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1.
J Neurooncol ; 167(1): 169-180, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38430419

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Fragilidad , Sarcopenia , Humanos , Femenino , Persona de Mediana Edad , Masculino , Fragilidad/complicaciones , Sarcopenia/complicaciones , Sarcopenia/patología , Factores de Riesgo , Hospitalización , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Estudios Retrospectivos
2.
Neurosurg Rev ; 47(1): 100, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38427140

RESUMEN

The comparability of endovascular coiling over neurosurgical clipping has not been firmly established in elderly patients with aneurysmal subarachnoid haemorrhage (aSAH). Data were obtained from all patients with aSAH aged ≥60 across three tertiary hospitals in Singapore from 2014 to 2019. Outcome measures included modified Rankin Scale (mRS) score at 3 and at 6 months, and in-hospital mortality. Of the 134 patients analyzed, 84 (62.7%) underwent coiling and 50 (37.3%) underwent clipping. The endovascular group showed a higher incidence of good mRS score 0-2 at 3 months (OR = 2.45 [95%CI:1.16-5.20];p = 0.018), and a lower incidence of in-hospital mortality (OR = 0.31 [95%CI:0.10-0.91];p = 0.026). There were no significant difference between the two treatment groups in terms of good mRS score at 6 months (OR = 1.98 [95%CI:0.97-4.04];p = 0.060). There were no significant differences in the incidence of complications, such as aneurysm rebleed, delayed hydrocephalus, delayed ischemic neurological deficit and venous thromboembolism between the two treatment groups. However, fewer patients in the coiling group developed large infarcts requiring decompressive craniectomy (OR = 0.32 [95%CI:0.12-0.90];p = 0.025). Age, admission WFNS score I-III, and coiling were independent predictors of good functional outcomes at 3 months. Only age and admission WFNS score I-III remained significant predictors of good functional outcomes at 6 months. Endovascular coiling, compared with neurosurgical clipping, is associated with significantly better short term outcomes in carefully selected elderly patients with aSAH. Maximal intervention is recommended for aSAH in the young elderly age group and those with favorable WFNS scores.


Asunto(s)
Aneurisma Roto , Procedimientos Endovasculares , Aneurisma Intracraneal , Hemorragia Subaracnoidea , Humanos , Persona de Mediana Edad , Aneurisma Roto/cirugía , Estudios de Cohortes , Aneurisma Intracraneal/terapia , Procedimientos Neuroquirúrgicos , Hemorragia Subaracnoidea/complicaciones , Resultado del Tratamiento
3.
Pituitary ; 26(4): 461-473, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37389776

RESUMEN

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.


Asunto(s)
Fragilidad , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/radioterapia , Neoplasias Hipofisarias/cirugía , Supervivencia sin Progresión , Pronóstico , Endoscopía , Resultado del Tratamiento , Estudios Retrospectivos
4.
J Stroke Cerebrovasc Dis ; 31(2): 106234, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34896819

RESUMEN

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.


Asunto(s)
Hemorragia Cerebral , Aprendizaje Automático , Hemorragia Cerebral/fisiopatología , Hemorragia Cerebral/terapia , Humanos , Redes Neurales de la Computación , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
5.
Eur Spine J ; 30(5): 1247-1260, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33387049

RESUMEN

INTRODUCTION: During the Coronavirus disease 2019 outbreak, while healthcare systems and hospitals are diverting their resources to combat the pandemic, patients who require spinal surgeries continue to accumulate. The aim of this study is to describe a novel hospital capacity versus clinical justification triage score (CCTS) to prioritize patients who require surgery during the "new normal state" of the COVID-19 pandemic. METHODOLOGY: A consensus study using the Delphi technique was carried out among clinicians from the Orthopaedic Surgery, Neurosurgery, and Anaesthesia departments. Three rounds of consensus were carried out via survey and Webinar discussions. RESULTS: A 50-points score system consisting of 4 domains with 4 subdomains was formed. The CCTS were categorized into the hospital capacity, patient factors, disease severity, and surgery complexity domains. A score between 30 and 50 points indicated that the proposed operation should proceed without delay. A score of less than 20 indicates that the proposed operation should be postponed. A score between 20 and 29 indicates that the surgery falls within a grey area where further discussion should be undertaken to make a joint justification for approval of surgery. CONCLUSION: This study is a proof of concept for the novel CCTS scoring system to prioritize surgeries to meet the rapidly changing demands of the COVID-19 pandemic. It offers a simple and objective method to stratify patients who require surgery and allows these complex and difficult decisions to be unbiased and made transparently among surgeons and hospital administrators.


Asunto(s)
COVID-19 , Pandemias , Hospitales , Humanos , SARS-CoV-2 , Triaje
6.
Br J Neurosurg ; 35(6): 719-724, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32530308

RESUMEN

AIM: This article aims to inform and share the experience of a Singaporean tertiary level neurosurgical unit in an academic medical centre during the COVID-19 outbreak. METHOD: This is a descriptive study of our segregation team model which is designed with the aim of optimizing manpower and ensuring the safety and welfare of the neurosurgical unit, while maintaining and prioritizing excellent patient care. RESULT: We describe our method of team segregation, rostering, and outline some principles that we adhere to in its design. We also summarise the restructuring of our inpatient and outpatient service, including the operating theatre and protocols for specific procedures, intensive care and general wards, as well as clinic services and multidisciplinary meetings. CONCLUSION: We end with a commentary on residency training and anticipated challenges. Given the likely protracted course of the pandemic, it is key to account for sustainability of such measures and the conservation of resource via the reduction of pateint volume, upkeep of staff emotional and physical health and harnessing technologies such as telemedicine.


Asunto(s)
COVID-19 , Centros Médicos Académicos , Brotes de Enfermedades , Humanos , SARS-CoV-2 , Singapur/epidemiología
7.
J Stroke Cerebrovasc Dis ; 30(8): 105910, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34119748

RESUMEN

OBJECTIVES: The role of flow-diversion in acute sub-arachnoid haemorrhage (SAH) is controversial. Many of the published data warns of high rates of procedure-related complications and aneurysmal rebleed. This study evaluates the safety, efficacy, clinical and angiographic outcomes of acute flow-diversion at our institute. METHODS: The institutional database from June 2015 to June 2020 was retrospectively reviewed for aneurysmal SAH (aSAH) treated with flow diversion. Clinical presentation, procedural details, complications, anti-platelet usage, rebleeding and aneurysm occlusion rates and outcomes were recorded. RESULTS: 22 (59% females; median age 56 years) consecutive patients were identified. None of them were on regular antiplatelets/anticoagulation in the 15-days preceding the treatment. The mean aneurysm diameter was 5.4 mm and the median delay to flow-diversion was 2 days. Almost 73% (16/22) of patients had adjunctive coiling in the same session. There was no aneurysmal rebleed at a median follow up of 8.5 months and 86.3% (19/22 patients) had good clinical outcomes (3-month MRS 0-2). Adverse events related to the flow diversion procedure were seen in 3 patients; none of them had a medium to long-term clinical consequence. Three patients died from complications of SAH, unrelated to the procedure. Vascular imaging follow-up was available for 20 patients and the complete aneurysm occlusion rate was 95%. CONCLUSION: Flow-diversion could be a reasonably safe and effective technique for treating ruptured aneurysms in appropriately selected patients when conventional options of surgical clipping and coiling are considered challenging.


Asunto(s)
Aneurisma Falso/terapia , Aneurisma Roto/terapia , Disección Aórtica/terapia , Procedimientos Endovasculares , Aneurisma Intracraneal/terapia , Hemorragia Subaracnoidea/terapia , Adulto , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/fisiopatología , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/fisiopatología , Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/fisiopatología , Circulación Cerebrovascular , Bases de Datos Factuales , Embolización Terapéutica , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/fisiopatología , Masculino , Persona de Mediana Edad , Flujo Sanguíneo Regional , Estudios Retrospectivos , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/fisiopatología , Resultado del Tratamiento , Adulto Joven
8.
Neurosurg Rev ; 43(2): 771-780, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31144196

RESUMEN

Parent vessel occlusion (PVO) is the conventional endovascular treatment (EVT) for dissecting distal cerebellar artery aneurysms (DCAA). The associated ischemic sequelae are often well-tolerated. However, at the outset, the magnitude of this risk is uncertain. Meanwhile, non-PVO endovascular treatments (EVT) are deemed to provide incomplete protection from a rebleed. This study reviews our experience in the management of dissecting DCAA with emphasis on the effectiveness of parent vessel-preserving endovascular strategies as compared to PVO. Our institutional database was reviewed for all the dissecting DCAA aneurysms treated by endovascular means between Nov 2015 and Oct 2018. Their clinical presentations, imaging findings, EVT techniques, and clinical outcomes were retrospectively evaluated. Eighteen dissecting DCAA were identified: 13 in the posterior-inferior cerebellar artery (PICA), 3 in anterior-inferior cerebellar artery (AICA), and 2 in superior cerebellar artery (SCA). Median patient age was 61 years (range 40-86; average 60.7 years) with a 5:1 female predominance. Nine (6 in the PICA and 3 in the AICA) patients were managed by parent vessel-preserving strategies (6 with isolated endosaccular coiling and 3 with telescoping stents) while the remaining 9 (7 in the PICA and 2 in the SCA) were treated by PVO.The frequency of early rebleed was the same (11%) in both the treatment arms. One patient from the PVO arm suffered an extensive cerebellar infarct that mandated decompressive craniectomy and adversely affected her recovery. There were no such complications in patients treated with parent vessel-preserving strategies. No recurrence/rebleed was encountered in the 3 aneurysms secured using telescoping stents. Overall, excellent clinical outcomes (mRS of 0 and 1) were sparsely seen in the patients who had PVO (89 vs 23%). In dissecting DCAA, aforedescribed, parent vessel-preserving strategies are as effective as the more frequently used option of PVO in preventing an early rebleed. However, these are technically challenging, may be feasible in a smaller proportion of patients, and would need meticulous imaging follow-up in the acute period. When successfully implemented, these strategies can deliver excellent clinical outcomes and eliminate the uncertain risk of ischemic complications associated with PVO.


Asunto(s)
Disección Aórtica/cirugía , Cerebelo/irrigación sanguínea , Procedimientos Endovasculares , Aneurisma Intracraneal/cirugía , Stents , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
9.
Brain Tumor Res Treat ; 12(2): 100-108, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38742258

RESUMEN

BACKGROUND: Gliomas, characterized by their invasive persistence and tendency to affect critical brain regions, pose a challenge in surgical resection due to the risk of neurological deficits. This study focuses on a personalized approach to achieving an optimal onco-functional balance in glioma resections, emphasizing maximal tumor removal while preserving the quality of life. METHODS: A retrospective analysis of 57 awake surgical resections of gliomas at the National University Hospital, Singapore, was conducted. The inclusion criteria were based on diagnosis, functional boundaries determined by direct electrical stimulation, preoperative Karnofsky Performance Status score, and absence of multifocal disease on MRI. The treatment approach included comprehensive neuropsychological evaluation, determination of suitability for awake surgery, and standard asleep-awake-asleep anesthesia protocol. Tumor resection techniques and postoperative care were systematically followed. RESULTS: The study included 53 patients (55.5% male, average age 39 years), predominantly right-handed. Over half reported seizures as their chief complaint. Tumors were mostly low-grade gliomas. Positive mapping of the primary motor cortex was conducted in all cases, with awake surgery completed in 77.2% of cases. New neurological deficits were observed in 26.3% of patients at 1 month after operation; most showed significant improvement at 6 months. CONCLUSION: The standardized treatment paradigm effectively achieved an optimal onco-functional balance in glioma patients. While some patients experienced neurological deficits postoperatively, the majority recovered to their preoperative baseline within 3 months. The approach prioritizes patient empowerment and customized utilization of functional mapping techniques, considering the challenge of preserving diverse languages in a multilingual patient population.

10.
J Clin Neurosci ; 119: 116-121, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38006812

RESUMEN

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.


Asunto(s)
Revascularización Cerebral , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Enfermedad de Moyamoya , Adulto , Humanos , Persona de Mediana Edad , Hemorragia Cerebral/etiología , Revascularización Cerebral/métodos , Ataque Isquémico Transitorio/etiología , Accidente Cerebrovascular Isquémico/etiología , Enfermedad de Moyamoya/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento
11.
J Clin Neurosci ; 126: 214-220, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943906

RESUMEN

BACKGROUND: Sarcopenia has been purported to be a pre-operative risk factor that affects patient outcomes in oncological surgery, but no study as of yet has investigated the effect of sarcopenia in patients with spinal tumours. Psoas muscle measurements, including the psoas muscle index (PMI), are an objective way to determine sarcopenia. OBJECTIVES: We investigated if PMI could predict post-operative outcomes (length of hospital stay and post-operative complications) in surgically treated spinal tumour patients in a multi-ethnic Asian population. METHODS: We conducted a retrospective cohort study of patients with spinal tumours who underwent surgery at our tertiary institution from January 2016 to January 2020. PMI was measured on T2-weighted MRI sequences, at the middle of the L3 vertebral body and measurements were collected by 2 independent raters. The primary outcome was length of hospital stay (LOS), and the secondary outcome was post-operative complications. ROC curve was used to attain the cut-off value for PMI and the population was then stratified into 2 groups; sarcopenic if PMI was less than 1.22 and non-sarcopenic if the PMI value was more than or equal to 1.22. Multivariable linear regression was used for LOS, while multivariate logistic regression was used for complications. RESULTS: 57 patients were included with a mean length of stay of 17.8 days (SD 25.1) and the total number of patients with complications were 20 (35.1 %). Mean LOS was significantly higher in the sarcopenic group compared to the non-sarcopenic group. Univariate analysis confirmed the association of lower psoas muscle index corresponding with longer lengths of stay and this was corroborated in a multivariable linear regression model. There were no significant associations between PMI and postoperative complications. CONCLUSIONS: Lower PMI values were significantly associated with a longer LOS. PMI may be warranted for risk stratifying Asian spinal tumour patients undergoing surgery.

12.
World Neurosurg ; 182: e262-e269, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38008171

RESUMEN

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.


Asunto(s)
Hemorragia Cerebral , Máquina de Vectores de Soporte , Humanos , Estudios Retrospectivos , Puntaje de Propensión , Hemorragia Cerebral/complicaciones , Hematoma/cirugía , Resultado del Tratamiento
13.
Cell Death Dis ; 15(5): 338, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744809

RESUMEN

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.


Asunto(s)
Glioblastoma , Subunidad alfa del Factor 1 Inducible por Hipoxia , Metiltransferasas , Células Madre Neoplásicas , Proteínas Proto-Oncogénicas c-akt , Humanos , Glioblastoma/metabolismo , Glioblastoma/patología , Glioblastoma/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Animales , Metiltransferasas/metabolismo , Metiltransferasas/genética , Ratones , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Carcinogénesis/genética , Carcinogénesis/patología , Carcinogénesis/metabolismo , Transducción de Señal , ARN de Transferencia/metabolismo , ARN de Transferencia/genética , Mitocondrias/metabolismo , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Proliferación Celular
14.
Asia Pac J Clin Oncol ; 19(1): 172-178, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35678489

RESUMEN

INTRODUCTION: Awake craniotomy is well-established for resection of brain tumor in the eloquent areas. Previous studies from Western countries have reported good level of patient tolerance and acceptance. However, its acceptability in non-Western populations, with different ethnic, social, cultural, religious, and linguistic backgrounds, has not been studied systematically. This study aims to evaluate the experience of patients from an Asian population who underwent awake craniotomy for tumor resection. METHODS: Data on patient experience were collected by interviewing patients using a structured questionnaire at follow-up appointment. Data on patient demographics and diagnosis were collected from medical records. RESULTS: Eighteen patients (age 16-68 years) who underwent 20 awake craniotomies were recruited. Preoperatively, all (100%) patients understood the indication for awake craniotomy. Almost all felt fully counseled by the neurosurgeon (90%), anesthetist (100%), and neuropsychologist (95%). Ninety-five percent reported their family to be supportive of awake craniotomy. Seventy-five percent felt adequately prepared on operation day. Intraoperatively, most patients did not experience pain/discomfort (55%) or anxiety (65%). Nearly all found intraoperative motor and language testing to be easy (100% and 90%, respectively). Postoperatively, 100% were satisfied with their care. One hundred percent rated their overall experience as good or excellent. Eighty percent were willing to undergo awake craniotomy again if indicated. CONCLUSION: Awake craniotomy is well-accepted in an Asian population. All patients had good-to-excellent overall experience, with most willing to undergo awake craniotomy again. Our findings underscore the generalizability of awake craniotomy across different socio-cultural backgrounds and support its utilization in countries with a significant Asian population.


Asunto(s)
Neoplasias Encefálicas , Vigilia , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Monitoreo Intraoperatorio , Neoplasias Encefálicas/cirugía , Craneotomía , Evaluación del Resultado de la Atención al Paciente
15.
Clin Neurol Neurosurg ; 226: 107617, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36753860

RESUMEN

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.


Asunto(s)
Neoplasias Encefálicas , Humanos , Femenino , Persona de Mediana Edad , Masculino , Factores de Riesgo , Neoplasias Encefálicas/cirugía , Periodo Posoperatorio , Estudios Retrospectivos , Hematoma/cirugía , Complicaciones Posoperatorias/epidemiología
16.
World Neurosurg ; 179: e428-e443, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37660841

RESUMEN

BACKGROUND: Awake craniotomy is an effective procedure for optimizing the onco-functional balance of resections in glioma. However, limited data exists on the cognition, emotional states, and health-related quality of life (HRQoL) of patients with glioma who undergo awake craniotomy. This study aims to describe 1) perioperative cognitive function and emotional states in a multilingual Asian population, 2) associations between perioperative cognitive function and follow-up HRQoL, and 3) associations between preoperative emotional states and follow-up HRQoL. METHODS: This is a case series of 14 adult glioma patients who underwent awake craniotomy in Singapore. Cognition was assessed with the Montreal Cognitive Assessment and the Repeatable Battery for the Assessment of Neuropsychological Status, emotional states with the Depression, Anxiety and Stress Scale-21 Items, and HRQoL using the EuroQol-5D-5L, the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, and the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-BN20. RESULTS: Patients with better preoperative cognitive scores on all domains reported better HRQoL. Better postoperative immediate memory and language scores were associated with better HRQoL. Moderate preoperative depression scores and mild and moderate preoperative stress scores were associated with poorer HRQoL compared to scores within the normal range. Mild preoperative anxiety scores were associated with better HRQoL compared to scores within the normal range. CONCLUSION: This descriptive case series showed that patients with higher preoperative cognitive scores reported better follow-up HRQoL, while patients who reported more preoperative depressive and stress symptomatology reported worse follow-up HRQoL. Future analytical studies may help to draw conclusions about whether perioperative cognition and emotional states predict HRQoL on follow-up.


Asunto(s)
Neoplasias Encefálicas , Glioma , Adulto , Humanos , Calidad de Vida , Neoplasias Encefálicas/complicaciones , Vigilia , Glioma/complicaciones , Glioma/cirugía , Glioma/psicología , Cognición , Craneotomía , Encuestas y Cuestionarios
17.
Clin Neurol Neurosurg ; 233: 107963, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37703616

RESUMEN

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.

18.
World Neurosurg ; 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37406798

RESUMEN

BACKGROUND: Craniopharyngiomas arise from the Rathke pouch and account for 1.2%-18.4% of pediatric primary brain tumors. Despite relatively good survival outcomes, patients face long-term morbidity from recurrences, visual impairment, and endocrinopathies, which reduce quality of life. We examined the management of pediatric craniopharyngiomas, their recurrences, and subsequent neuroendocrine sequelae in a tertiary center in South-East Asia. METHODS: A retrospective cohort of 12 paediatric patients (aged ≤18 years) with histologically confirmed diagnosis of craniopharyngioma treated from January 2002 to June 2017 was conducted. Data collected included demographics, clinical presentation, imaging data, treatment details, postoperative sequelae, and outcomes on mortality and recurrence. Survival analysis was conducted using Cox-proportional hazards model. RESULTS: The median follow-up time was 6.60 years (1.9-11.5 years). The mean age was 7.6 years (standard deviation 4.8) and 7 patients (58.3%) were male. The most common presenting symptoms were raised intracranial pressure (7, 58.3%), visual deficits (6, 50.0%), and preoperative endocrine abnormalities (2, 16.7%). Five patients underwent gross total resection (41.7%), and 7 underwent subtotal resection (58.3%). Overall survival was 75.0% (9 patients), and recurrence was 58.0% (7 patients). Median time-to-recurrence was 5.87 months (0.23-33.7, interquartile range 15.8), and median progression-free survival was 4.16 years (0.18-10.1, interquartile range 5.29). CONCLUSIONS: Long-term management of pediatric craniopharyngioma remains difficult, with multiple recurrences and long-term neuroendocrine sequelae impairing quality of life for patients. Further research into management of recurrences and neuroendocrine sequelae, as well as novel therapies to improve outcomes in these patients, may be warranted.

19.
Singapore Med J ; 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37675681

RESUMEN

Introduction: The most recent local study on the incidence of histological subtypes of all brain and spinal tumours treated surgically was published in 2000. In view of the outdated data, we investigated the presenting characteristics, histological subtypes and outcomes of adult patients who underwent surgery for brain or spinal tumours at our institution. Methods: A single-centre retrospective review of 501 patients who underwent surgery for brain or spinal tumours from 2016 to 2020 was conducted. The inclusion criteria were (a) patients who had a brain or spinal tumour that was histologically verified and (b) patients who were aged 18 years and above at the time of surgery. Results: Four hundred and thirty-five patients (86.8%) had brain tumours and 66 patients (13.2%) had spinal tumours. Patients with brain tumours frequently presented with cranial nerve palsy, headache and weakness, while patients with spinal tumours frequently presented with weakness, numbness and back pain. Overall, the most common histological types of brain and spinal tumours were metastases, meningiomas and tumours of the sellar region. The most common complications after surgery were cerebrospinal fluid leak, diabetes insipidus and urinary tract infection. In addition, 15.2% of the brain tumours and 13.6% of the spinal tumours recurred, while 25.7% of patients with brain tumours and 18.2% of patients with spinal tumours died. High-grade gliomas and metastases had the poorest survival and highest recurrence rates. Conclusion: This study serves as a comprehensive update of the epidemiology of brain and spinal tumours and could help guide further studies on brain and spinal tumours.

20.
BMJ Open ; 13(10): e077219, 2023 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-37879700

RESUMEN

INTRODUCTION: Conventional interventional modalities for preserving or improving cognitive function in patients with brain tumour undergoing radiotherapy usually involve pharmacological and/or cognitive rehabilitation therapy administered at fixed doses or intensities, often resulting in suboptimal or no response, due to the dynamically evolving patient state over the course of disease. The personalisation of interventions may result in more effective results for this population. We have developed the CURATE.AI COR-Tx platform, which combines a previously validated, artificial intelligence-derived personalised dosing technology with digital cognitive training. METHODS AND ANALYSIS: This is a prospective, single-centre, single-arm, mixed-methods feasibility clinical trial with the primary objective of testing the feasibility of the CURATE.AI COR-Tx platform intervention as both a digital intervention and digital diagnostic for cognitive function. Fifteen patient participants diagnosed with a brain tumour requiring radiotherapy will be recruited. Participants will undergo a remote, home-based 10-week personalised digital intervention using the CURATE.AI COR-Tx platform three times a week. Cognitive function will be assessed via a combined non-digital cognitive evaluation and a digital diagnostic session at five time points: preradiotherapy, preintervention and postintervention and 16-weeks and 32-weeks postintervention. Feasibility outcomes relating to acceptability, demand, implementation, practicality and limited efficacy testing as well as usability and user experience will be assessed at the end of the intervention through semistructured patient interviews and a study team focus group discussion at study completion. All outcomes will be analysed quantitatively and qualitatively. ETHICS AND DISSEMINATION: This study has been approved by the National Healthcare Group (NHG) DSRB (DSRB2020/00249). We will report our findings at scientific conferences and/or in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04848935.


Asunto(s)
Inteligencia Artificial , Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/radioterapia , Cognición , Estudios de Factibilidad , Estudios Prospectivos
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