male patient presented with a year history of ataxia. Radiological examination revealed lesions in the nasopharyngeal space and ventral foramen magnum. A needle aspiration biopsy for nasopharyngeal space and surgical removal for foramen magnum lesion were performed. The pathological diagnoses were nasopharyngeal cancer and meningioma, respectively. The concomitant occurrence of these two tumors is very rare and there is no known association between these two tumors. We report a case of ventral foramen magnum meningioma simultaneously present with nasopharyngeal carcinoma.
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Objective: Cavernous sinus (CS) invasion is frequently encountered in the management of skull base tumors. Surgical treatment of tumors in the CS is technically demanding, and selection of an optimal surgical approach is critical for maximal tumor removal and patient safety. We aimed to evaluate the feasibility of an endoscopic transorbital approach (ETOA) to the CS based on a cadaveric study. Methods: Five cadaveric heads were used for dissection under the ETOA in the comparison with the endoscopic endonasal approach (EEA) and the microscopic transcranial approach (TCA). The CS was exposed, accessed, and explored, first using the ETOA, followed by the EEA and TCA. A dedicated endoscopic system aided by neuronavigation guidance was used for the procedures. During the ETOA, neurovascular structures inside the CS were approached through different surgical triangles. Results: After completing the ETOA with interdural dissection, the lateral wall of the CS was fully exposed. The lateral and posterior compartments of the CS, of which accessibility is greatly limited under the EEA, were effectively approached and explored under the ETOA. The anteromedial triangle was the largest window via which most of the lateral compartment was freely approached. The internal carotid artery and abducens nerve were also observed through the anteromedial triangle and just behind V1. During the ETOA, the approaching view through the supratrochlear and infratrochlear triangles was more directed towards the posterior compartment. After validation of the feasibility and safety based on the cadaveric study, ETOA was successfully performed in a patient with a pituitary adenoma with extensive CS invasion. Conclusions: Based on the cadaveric study, we demonstrated that the lateral CS wall was reliably accessed under the ETOA. The lateral and posterior compartments of the CS were effectively explored via surgical triangles under the ETOA. ETOA provides a unique and valuable surgical route to the CS with a promising synergy when used with EEA and TCA. Our experience with a clinical case convinces us of the efficacy of the ETOA during surgical management of skull base tumors with CS-invasion.
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In this study, we aimed to investigate the recovery after traumatic spinal cord injury (SCI) by inducing cellular differentiation of transplanted neural stem cells (NSCs) into neurons. We dissociated NSCs from the spinal cords of Fisher 344 rat embryos. An injectable gel crosslinked with glycol chitosan and oxidized hyaluronate was used as a vehicle for NSC transplantation. The gel graft containing the NSC and positively charged gold nanoparticles (pGNP) was implanted into spinal cord lesions in Sprague-Dawley rats (NSC-pGNP gel group). Cellular differentiation of grafted NSCs into neurons (stained with ß-tubulin III [also called Tuj1]) was significantly increased in the NSC-pGNP gel group (***p < 0.001) compared to those of two control groups (NSC and NSC gel groups) in the SCI conditions. The NSC-pGNP gel group showed the lowest differentiation into astrocytes (stained with glial fibrillary acidic protein). Regeneration of damaged axons (stained with biotinylated dextran amines) within the lesion was two-fold higher in the NSC-pGNP gel group than that in the NSC gel group. The highest locomotor scores were also found in the NSC-pGNP gel group. These outcomes suggest that neuron-inducing pGNP gel graft embedding embryonic spinal cord-derived NSCs can be a useful type of stem cell therapy after SCI.
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Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.