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1.
Clin Neurol Neurosurg ; 237: 108170, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38354425

RESUMO

BACKGROUND AND PURPOSE: Tenecteplase is increasingly being used as a first-line treatment for acute ischemic stroke after several randomized studies demonstrated its safety and efficacy, resulting in a massive increase in the number of published studies on this topic. Our aim was to investigate the most impactful authors and relevant journals that have been instrumental in validating this treatment, in hopes of identifying objective research trends that may assist scientists, health organizations, and funding agencies to collaborate and plan future avenues of research. METHODS: Using the search terms "Tenecteplase" and "Tenecteplase" AND "Stroke," 2683 and 1150 references were queried, respectively, using the abstract and citation database, Scopus. Scopus Citation Analysis was used to categorize the countries and authors who produced the most research. Metadata was retrieved and transferred to bibliographic visualization software, VOSviewer, for co-authorship and co-occurrence analyses to identify trends in tenecteplase research. RESULTS: Data visualization software identified three tenecteplase research clusters - myocardial infarction, pulmonary embolism, and acute ischemic stroke. Our bibliographic analysis graphically identified that ischemic stroke currently leads both myocardial infarction and pulmonary embolism in annual publications pertaining to tenecteplase therapy, and further pinpointed perfusion imaging and wake-up strokes as the most relevant areas of study. The United States led all countries in tenecteplase publications, including exclusively stroke studies. The European Heart Journal led all journals in overall publications, while Stroke led all journals in stroke-related studies. CONCLUSIONS: Through the use of bibliographic analysis and data visualization, we identified major articles and journals that reflected and shaped the current landscape of tenecteplase; recognized authors who engaged in tenecteplase research as it progressed from cardiopulmonary disease to stroke; and postulated future avenues of research.


Assuntos
AVC Isquêmico , Infarto do Miocárdio , Embolia Pulmonar , Acidente Vascular Cerebral , Humanos , Tenecteplase/uso terapêutico , Bibliometria
2.
Open Access Emerg Med ; 15: 367-371, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868690

RESUMO

Background: Door-in to door-out (DIDO) time for large vessel occlusion (LVO) stroke is an emerging stroke performance measure. Initial presentation at a non-Comprehensive Stroke Center (CSC) requires a transfer process that minimizes delays. Our objective was to assess whether DIDO time for stroke patients was reduced after implementation of an AutoLaunch protocol for interfacility transfers. Methods: This was a pre-post analysis of an AutoLaunch protocol for all acute stroke patients transferred to a CSC for mechanical thrombectomy. The distribution of DIDO times between patients transferred via the AutoLaunch and traditional dispatch protocols were compared. Results: We evaluated 92 interfacility transfers, with 22 utilizing the AutoLaunch protocol and 70 utilizing traditional dispatch. Among AutoLaunch transfers, the median DIDO time was 85 minutes (IQR: 71, 133), while the median DIDO time among the traditional transfers was 109 minutes (IQR, 84, 144) (p=0.044). Conclusion: Implementation of an AutoLaunch protocol for patients with suspected LVO was associated with a reduction in DIDO time to CSCs. Further studies should evaluate patient outcomes based on transfer strategies.

3.
Cureus ; 15(6): e41099, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37519518

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder that was first described in the late 1800s as a variant of multiple sclerosis (MS). However, it has recently been categorized, as a disease, especially with the discovery of aquaporin-4 (AQP4-Ab) and myelin oligodendrocyte glycoprotein antibodies (MOG-Ab). Unfortunately, patient presentation is not always clear, and NMOSD may initially be diagnosed as an alternative neurological disease. We present a 58-year-old woman who was hospitalized several times for what was initially perceived as a pontine stroke. However, given worsening symptoms, serologic testing confirmed AQP4-Ab positivity and, subsequently, the NMOSD diagnosis. In addition to the case report, a systematic literature review was performed to identify NMOSD cases initially misdiagnosed as stroke. Publications were selected and curated in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Six NMOSD patients were initially thought to have had acute strokes. However, steady progression and/or the recurrence of symptoms suggested that further investigations with neuroimaging studies and serological immune assays were necessary to exclude alternative etiologies. Notably, the age at onset in all cases was significantly more advanced than patients with typical NMOSD presentations (median age 32-41). In conclusion, the NMOSD diagnosis should be considered in cases with atypical stroke-like presentations, particularly those of later onset (defined as equal to or greater than 50 years of age). This is important as early recognition and treatment with immune therapies can improve functional outcomes.

4.
J Neuroimaging ; 33(4): 598-605, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37158754

RESUMO

BACKGROUND AND PURPOSE: We aimed to investigate the relationship between the degree and location of vertebrobasilar stenosis and quantitative magnetic resonance angiography (QMRA) distal flow. METHODS: We retrospectively reviewed patients who presented with acute ischemic stroke with ≥50% stenosis of the extracranial or intracranial vertebral or basilar arteries, and QMRA performed within 1 year of stroke. Standardized techniques were used to measure stenosis and to dichotomize vertebrobasilar distal flow status. Patients were grouped based on the involved artery and the severity of disease. All p-values were calculated using chi-squared analysis and Fisher exact test with statistical significance defined as p < .05. RESULTS: Sixty-nine patients met study inclusion, consisting of 31 with low distal flow and 38 with normal distal flow. The presence of severe stenosis or occlusion was 100% sensitive, but only 47% predictive and 26% specific of a low distal flow state. Bilateral vertebral disease was only 55% sensitive but was 71% predictive and 82% specific of a low-flow state and was five times and nearly three times more likely to result in a low-flow state compared to unilateral vertebral disease (14%) and isolated basilar disease (28%), respectively. CONCLUSIONS: Severe stenosis of ≥70% may mark the minimal threshold required to cause hemodynamic insufficiency in the posterior circulation, but nearly half of these patients may remain hemodynamically sufficient. Bilateral vertebral stenosis resulted in a fivefold increase in QMRA low distal flow status compared to unilateral vertebral disease. These results may have implications in the design of future treatment trials of intracranial atherosclerotic disease.


Assuntos
AVC Isquêmico , Insuficiência Vertebrobasilar , Humanos , Angiografia por Ressonância Magnética/métodos , Estudos Retrospectivos , Constrição Patológica/diagnóstico por imagem , Insuficiência Vertebrobasilar/diagnóstico por imagem , Infarto
5.
J Stroke Cerebrovasc Dis ; 32(12): 107447, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38745444

RESUMO

INTRODUCTION: Flow augmentation is the mainstay treatment for moyamoya disease as hemodynamic failure is believed to be the dominant mechanism. We aimed to investigate the mechanisms of stroke in moyamoya disease by assessing the relationship between infarction patterns and quantitative magnetic resonance angiography flow state. METHODS: A retrospective study of adult patients with suspected MMD who presented with MRI confirmed acute ischemic stroke predating or following QMRA by a maximum of six months between 2009 and 2021 was conducted. Of the 177 consecutive patients with MMD who received QMRA, 35 patients, consisting of 41 hemispheres, met inclusion criteria. Flow-status was dichotomized into low-flow and normal-flow state based on previously established criteria. RESULTS: Mixed infarction pattern was the most frequent finding (70.7 %), followed by embolic (17.1 %), perforator (7.3 %), and internal borderzone (IBZ) (4.9 %). Infarction patterns were further dichotomized into IBZ+ (internal borderzone alone or mixed) and IBZ- (no internal borderzone constituent). Low-flow states were not significantly more frequent in the IBZ+ compared to IBZ- population (48.4 % vs. 20.0 %, p = 0.14). Ipsilateral posterior cerebral artery fractional flow was significantly higher with IBZ+ compared to IBZ- (345.0 % vs. 214.7 %, p = 0.04). CONCLUSION: Mixed infarction pattern was the most common pattern of infarction in patients with moyamoya disease, implying hypoperfusion and thromboembolism are codominant stroke mechanisms. An association between ICA flow status and infarction pattern was not found, although QMRA evidence of more robust posterior cerebral artery leptomeningeal collaterals was found in patients with a hypoperfusion contribution to their stroke mechanism.


Assuntos
Angiografia Cerebral , Circulação Cerebrovascular , Angiografia por Ressonância Magnética , Doença de Moyamoya , Valor Preditivo dos Testes , Humanos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/fisiopatologia , Doença de Moyamoya/complicações , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , AVC Isquêmico/fisiopatologia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etiologia , Fatores de Risco , Velocidade do Fluxo Sanguíneo , Imagem de Perfusão , Idoso , Adulto Jovem
6.
Tuberculosis (Edinb) ; 133: 102173, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35158296

RESUMO

In an attempt to uncover genotypic indicators for isoniazid (INH) resistance in M. tuberculosis, in addition to the canonical mutations in genes associated with INH resistance, including katG, inhA and fabG promoter; we analyzed, two INH monoresistant isolates, ASTS24/13 (INHR1) and SHR1/14 (INHR2). Targeted Sanger sequencing detected a canonical mutation at katG315 only in INHR2. Infection of THP-1 cells and exposure to antituberculosis drugs led to two-fold increase in the minimum inhibitory concentration of INH in INHR2. Whole genome sequences revealed that INHR1 and INHR2 belonged to Delhi Central Asian Strain and East African Indian lineages, respectively. The sequences were compared with INH susceptible isolates with the same lineage as the INH monoresistant strains. INHR1 had a novel unique mutation STOP420Trp in the efflux pump gene Rv0849, while INHR2 had a novel mutation Arg579Ser in efflux pump gene mmpL5. Comparison of lipid associated genes showed novel mutations in INHR1 in fadE16, fadD3 and fbpD; while INHR2 had mutations in fadE1, Rv0145, Rv1425, fadD9 and mmaA3. Both isolates also demonstrated novel mutations in cell wall associated genes. Our study highlights the importance of searching for alternate mechanisms of INH resistance that may contribute to the development of more comprehensive diagnostic tools.


Assuntos
Isoniazida , Mycobacterium tuberculosis , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Proteínas de Bactérias/genética , Catalase/genética , Farmacorresistência Bacteriana/genética , Isoniazida/farmacologia , Testes de Sensibilidade Microbiana , Mutação , Polimorfismo Genético , Sequenciamento Completo do Genoma
8.
Sci Adv ; 7(41): eabg4216, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34613768

RESUMO

Bdelloid rotifers are notorious as a speciose ancient clade comprising only asexual lineages. Thanks to their ability to repair highly fragmented DNA, most bdelloid species also withstand complete desiccation and ionizing radiation. Producing a well-assembled reference genome is a critical step to developing an understanding of the effects of long-term asexuality and DNA breakage on genome evolution. To this end, we present the first high-quality chromosome-level genome assemblies for the bdelloid Adineta vaga, composed of six pairs of homologous (diploid) chromosomes with a footprint of paleotetraploidy. The observed large-scale losses of heterozygosity are signatures of recombination between homologous chromosomes, either during mitotic DNA double-strand break repair or when resolving programmed DNA breaks during a modified meiosis. Dynamic subtelomeric regions harbor more structural diversity (e.g., chromosome rearrangements, transposable elements, and haplotypic divergence). Our results trigger the reappraisal of potential meiotic processes in bdelloid rotifers and help unravel the factors underlying their long-term asexual evolutionary success.

9.
Stroke Res Treat ; 2021: 8653396, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336181

RESUMO

INTRODUCTION: The World Health Organization declared COVID-19 a global pandemic last year. While a clear impact of COVID-19 on the declining stroke volume has been reported, its overall impact on stroke presentation and clinical outcomes has not been established. The purpose of this study was to assess the impact of COVID-19 on acute ischemic stroke volume, presentation, treatment, and outcomes at comprehensive stroke centers. METHODS: A retrospective review of patients with a discharge diagnosis of acute ischemic stroke from the Get With The Guidelines database was performed from January 1, 2019, to July 1, 2020. The following time periods were defined: Pre-COVID (January/February), Peak-COVID (March/April), and Post-COVID (May/June). Bivariate analyses were performed comparing the 2020 and 2019 time periods to determine differences in stroke volume, presentation, treatment, and outcomes. RESULTS: Stroke volumes were significantly lower during the Peak-COVID period in 2020 compared to that in 2019, with an absolute decline of 49.5% (P < 0.001). Patients were more likely to present after 24 hours from last known well during the 2020 Peak-COVID period (P = 0.03). However, there was not a significant difference in the rate of treatment with either the tissue plasminogen activator (tPA) or mechanical thrombectomy during the Peak-COVID period. Interestingly, relative treatment rates increased during the 2020 Post-COVID period to 11.4% (P = 0.01). CONCLUSIONS: The overall ischemic stroke volume decreased during the pandemic, and patients had a tendency to present later, beyond eligible treatment windows. However, rates of treatment, patient demographics, and stroke outcomes did not significantly change when compared to the prior year.

11.
Sustain Cities Soc ; 66: 102692, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33425664

RESUMO

Face mask detection had seen significant progress in the domains of Image processing and Computer vision, since the rise of the Covid-19 pandemic. Many face detection models have been created using several algorithms and techniques. The proposed approach in this paper uses deep learning, TensorFlow, Keras, and OpenCV to detect face masks. This model can be used for safety purposes since it is very resource efficient to deploy. The SSDMNV2 approach uses Single Shot Multibox Detector as a face detector and MobilenetV2 architecture as a framework for the classifier, which is very lightweight and can even be used in embedded devices (like NVIDIA Jetson Nano, Raspberry pi) to perform real-time mask detection. The technique deployed in this paper gives us an accuracy score of 0.9264 and an F1 score of 0.93. The dataset provided in this paper, was collected from various sources, can be used by other researchers for further advanced models such as those of face recognition, facial landmarks, and facial part detection process.

12.
Curr Probl Cardiol ; 46(3): 100675, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32888698

RESUMO

The coronavirus disease-2019 (COVID-19) pandemic has overwhelmed healthcare systems around the world, resulting in morbidity, mortality, and a dramatic economic downturn In the United States. Urgent responses to the pandemic halted routine hospital workflow in an effort to increase hospital capacity, maintain staffing, and ration protective gear. Most notably, New York saw the largest surge of COVID-19 cases nationwide. Healthcare personnel and physician leaders at Northwell Health, the largest healthcare system in New York, have worked together to successfully implement operational changes resulting in a paradigm shift in cardiac care delivery. In this manuscript, we detail specific protocol adjustments made in our cardiology department, cardiology service line, and healthcare system in the face of the COVID-19 pandemic. We discuss the sustainability of this shift moving forward and the opportunity to optimize care for cardiovascular patients in the post COVID-19 era.


Assuntos
COVID-19/epidemiologia , Doenças Cardiovasculares/terapia , Gerenciamento Clínico , Serviço Hospitalar de Emergência/organização & administração , Pandemias , Doenças Cardiovasculares/epidemiologia , Comorbidade , Humanos , New York/epidemiologia , SARS-CoV-2
14.
Int J Stroke ; 15(7): 704-721, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32746751

RESUMO

BACKGROUND: Correct diagnosis of stroke and its subtypes is pivotal in early stages for optimum treatment. AIMS: The aim of this systematic review and meta-analysis is to summarize the published evidence on the potential of blood biomarkers in the diagnosis and differentiation of stroke subtypes. METHODS: A literature search was conducted for papers published until 20 April 2020 in PubMed, EMBASE, Cochrane Library, TRIP, and Google Scholar databases to search for eligible studies investigating the role of blood biomarkers in diagnosing stroke. Quality assessment was done using modified Quality Assessment of Diagnostic Accuracy Studies questionnaire. Pooled standardized mean difference and 95% confidence intervals were calculated. Presence of heterogeneity among the included studies was investigated using the Cochran's Q statistic and I2 metric tests. If I2 was < 50% then a fixed-effect model was applied else a random-effect model was applied. Risk of bias was assessed using funnel plots and between-study heterogeneity was assessed using meta-regression and sensitivity analyses. Entire statistical analysis was conducted in STATA version 13.0. RESULTS: A total of 40 studies including patients with 5001 ischemic strokes, 756 intracerebral hemorrhage, 554 stroke mimics, and 1774 healthy control subjects analyzing 25 biomarkers (within 24 h after symptoms onset/after the event) were included in our meta-analysis; 67.5% of studies had moderate evidence of quality. Brain natriuretic peptide, matrix metalloproteinase-9, and D-dimer significantly differentiated ischemic stroke from intracerebral hemorrhage, stroke mimics, and health control subjects (p < 0.05). Glial fibrillary acidic protein successfully differentiated ischemic stroke from intracerebral hemorrhage (standardized mean difference -1.04; 95% confidence interval -1.46 to -0.63) within 6 h. No studies were found to conduct a meta-analysis of blood biomarkers differentiating transient ischemic attack from healthy controls and stroke mimics. CONCLUSION: This meta-analysis highlights the potential of brain natriuretic peptide, matrix metalloproteinase-9, D-dimer, and glial fibrillary acidic protein as diagnostic biomarkers for stroke within 24 h. Results of our meta-analysis might serve as a platform for conducting further targeted proteomics studies and phase-III clinical trials.PROSPERO Registration ID: CRD42019139659.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Biomarcadores , Hemorragia Cerebral/diagnóstico , Proteína Glial Fibrilar Ácida , Humanos , Acidente Vascular Cerebral/diagnóstico
15.
J Stroke Cerebrovasc Dis ; 29(8): 104989, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689590

RESUMO

OBJECTIVE: Identify clinical and radiographic features of venous infarct as a presenting feature of COVID-19 in the young. BACKGROUND: SARS-CoV-2 infection causes hypercoagulability and inflammation leading to venous thrombotic events (VTE). Although elderly patients with comorbidities are at higher risk, COVID-19 may also cause VTE in a broader patient population without these risks. Neurologic complications and manifestations of COVID-19, including neuropathies, seizures, strokes and encephalopathy usually occur in severe established cases of COVID-19 infection who primarily present with respiratory distress. CASE DESCRIPTION: Case report of a 29-year-old woman, with no significant past medical history or comorbidities, presenting with new onset seizures. Further questioning revealed a one-week history of headaches, low-grade fever, mild cough and shortness of breath, diagnosed as COVID-19. Imaging revealed a left temporoparietal hemorrhagic venous infarction with left transverse and sigmoid sinus thrombosis treated with full dose anticoagulation and antiepileptics. CONCLUSION: Although elderly patients with comorbidities are considered highest risk for COVID-19 neurologic complications, usually when systemic symptoms are severe, this case report emphasizes that young individuals are at risk for VTE with neurologic complications even when systemic symptoms are mild, likely induced by COVID-19 associated hypercoagulable state.


Assuntos
Betacoronavirus/patogenicidade , Infarto Encefálico/virologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Trombose dos Seios Intracranianos/virologia , Trombose Venosa/virologia , Adulto , Fatores Etários , Anticoagulantes/uso terapêutico , Anticonvulsivantes/uso terapêutico , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/tratamento farmacológico , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Feminino , Interações entre Hospedeiro e Microrganismos , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Fatores de Risco , SARS-CoV-2 , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/tratamento farmacológico , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico , Tratamento Farmacológico da COVID-19
16.
Open Access Emerg Med ; 11: 297-303, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814782

RESUMO

PURPOSE: Many strokes are not recognized by emergency medical services (EMS) providers and many providers do not prenotify emergency departments (EDs) of incoming stroke patients. The objectives of this project were to survey EMS providers to (1) assess knowledge of prehospital care related to stroke identification, time window for intravenous tissue plasminogen activator (IV tPA) administration, and comprehensive stroke centers in our health system, (2) gain insight from EMS providers regarding barriers to providing prenotification, information they provide for a prenotification, and optimal methods of providing feedback, and (3) provide EMS providers with stroke care and management information. METHODS: A survey was administered to EMS providers at four hospital EDs. The survey included questions related to knowledge of prehospital stroke care and barriers to providing prenotification. EMS providers were also provided a one-page flyer with information related to prehospital stroke care. Descriptive statistics were used to describe results. RESULTS: Of 301 EMS providers surveyed, 96.0% report that they use the Cincinnati Prehospital Stroke Scale to identify stroke, and 11.0% correctly identified the time window for IV tPA administration for acute ischemic stroke as within 4.5 hrs from the last known well time. The majority (82.7%) correctly identified the comprehensive stroke center in our health system. Barriers to providing prenotification included short transport time (40.5%), information being lost in dispatch (39.5%), and not having direct communication with ED staff (30.2%). Most reported wanting to receive feedback on the stroke patients they transported (93.7%), and 49.5% reported that the optimal method of providing feedback is via a mobile application. CONCLUSION: Deficits in stroke care knowledge among EMS providers were identified. Short transport time, inability to communicate with ED staff, and information lost in dispatch were cited as barriers to providing prenotification. Most EMS providers desire real-time feedback regarding patients via a mobile application.

17.
J Neurol ; 265(10): 2237-2242, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30043320

RESUMO

OBJECTIVE: To determine the prevalence and risk factors for paroxysmal atrial fibrillation (PAF) diagnosis in non- cryptogenic ischemic stroke (CIS) patients. METHODS: In this pilot-prospective cohort study of non-CIS patients from September 2014 to September 2017, 53 patients were enrolled. 51/53 patients were implanted within 10 days of stroke onset with the Reveal LINQ insertable cardiac monitor and monitored until PAF detection or a minimum of 12 months. Inclusion required diagnosis of a non-AF stroke etiology, age ≥ 40, and either a virtual CHADS2 score ≥ 3 or ≥ 2 PAF-related comorbidities. RESULTS: Over a median monitoring period of 398 days, PAF was detected in 6/51 (11.8%) patients and anticoagulation was initiated in 5/6 (83.3%). Median time to PAF detection was 87 days (range 0-356 days). Median longest PAF episode was 96 min (range 1 to 1122 min), and 4/6 had multiple PAF recordings. Mean left atrial volume index was significantly higher in PAF patients (31.0 vs. 23.2 cc/m2; p = 0.04). CONCLUSION: Long-term monitoring of non-CIS patients detected PAF in a clinically relevant proportion of patients, resulting in stroke prevention therapy optimization. Further study to confirm these findings and refine the subset that would benefit from long-term cardiac monitoring is warranted.


Assuntos
Fibrilação Atrial/complicações , Isquemia Encefálica/complicações , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia
18.
Front Oncol ; 7: 104, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28611939

RESUMO

Lung cancer remains one of today's most deadly and intractable cancers. Non-small cell lung cancer (NSCLC) accounts for roughly 85% of lung cancers, with an extremely poor survival rate. To ensure patient comfort and survival, the development of a selective therapy is imperative. However, lung cancer does not display surface proteins associated uniquely with tumor cells; thus, it is very difficult to develop a tumor-specific drug. Current techniques that target overexpression of proteins or inhibit growth pathways are either non-specific or prone to rapid drug resistance. The goal was to design a drug targeted to structural mutations expressed by tumor-associated general surface proteins, thereby combating the lack of tumor-unique markers in lung cancer. Mutant EGFR was identified as a potential target due to its prominence in tumor cells. Due to their size, it was determined that small molecules would be most effective at targeting isolated changes in protein structure, and thereby differentiating between the tumor-associated mutant EGFR and the healthy wild type. Conformational analysis of a virtual binding study conducted in VINA predicted a set of drug-like small molecules specific for the L858R mutation in EGFR. One molecule (ZN47) was then acquired and conjugated to a carrier protein to form a multifaceted hapten-protein conjugate. Multiple ELISAs were conducted to confirm the specificity of the conjugate to both tumor-associated mutant EGFRs. The results indicate that the identified molecule may be highly selective for tumor-associated L858R-EGFR, but further research, including a complete dosage-binding study, is necessary for full validation.

19.
Stroke ; 47(9): 2347-54, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27491734

RESUMO

BACKGROUND AND PURPOSE: Intravenous tissue-type plasminogen activator (tPA) is a proven treatment for acute ischemic stroke, but there has been limited evaluation among patients aged ≥90 years. METHODS: We analyzed data from the Get With The Guidelines-Stroke national quality improvement registry from January 2009 to April 2013. Frequency, determinants, and outcomes of tPA use were compared among patients aged ≥90 and 3 younger age groups (18-64, 65-79, and 80-89 years). RESULTS: Among 35 708 patients from 1178 sites who arrived within 2 hours of time last known well and received tPA, 2585 (7.2%) were ≥90 years. Compared with younger patients, the rate of tPA use among patients without a documented contraindication was lower among patients aged ≥90 years (67.4% versus 84.1% in 18-89-year olds; P<0.0001). Discharge outcomes among individuals aged ≥90 years included discharge to home or acute rehabilitation in 31.4%, independent ambulation at discharge in 13.4%, symptomatic hemorrhage in 6.1%, and in-hospital mortality or hospice discharge in 36.4%. On multivariable analysis, good functional outcomes generally occurred less often and mortality more often among patients aged ≥90 years. The risk of symptomatic hemorrhage was increased compared with patients <65 years but was not significantly different than the risk in 66- to 89-year olds. CONCLUSIONS: The use of intravenous tPA among those aged ≥90 years is lower than in younger patients. When fibrinolytic therapy is used, the risk of symptomatic hemorrhage is not higher than in 66- to 89-year olds; however, mortality is higher and functional outcomes are lower.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/uso terapêutico , Administração Intravenosa , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/mortalidade , Feminino , Fibrinolíticos/efeitos adversos , Mortalidade Hospitalar , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/mortalidade , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Acidente Vascular Cerebral/mortalidade , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento , Adulto Jovem
20.
J Stroke Cerebrovasc Dis ; 25(8): 1887-90, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27160383

RESUMO

BACKGROUND: The "drip-and-ship" paradigm is an important treatment modality for acute ischemic stroke (AIS) patients who do not have immediate access to a comprehensive stroke center (CSC). Intravenous thrombolysis is initiated at a primary stroke center followed by expeditious transfer to a CSC. We sought to determine factors associated with poor outcomes in drip-and-ship AIS patients transferred to a CSC. METHODS: This study is a retrospective analysis of 130 consecutive drip-and-ship patients transferred by ambulance to a single CSC between July 2012 and June 2014. Multiple patient and transport factors were analyzed. Transport blood pressure (BP) control was considered inadequate if the systolic BP was greater than 180 mmHg and/or diastolic BP was greater than 105 mmHg upon CSC arrival. Poor patient outcome was defined as discharge to hospice or expiry, a discharge modified Rankin Scale (mRS) score higher than 2, or symptomatic intracerebral hemorrhage (ICH). RESULTS: There was a significant association between inadequate BP control upon CSC arrival and in-hospital mortality or discharge to hospice (P < .0007). Arrival BP was not associated with the risk of post-thrombolysis symptomatic ICH. Longer transport time was significantly associated with a poorer mRS score at discharge (P < .0174) and death (P < .0351). CONCLUSIONS: Post-thrombolysis BP guideline violations and longer transport times during drip-and-ship transfers were significantly associated with poor outcome. Guidelines for strict transport BP management and alternative modes of transfer for longer-distance transports may be warranted.


Assuntos
Hipertensão/etiologia , Hipertensão/terapia , Transferência de Pacientes , Acidente Vascular Cerebral/complicações , Terapia Trombolítica/métodos , Resultado do Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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