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1.
J Stroke Cerebrovasc Dis ; 33(4): 107553, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38340555

RESUMO

INTRODUCTION: Delayed Cerebral Ischemia (DCI) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH) that can lead to poor outcomes. Machine learning techniques have shown promise in predicting DCI and improving risk stratification. METHODS: In this study, we aimed to develop machine learning models to predict the occurrence of DCI in patients with aSAH. Patient data, including various clinical variables and co-factors, were collected. Six different machine learning models, including logistic regression, multilayer perceptron, decision tree, random forest, gradient boosting machine, and extreme gradient boosting (XGB), were trained and evaluated using performance metrics such as accuracy, area under the curve (AUC), precision, recall, and F1 score. RESULTS: After data augmentation, the random forest model demonstrated the best performance, with an AUC of 0.85. The multilayer perceptron neural network model achieved an accuracy of 0.93 and an F1 score of 0.85, making it the best performing model. The presence of positive clinical vasospasm was identified as the most important feature for predicting DCI. CONCLUSIONS: Our study highlights the potential of machine learning models in predicting the occurrence of DCI in patients with aSAH. The multilayer perceptron model showed excellent performance, indicating its utility in risk stratification and clinical decision-making. However, further validation and refinement of the models are necessary to ensure their generalizability and applicability in real-world settings. Machine learning techniques have the potential to enhance patient care and improve outcomes in aSAH, but their implementation should be accompanied by careful evaluation and validation.


Assuntos
Isquemia Encefálica , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/complicações , Infarto Cerebral/complicações , Aprendizado de Máquina , Fatores de Tempo
2.
J Clin Neurosci ; 110: 27-38, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36787670

RESUMO

BACKGROUND: Dural arteriovenous fistulas (DAVF) of the craniocervical junction (CCF) are an uncommon entity with the following venous drainage pattern: inferior, superior and mixed. Patients may present with subarachnoid hemorrhage, myelopathy or brainstem dysfunction. CCJ DAVF can be treated with microsurgery or with transarterial and transvenous embolization, depending on the venous drainage pattern. We present our institutional experience of treating CCJ DAVFs along with a systematic review of the literature. METHODS: Six patients with CCJ DAVF were treated at our institution over five years. Data was collected using electronic medical record review. Systematic review was performed on CCJ DAVF using the PubMed database from 1990 to 2021. We characterized venous drainage patterns, treatment choices, and outcomes to create a classification system. RESULTS: 50 case reports, consisting of 115 patients, were included in our review. 61 (53.0 %) patients had inferior drainage while 32 (27.8 %) patients had superior drainage and 22 (19.2 %) patients had mixed venous drainage. Patients with inferior drainage had the fistulous connection at the foramen magnum while patients with superior drainage had a fistulous connection at C1-C2 (p value = 0.026). Patients with inferior drainage were more likely to present with myelopathy while patients with superior drainage presented with hemorrhage (p value = 0.000). CONCLUSIONS: Classifying the venous drainage pattern is essential in making treatment decision. Transvenous embolization works best with large superior venous drainage. If endovascular treatment is not an option, then surgical clipping can achieve successful cure. Transarterial embolization is a reasonable option in cases with a large arterial feeder.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Hemorragia Subaracnóidea , Humanos , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/cirurgia , Forame Magno , Hemorragia Subaracnóidea/terapia , Drenagem
3.
Interv Neuroradiol ; 29(5): 561-569, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35837721

RESUMO

INTRODUCTION: Woven EndoBridge (WEB) is a new endovascular treatment option for wide necked bifurcation aneurysms. Results from the WEB-IT trial showed a 0% risk of thromboembolic complications within 30 days post-op but the rate reported in the literature is as high as 10%. We are exploring potential risk factors associated with immediate thromboembolic complications in patients treated with the WEB device. METHODS: Retrospective study of forty-two patients with intracranial aneurysms who were treated with WEB at a single center from 2019-2021. Data was collected on patient demographics, comorbidities, aneurysm characteristics, procedural details, and hospital course. Bivariate analyses were performed to compare patients who experienced a periprocedural ischemic stroke to those who did not. Multiple logistic regression modeling was performed to identify independent risk factors for thromboembolic complications. RESULTS: Of the 42 patients that were treated with WEB, 6 suffered an ischemic stroke (AIS). These patients were more likely to have an underlying diagnosis of arrythmias (p value = 0.007). Furthermore, they had a median angle of 32.0° in the true neck view on diagnostic angiogram compared to 19.5° (p value = 0.046). Lastly, they had a longer procedure length of 228 min compared to 178 min (p value = 0.002). Patients with thromboembolic complications had a longer length of stay in the hospital and worse outcomes at three months follow up. On logistic regression modeling, these risk factors did not reach statistical significance. CONCLUSION: Risk factors of thromboembolic complications after WEB placement include cardiac arrythmias, acute aneurysmal angle in the true neck view and a longer procedure length.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Tromboembolia , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Tromboembolia/etiologia
4.
Interv Neuroradiol ; 29(3): 260-267, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35253525

RESUMO

BACKGROUND: The Woven EndoBridge device is a novel treatment option for wide-necked bifurcation intracranial aneurysms (WNBA). While this device has had good results, there remains a subset of WNBA that fail this treatment. The main objective of this study is to identify risk factors that are associated with incomplete occlusion of WEB treated aneurysms at short-term follow up. METHODS: This was a retrospective study of 31 patients with intracranial aneurysms who were treated with WEB at a single institution in the USA in 2019-2021. Data was collected via chart review on patient demographics, aneurysm characteristics, procedural details, and occlusion status at six months follow up. Bivariate analyses were performed comparing completely occluded aneurysms with neck remnants and residual aneurysms. RESULTS: 16 (52%) had completely occluded aneurysms while 11 (35%) patients had a neck remnant, and 4 (13%) patients had a residual aneurysm at follow up. Patients with neck remnants and residual aneurysms had aneurysms with a larger diameter. A large aneurysm diameter is an independent risk factor for incomplete occlusion (OR 4.23 95% CI 1.08-16.53 P value = 0.038). Patients with residual aneurysms had an average difference between the aneurysm width and WEB diameter of -0.08mm compared to 1.2 mm in patients with occluded aneurysms. 75% of patients with a residual aneurysm presented with a ruptured aneurysm. Lastly, more patients with a residual aneurysm had an immediate angiographic outcome of incomplete occlusion. CONCLUSION: Larger aneurysms are at risk for incomplete occlusion status post WEB treatment. Larger, ruptured aneurysms with minimal difference in aneurysm and WEB diameter that fail to occlude immediately post-treatment are more likely to present as residual aneurysms at short-term follow up.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Resultado do Tratamento , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/terapia , Angiografia Cerebral
5.
Cureus ; 14(4): e24449, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35637796

RESUMO

Background Endovascular therapy is known to achieve a high rate of recanalization in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) and is currently the standard of care. Hemorrhagic conversion is a severe complication that may occur following AIS in patients undergoing endovascular thrombectomy (EVT). There is a scarcity of data on the risk factors related to HV in post-EVT patients, especially those who develop symptomatic hemorrhagic conversion. The main objective of our study is to identify independent predictors of radiographic and symptomatic hemorrhagic conversion in our diverse patient population with multiple baseline comorbidities that presented with AIS and were treated with EVT as per the most updated guidelines and practices. Methodology This is a retrospective chart review in which we enrolled adult patients treated with EVT for AIS at a comprehensive stroke center in the Bronx, NY, over a four-year period. Bivariate analyses followed by multiple logistic regression modeling were performed to determine the independent predictors of all and symptomatic hemorrhagic conversion. Results A total of 326 patients who underwent EVT for AIS were enrolled. Of these, 74 (22.7%) had an HC, while 252 (77.3%) did not. In total, 25 out of the 74 (33.7%) patients were symptomatic. In the logistic regression model, a history of prior ischemic stroke (odds ratio (OR) = 2.197; 95% confidence interval (CI) = 1.062-4.545; p-value = 0.034), Alberta Stroke Program Early CT Score (ASPECTS) of <6 (OR = 2.207; 95% CI = 1.477-7.194; p-value = 0.019), and Thrombolysis in Cerebral Infarction (TICI) 2B-3 recanalization (OR = 2.551; 95% CI = 1.998-6.520; p-value=0.045) were found to be independent predictors of all types of hemorrhagic conversion. The only independent predictor of symptomatic hemorrhagic conversion on multiple logistic regression modeling was an elevated international normalized ratio (INR) (OR = 11.051; 95% CI = 1.866-65.440; p-value = 0.008). Conclusions History of prior ischemic stroke, low ASPECTS score, and TICI 2B-3 recanalization are independent predictors of hemorrhagic conversion while an elevated INR is the only independent predictor of symptomatic hemorrhagic conversion in post-thrombectomy patients.

6.
J Clin Neurosci ; 99: 94-98, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35278935

RESUMO

Mechanical thrombectomy (MT) has been established as a standard of care for patients with acute ischemic stroke for the past five years. However, the direct benefits of this treatment in patients with baseline disability remains unclear. This study aims to elucidate the cost impact of performing MT on patients with moderate-to-severe baseline disability to work towards an optimized system of care for acute ischemic stroke. We developed a Markov economic model with a life-time horizon analysis of costs associated with mechanical thrombectomy in patients grouped on baseline disability as defined by modified Rankin Score. Our clinical and economic data is based on an American payer perspective. Our results identified a marginal cost-effective ratio (mCER) of $18,835.00 per quality-adjusted life year (QALY) when mechanical thrombectomy is reserved as a treatment only for patients with no-to-minimal baseline disability as compared to those with any level of baseline disability. Our results provide a framework for these future studies and highlight key sectors that drive cost in the surgical treatment and life-long care of patients with acute ischemic stroke.


Assuntos
Isquemia Encefálica , Pessoas com Deficiência , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/cirurgia , Análise Custo-Benefício , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Resultado do Tratamento
7.
Interv Neuroradiol ; 28(2): 219-228, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34121487

RESUMO

INTRODUCTION: Flow diversion is an effective treatment modality for intracranial aneurysms but is associated with ischemic and hemorrhagic complications. Patients treated with flow diversion require dual antiplatelet therapy and subsequent platelet function tests. At our institution, Thromboelastography with Platelet Mapping (TEG-PM) is the test of choice. The primary objective of this study was to identify TEG parameters that are predictive of postoperative complications in patients treated with elective flow diversion. METHODS: This was a retrospective study of 118 patients with unruptured intracranial aneurysms treated with flow diversion. Data was collected via chart review. Bivariate analyses were performed to identify significant variables in patients who suffered an ischemic stroke or a groin hematoma. ROC curves were constructed for the TEG parameters with statistical significance. Bivariate analyses were repeated using dichotomized TEG results. RESULTS: Patients who experienced a symptomatic ischemic stroke had a history of stroke (p value = 0.007), larger aneurysm neck width (p value = 0.017), and a higher alpha angle (p value = 0.013). Cut off point for ischemic complication is 63° on ROC curve with a sensitivity of 100% and specificity of 65%. Patients who experienced a groin hematoma were no different from their healthy peers but had a lower alpha angle (p value = 0.033). Cut off point for hemorrhagic complication is 53.3° with a sensitivity of 82% and specificity of 67%. CONCLUSION: The Alpha Angle parameter of TEG-PM has a sizeable predictive ability for both ischemic complications of the central nervous system and hemorrhagic complications of the access site after elective flow diversion.


Assuntos
Aneurisma Intracraniano , AVC Isquêmico , Hematoma , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Isquemia , Estudos Retrospectivos , Tromboelastografia/métodos , Resultado do Tratamento
8.
Cureus ; 13(7): e16124, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34350083

RESUMO

BrainPath (NICO, Indianapolis, Indiana) is a tool that can be used to evacuate supratentorial hematomas due to spontaneous intracerebral hemorrhage (ICH). However, when ICH occurs in the posterior fossa, an open approach is often undertaken to evacuate the hematoma. The application of minimally invasive technology, while available, has not been well established. Our objective was to describe the use of the image-guided, minimally invasive BrainPath system to evacuate a spontaneous cerebellar hemorrhage. We present the case of a sixty-four-year-old male patient with a cerebellar hematoma due to hypertensive hemorrhage. The patient's medical record, including the history and physical, progress notes, operative notes, discharge summary, and imaging studies were reviewed to document the clinical presentation as well as the details of the operative technique and postoperative outcomes in this paper. We discuss the technical nuances of the operative points in detail. In our example case, the BrainPath system was successfully used to evacuate the cerebellar hematoma and no procedural-related complications occurred. The patient's recovery remained uncomplicated at three months of follow-up. In summary, the BrainPath system offers a less invasive alternative to open evacuation for cerebellar bleeds.

9.
Neurosurg Focus Video ; 4(2): V18, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36284853

RESUMO

Here the authors demonstrate open craniofacial reconstruction for the correction of craniosynostosis, using techniques refined by Dr. James T. Goodrich at Montefiore Medical Center. They present the operative management of a case of unilateral coronal synostosis in a 12-month-old child, who presented with right forehead prominence and calvarial asymmetry. The patient had an excellent correction of her head shape with an uneventful postoperative course. This video highlights the authors' multidisciplinary approach to complete cranial vault remodeling, utilizing a Marchac bandeau construct and split calvarial graft mosaic technique. The video can be found here: https://vimeo.com/519489422.

10.
Clin Neurol Neurosurg ; 198: 106112, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32738585

RESUMO

OBJECTIVE: We aim to characterize the incidence, risk for mortality, and identify risk factors for mortality in patients presenting with hemorrhage and COVID-19. METHODS: This retrospective cohort study included a cohort of patients admitted to one of three major hospitals of our healthcare network including, an academic medical center and comprehensive stroke center, which accepts transfers for complex cases from eight community hospitals, during March 1 to May 1, 2020. All patients that received imaging of the neuroaxis and had positive PCR testing for COVID-19 were identified and reviewed by an attending neuroradiologist. Demographics and comorbidities were recorded. Biomarkers were recorded from the day of the hemorrhagic event. Vital signs from the day of the hemorrhagic event mechanical ventilation orders at admission were recorded. Imaging findings were divided into 5 subtypes; acute subdural hematoma (SDH), subarachnoid hemorrhage (SAH), multi-compartmental hemorrhage (MCH), multi-focal intracerebral hemorrhage (MFH), and focal intracerebral hemorrhage (fICH). Outcomes were recorded as non-routine discharge and mortality. RESULTS: We found a total of 35 out of 5227 patients with COVID-19 that had hemorrhage of some kind. Mortality for the entire cohort was 45.7 % (n = 16). SDH patients had a mortality rate of 35.3 % (n = 6), SAH had a mortality of 50 % (n = 1), MCH patients had a mortality of 71.4 % (n = 5), MFH patients had a mortality of 50 % (n = 2), fICH patients had a mortality of 40 % (n = 2). Patients with severe pulmonary COVID requiring mechanical ventilation (OR 10.24 [.43-243.12] p = 0.015), with INR > 1.2 on the day of the hemorrhagic event (OR 14.36 [1.69-122.14] p = 0.015], and patients presenting with spontaneous vs. traumatic hemorrhage (OR 6.11 [.31-118.89] p = 0.023) had significantly higher risk for mortality. CONCLUSIONS: Hemorrhagic presentations with COVID-19 are a rare but serious way in which the illness can manifest. It is important for neurosurgeons to realize that patients can present with these findings without primary pulmonary symptoms, and that severe pulmonary symptoms, elevated INR, and spontaneous hemorrhagic presentations is associated with increased risk for mortality.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/virologia , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Incidência , Hemorragias Intracranianas/diagnóstico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Taxa de Sobrevida
11.
Cureus ; 11(8): e5350, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31602354

RESUMO

Introduction Mechanical thrombectomy has become the standard treatment for large vessel occlusion (LVO) in acute ischemic stroke (AIS) in well-selected patients. Although many devices and strategies exist, the use of a balloon-tip guide catheter (BGC) with stent-retriever (SR) may hold several advantages. We aim to assess the efficacy and identify predictors of technical success of this unique approach. Methods From our prospectively maintained database, we identified consecutive cases in which a BGC was used for stent-retriever thrombectomy in anterior circulation LVO between 2015 and 2016. Baseline and procedural characteristics were captured and analyzed. Predictors of technical and clinical outcomes were identified by multivariable logistic regression analysis. Results Ninety-three patients with AIS-LVO were treated with BGC-assisted mechanical thrombectomy. The mean age was 71 years old (SD 14), with 49.5% male (n=46). Pre-operative IV-tPA was administered in 55.9% (n=52) of cases. The most common location of occlusive thrombus was M1 (64.5%, n=60). Successful recanalization (mTICI=2b-3) was achieved in 86.0% (n=80) of cases while complete revascularization (mTICI-3) was achieved in 56.5% (n=52). There was a first-pass success rate of 52.7% (n=49). At discharge, 38.7% of the patients were functionally independent (mRS≤2). Multivariate analysis revealed that the middle cerebral artery location was strongly predictive of first-pass success, resulting in mTICI =2b revascularization (OR 7.10, p=0.018). Additionally, female gender (OR 2.85, p=0.042) and decreasing mTICI were associated with a poor clinical outcome (mRS≥4; OR 1.76, p=0.008). Conclusions BGC assistance in stent retrieval thrombectomy is safe and effective for AIS due to anterior circulation LVO. Further investigation is required to elucidate the optimal treatment strategy based on patient and disease characteristics.

12.
J Neurosurg Spine ; : 1-6, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31419804

RESUMO

OBJECTIVE: Minimally invasive techniques are increasingly used in adult deformity surgery as surgeon familiarity improves and long-term data are published. Concerns raised in such cases include pseudarthrosis at levels where interbody grafts are not utilized. Few previous studies have specifically examined the thoracolumbar component of long surgical constructs, which is commonly instrumented without interbody or intertransverse fusion. METHODS: A retrospective analysis was performed on all patients who underwent hybrid minimally invasive deformity corrections in two academic spine centers over a 9-year period. Inclusion criteria were at least 2 rostral levels instrumented percutaneously, ranging from T8 to L1 as the upper end of the construct. Fusion assessment was made using CT when possible or radiography. Common radiographic parameters and clinical variables were assessed pre- and postoperatively. RESULTS: A total of 36 patients fit the inclusion criteria. Baseline characteristics included a 1:1.8 male/female ratio, average age of 65.7 years, and BMI of 30.2 kg/m2. Follow-up imaging was obtained at a mean of 35.7 months. The average number of levels fused was 7.5, with an average of 3.4 instrumented percutaneously between T8 and L1, representing a total of 120 rostral levels instrumented percutaneously. Fusion assessment was performed using CT in 69 levels and radiography in 51 levels. Among the 120 rostral levels instrumented percutaneously, robust fusion was noted in 25 (20.8%), with 53 (44.2%) exhibiting some evidence of fusion. Pseudarthrosis was noted in 2 rostral segments (1.7%). There were no instances of proximal hardware revision. Eight patients exhibited radiographic proximal junctional kyphosis (PJK; 22.2%), none of whom underwent surgical intervention. CONCLUSIONS: In the present series of adult patients with scoliosis undergoing thoracolumbar deformity correction, rostral segments instrumented percutaneously have a very low rate of pseudarthrosis, with radiographic evidence of bone fusion occurring in more than 60% of patients. The rate of PJK was acceptable and similar to other published series.

13.
Artigo em Inglês | MEDLINE | ID: mdl-28925907

RESUMO

AIMS: Atrial fibrillation (AF) ablation is associated with increased circulating markers of inflammation. Innate immune or inflammation pathways up-regulate mononuclear cell responses and may increase the risk for recurrent arrhythmia. Chemokines and serine protease coagulation pathways both activate innate immune responses. Here, we measured inflammatory markers in peripheral blood samples from patients after cryoballoon and/or radiofrequency pulmonary vein isolation and assessed the capacity for the inhibition of chemokine and serine protease pathways to block cell activation. METHODS: Markers of inflammation were measured in 55 patients immediately before and one day after AF ablation. Peripheral blood mononuclear cells (PBMCs) isolated from 19 patients were further tested for responsiveness to two anti-inflammatory proteins ex vivo using fluorescence assays and RT-qPCR analysis of gene expression. RESULTS: White blood cells (WBC), C-reactive protein, fibrinogen and troponin T levels were significantly elevated after ablation. PBMCs isolated from the circulating blood had increased activation with Phorbol 12-myristate 13-acetate. Cell activation, as measured by membrane fluidity, was blunted after treatment with a broad-spectrum chemokine modulating protein, M-T7, which interferes with chemokine/glycosaminoglycan (GAG) interactions, but not by Serp-1, a serine protease inhibitor (serpin) that targets both thrombotic and thrombolytic pathway proteases. Differential gene expression changes in the apoptotic pathway were identified with M-T7 and Serp-1. CONCLUSIONS: Patients undergoing AF ablation have significantly increased inflammatory markers. Inhibition of chemokine signaling, but not serine proteases, reduced the activation of monocytes isolated from patients, in vitro. Targeting chemokines have the potential to reduce post-ablation activation of circulating leukocytes.


Assuntos
Fibrilação Atrial/terapia , Ablação por Cateter/efeitos adversos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Leucócitos , Idoso , Fibrilação Atrial/patologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Quimiocinas/antagonistas & inibidores , Quimiocinas/sangue , Quimiocinas/metabolismo , Feminino , Expressão Gênica/genética , Humanos , Inflamação/sangue , Contagem de Leucócitos , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Inibidores de Proteases/farmacologia , Inibidores de Serina Proteinase/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
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