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1.
Pain Pract ; 24(4): 584-599, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38078593

RESUMO

INTRODUCTION: The use of spinal cord stimulation (SCS) therapy to treat chronic pain continues to rise. Optimal patient selection remains one of the most important factors for SCS success. However, despite increased utilization and the existence of general indications, predicting which patients will benefit from neuromodulation remains one of the main challenges for this therapy. Therefore, this study aims to identify the variables that may correlate with nonresponders to high-frequency (10 kHz) SCS to distinguish the subset of patients less likely to benefit from this intervention. MATERIALS AND METHODS: This was a retrospective single-center observational study of patients who underwent 10 kHz SCS implant. Patients were divided into nonresponders and responders groups. Demographic data and clinical outcomes were collected at baseline and statistical analysis was performed for all continuous and categorical variables between the two groups to calculate statistically significant differences. RESULTS: The study population comprised of 237 patients, of which 67.51% were responders and 32.49% were nonresponders. There was a statistically significant difference of high levels of kinesiophobia, high self-perceived disability, greater pain intensity, and clinically relevant pain catastrophizing at baseline in the nonresponders compared to the responders. A few variables deemed potentially relevant, such as age, gender, history of spinal surgery, diabetes, alcohol use, tobacco use, psychiatric illness, and opioid utilization at baseline were not statistically significant. CONCLUSION: Our study is the first in the neuromodulation literature to raise awareness to the association of high levels of kinesiophobia preoperatively in nonresponders to 10 kHz SCS therapy. We also found statistically significant differences with greater pain intensity, higher self-perceived disability, and clinically relevant pain catastrophizing at baseline in the nonresponders relative to responders. It may be appropriate to screen for these factors preoperatively to identify patients who are less likely to respond to SCS. If these modifiable risk factors are present, it might be prudent to consider a pre-rehabilitation program with pain neuroscience education to address these factors prior to SCS therapy, to enhance successful outcomes in neuromodulation.


Assuntos
Dor Crônica , Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/efeitos adversos , Estudos Retrospectivos , Dor Crônica/terapia , Dor Crônica/etiologia , Manejo da Dor , Catastrofização , Resultado do Tratamento , Medula Espinal
2.
Climacteric ; 26(3): 193-197, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37011667

RESUMO

This study on the longer-term health consequences of ovarian hormone deficiency (OHD) received the Henry Burger Prize in 2022. Osteoporosis, cardiovascular disease and dementia are major degenerative diseases that are also causally associated with OHD. Two randomized controlled trials (RCTs) revealed no significant difference in bone mineral density by adding alendronate to ongoing menopausal hormone therapy (MHT) or combining alendronate at MHT initiation. Another RCT pursuing the effects on fracture recurrence and total mortality in women with hip fracture disclosed that MHT with percutaneous estradiol gel (PEG) and micronized progesterone (MP4) was comparable to risedronate. Basic studies reported that 17ß-estradiol exerted direct beneficial actions on vascular smooth muscle in cell proliferation, fibrinolysis and apoptosis. A fourth RCT showed that MP4 had a neutral impact on the PEG response of blood pressure and arterial stiffness. A fifth RCT suggested that the combination therapy of conjugated equine estrogen and MP4 was superior to tacrine in preserving activities in daily living in women with Alzheimer's disease. In addition, PEG plus MP4 attenuated cognitive decline in women with mild cognitive impairment in a sixth RCT. Finally, the all-cause mortality in recently menopausal women receiving MHT was updated using an adaptive meta-analysis of four RCTs.


Assuntos
Terapia de Reposição de Estrogênios , Fraturas Ósseas , Humanos , Feminino , Alendronato , Menopausa , Estradiol , Progesterona
4.
Climacteric ; 24(4): 408-414, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240673

RESUMO

OBJECTIVES: An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture. METHODS: Among 1165 eligible women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD). RESULTS: Kaplan-Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (p = 0.180); that of clinical fracture was 4.75 and 6.99, respectively (p = 0.265); and that of asymptomatic vertebral fracture was 4.87 and 5.58, respectively (p = 0.764). The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503). BMD increased comparably at the lumbar spine in both groups. BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group. CONCLUSIONS: MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture.


Assuntos
Fraturas do Quadril , Terapia de Reposição Hormonal , Menopausa , Ácido Risedrônico/uso terapêutico , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Humanos
5.
AJNR Am J Neuroradiol ; 42(5): 831-837, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33541897

RESUMO

BACKGROUND AND PURPOSE: Severe respiratory distress in patients with COVID-19 has been associated with higher rate of neurologic manifestations. Our aim was to investigate whether the severity of chest imaging findings among patients with coronavirus disease 2019 (COVID-19) correlates with the risk of acute neuroimaging findings. MATERIALS AND METHODS: This retrospective study included all patients with COVID-19 who received care at our hospital between March 3, 2020, and May 6, 2020, and underwent chest imaging within 10 days of neuroimaging. Chest radiographs were assessed using a previously validated automated neural network algorithm for COVID-19 (Pulmonary X-ray Severity score). Chest CTs were graded using a Chest CT Severity scoring system based on involvement of each lobe. Associations between chest imaging severity scores and acute neuroimaging findings were assessed using multivariable logistic regression. RESULTS: Twenty-four of 93 patients (26%) included in the study had positive acute neuroimaging findings, including intracranial hemorrhage (n = 7), infarction (n = 7), leukoencephalopathy (n = 6), or a combination of findings (n = 4). The average length of hospitalization, prevalence of intensive care unit admission, and proportion of patients requiring intubation were significantly greater in patients with acute neuroimaging findings than in patients without them (P < .05 for all). Compared with patients without acute neuroimaging findings, patients with acute neuroimaging findings had significantly higher mean Pulmonary X-ray Severity scores (5.0 [SD, 2.9] versus 9.2 [SD, 3.4], P < .001) and mean Chest CT Severity scores (9.0 [SD, 5.1] versus 12.1 [SD, 5.0], P = .041). The pulmonary x-ray severity score was a significant predictor of acute neuroimaging findings in patients with COVID-19. CONCLUSIONS: Patients with COVID-19 and acute neuroimaging findings had more severe findings on chest imaging on both radiographs and CT compared with patients with COVID-19 without acute neuroimaging findings. The severity of findings on chest radiography was a strong predictor of acute neuroimaging findings in patients with COVID-19.


Assuntos
Encefalopatias/virologia , COVID-19/patologia , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/virologia , Idoso , Encefalopatias/diagnóstico por imagem , COVID-19/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X/métodos
6.
AJNR Am J Neuroradiol ; 41(10): 1791-1796, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912875

RESUMO

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) is increasingly being recognized for its multiorgan involvement, including various neurological manifestations. We examined the frequency of acute intracranial abnormalities seen on CT and/or MR imaging in patients with COVID-19 and investigated possible associations between these findings and clinical parameters, including length of hospital stay, requirement for intubation, and development of acute kidney injury. MATERIALS AND METHODS: This was a retrospective study performed at a large academic hospital in the United States. A total of 641 patients presented to our institution between March 3, 2020, and May 6, 2020, for treatment of coronavirus disease 2019, of whom, 150 underwent CT and/or MR imaging of the brain. CT and/or MR imaging examinations were evaluated for the presence of hemorrhage, infarction, and leukoencephalopathy. The frequency of these findings was correlated with clinical variables, including body mass index, length of hospital stay, requirement for intubation, and development of acute kidney injury as documented in the electronic medical record. RESULTS: Of the 150 patients, 26 (17%) had abnormal CT and/or MR imaging findings, with hemorrhage in 11 of the patients (42%), infarction in 13 of the patients (50%), and leukoencephalopathy in 7 of the patients (27%). Significant associations were seen between abnormal CT/MR imaging findings and intensive care unit admission (P = .039), intubation (P = .004), and acute kidney injury (P = .030). CONCLUSIONS: A spectrum of acute neuroimaging abnormalities was seen in our cohort of patients with coronavirus disease 2019, including hemorrhage, infarction, and leukoencephalopathy. Significant associations between abnormal neuroimaging studies and markers of disease severity (intensive care unit admission, intubation, and acute kidney injury) suggest that patients with severe forms of coronavirus disease 2019 may have higher rates of neuroimaging abnormalities.


Assuntos
Betacoronavirus , Doenças do Sistema Nervoso Central/etiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Injúria Renal Aguda/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Doenças do Sistema Nervoso Central/diagnóstico por imagem , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Leucoencefalopatias , Masculino , Pessoa de Meia-Idade , Neuroimagem , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
8.
AJNR Am J Neuroradiol ; 41(10): 1949-1952, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32763902

RESUMO

Myalgia is a previously reported symptom in patients with COVID-19 infection; however, the presence of paraspinal myositis has not been previously reported. We report MR imaging findings of the spine obtained in a cohort of 9 patients with COVID-19 infection who presented to our hospital between March 3, 2020 and May 6, 2020. We found that 7 of 9 COVID-19 patients (78%) who underwent MR imaging of the spine had MR imaging evidence of paraspinal myositis, characterized by intramuscular edema and/or enhancement. Five of these 7 patients had a prolonged hospital course (greater than 25 days). Our knowledge of the imaging manifestations of COVID-19 infection is expanding. It is important for clinicians>a to be aware of the relatively high frequency of paraspinal myositis in this small cohort of patients with COVID-19 infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Miosite/diagnóstico por imagem , Miosite/etiologia , Pneumonia Viral/complicações , Coluna Vertebral/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2
10.
AJNR Am J Neuroradiol ; 41(7): 1245-1250, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32554422

RESUMO

BACKGROUND AND PURPOSE: For primary squamous cell carcinoma of the oral tongue, accurate assessment of tumor thickness and depth of invasion is critical for staging and operative management. Currently, typical imaging modalities used for preoperative staging are CT and MR imaging. Intraoperatively, CT or MR imaging cannot provide real-time guidance, and assessment by manual palpation is limited in precision. We investigated whether intraoperative sonography is a feasible technique for assessment of tumor thickness and depth of invasion and validated its accuracy by comparing it with histopathologic evaluation of the resected specimen. MATERIALS AND METHODS: Twenty-six patients with squamous cell carcinoma of the oral tongue who underwent tumor resection by a single surgeon between March 31, 2016, and April 26, 2019, were prospectively identified. Intraoperative sonography was obtained in planes longitudinal and transverse to the long axis of the tumor. Twenty-two patients had archived images that allowed measurements of tumor thickness and depth of invasion sonographically. Two patients had dysplasia and were excluded. The remaining 20 patients had histologic tumor thickness and histologic depth of invasion measured by a single pathologist. RESULTS: The mean sonographic tumor thickness was 7.5 ± 3.5 mm, and the mean histologic tumor thickness was 7.0 ± 4.2 mm. Mean sonographic depth of invasion and histologic depth of invasion were 6.6 ± 3.4 and 6.4 ± 4.4 mm, respectively. There was excellent correlation between sonographic and histologic measurements for both tumor thickness and depth of invasion with Pearson correlation coefficients of 0.95 (95% CI, 0.87-0.98) and 0.95 (95% CI, 0.87-0.98), respectively. CONCLUSIONS: Intraoperative sonography can provide reliable, real-time assessment of the extent of tongue tumors.


Assuntos
Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias da Língua/patologia , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico por imagem , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias/métodos , Projetos Piloto , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias da Língua/diagnóstico por imagem
11.
Osteoporos Int ; 31(2): 267-275, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31776636

RESUMO

Bone mineral density (BMD) is significantly decreased after gastrectomy in patients with gastric cancer. Calcium malabsorption, secondary hyperparathyroidism, and dominant bone resorption appear to contribute to bone loss in these patients. Patients should undergo early surveillance and nutritional or pharmacologic intensive interventions for bone health. PURPOSE: Survivorship care, including bone health, has become an important issue in gastric cancer. We performed a meta-analysis of the available observational studies to determine whether and how osteoporosis risk is increased after gastrectomy in patients with gastric cancer. METHODS: A total of 1204 patients (802 men) from 19 cohort studies were included. We evaluated the prevalence of osteoporosis in postgastrectomy patients, comparing the incidence according to the type of gastrectomy and sex. Additionally, we evaluated changes in bone mineral density (BMD) and bone metabolism-related markers pre- to postoperatively and between patients who underwent gastrectomy and matched controls. Proportion meta-analysis was performed and pooled odds ratios (ORs) were calculated. RESULTS: The pooled incidence estimate was 36% [95% confidence interval (CI), 32-40]. The incidence of osteoporosis was significantly higher in women than in men (OR = 1.90, p < 0.001) but was similar between partial and total gastrectomy groups (OR = 0.983, p = 0.939). BMD was significantly decreased, and calcium, phosphorous, and parathyroid hormone levels were significantly increased in patients after gastrectomy compared to those before gastrectomy. BMD and calcium and 25OH-vitamin D levels were significantly decreased, and parathyroid hormone and 1,25OH-vitamin D levels were significantly increased in the gastrectomy group compared to that in the control group. CONCLUSION: We found that BMD is significantly decreased after gastrectomy in patients with gastric cancer. Vitamin D deficiency and secondary hyperparathyroidism are suggested to be common mechanism underlying BMD impairment. After resection, patients should undergo long-term nutritional and bone health surveillance, in addition to their oncological follow-up.


Assuntos
Densidade Óssea , Gastrectomia , Osteoporose , Neoplasias Gástricas , Cálcio , Feminino , Gastrectomia/efeitos adversos , Humanos , Masculino , Osteoporose/epidemiologia , Osteoporose/etiologia , Hormônio Paratireóideo , Neoplasias Gástricas/cirurgia , Vitamina D
12.
Bone Joint J ; 101-B(8): 897-901, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31362553

RESUMO

Ceramic bearings have several desirable properties, such as resistance to wear, hardness, and biocompatibility, that favour it as an articulating surface in hip arthroplasty. However, ceramic fracture remains a concern. We have reviewed the contemporary literature, addressing the factors that can influence the incidence of ceramic bearing surface fracture. Cite this article: Bone Joint J 2019;101-B:897-901.


Assuntos
Artroplastia de Quadril/instrumentação , Cerâmica , Prótese de Quadril , Desenho de Prótese , Falha de Prótese , Cerâmica/efeitos adversos , Prótese de Quadril/efeitos adversos , Humanos , Falha de Prótese/efeitos adversos , Falha de Prótese/etiologia
13.
Biomaterials ; 206: 73-86, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30953907

RESUMO

Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness and relatively broad drug spatial distribution. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body with high spatial and temporal precision. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle meet these needs, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs, beyond a few niche applications. Here, we develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted delivery of hydrophobic drugs with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that are scalable and yield sterile, stable, and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, we exhibit a new potential application of these nanoemulsions for local control of vascular tone. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for efficacious, noninvasive, and localized ultrasonic drug uncaging for myriad targets in the brain and body.


Assuntos
Emulsões/química , Fluorocarbonos/química , Nanopartículas/química , Polímeros/química , Sistemas de Liberação de Medicamentos/métodos
14.
Eur J Neurol ; 26(2): 261-267, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30168901

RESUMO

BACKGROUND AND PURPOSE: The P2Y12 receptor, a well-known factor in the platelet activation pathway, plays a role in thrombosis as well as systemic inflammation. Clopidogrel, a prototype P2Y12 receptor antagonist, reportedly decreases inflammation and systemic infection. The aim of this study was to evaluate whether clopidogrel use decreases the risk of post-stroke infection following ischaemic stroke. METHODS: A total of 1643 patients with acute ischaemic stroke (within 7 days after onset) were included for analysis between March 2010 and December 2015. Patients were categorized into two groups (clopidogrel users versus clopidogrel non-users), and clinical characteristics and risks of post-stroke infection were compared between the two groups. The inverse probability of treatment weighting using propensity scores for baseline imbalance adjustments was applied. RESULTS: Of the included patients (mean age 67.7 years; men 60.6%), 670 (40.8%) patients were clopidogrel users and 164 (10.0%) patients had post-stroke infection. The proportion of patients with post-stroke infection was significantly lower in clopidogrel users compared to clopidogrel non-users (6.7% vs. 12.2%, P ≤ 0.001). Moreover, clopidogrel users were less likely to be admitted to the intensive care unit (13.3% vs. 35.3%, P = 0.006). A multivariate analysis with inverse probability of treatment weighting revealed that clopidogrel users exhibited a lower risk of post-stroke infection (odds ratio 0.56, 95% confidence interval 0.42-0.75) and intensive care unit admission (odds ratio 0.34, 95% confidence interval 0.22-0.53). CONCLUSIONS: The study suggested that clopidogrel users exhibit a lower risk of infection and develop less severe infections after ischaemic stroke. Further prospective studies are needed.


Assuntos
Isquemia Encefálica/complicações , Clopidogrel/uso terapêutico , Controle de Infecções/métodos , Infecções/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Idoso , Isquemia Encefálica/tratamento farmacológico , Feminino , Humanos , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Acidente Vascular Cerebral/tratamento farmacológico
15.
AJNR Am J Neuroradiol ; 39(9): 1635-1642, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30093483

RESUMO

BACKGROUND AND PURPOSE: Early and accurate identification of cerebral metastases is important for prognostication and treatment planning although this process is often time consuming and labor intensive, especially with the hundreds of images associated with 3D volumetric imaging. This study aimed to evaluate the benefits of thick-slab overlapping MIPs constructed from contrast-enhanced T1-weighted CUBE (overlapping CUBE MIP) for the detection of brain metastases in comparison with traditional CUBE and inversion-recovery prepared fast-spoiled gradient recalled brain volume (IR-FSPGR-BRAVO) and nonoverlapping CUBE MIP. MATERIALS AND METHODS: A retrospective review of 48 patients with cerebral metastases was performed at our institution from June 2016 to October 2017. Brain MRIs, which were acquired on multiple 3T scanners, included gadolinium-enhanced T1-weighted IR-FSPGR-BRAVO and CUBE, with subsequent generation of nonoverlapping CUBE MIP and overlapping CUBE MIP. Two blinded radiologists identified the total number and location of metastases on each image type. The Cohen κ was used to determine interrater agreement. Sensitivity, interpretation time, and lesion contrast-to-noise ratio were assessed. RESULTS: Interrater agreement for identification of metastases was fair-to-moderate for all image types (κ = 0.222-0.598). The total number of metastases identified was not significantly different across the image types. Interpretation time for CUBE MIPs was significantly shorter than for CUBE and IR-FSPGR-BRAVO, saving at least 50 seconds per case on average (P < .001). The mean lesion contrast-to-noise ratio for both CUBE MIPs was higher than for IR-FSPGR-BRAVO. The mean contrast-to-noise ratio for small lesions (<4 mm) was lower for nonoverlapping CUBE MIP (1.55) than for overlapping CUBE MIP (2.35). For both readers, the sensitivity for lesion detection was high for all image types but highest for overlapping CUBE MIP and CUBE (0.93-0.97). CONCLUSIONS: This study suggests that the use of overlapping CUBE MIP or nonoverlapping CUBE MIP for the detection of brain metastases can reduce interpretation time without sacrificing sensitivity, though the contrast-to-noise ratio of lesions is highest for overlapping CUBE MIP.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Metástase Neoplásica/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Projetos Piloto , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo
16.
Mol Psychiatry ; 23(4): 1021-1030, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29565042

RESUMO

The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.


Assuntos
Aquaporina 4/metabolismo , Astrócitos/citologia , Desenvolvimento da Linguagem , Aprendizagem/fisiologia , Neuroglia/citologia , Plasticidade Neuronal/fisiologia , Adulto , Animais , Aquaporina 4/biossíntese , Aquaporina 4/genética , Astrócitos/metabolismo , Encéfalo/metabolismo , Estudos Transversais , Modelos Animais de Doenças , Feminino , Seguimentos , Frequência do Gene , Substância Cinzenta/citologia , Substância Cinzenta/metabolismo , Hipocampo/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , Neuroglia/metabolismo , Neurônios/metabolismo , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos
17.
Spine J ; 17(6): 855-862, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28126356

RESUMO

BACKGROUND CONTEXT: Spinal fusion procedures are intended to stabilize the spinal column for a multitude of disorders including abnormal curvature, traumatic instability, degenerative instability, and damage from infections or tumors. As an aid in the bone healing response, bone graft materials are used to bridge joints for arthrodesis and promote unions in pseudoarthrosis. Currently, the gold standard for stabilizing fusion masses in spinal procedures involves using the osteogenic, osteoinductive, and osteoconductive properties of autologous iliac crest corticocancellous bone. However, considerable morbidity is associated with harvesting the autologous graft. Donor site complications including infection, large hematomas, and pain have been reported at rates as high as 50% (Boden and Jeffrey, 1995). Biologically, the rate of bone repair dictates the rate at which the fusion mass will unite under autologous graft conditions. PURPOSE: The purpose of this study is to compare the quality and rate of fusion between Accell Evo3 and Grafton demineralized bone matrix (DBM), with the gold standard iliac crest bone graft (ICBG) as the control, in athymic rat posterolateral fusion. STUDY DESIGN: This study was a randomized, controlled study in a laboratory setting at the Hospital for Special Surgery in New York City. Blinded observations were made, which created an assessment of outcomes for successful fusions between each method. PATIENT SAMPLE: Forty-eight (48) athymic rats were used in this study and underwent posterolateral lumbar fusion. They were assessed at either 3 weeks or 9 weeks to see the rate and efficacy of fusion. OUTCOME MEASURES: Outcome measures will be the efficacy of the different bone grafts and their success rates of fusion in the rats. METHODS: A comparison of the quality and rate of fusion between Accell Evo3® (DBM A) and Grafton (DBM B), with the gold standard iliac crest bone graft (ICBG) as the control, was performed using the established posterolateral intertransverse process on an athymic rat model. Materials were evaluated for fusion by several criteria, including manual palpation, standard and high-resolution radiographic imaging, micro-computed topography, and histologic analysis. Forty-eight (48) athymic rats received a bilateral intertransverse process fusion, using either bone from the iliac crest (control group), Accell Evo3, or Grafton. Twelve (12) rats (four from each group) were sacrificed at 3 weeks postoperatively, whereas the remaining thirty-six (36) were sacrificed at 9 weeks postoperatively. Three blinded observers examined the spines after the rats were euthanized, and they blindly assessed each rat for fusion success. RESULTS: Manual palpation of the three different groups at 3 weeks postoperatively found successful fusion in 1 of 4 (25%) of the autologous bone graft (ABG) group and 4 of 4 (100%) of both DBM A and B groups. Manual palpation of the remaining animals that were sacrificed at 9 weeks postoperatively showed successful fusion in 4 of 12 (33%) of the ABG group, 8 of 12 (66%) of the DBM A group, and 12 of 12 (100%) of the DBM B group. Radiography found that 9 of 16 (56%) of the ABG group and 16 of 16 (100%) of both DBM Putty A and B groups had fused. Histologic analysis of the ABG group demonstrated less mature and less organized osteoid at both 3 and 9 weeks than the DBM Putty A and B groups. Nondestructive mechanical testing demonstrated increased stiffness in 4-point bending of both DBM A and B compared with ABG. CONCLUSIONS: Both DBM-treated groups achieved a significantly higher rate of fusion than the ABG-treated group at 9 weeks in this model. Successful fusion was also demonstrated in the DBM-treated groups at 3 weeks.


Assuntos
Cimentos Ósseos/efeitos adversos , Matriz Óssea/química , Substitutos Ósseos/efeitos adversos , Fusão Vertebral/métodos , Animais , Cimentos Ósseos/química , Cimentos Ósseos/uso terapêutico , Matriz Óssea/transplante , Substitutos Ósseos/química , Substitutos Ósseos/uso terapêutico , Região Lombossacral/cirurgia , Osteogênese , Ratos , Fusão Vertebral/efeitos adversos , Transplante Autólogo
18.
Eur J Neurol ; 24(1): 205-211, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27766716

RESUMO

BACKGROUND AND PURPOSE: The occurrence of stroke in cancer patients is caused by conventional vascular risk factors and cancer-specific mechanisms. However, cryptogenic stroke in patients with cancer was considered to be more related to cancer-specific hypercoagulability. In this study, we investigated the potential of the D-dimer level to serve as a predictor of early neurologic deterioration (END) in cryptogenic stroke patients with active cancer. METHODS: We recruited 109 cryptogenic stroke patients with active cancer within 72 h of symptom onset. We defined END as an increase of ≥1 point in the motor National Institutes of Health Stroke Scale (NIHSS) score or ≥2 points in the total NIHSS score within 72 h of admission. After adjusting for potential confounding factors in the multivariate analysis, we calculated the odds ratios (ORs) and confidence intervals (CIs) of D-dimer in the prediction of END. RESULTS: Among 109 patients, END events were identified in 34 (31%) patients within 72 h. END was significantly associated with systemic metastasis, multiple vascular territory lesions on the initial magnetic resonance imaging (MRI), initial NIHSS score and D-dimer levels. In the multivariate analysis, the D-dimer level (adjusted OR, 1.11; 95% CI, 1.04-1.17; P < 0.01) and initial NIHSS score (adjusted OR, 1.08; 95% CI, 1.01-1.15; P = 0.03) predicted END after adjusting for potential confounding factors. In the subgroup analysis of 72 follow-up MRIs, D-dimer level was also correlated with new territory lesions on the follow-up MRI in a dose-dependent manner. CONCLUSION: Ischemic stroke patients with active cancer and elevated D-dimer levels appear to be at increased risk for END recurrent thromboembolic stroke.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Neoplasias/complicações , Acidente Vascular Cerebral/complicações , Idoso , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/diagnóstico por imagem , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de Tempo
20.
Eur J Neurol ; 23(6): 1036-43, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26945678

RESUMO

BACKGROUND AND PURPOSE: Although abnormal sleep duration is positively associated with increased risk for cardiovascular disease and mortality, the specific impact on intracerebral haemorrhage (ICH) risk remains unclear. The relationship between sleep duration and the risk of ICH was investigated in our study. METHODS: A nationwide, multicentre matched case-control study was performed to investigate the risk factors for haemorrhagic stroke, using patients from 33 hospitals in Korea. In all, 490 patients with ICH and 980 age- and sex-matched controls were enrolled. Detailed information regarding sleep, sociodemographic factors, lifestyle and medical history before ICH onset was obtained using qualified structured questionnaires. Sleep duration was categorized and the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression with 7 h as the reference duration. RESULTS: The number of subjects with long sleep duration, more than 8 h, was significantly greater in the ICH group than in the control group (≥8 h, 30.4% vs. 22.6%, P = 0.002). After controlling for relevant confounding factors, longer sleep duration was found to be independently associated with the risk of ICH in a dose-response manner (8 h, OR 1.57, 95% CI 1.00-2.47; ≥9 h, OR 5.00, 95% CI 2.18-11.47). CONCLUSIONS: Our study suggested that long sleep duration is positively associated with an increased ICH risk in a dose-dependent manner. Further studies on the relationship linking long sleep duration with increased risk of ICH are required.


Assuntos
Hemorragia Cerebral/etiologia , Sono/fisiologia , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores de Risco , Fatores de Tempo
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