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1.
BMC Med Imaging ; 24(1): 125, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802734

RESUMO

PURPOSE: Accurate prognostication may aid in the selection of patients who will benefit from surgery at recurrent WHO grade 4 glioma. This study aimed to evaluate the role of serial tumour volumetric measurements for prognostication at first tumour recurrence. METHODS: We retrospectively analyzed patients with histologically-diagnosed WHO grade 4 glioma at initial and at first tumour recurrence at a tertiary hospital between May 2000 and September 2018. We performed auto-segmentation using ITK-SNAP software, followed by manual adjustment to measure serial contrast-enhanced T1W (CE-T1W) and T2W lesional volume changes on all MRI images performed between initial resection and repeat surgery. RESULTS: Thirty patients met inclusion criteria; the median overall survival using Kaplan-Meier analysis from second surgery was 10.5 months. Seventeen (56.7%) patients received treatment post second surgery. Univariate cox regression analysis showed that greater rate of increase in lesional volume on CE-T1W (HR = 2.57; 95% CI [1.18, 5.57]; p = 0.02) in the last 2 MRI scans leading up to the second surgery was associated with a higher mortality likelihood. Patients with higher Karnofsky Performance Score (KPS) (HR = 0.97; 95% CI [0.95, 0.99]; p = 0.01) and who received further treatment following second surgery (HR = 0.43; 95% CI [0.19, 0.98]; p = 0.04) were shown to have a better survival. CONCLUSION: Higher rate of CE-T1W lesional growth on the last 2 MRI images prior to surgery at recurrence was associated with increase mortality risk. A larger prospective study is required to determine and validate the threshold to distinguish rapidly progressive tumour with poor prognosis.


Assuntos
Neoplasias Encefálicas , Glioma , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia , Humanos , Glioma/diagnóstico por imagem , Glioma/mortalidade , Glioma/cirurgia , Glioma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Estudos Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Prognóstico , Idoso , Gradação de Tumores , Carga Tumoral , Estimativa de Kaplan-Meier
2.
J Clin Neurosci ; 115: 60-65, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37487449

RESUMO

Overall survival (OS)for glioblastoma multiforme (GBM) has a known association with the extent of tumor resection with gross total resection (GTR) typically considered as the upper limit. In certain regions such as the anterior temporal lobe, more extensive resection by means of a lobectomy may be feasible. In our systematic review and meta-analysis, we aimed to compare the outcomes of lobectomy and GTR for GBM. PubMed and Embase were queriedfor studies that compared the outcomes after lobectomy or GTR for GBM. The primary outcomes were OS, progression-free survival (PFS), and Karnofksy Performance Status (KPS) score at the latest follow-up. The secondary outcomes were seizure control at the latest follow-up and complication rates. Meta-analysis for OS and PFS was performed using individual-participant data reconstructed from published Kaplan-Meier curves. Random-effect meta-analysis was performed for KPS. The secondary outcomes were pooled using descriptive statistics. Of the 795 records screened, 6 were included in our study. Meta-analysis revealed that anterior temporal, frontal, or occipital lobectomy was associated with significantly better OS (p < 0.001) and PFS (p < 0.001) than GTR, but not KPS (MD = 6.37; 95% CI=(-13.80, 26.54); p = 0.536). Anterior temporal lobectomy was associated with significantly better seizure control rates than GTR for temporal GBM (OR = 27; 95% CI=(1.4, 515.9); p = 0.002). There was no statistically significant difference in complication rates between anterior temporal, frontal, or occipital lobectomy and GTR. In conclusion, lobectomy was associated with significantly better OS, PFS, and seizure control than GTR for GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Psicocirurgia , Humanos , Glioblastoma/patologia , Neoplasias Encefálicas/patologia , Intervalo Livre de Progressão , Convulsões/cirurgia , Estudos Retrospectivos , Procedimentos Neurocirúrgicos/efeitos adversos
3.
Opt Express ; 31(9): 13751-13762, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37157256

RESUMO

The inter-satellite laser ranging heterodyne interferometer is vital for future gravity missions to achieve high ranging accuracy. This paper proposes a novel off-axis optical bench design which integrates merits of the off-axis optical bench design of GRACE Follow-On mission and other on-axis designs. This design makes use of lens systems subtly to restrict the tilt-to-length coupling noise and takes advantage of the DWS feedback loop to maintain the transmitting beam and receiving beam anti-parallel. The critical parameters of the optical components are determined and the carrier-to-noise ratio for a single channel of the photoreceiver is calculated to be more than 100 dB-Hz for the high case. The off-axis optical bench design is a potential candidate for China's future gravity missions.

4.
Pilot Feasibility Stud ; 9(1): 6, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635739

RESUMO

BACKGROUND: In Singapore, research teams seek informed patient consent on an ad hoc basis for specific clinical studies and there is typically a role separation between operational and research staff. With the enactment of the Human Biomedical Research Act, there is increased emphasis on compliance with consent-taking processes and research documentation. To optimize resource use and facilitate long-term research sustainability at our institution, this study aimed to design and pilot an institution level informed consent workflow (the "intervention") that is integrated with clinic operations. METHODS: We used the Consolidated Framework for Implementation Research (CFIR) as the underpinning theoretical framework and conducted the study in three stages: Stage 1, CFIR constructs were used to systematically identify barriers and facilitators of intervention implementation, and a simple time-and-motion study of the patient journey was used to inform the design of the intervention; Stage 2, implementation strategies were selected and mapped to the Expert Recommendations for Implementing Change (ERIC) taxonomy; Stage 3, we piloted and adapted the implementation process at two outpatient clinics and evaluated implementation effectiveness through patient participation rates. RESULTS: We identified 15 relevant CFIR constructs. Implementation strategies selected to address these constructs were targeted at three groups of stakeholders: institution leadership (develop relationships, involve executive boards, identify and prepare champions), clinic management team (develop relationships, identify and prepare champions, obtain support and commitment, educate stakeholders), and clinic operations staff (develop relationships, assess readiness, conduct training, cyclical tests of change, model and simulate change, capture and share local knowledge, obtain and use feedback). Time-and-motion study in clinics identified the pre-consultation timepoint as the most appropriate for the intervention. The implementation process was adapted according to clinic operations staff and service needs. At the conclusion of the pilot, 78.3% of eligible patients provided institution level informed consent via the integrated workflow implemented. CONCLUSIONS: Our findings support the feasibility of implementing an institution level informed consent workflow that integrates with service operations at the outpatient setting to optimize healthcare resources for research. The CFIR provided a useful framework to identify barriers and facilitators in the design of the intervention and its implementation process.

7.
Psychogeriatrics ; 20(5): 608-619, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32654358

RESUMO

AIM: Early-onset dementia (EOD) (defined as dementia onset before age 65) presents specific challenges and issues, adding to the negative impact of dementia on the health-related quality of life (HRQOL) of both patients and their caregivers. However, very few published studies have specifically compared the HRQOL of caregivers of people with EOD and late-onset dementia (LOD). This information is critical in allocating and prioritizing scarce health-care resources. We aimed to assess the HRQOL of primary informal caregivers of community-dwelling individuals with EOD in Singapore and compare it with that of caregivers of individuals with LOD. METHODS: This was a cross-sectional study of consecutive patient-caregiver dyads from a tertiary dementia clinic. RESULTS: No significant differences in disease severity were found between the 111 EOD and 235 LOD patient-caregiver dyads. The mean Mental Component Summary score of the 36-item Short-Form Health Survey version 2 was significantly worse in caregivers of EOD patients than in LOD caregivers (mean: 41.42 vs 45.12, P = 0.001), although the mean Physical Component Summary scores were comparable (49.71 vs 49.53, P = 0.934). However, the impact of dementia early onset on caregivers' mental health diminished immediately after adjustment for the disease severity indicators, of which the Neuropsychiatric Inventory Questionnaire distress score was the only significant clinical factor (regression coefficient ß = -0.29, P < 0.001). The amount of variability in the HRQOL of the caregivers explained by patient and caregiver factors across all the models was rather small (adjusted R2 = 19.3% for the Mental Composite Score, 5.2% for Physical Composite Score). CONCLUSION: Caregivers of EOD patients had worse mental health than LOD caregivers probably because individual with EOD have more behavioural disturbances. This reinforces the indispensable role of managing behavioural problems when caring for a family member with dementia, especially for EOD. HRQOL ideally needs to be assessed based on self-report rather than inferences from indirect data such as the subjective caregiver burden.


Assuntos
Cuidadores , Demência , Qualidade de Vida , Idade de Início , Idoso , Cuidadores/psicologia , Estudos Transversais , Demência/enfermagem , Nível de Saúde , Humanos , Singapura
8.
J Neurooncol ; 148(3): 599-606, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32506369

RESUMO

PURPOSE: The CellSearch® system has been used to identify circulating tumor cells (CTCs) in cerebrospinal fluid (CSF) to diagnose leptomeningeal metastasis (LM) in patients with epithelial cancers. Using this system, we prospectively explored sequential CSF CTC enumeration in patients with LM from HER2+ cancers receiving intrathecal (IT) trastuzumab to capture dynamic changes in CSF CTC enumeration. METHODS: CSF from patients enrolled in an IRB-approved phase I/II dose escalation trial of IT trastuzumab for LM in HER2+ cancer (NCT01325207) was obtained on day 1 of each cycle and was evaluated by the CellSearch® platform for CTC enumeration. The results were correlated with CSF cytology from the same sample, along with clinical and radiographic response. RESULTS: Fifteen out of 34 patients with HER2+ LM were enrolled in CSF CTC analysis; 14 were women. Radiographic LM was documented in 14 (93%) patients; CSF cytology was positive in 6 (40%) and CSF CTCs were identified in 13 (87%). Median CSF CTC was 22 CTCs (range 0-200 +) per 3 ml. HER2/neu expression analysis of CTCs was performed in 8 patients; 75% had confirmed expression of HER2/neu positivity in CSF and HER2/neu expression was absent in 25%. Four of 10 patients received 7 or more cycles of IT trastuzumab; in 3 of these patients, increase in CSF CTCs enumeration from baseline was detected 2-3 months prior to changes seen on MRI, and while CSF cytology remained negative. CONCLUSION: Our study demonstrates that enumeration of CSF CTCs may provide dynamic, quantitative assessment of tumor burden in the central nervous system compartment during treatment for LM and prior to changes on MRI or CSF cytology. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01325207; registered March 29th, 2011.


Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias da Mama/patologia , Carcinomatose Meníngea/secundário , Células Neoplásicas Circulantes/patologia , Receptor ErbB-2/metabolismo , Trastuzumab/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/líquido cefalorraquidiano , Neoplasias da Mama/tratamento farmacológico , Feminino , Seguimentos , Humanos , Injeções Espinhais , Carcinomatose Meníngea/líquido cefalorraquidiano , Carcinomatose Meníngea/tratamento farmacológico , Células Neoplásicas Circulantes/metabolismo , Prognóstico , Taxa de Sobrevida
9.
Neuro Oncol ; 22(5): 675-683, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32352148

RESUMO

BACKGROUND: Improvements in detection and molecular characterization of leptomeningeal metastasis from lung cancer (LC-LM) coupled with cerebrospinal fluid (CSF)-penetrating targeted therapies have altered disease management. A barrier to formal study of these therapies in LM is quantification of disease burden. Also, outcomes of patients with targetable mutations in LC-LM are not well defined. This study employs molecular and radiographic measures of LM disease burden and correlates these with outcome. METHODS: We reviewed charts of 171 patients with LC-LM treated at Memorial Sloan Kettering. A subset had MRI and CSF studies available. Radiographic involvement (n = 76) was scored by number of gadolinium-enhancing sites in 8 locations. CSF studies included cytopathology, circulating tumor cell (CTC) quantification (n = 16), and cell-free DNA (cfDNA) analysis (n = 21). Clinical outcomes were compared with Kaplan-Meier log-rank test and Cox proportional hazards methodologies. RESULTS: Median overall survival was 4.2 months (95% CI: 3.6-4.9); 84 patients (49%) harbored targetable mutations. Among bevacizumab-naïve patients with MRI and CSF cytology at time of LC-LM diagnosis, extent of radiographic involvement correlated with risk of death (hazard ratio [HR]: 1.16; 95% CI: 1.02-1.33; P = 0.03), as did CSF CTC (HR: 3.39, 95% CI: 1.01-11.37; P = 0.048) and CSF cfDNA concentration (HR: 2.58; 95% CI: 0.94-7.05; P = 0.06). Those without a targetable mutation were almost 50% more likely to die (HR: 1.49; 95% CI: 1.06-2.11; P = 0.02). CONCLUSIONS: Extent of radiographic involvement and quantification of CSF CTC and cfDNA show promise as prognostic indicators. These findings support molecular characterization and staging for clinical management, prognostication, and clinical trial stratification of LC-LM.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinomatose Meníngea , Neoplasias Meníngeas , Carcinoma Pulmonar de Células não Pequenas/genética , Efeitos Psicossociais da Doença , Humanos , Neoplasias Pulmonares/genética , Neoplasias Meníngeas/genética , Estudos Retrospectivos
10.
Neuroradiology ; 62(6): 765, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32211926

RESUMO

The above article was published with incorrect list of authors. We have added Seyed Ehasan Saffari and his affiliation as the addition of the new author to the author list was requested at revision stage.

11.
Neuroradiology ; 62(6): 669-676, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32077984

RESUMO

PURPOSE: Primary central nervous system lymphoma (PCNSL) presenting with atypical radiological findings often leads to delayed diagnosis. We aim to characterize the radiological features and apparent diffusion coefficient (ADC) values of PCNSL with atypical neuroimaging presentation in our local population. METHODS: We retrospectively reviewed all patients with histological diagnosis of CNS lymphoma at our tertiary center from 2005 to 2016. We screened all initial pre-treatment MRIs and excluded cases with typical imaging findings of contrast-enhancing lesions without intra-lesional susceptibility and central non-enhancement. Additional exclusion criteria included (i) relapsed PCNSL, (ii) secondary CNS lymphoma, and (iii) positive HIV status. Two independent raters scored MRI and CT scans at presentation. We computed ADC values in the tumors by 2 methods: single region of interest (ROI1) and multiple ROI (ROI2). RESULTS: Sixteen (25.4%) of 63 patients with CNS lymphoma met inclusion criteria. There were 8 men; median age was 61 (range 22-81) years. Histological diagnoses were diffuse large B cell lymphoma (n = 14) and intravascular lymphoma (n = 2). Fifteen (93%) patients had enhancing lesions (5 solitary; 10 multifocal); most enhancing lesions had T1 hypointense (67%) and T2 mixed (53%) signals, and 6 (40%) had central non-enhancing regions. Nine (56%) patients had lesions with susceptibility. Using the ROI methods, median values for minimum ADC and mean ADC ranged 0.65-0.71 × 10-3 mm2/s and 0.79-0.84 × 10-3 mm2/s respectively. CONCLUSION: PCNSL with atypical radiological features represented one-fourth of our histologically diagnosed lymphoma cases; low ADC values in atypical lesions should prompt clinicians to consider early biopsy for definitive diagnosis.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Neuroimagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/patologia , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Linfoma/patologia , Masculino , Meglumina , Pessoa de Meia-Idade , Compostos Organometálicos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
12.
Curr Oncol Rep ; 21(7): 61, 2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31102038

RESUMO

PURPOSE OF REVIEW: Targeted therapies are part of biomarker-driven strategies that exploit actionable molecular targets and have gained traction following survival benefits demonstrated in various systemic malignancies. In glioblastoma, where therapeutic options remain scarce and prognosis poor, targeted therapies offer an attractive treatment alternative and are actively examined in clinical trials. In this review, we summarize the targeted therapies, including traditional small molecule inhibitors and monoclonal antibodies as well as immunotherapeutic approaches that are examined in clinical trials, and discuss the challenges of using them for the treatment of glioblastoma. RECENT FINDINGS: Despite initial speculations, phase II/III trials of targeted therapies in adult patients with glioblastoma have largely failed. Recent trials have focused on improving patient stratification, drug-tissue penetration, and target and compensatory pathway inhibition to optimize treatment response. In contrast to traditional small molecule and monoclonal antibody therapies, cancer immunotherapy may target specific molecular or immune checkpoint target(s) to trigger immune responses against glioblastoma. Early phase clinical trials of immunotherapy have shown encouraging results, and larger randomized trials are ongoing. Targeted therapies are being actively studied in clinical trials. Patients with glioblastoma should be prioritized for clinical trial participation.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Adulto , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Prognóstico
13.
J Neurooncol ; 140(2): 351-358, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30073640

RESUMO

PURPOSE: Prediction of clinical outcomes in patients with primary central nervous system lymphoma (PCNSL) is important for optimization of treatment planning. Quantitative imaging biomarkers for PCNSL have not yet been established. This study evaluated the prognostic value of pretreatment dynamic contrast-enhanced MRI and diffusion-weighted imaging for progression-free survival (PFS) in patients with PCNSL. METHODS: Pretreatment dynamic contrast-enhanced MRI and diffusion-weighted imaging were retrospectively analyzed in 18 immunocompetent patients with PCNSL. Volumes of interest encompassing the tumors were assessed for measurements of blood plasma volume (Vp), volume transfer constant (Ktrans), and apparent diffusion coefficient. Patients were divided into short and long PFS groups based on median PFS. Imaging and clinical variables were correlated with PFS. RESULTS: Median PFS was 19.6 months. Lower Vpmean and Ktransmean values increased risk for rapid progression (< 19.6 months). Receiver operating characteristic curve analysis demonstrated an optimal Vpmean cutoff value of 2.29 (area under the curve [AUC] = 0.74, sensitivity and specificity = 0.78, p = 0.023) for separating patients with short and long PFS. The optimal Ktransmean cutoff was 0.08 (AUC = 0.74, sensitivity = 0.67, specificity = 0.78, p = 0.025). Kaplan-Meier survival analysis with log-rank test demonstrated significantly (p = 0.015) increased risk of rapid progression for patients with Vpmean < 2.29. Vpmean was significantly (p = 0.03) associated with PFS on univariate Cox analysis. Apparent diffusion coefficient values and clinical factors did not influence PFS. CONCLUSIONS: Pretreatment Vp and Ktrans derived from dynamic contrast-enhanced MRI may be novel prognostic quantitative imaging biomarkers of progression-free survival in patients with PCNSL. These data should be prospectively validated in larger patient cohorts.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Meios de Contraste , Linfoma/diagnóstico por imagem , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Humanos , Linfoma/terapia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Tempo
14.
J Clin Oncol ; 36(17): 1702-1709, 2018 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-29683790

RESUMO

Purpose Carboxyamidotriazole orotate (CTO) is a novel oral inhibitor of non-voltage-dependent calcium channels with modulatory effects in multiple cell-signaling pathways and synergistic effects with temozolomide (TMZ) in glioblastoma (GBM) models. We conducted a phase IB study combining CTO with two standard TMZ schedules in GBM. Methods In cohort 1, patients with recurrent anaplastic gliomas or GBM received escalating doses of CTO (219 to 812.5 mg/m2 once daily or 600 mg fixed once-daily dose) combined with TMZ (150 mg/m2 5 days during each 28-day cycle). In cohort 2, patients with newly diagnosed GBM received escalating doses of CTO (219 to 481 mg/m2/d once daily) with radiotherapy and TMZ 75 mg/m2/d, followed by TMZ 150 mg to 200 mg/m2 5 days during each 28-day cycle. Results Forty-seven patients were enrolled. Treatment was well tolerated; toxicities included fatigue, constipation, nausea, and hypophosphatemia. Pharmacokinetics showed that CTO did not alter TMZ levels; therapeutic concentrations were achieved in tumor and brain. No dose-limiting toxicities were observed; the recommended phase II dose was 600 mg/d flat dose. Signals of activity in cohort 1 (n = 27) included partial (n = 6) and complete (n = 1) response, including in O6-methylguanine-DNA methyltransferase unmethylated and bevacizumab-refractory tumors. In cohort 2 (n = 15), median progression-free survival was 15 months and median overall survival was not reached (median follow-up, 28 months; 2-year overall survival, 62%). Gene sequencing disclosed a high rate of responses among EGFR-amplified tumors ( P = .005), with mechanisms of acquired resistance possibly involving mutations in mismatch-repair genes and/or downstream components TSC2, NF1, NF2, PTEN, and PIK3CA. Conclusion CTO can be combined safely with TMZ or chemoradiation in GBM and anaplastic gliomas, displaying favorable brain penetration and promising signals of activity in this difficult-to-treat population.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Glioma/tratamento farmacológico , Triazóis/administração & dosagem , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/efeitos adversos , Quimiorradioterapia , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Glioblastoma/patologia , Glioblastoma/radioterapia , Glioma/patologia , Glioma/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Triazóis/efeitos adversos , Adulto Jovem
16.
Sci Rep ; 7(1): 12441, 2017 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-28963553

RESUMO

Post-stroke cognitive impairment (PSCI) warrants early detection and management. We sought to develop a risk score for screening patients at bedside for risk of delayed PSCI. Ischemic stroke survivors with PSCI and no cognitive impairments (NCI) 3-6 months post-stroke were studied to identify candidate variables predictive of PSCI. These variables were used to develop a risk score using regression models. The score, and the best identified clinical cutoff point, underwent development, stability testing, and internal and external validation in three independent cohorts from Singapore and Hong Kong. Across 1,088 subjects, the risk score, dubbed CHANGE, had areas under the receiver operating characteristics curve (AUROC) from 0.74 to 0.82 in detecting significant risk for PSCI, and had predicted values following actual prevalence. In validation data 3-6 and 12-18 months post-stroke, subjects with low, medium, and high scores had PSCI prevalence of 7-23%, 25-58%, and 67-82%. CHANGE was effective in screening ischemic stroke survivors for significant risk of developing PSCI up to 18 months post-stroke. CHANGE used readily available and reliable clinical data, and may be useful in identifying at-risk patients for PSCI.


Assuntos
Isquemia Encefálica/diagnóstico , Disfunção Cognitiva/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Estudos de Coortes , Diagnóstico Precoce , Feminino , Hong Kong , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Curva ROC , Análise de Regressão , Projetos de Pesquisa , Fatores de Risco , Singapura , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia
17.
J Alzheimers Dis ; 60(3): 867-875, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28922154

RESUMO

BACKGROUND: While atrial fibrillation (AF) is an important risk factor for ischemic strokes and mild cognitive impairment (MCI) in Alzheimer's disease, the association between AF and post-stroke cognitive impairment (PSCI), and the factors mediating this association, is unclear. OBJECTIVE: To investigate the role of AF in PSCI, especially in relation to other markers of cerebrovascular disease. METHODS: 445 subjects with mild ischemic stroke without pre-stroke cognitive decline were assessed 3-6 months post-stroke for cognitive deficits. MRIs were reviewed by trained raters for acute infarct characteristics, global cortical atrophy, white matter hyperintensities, cerebral microbleeds, and intracranial stenosis. Logistic regression analysis was used to identify factors independently associated with PSCI. Subjects were also categorized according to paroxysmal (pAF) or persistent/chronic AF (p/cAF), and presence or absence of AF or large cortical infarcts (LCI) to study cognitive trends. RESULTS: 80 (18.0%) subjects had AF. 76.3% of AF subjects and 42.7% of subjects without AF had PSCI. The odds ratio (OR) of AF in developing PSCI was 2.31 (95% CI: 1.12-4.75; p = 0.035), after correcting for other risk factors. pAF subjects and AF subjects with LCIs had higher ORs for PSCI. AF subjects performed worse in neuropsychological tasks associated with global cognition, episodic memory, and executive function. CONCLUSION: AF is a significant risk factor for PSCI, even after correcting for AF-related infarcts. Other mechanisms, such as hypoperfusion, microhemorrhages, and neuroinflammation, may be at play. All stroke patients with AF, regardless of the type of infarction, should be closely monitored for PSCI.


Assuntos
Fibrilação Atrial/epidemiologia , Isquemia Encefálica/epidemiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Acidente Vascular Cerebral/epidemiologia , Fibrilação Atrial/complicações , Encéfalo/diagnóstico por imagem , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/psicologia , Angiografia Cerebral , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Razão de Chances , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/psicologia
18.
Neuro Oncol ; 19(9): 1248-1254, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28821205

RESUMO

BACKGROUND: Diagnosis of leptomeningeal metastasis (LM) remains challenging due to low sensitivity of CSF cytology and infrequent unequivocal MRI findings. In a previous pilot study, we showed that rare cell capture technology (RCCT) could be used to detect circulating tumor cells (CTC) in the CSF of patients with LM from epithelial tumors. To establish the diagnostic accuracy of CSF-CTC in the diagnosis of LM, we applied this technique in a distinct, larger cohort of patients. METHODS: In this institutional review board-approved prospective study, patients with epithelial tumors and clinical suspicion of LM underwent CSF-CTC evaluation and standard MRI and CSF cytology examination. CSF-CTC enumeration was performed through an FDA-approved epithelial cell adhesion molecule-based RCCT immunomagnetic platform. LM was defined by either positive CSF cytology or imaging positive for LM. ROC analysis was utilized to define an optimal cutoff for CSF-CTC enumeration. RESULTS: Ninety-five patients were enrolled (36 breast, 31 lung, 28 others). LM was diagnosed in 30 patients (32%) based on CSF cytology (n = 12), MRI findings (n = 2), or both (n = 16). CSF-CTC were detected in 43/95 samples (median 19.3 CSF-CTC/mL, range 0.3 to 66.7). Based on ROC analysis, 1 CSF-CTC/mL provided the best threshold to diagnose LM, achieving a sensitivity of 93%, specificity of 95%, positive predictive value 90%, and negative predictive value 97%. CONCLUSIONS: We defined ≥1 CSF-CTC/mL as the optimal cutoff for diagnosis of LM. CSF-CTC enumeration through RCCT is a robust tool to diagnose LM and should be considered in the routine LM workup in solid tumor patients.


Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias Meníngeas/líquido cefalorraquidiano , Neoplasias Meníngeas/diagnóstico , Metástase Neoplásica/diagnóstico , Neoplasias Epiteliais e Glandulares/secundário , Células Neoplásicas Circulantes , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Alzheimers Dement (Amst) ; 7: 11-23, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28138511

RESUMO

INTRODUCTION: The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). METHODS: Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. RESULTS: Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years. DISCUSSION: Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.

20.
Neurol Clin Pract ; 7(1): 53-64, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29849229

RESUMO

BACKGROUND: There are limited data to guide clinicians in differentiating tumefactive multiple sclerosis (TMS) from CNS neoplasms. Identifying distinguishing features will inform diagnosis and management and avoid unnecessary diagnostic biopsy. Our study aimed to determine the clinical and radiologic features that differentiate TMS from glioma and CNS lymphoma (CNSL) in patients who present with tumefactive lesions. METHODS: We retrospectively reviewed all patients with tumefactive lesions and histologically proven or clinically diagnosed TMS, glioma, or CNSL at our tertiary center from 1999 to 2012. Two independent blinded neuroradiologists rated MRI brain scans at presentation. We correlated patients' demographic, clinical, laboratory, and radiologic data to final diagnosis. RESULTS: A total of 133 patients (10 TMS, 85 glioma, 38 CNSL) were analyzed. Patients with TMS were younger and a greater proportion were women. Presenting symptoms did not distinguish between diagnoses. TMS lesions were smaller compared to glioma and CNSL, had no or mild mass effect, and were always associated with contrast enhancement. Radiologic features that were more frequent in TMS lesions were incomplete rim (open-ring) enhancement, incomplete peripheral diffusion restriction, and mixed T2 signal and CT hypoattenuation of MRI-enhancing components (all p < 0.05). CONCLUSIONS: Radiologic features but not presenting symptoms are useful in distinguishing TMS from CNS neoplasms.

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