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PURPOSE: Sarcopenia and frailty have been associated with increased mortality and duration of hospitalization in cancer. However, data investigating these effects in patients with brain metastases remain limited. This study aimed to investigate the effects of sarcopenia and frailty on clinical outcomes in patients with surgically treated brain metastases. METHODS: Patients who underwent surgical resection of brain metastases from 2011 to 2019 were included. Psoas cross-sectional area and temporalis thickness were measured by two independent radiologists (Cronbach's alpha > 0.98). Frailty was assessed using the Clinical Frailty Scale (CFS) pre-operatively and post-operatively. Overall mortality, recurrence, and duration of hospitalization were collected. Cox regression was performed for mortality and recurrence, and multiple linear regression for duration of hospitalization. RESULTS: 145 patients were included, with median age 60.0 years and 52.4% female. Psoas cross-sectional area was an independent risk factor for overall mortality (HR = 2.68, 95% CI 1.64-4.38, p < 0.001) and recurrence (HR = 2.31, 95% CI 1.14-4.65, p = 0.020), while post-operative CFS was an independent risk factor for overall mortality (HR = 1.88, 95% CI 1.14-3.09, p = 0.013). Post-operative CFS (ß = 15.69, 95% CI 7.67-23.72, p < 0.001) and increase in CFS (ß = 11.71, 95% CI 3.91-19.51, p = 0.004) were independently associated with increased duration of hospitalization. CONCLUSION: In patients with surgically treated brain metastases, psoas cross-sectional area was an independent risk factor for mortality and recurrence, while post-operative CFS was an independent risk factor for mortality. Post-operative frailty and increase in CFS significantly increased duration of hospitalization. Measurement of psoas cross-sectional area and CFS may aid in risk stratification of surgical candidates for brain metastases.
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Neoplasias Encefálicas , Fragilidade , Sarcopenia , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Fragilidade/complicações , Sarcopenia/complicações , Sarcopenia/patologia , Fatores de Risco , Hospitalização , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: Two-staged gamma knife surgery (GKS) is a method that may extend the upper tumor volume limit for using GKS in the management of brain metastases. However, the safety of treating very large posterior fossa lesions with this technique has not been well demonstrated. Therefore, we analyzed our experience in treating cerebellar metastases larger than 12 cm3 with two-staged GKS. METHODS: Four consecutive patients harboring 12 to 30 cm3 cerebellar metastases scheduled two-staged GKS were included in the study, and all but one patient completed the treatment. The treatment doses were 10-13 Gy. All patients were followed with regular MR imaging and clinical assessments, and the tumor volumes were measured on all treatment and follow-up images. RESULTS: Tumor progression was not demonstrated in any of the patients. Tumor volumes decreased by, on average, more than half between the two stages. The median survival was 22 months, and no patient died due to intracranial tumor progression. Peritumoral edema at the first GKS resolved in all patients, replaced by asymptomatic mild T2 changes in two of them not requiring any treatment. No radiation-induced complication has developed thus far. CONCLUSION: Staged GKS seems to be a feasible management option for very large cerebellar metastases.
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Neoplasias Encefálicas , Radiocirurgia , Humanos , Estudos Retrospectivos , Radiocirurgia/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Resultado do Tratamento , SeguimentosRESUMO
BACKGROUND: Surgical resection is the main treatment for symptomatic nonfunctioning pituitary adenomas (NFPA). We aimed to analyze the impact of surgical approach, completeness of resection, and postoperative radiotherapy on long-term progression-free survival (PFS) of NFPA, using individual patient data (IPD) meta-analysis. METHODS: An electronic literature searched was conducted on PubMed, EMBASE, and Web of Science from database inception to 6 November 2022. Studies describing the natural history of surgically resected NFPA, with provision of Kaplan-Meier curves, were included. These were digitized to obtain IPD, which was pooled in one-stage and two-stage meta-analysis to determine hazard ratios (HRs) and 95%CIs of gross total resection (GTR) versus subtotal resection (STR), and postoperative radiotherapy versus none. An indirect analysis of single-arm data between endoscopic endonasal (EES) and microscopic transsphenoidal (MTS) surgical technique was also performed. RESULTS: Altogether, eleven studies (3941 patients) were retrieved. PFS was significantly lower in STR than GTR (shared-frailty HR 0.32, 95%CI 0.27-0.39, p < 0.001). Postoperative radiotherapy significantly improved PFS compared to no radiotherapy (shared-frailty HR 0.20, 95%CI 0.15-0.26, p < 0.001), including in the subgroup of patients with STR (shared-frailty HR 0.12, 95%CI 0.08-0.18, p < 0.001). Similar PFS was observed between EES and MTS (indirect HR 1.09, 95%CI 0.92-1.30, p = 0.301). CONCLUSIONS: This systematic review and patient-level meta-analysis provides a robust prognostication of surgically treated NFPA. We reinforce current guidelines stating that GTR should be the standard of surgical resection. Postoperative radiotherapy is of considerable benefit, especially for patients with STR. Surgical approach does not significantly affect long-term prognosis. REGISTRATION: PROSPERO CRD42022374034.
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Fragilidade , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Intervalo Livre de Progressão , Prognóstico , Endoscopia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
OBJECTIVE: Subarachnoid hemorrhage (SAH) has been reported as a neurological manifestation in 0.1% of COVID-19 patients. This systematic review investigated the outcomes and predictive factors of SAH in patients with COVID-19. MATERIALS AND METHODS: An electronic literature search was conducted on PubMed, Embase, and Scopus from inception to 10th September 2021. Studies reporting SAH in COVID-19 patients were included. Demographic characteristics, risk factors for disease, severity of COVID-19, and mortality of SAH in COVID-19 patients were analyzed. Subgroup analyses stratified by COVID-19 severity and mortality were conducted. RESULTS: 17 case reports, 11 case series, and 2 retrospective cohort studies, with a total of 345 cases of SAH in COVID-19 patients, were included for analysis. Most published cases were reported in the US. Mean age was 55±18.4 years, and 162 patients (48.5%) were female. 242 patients (73.8%) had severe-to-critical COVID-19, 56.7% had aneurysmal SAH, 71.4% were on anticoagulation, and 10.8% underwent surgical treatment. 136 out of 333 patients (40.8%) died. Among patients with severe-to-critical COVID-19, 11 out of 18 (61.1%) died, and 8 out of 8 (100.0%) were non-aneurysmal SAH. CONCLUSIONS: SAH is a rare but morbid occurrence in COVID-19. The mortality rate of COVID-SAH patients was 40.8%, with a higher prevalence of severe-to-critical COVID-19 (100% versus 53.8%) and non-aneurysmal SAH (85.7% versus 44.6%) among COVID-SAH deaths. Given the changing landscape of COVID-19 variants, further studies investigating the association between COVID-19 and SAH may be warranted to identify the long-term effects of COVID-19.
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COVID-19 , Hemorragia Subaracnóidea , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Estudos Retrospectivos , COVID-19/complicações , COVID-19/diagnóstico , SARS-CoV-2RESUMO
To analyze the efficacy and safety of high-frequency VNS versus control (low-frequency VNS or no VNS) in patients with DRE using data from randomized controlled trials (RCTs). An electronic literature search was conducted on PubMed, EMBASE, and Cochrane Controlled Register of Trials (CENTRAL); 12 RCTs reporting seizure frequency or treatment response in studies containing a high-frequency VNS treatment arm (conventional VNS or transcutaneous VNS [tVNS]) compared to control (low-frequency VNS or no VNS) were included. Seizure frequency, treatment response (number of patients with ≥ 50% reduction in seizure frequency), quality of life (QOL), and adverse effects were analyzed. Seizure frequency was reported in 9 studies (718 patients). Meta-analysis with random-effects models favored high-frequency VNS over control (standardized mean difference = 0.82, 95%-CI = 0.39-1.24, p < .001). This remained significant for subgroup analyses of low-frequency VNS as the control, VNS modality, and after removing studies with moderate-to-high risk of bias. Treatment response was reported in 8 studies (758 patients). Random-effects models favored high-frequency VNS over control (risk ratio = 1.57, 95%-CI = 1.19-2.07, p < .001). QOL outcomes were reported descriptively in 4 studies (363 patients), and adverse events were reported in 11 studies (875 patients). Major side effects and death were not observed to be more common in high-frequency VNS compared to control. High-frequency VNS results in reduced seizure frequency and improved treatment response compared to control (low-frequency VNS or no VNS) in patients with drug-resistant epilepsy. Greater consideration for VNS in patients with DRE may be warranted to decrease seizure frequency in the management of these patients.
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Epilepsia Resistente a Medicamentos , Estimulação do Nervo Vago , Protocolos Clínicos , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/terapia , Humanos , Qualidade de Vida , Convulsões/etiologia , Resultado do Tratamento , Estimulação do Nervo Vago/efeitos adversos , Estimulação do Nervo Vago/métodosRESUMO
OBJECTIVE: This study aims to develop and compare the use of deep neural networks (DNN) and support vector machines (SVM) to clinical prognostic scores for prognosticating 30-day mortality and 90-day poor functional outcome (PFO) in spontaneous intracerebral haemorrhage (SICH). MATERIALS AND METHODS: We conducted a retrospective cohort study of 297 SICH patients between December 2014 and May 2016. Clinical data was collected from electronic medical records using standardized data collection forms. The machine learning workflow included imputation of missing data, dimensionality reduction, imbalanced-class correction, and evaluation using cross-validation and comparison of accuracy against clinical prognostic scores. RESULTS: 32 (11%) patients had 30-day mortality while 177 (63%) patients had 90-day PFO. For prognosticating 30-day mortality, the class-balanced accuracies for DNN (0.875; 95% CI 0.800-0.950; McNemar's p-value 1.000) and SVM (0.848; 95% CI 0.767-0.930; McNemar's p-value 0.791) were comparable to that of the original ICH score (0.833; 95% CI 0.748-0.918). The c-statistics for DNN (0.895; DeLong's p-value 0.715), and SVM (0.900; DeLong's p-value 0.619), though greater than that of the original ICH score (0.862), were not significantly different. For prognosticating 90-day PFO, the class-balanced accuracies for DNN (0.853; 95% CI 0.772-0.934; McNemar's p-value 0.003) and SVM (0.860; 95% CI 0.781-0.939; McNemar's p-value 0.004) were better than that of the ICH-Grading Scale (0.706; 95% CI 0.600-0.812). The c-statistic for SVM (0.883; DeLong's p-value 0.022) was significantly greater than that of the ICH-Grading Scale (0.778), while the c-statistic for DNN was 0.864 (DeLong's p-value 0.055). CONCLUSION: We showed that the SVM model performs significantly better than clinical prognostic scores in predicting 90-day PFO in SICH.
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Hemorragia Cerebral , Aprendizado de Máquina , Hemorragia Cerebral/fisiopatologia , Hemorragia Cerebral/terapia , Humanos , Redes Neurais de Computação , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Juvenile pilocytic astrocytoma (JPA) is a World Health Organization (WHO) grade I tumor that is the commonest to occur in the 0-19 age group, with an excellent prognosis of 96% 10-year survival in pediatric patients. Complete resection is the treatment of choice for JPAs. However, this is not always feasible due to the location of certain tumors, and the management following subtotal resection is controversial. Fractionated radiotherapy, chemotherapy, radiosurgery, and observation have all been used to treat tumor remnants. We report a young patient with good tumor control 23 years following low-dose Gamma Knife surgery (GKS) of a subtotally resected brainstem JPA and recommend that GKS may be a feasible treatment option to achieve long-term tumor control when subtotal resection cannot be achieved, even if the GKS prescription dose must be significantly reduced due to large tumor volume or proximity to critical structures sensitive to radiation.
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Astrocitoma/radioterapia , Neoplasias do Tronco Encefálico/radioterapia , Tronco Encefálico/diagnóstico por imagem , Radiocirurgia , Astrocitoma/diagnóstico por imagem , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Seguimentos , Humanos , Lactente , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The role of adjuvant radiotherapy (RT) after gross total resection (GTR) of the World Health Organization (WHO) grade II ependymoma is controversial. Therefore, we aimed to compare the outcomes of adjuvant RT against observation after GTR of WHO grade II ependymoma. We also compared the outcomes of adjuvant RT against observation after subtotal resection (STR) of WHO grade II ependymoma and performed further subgroup analysis by age and tumor location. METHODS: PubMed and Embase were systematically reviewed for studies published up till 25 November 2022. Studies that reported individual-participant data on patients who underwent surgery followed by adjuvant RT/observation for WHO grade II ependymoma were included. The exposure was whether adjuvant RT was administered, and the outcomes were recurrence and overall survival (OS). Subgroup analyses were performed by the extent of resection (GTR or STR), tumor location (supratentorial or infratentorial), and age at the first surgery (<18 or ≥18 years old). RESULTS: Of the 4,647 studies screened, three studies reporting a total of 37 patients were included in the analysis. Of these 37 patients, 67.6% (25 patients) underwent GTR, and 51.4% (19 patients) underwent adjuvant RT. Adjuvant RT after GTR was not significantly associated with both recurrence (odds ratio =5.50; 95% confidence interval: 0.64-60.80; P=0.12) and OS (P=0.16). Adjuvant RT was also not significantly associated with both recurrence and OS when the cohort was analyzed as a whole and on subgroup analysis by age and tumor location. However, adjuvant RT was associated with significantly longer OS after STR (P=0.03) with the median OS being 6.33 years, as compared to 0.40 years for patients who underwent STR followed by observation. CONCLUSIONS: Based on our meta-analysis of 37 patients, administration of adjuvant RT after GTR was not significantly associated with improvement in OS or recurrence in patients with WHO grade II ependymoma. However, due to the small number of patients included in the analysis, further prospective controlled studies are warranted.
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Ependimoma , Humanos , Ependimoma/radioterapia , Ependimoma/cirurgia , Radioterapia Adjuvante/métodos , Feminino , Masculino , Gradação de Tumores , Organização Mundial da SaúdeRESUMO
INTRODUCTION: High-quality epidemiological data on hemorrhagic stroke (HS) and its subtypes, intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), remains limited in Asian ethnicities. We investigated the trends in HS incidence and 30-day mortality from 2005 to 2019 in a multi-ethnic Asian population from a national registry. PATIENTS AND METHODS: Data on all stroke cases from the Singapore Stroke Registry from 2005 to 2019 were collected. Cases were defined using centrally adjudicated review of diagnosis codes. Death outcomes were obtained by linkage with the national death registry. Incidence (per 100,000 people) and 30-day mortality (per 100 people) were measured as crude and age-standardized rates. Trends were analyzed using linear regression. RESULTS: We analyzed 19,017 cases of HS (83.9% ICH; 16.1% SAH). From 2005 to 2019, age-standardized incidence rates (ASIR) for HS remained stable from 34.4 to 34.5. However, age-standardized mortality rates (ASMR) decreased significantly from 29.5 to 21.4 (p < 0.001). For ICH, ASIR remained stable while ASMR decreased from 30.4 to 21.3 (p < 0.001); for SAH, ASIR increased from 2.7 to 6.0 (p = 0.006) while ASMR remained stable. In subgroup analyses, HS incidence increased significantly in persons <65 years (from 18.1 to 19.6) and Malays (from 39.5 to 49.7). DISCUSSION: From 2005 to 2019, ASIR of HS remained stable while ASMR decreased. Decreasing ASMR reflects improvements in the overall management of HS, consistent with global trends. CONCLUSION: Population health efforts to address modifiable risk factors for HS in specific demographic subgroups may be warranted to reduce incidence and mortality of HS.
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Acidente Vascular Cerebral Hemorrágico , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Humanos , Incidência , Acidente Vascular Cerebral Hemorrágico/complicações , Acidente Vascular Cerebral/epidemiologia , Hemorragia Cerebral/epidemiologia , Hemorragia Subaracnóidea/complicações , Sistema de RegistrosRESUMO
There are numerous studies on the natural history and outcomes of adult Moyamoya disease (MMD) in the literature, but limited data from Southeast Asian cohorts. Hence, we aimed to retrospectively review the clinical characteristics and outcomes after surgical revascularization for adult MMD in our Southeast Asian cohort. Patients were included if they were above 18 years old at the first surgical revascularization for MMD, and underwent surgery between 2012 and 2022 at the National University Hospital, Singapore. The outcomes were transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, and all-cause mortality during the postoperative follow-up period. In total, 26 patients who underwent 27 revascularization procedures were included. Most patients were of Chinese ethnicity, and the mean (SD) age at the time of surgery was 47.7 (12.6) years. The commonest clinical presentation was intracerebral hemorrhage, followed by TIA and ischemic stroke. Direct revascularization with superficial temporal artery-middle cerebral artery (STA-MCA) bypass was the most common procedure (24/27 surgeries, 88.9 %). The mean (SD) follow-up duration was 4.2 (2.5) years, during which the overall incidence of postoperative TIA/stroke was 25.9 % (7/27 surgeries), with most cases occurring within 7 days postoperatively. There were no mortalities during the postoperative follow-up period. Risk factors for 30-day postoperative TIA/stroke included a higher number of TIAs/strokes preoperatively (p = 0.044) and indirect revascularization (p = 0.028). Diabetes mellitus demonstrated a trend towards an increased risk of 30-day postoperative TIA/stroke, but this was not statistically significant (p = 0.056). These high-risk patients may benefit from more aggressive perioperative antithrombotic and hydration regimens.
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Revascularização Cerebral , Ataque Isquêmico Transitório , AVC Isquêmico , Doença de Moyamoya , Adulto , Humanos , Pessoa de Meia-Idade , Hemorragia Cerebral/etiologia , Revascularização Cerebral/métodos , Ataque Isquêmico Transitório/etiologia , AVC Isquêmico/etiologia , Doença de Moyamoya/complicações , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: The role of surgery in spontaneous intracerebral hemorrhage (SICH) remains controversial. We aimed to use explainable machine learning (ML) combined with propensity-score matching to investigate the effects of surgery and identify subgroups of patients with SICH who may benefit from surgery in an interpretable fashion. METHODS: We conducted a retrospective study of a cohort of 282 patients aged ≥21 years with SICH. ML models were developed to separately predict for surgery and surgical evacuation. SHapley Additive exPlanations (SHAP) values were calculated to interpret the predictions made by ML models. Propensity-score matching was performed to estimate the effect of surgery and surgical evacuation on 90-day poor functional outcomes (PFO). RESULTS: Ninety-two patients (32.6%) underwent surgery, and 57 patients (20.2%) underwent surgical evacuation. A total of 177 patients (62.8%) had 90-day PFO. The support vector machine achieved a c-statistic of 0.915 when predicting 90-day PFO for patients who underwent surgery and a c-statistic of 0.981 for patients who underwent surgical evacuation. The SHAP scores for the top 5 features were Glasgow Coma Scale score (0.367), age (0.214), volume of hematoma (0.258), location of hematoma (0.195), and ventricular extension (0.164). Surgery, but not surgical evacuation of the hematoma, was significantly associated with improved mortality at 90-day follow-up (odds ratio, 0.26; 95% confidence interval, 0.10-0.67; P = 0.006). CONCLUSIONS: Explainable ML approaches could elucidate how ML models predict outcomes in SICH and identify subgroups of patients who respond to surgery. Future research in SICH should focus on an explainable ML-based approach that can identify subgroups of patients who may benefit functionally from surgical intervention.
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Hemorragia Cerebral , Máquina de Vetores de Suporte , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Hemorragia Cerebral/complicações , Hematoma/cirurgia , Resultado do TratamentoRESUMO
INTRODUCTION: High grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients. METHODS: This is an interventional, non-randomized, open-label study, which aims to enroll 10 patients who will receive QPOP-guided chemotherapy at the time of first HGG recurrence following progression on standard first-line therapy. At the initial presentation of HGG, tumor will be harvested for primary PDO generation during the first biopsy/surgery. At the point of tumor recurrence, patients will be enrolled onto the main study to receive systemic therapy as second-line treatment. Subjects who undergo surgery at the time of recurrence will have a second harvest of tissue for PDO generation. Established PDOs will be subject to QPOP analyses to determine their therapeutic sensitivities to specific panels of drugs. A QPOP-guided treatment selection algorithm will then be used to select the most appropriate drug combination. The primary endpoint of the study is six-month progression-free survival. The secondary endpoints include twelve-month overall survival, RANO criteria and toxicities. In our radiological biomarker sub-study, we plan to evaluate novel radiopharmaceutical-based neuroimaging in determining blood-brain barrier permeability and to assess in vivo drug effects on tumor vasculature over time. TRIAL REGISTRATION: This trial was registered on 8th September 2022 with ClinicalTrials.gov Identifier: NCT05532397.
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Neoplasias Encefálicas , Recidiva Local de Neoplasia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Astrocitoma/tratamento farmacológico , Astrocitoma/patologia , Astrocitoma/diagnóstico por imagem , Organoides/efeitos dos fármacos , Organoides/patologia , Organoides/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gradação de TumoresRESUMO
Epitranscriptomic RNA modifications are crucial for the maintenance of glioma stem cells (GSCs), the most malignant cells in glioblastoma (GBM). 3-methylcytosine (m3C) is a new epitranscriptomic mark on RNAs and METTL8 represents an m3C writer that is dysregulated in cancer. Although METTL8 has an established function in mitochondrial tRNA (mt-tRNA) m3C modification, alternative splicing of METTL8 can also generate isoforms that localize to the nucleolus where they may regulate R-loop formation. The molecular basis for METTL8 dysregulation in GBM, and which METTL8 isoform(s) may influence GBM cell fate and malignancy remain elusive. Here, we investigated the role of METTL8 in regulating GBM stemness and tumorigenicity. In GSC, METTL8 is exclusively localized to the mitochondrial matrix where it installs m3C on mt-tRNAThr/Ser(UCN) for mitochondrial translation and respiration. High expression of METTL8 in GBM is attributed to histone variant H2AZ-mediated chromatin accessibility of HIF1α and portends inferior glioma patient outcome. METTL8 depletion impairs the ability of GSC to self-renew and differentiate, thus retarding tumor growth in an intracranial GBM xenograft model. Interestingly, METTL8 depletion decreases protein levels of HIF1α, which serves as a transcription factor for several receptor tyrosine kinase (RTK) genes, in GSC. Accordingly, METTL8 loss inactivates the RTK/Akt axis leading to heightened sensitivity to Akt inhibitor treatment. These mechanistic findings, along with the intimate link between METTL8 levels and the HIF1α/RTK/Akt axis in glioma patients, guided us to propose a HIF1α/Akt inhibitor combination which potently compromises GSC proliferation/self-renewal in vitro. Thus, METTL8 represents a new GBM dependency that is therapeutically targetable.
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Glioblastoma , Subunidade alfa do Fator 1 Induzível por Hipóxia , Metiltransferases , Células-Tronco Neoplásicas , Proteínas Proto-Oncogênicas c-akt , Metilação de RNA , Animais , Humanos , Camundongos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Carcinogênese/genética , Carcinogênese/patologia , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos Nus , Mitocôndrias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA de Transferência/metabolismo , RNA de Transferência/genética , Transdução de Sinais , Metilação de RNA/genética , Receptores Proteína Tirosina Quinases/metabolismoRESUMO
The initial management of craniopharyngioma is generally either gross total resection (GTR) or subtotal resection (STR) with adjuvant radiotherapy (RT). However, the optimal management strategy for recurrent/progressive craniopharyngioma remains unclear. In this systematic review and individual participant data meta-analysis, we aimed to compare the outcomes of surgery and/or RT for the first recurrence/progression of craniopharyngioma after resection alone. The exposure was the treatment that was administered for the first recurrence/progression, and the outcomes were tumor regrowth and overall survival (OS). Subgroup analyses were performed by age at the treatment for the first recurrence/progression (<18 or ≥ 18 years old), duration between the first treatment and the first recurrence/progression (<2 or ≥ 2 years), and the initial treatment that was administered (STR or GTR). Of the 2932 studies screened, 11 studies reporting a total of 80 patients were included. Across almost all subgroups, patients who received RT for the first recurrence/progression had a significantly lower risk of tumor regrowth than those who did not, regardless of whether surgery was performed and the extent of resection. There was no significant association between the treatment administered for the first recurrence/progression and OS, except for patients with a recurrence/progression < 2 years after the first treatment, where GTR was associated with a higher risk of mortality. For patients with the first recurrence/progression of craniopharyngioma after resection alone, RT should be considered for better local control. In cases where RT is not administered, GTR is preferred over STR provided it can be safely performed, for improved local control.
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Craniofaringioma , Neoplasias Hipofisárias , Humanos , Adolescente , Craniofaringioma/radioterapia , Craniofaringioma/cirurgia , Craniofaringioma/patologia , Resultado do Tratamento , Neoplasias Hipofisárias/radioterapia , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Radioterapia Adjuvante , Recidiva Local de Neoplasia/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: To identify the risk factors for a 30-day postoperative surgical site hematoma requiring evacuation (POH) after surgical resection of brain metastases. METHODS: Patients who underwent surgical resection of brain metastases between 2011 and 2019 at our institution were included. Risk factors for a 30-day POH were identified using a multivariate logistic regression model. RESULTS: A total of 158 patients were included in the analysis. The mean (SD) age of the study population was 59.3 (12.0) years, and 82 (53.2%) patients were female. The incidence of a 30-day POH was 8.2% (13 patients). There was no statistically significant association between the occurrence of a 30-day POH and overall mortality (p = 0.100). On multivariate analysis, there was a statistically significant association between a 30-day POH and younger age (OR=0.91; 95% CI=0.83, 0.99; p = 0.035), higher BMI (OR=1.61; 95% CI=1.16, 2.46; p = 0.010), and blood type AB (OR=21.7; 95% CI=1.66, 522; p = 0.031). On receiver operating characteristic analysis, a threshold BMI of 25.1 kg/m2 and threshold age of 57 gave the optimum balance of sensitivity and specificity in predicting the occurrence of a 30-day POH. CONCLUSIONS: Patients below 57 years old, who have a BMI of above 25, and/or have blood type AB were at higher risk of developing a 30-day POH after surgical resection of brain metastases. Additional care in intraoperative hemostasis and postoperative monitoring may be indicated among patients who have these risk factors.
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Neoplasias Encefálicas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Fatores de Risco , Neoplasias Encefálicas/cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Hematoma/cirurgia , Complicações Pós-Operatórias/epidemiologiaRESUMO
OBJECTIVE: ABO blood type has been associated with mortality among patients with cancer, but this association has thus far not been investigated among patients with brain metastases. Hence, we aimed to investigate the association between ABO blood type and mortality among patients who underwent surgical resection of brain metastases. METHODS: A single-center retrospective study of patients who underwent surgical resection of brain metastases between 2011 and 2019 was conducted. Cox proportional hazards models were constructed, adjusting for potential confounders, to evaluate whether blood type was independently associated with overall mortality. RESULTS: A total of 158 patients were included in the analysis. The mean (SD) age of the cohort was 59.3 (12.0) years, and 67.7% of patients were female. The median overall survival of patients with blood type AB was 11.2 months, while the median overall survival of patients with blood types O, B, and A were 11.7, 13.5, and 14.4 months respectively. On univariate analysis, patients with blood type AB had a higher risk of overall mortality (p = 0.017). On multivariate analysis adjusting for potential confounders, blood type AB was again associated with a higher risk of overall mortality (HR: 2.29, 95% CI: 1.11-4.72, p = 0.025). CONCLUSION: Blood type AB was independently associated with a higher risk of overall mortality among patients who underwent surgical resection of brain metastases, indicating the potential prognostic value of ABO blood type in brain metastases.
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BACKGROUND: There remains uncertainty regarding optimal definitive management for malignant posterior circulation infarcts (MPCI). While guidelines recommend neurosurgery for malignant cerebellar infarcts that are refractory to medical therapy, concerns exist about the functional outcome and quality of life after decompressive surgery. OBJECTIVE: This study aims to evaluate the outcomes of surgical intervention compared to medical therapy in MPCI. METHODS: In this systematic review, MEDLINE, Embase and Cochrane databases were searched from inception until 2 April 2021. Studies were included if they involved posterior circulation strokes treated with neurosurgical intervention and reported mortality and functional outcome data. Data were collected according to PRISMA guidelines. RESULTS: The search yielded 6677 studies, of which 31 studies (comprising 723 patients) were included for analysis. From the included studies, we found that surgical therapy led to significant differences in mortality and functional outcomes in patients with severe disease. Neurological decline and radiological criteria were often used to decide the timing for surgical intervention, as there is currently limited evidence for preventative neurosurgery. There is also limited evidence for the superiority of one surgical modality over another. CONCLUSION: For patients with MPCI who are clinically stable at the time of presentation, in terms of mortality and functional outcome, surgical therapy appears to be equivocal to medical therapy. Reliable evidence is lacking, and further prospective studies are rendered.
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OBJECTIVE: Intracranial pressure (ICP) monitoring is a widely utilized and essential tool for tracking neurosurgical patients, but there are limitations to the use of a solely ICP-based paradigm for guiding management. It has been suggested that ICP variability (ICPV), in addition to mean ICP, may be a useful predictor of neurological outcomes, as it represents an indirect measure of intact cerebral pressure autoregulation. However, the current literature regarding the applicability of ICPV shows conflicting associations between ICPV and mortality. Thus, the authors aimed to investigate the effect of ICPV on intracranial hypertensive episodes and mortality using the eICU Collaborative Research Database version 2.0. METHODS: The authors extracted from the eICU database 1,815,676 ICP readings from 868 patients with neurosurgical conditions. ICPV was computed using two methods: the rolling standard deviation (RSD) and the absolute deviation from the rolling mean (DRM). An episode of intracranial hypertension was defined as at least 25 minutes of ICP > 22 mm Hg in any 30-minute window. The effects of mean ICPV on intracranial hypertension and mortality were computed using multivariate logistic regression. A recurrent neural network with long short-term memory was used for time-series predictions of ICP and ICPV to prognosticate future episodes of intracranial hypertension. RESULTS: A higher mean ICPV was significantly associated with intracranial hypertension using both ICPV definitions (RSD: aOR 2.82, 95% CI 2.07-3.90, p < 0.001; DRM: aOR 3.93, 95% CI 2.77-5.69, p < 0.001). ICPV was significantly associated with mortality in patients with intracranial hypertension (RSD: aOR 1.28, 95% CI 1.04-1.61, p = 0.026, DRM: aOR 1.39, 95% CI 1.10-1.79, p = 0.007). In the machine learning models, both definitions of ICPV achieved similarly good results, with the best F1 score of 0.685 ± 0.026 and an area under the curve of 0.980 ± 0.003 achieved with the DRM definition over 20 minutes. CONCLUSIONS: ICPV may be useful as an adjunct for the prognostication of intracranial hypertensive episodes and mortality in neurosurgical critical care as part of neuromonitoring. Further research on predicting future intracranial hypertensive episodes with ICPV may help clinicians react expediently to ICP changes in patients.
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Lesões Encefálicas Traumáticas , Hipertensão Intracraniana , Humanos , Pressão Intracraniana/fisiologia , Estado Terminal , Monitorização Fisiológica , Modelos Logísticos , Hipertensão Intracraniana/diagnóstico , Hipertensão Intracraniana/etiologia , Lesões Encefálicas Traumáticas/cirurgiaRESUMO
BACKGROUND: Functional recovery and return to work (RTW) after stroke are important rehabilitation goals that have significant impact on quality of life. Comparisons of functional outcomes and RTW between ischemic stroke (IS) and hemorrhagic stroke (HS), especially among young adults with stroke, have either been limited or yielded inconsistent results. We aimed to assess functional outcomes and ability to RTW in young adults with IS and HS, specifically primary spontaneous intracranial hemorrhage (SICH). METHODS: Young adults with IS or SICH aged 18-50-years-old were included. Outcome measures were modified Rankins score (mRS) on discharge and 3-months and RTW at 3-months after stroke. Good functional outcome was defined as an mRS of 0-2. RESULTS: We included 459 patients (71.5% male) with a mean age of 43.3 ± 5.7 years, comprising 49.2% IS and 50.8% SICH. Patients with SICH were more likely to have unfavourable shifts in ordinal mRS on discharge (OR 7.52, CI 5.18-10.87, p < 0.001) and at 3-months (OR 6.41, CI 4.17-9.80, p < 0.001). Patients with IS more likely achieved good functional outcomes (80.2% vs. 51.8%, p < 0.001) and were able to RTW at 3-months (54.4% vs. 36.3%, p = 0.004). Among all stroke patients with good functional outcomes, one-third did not RTW at 3-months. Patients with longer length of hospitalisation and higher National Institutes of Health Stroke Scale (NIHSS) score on admission, especially in the domain categories of level of consciousness, vision, motor function, language and neglect, were less likely to RTW at 3-months. CONCLUSION: Patients with IS were more likely to RTW when compared to SICH patients. Many young stroke patients did not RTW despite good functional outcomes. Further research should therefore address differences in prognosis and identify predictors that influence ability to RTW after stroke in the young adult population.
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BACKGROUND: The benefits of adding upfront post-operative radiation, either whole-brain (WBRT) or cavity, after resection of brain metastases have been debated, particularly due to the long-term sequalae post radiation. We sought to compare the efficacy and safety between post-operative radiation versus resection alone. METHODS: We searched various biomedical databases from 1983 to 2018, for eligible randomized controlled trials (RCT). Outcomes studied were local recurrence (LR), overall survival (OS) and serious (Grade 3 + ) adverse events. We used the random effects model to pool outcomes. Methodological quality of each study was assessed using the Cochrane Risk of Bias tool. We employed the GRADE approach to assess the certainty of evidence. RESULTS: We included 5 RCTs comprising of 673 patients. The pooled odds ratio (OR) for LR is 0.26 (95% confidence interval (CI) 0.19-0.37, P < 0.001, GRADE certainty high), strongly supporting the use of post-operative radiation. Meta-regression analysis done comparing cavity and WBRT, did not show any difference in LR. The pooled hazard ratio (HR) for overall survival (OS) is 1.1 (95% CI 0.90-1.34, P = 0.37, GRADE certainty high). The treatment-related toxicities could not be pooled; the 2 studies which reported this did not find differences between the approaches. The risk of bias across the included studies was low. CONCLUSION: Our analysis confirms that upfront post-operative radiation significantly reduces the risk of LR. However, the lack of improvement in OS suggests that local control alone may not impact survival. Balancing local control, and neuro-cognitive effects of WBRT, cavity radiation seems to be a safe and effective option.