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1.
Surg Today ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421439

RESUMO

ChatGPT has brought about a new era of digital health, as this model has become prominent and been rapidly developing since its release. ChatGPT may be able to facilitate improvements in surgery as well; however, the influence of ChatGPT on surgery is largely unknown at present. Therefore, the present study reports on the current applications of ChatGPT in the field of surgery, evaluating its workflow, practical implementations, limitations, and future perspectives. A literature search was performed using the PubMed and Embase databases. The initial search was performed from its inception until July 2023. This study revealed that ChatGPT has promising capabilities in areas of surgical research, education, training, and practice. In daily practice, surgeons and surgical residents can be aided in performing logistics and administrative tasks, and patients can be more efficiently informed about the details of their condition. However, priority should be given to establishing proper policies and protocols to ensure the safe and reliable use of this model.

2.
Neuropsychobiology ; 81(4): 271-285, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35093946

RESUMO

INTRODUCTION: Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD. METHODS: We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck's Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies. RESULTS: Clinical scores decreased in both groups (p = 0.0001); Beck's presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks. CONCLUSION: Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.


Assuntos
Transtorno Depressivo Maior , Inibidores de Hidroximetilglutaril-CoA Redutases , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Giro do Cíngulo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Perfusão , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único/métodos
3.
World J Surg ; 46(12): 3100-3110, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36109367

RESUMO

BACKGROUND: Machine learning (ML) has been introduced in various fields of healthcare. In colorectal surgery, the role of ML has yet to be reported. In this systematic review, an overview of machine learning models predicting surgical outcomes after colorectal surgery is provided. METHODS: Databases PubMed, EMBASE, Cochrane, and Web of Science were searched for studies using machine learning models for patients undergoing colorectal surgery. To be eligible for inclusion, studies needed to apply machine learning models for patients undergoing colorectal surgery. Absence of machine learning or colorectal surgery or studies reporting on reviews, children, study abstracts were excluded. The Probast risk of bias tool was used to evaluate the methodological quality of machine learning models. RESULTS: A total of 1821 studies were analysed, resulting in the inclusion of 31 articles. A vast proportion of ML algorithms have been used to predict the course of disease and response to neoadjuvant chemoradiotherapy. Radiomics have been applied most frequently, along with predictive accuracies up to 91%. However, most studies included a retrospective study design without external validation or calibration. CONCLUSIONS: Machine learning models have shown promising potential in predicting surgical outcomes after colorectal surgery. However, large-scale data is warranted to bridge the gap between calibration and external validation. Clinical implementation is needed to demonstrate the contribution of ML within daily practice.


Assuntos
Cirurgia Colorretal , Criança , Humanos , Estudos Retrospectivos , Aprendizado de Máquina , Algoritmos , Resultado do Tratamento
4.
PLoS Med ; 18(3): e1003415, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657114

RESUMO

BACKGROUND: Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression. METHODS AND FINDINGS: The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion. CONCLUSIONS: In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration. TRIAL REGISTRATION: NCT04375098.


Assuntos
COVID-19/terapia , Intervenção Médica Precoce/métodos , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/mortalidade , COVID-19/patologia , Chile , Progressão da Doença , Intervenção Médica Precoce/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Imunização Passiva/métodos , Imunização Passiva/mortalidade , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Mortalidade , Respiração Artificial/mortalidade , Respiração Artificial/estatística & dados numéricos , Tempo para o Tratamento/normas , Resultado do Tratamento , Soroterapia para COVID-19
5.
BMC Cancer ; 21(1): 1114, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663256

RESUMO

BACKGROUND: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage. METHODOLOGY: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage. DISCUSSION: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.


Assuntos
Cardiotoxicidade/diagnóstico por imagem , Ecocardiografia/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias/radioterapia , Lesões por Radiação/diagnóstico , Neoplasias da Mama/radioterapia , Cardiotoxicidade/etiologia , Protocolos Clínicos , Células Endoteliais , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Contração Miocárdica/fisiologia , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos/análise , Doses de Radiação , Volume Sistólico , Troponina T/análise , Disfunção Ventricular Esquerda
6.
Neuropsychobiology ; 80(3): 214-224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32726779

RESUMO

BACKGROUND: Major depressive disorder (MDD) is an important independent risk factor for cardiovascular disease. Cumulative data suggest that depressive patients exhibit derangement in regional cerebral blood flow (rCBF), although underlying mechanisms remain mostly unknown. Endothelial dysfunction (ED), defined as different forms of abnormal endothelial activity, plays a key role in the pathogenesis of vascular disease. ED is associated with several clinical conditions characterized by high cardiovascular risk. Diverse ED markers have been found in mood disorders. PURPOSE: To evaluate the association between rCBF and peripheral ED markers in MDD patients, at baseline and after selective serotonin receptor inhibitors (SSRIs) therapy. PATIENTS AND METHODS: Twenty-seven untreated unipolar MDD patients in their first episode were evaluated with the Hamilton Depression Rating Scale (HAM-D) and brain perfusion SPECT at baseline and after 2 months of SSRIs. Statistical Parametric Mapping (SPM) was employed to evaluate rCBF; circulating endothelial cells (CECs), plasma soluble intercellular adhesion molecule (sICAM), and high-sensitivity C-reactive protein (hsCRP) were used as independent covariates. RESULTS: Baseline CECs and sICAM were increased in MDD patients compared with matching controls (p = 0.0001) and hsCRP (p = 0.03). HAM-D scores (21 items) and CECs diminished after SSRI therapy in MDD patients (p < 0.0001). There was a significant rCBF decrease, mainly in deep central structures. HAM-D change was associated with rCBF decrease at the left amygdala, right striatum levels, and Brodmann area 25. CEC change was associated with rCBF at deep brain level and sICAM with large rCBF areas at the left caudate and tectum; hsCRP was associated, to a lesser extent, with the left dorsal striatum and mesencephalic tectum. CONCLUSION: ED markers in patients with MDD are associated with significant changes in rCBF which are features of depression. These findings suggest that systemic damage/activation of the endothelium may contribute to the abnormal rCBF observed in MDD patients.


Assuntos
Circulação Cerebrovascular/fisiologia , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Endotélio Vascular/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto , Circulação Cerebrovascular/efeitos dos fármacos , Transtorno Depressivo Maior/diagnóstico por imagem , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Fluxo Sanguíneo Regional/efeitos dos fármacos , Tomografia Computadorizada de Emissão de Fóton Único , Adulto Jovem
7.
Acta Haematol ; 144(6): 620-626, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34111867

RESUMO

INTRODUCTION: Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2. METHODS: In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments. RESULTS: Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (p < 0.005). CONCLUSION: In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial.


Assuntos
COVID-19/complicações , Inflamação/tratamento farmacológico , Nitrilas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/patologia , COVID-19/virologia , Chile , Feminino , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/etiologia , SARS-CoV-2/isolamento & purificação , Esteroides/uso terapêutico , Trombocitopenia/etiologia , Resultado do Tratamento
8.
Rev Chil Pediatr ; 90(5): 492-499, 2019 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31859732

RESUMO

INTRODUCTION: Screening for Autism Spectrum Disorders (ASD) using the Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) increases early detection, allowing early interventions and improving prognosis. This tool is part of the management in case of suspected ASD in several clinical guidelines. The objective of this article was to conduct the concurrent and discrimi nant validation and the reliability analysis of M-CHAT-R/F in the Chilean population. PATIENTS AND METHOD: This is the second stage of the cross-cultural adaptation of cross-sectional design. M-CHAT- R/F was applied to a sample of 20 children with suspected ASD and 100 randomly selected healthy control children, aged between 16-30 months. Autism Diagnostic Observation Schedule (ADOS-2), considered as reference, was applied to the 20 patients of the clinical sample, to 20 children of the healthy control sample and to those cases of the healthy control sample with M-CHAT-R/F positive. Cronbach alpha was calculated, as well as M-CHAT-R/F and ADOS-2 correlation, sensitivity, and specificity analyses. RESULTS: In the healthy sample, M-CHAT-R/F was positive in two patients, with one of them positive and the other one negative for ASD with ADOS-2 test. In the clinical sample, M- CHAT-R/F was positive in all cases, three of them were negative in the ADOS-2 test. The Alfa relia bility of M-CHART-R/T was 0,889, the discriminant sensitivity and specificity were 100% and 98%, and the concurrent ones were 100% and 87.5% respectively. CONCLUSIONS: The Chilean M-CHAT- R/F version was reliable, sensitive and specific, similar to the original test, which opens the possibility for its use in clinical samples and for research. Validating M-CHAT-R/F is an ongoing process which must be further developed.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Programas de Rastreamento/métodos , Estudos de Casos e Controles , Pré-Escolar , Chile , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Rev Med Chil ; 144(9): 1103-1111, 2016 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-28060970

RESUMO

BACKGROUND: Atrial fibrillation (AF) generates a hypercoagulable state with an increased thrombin generation and raised levels of thrombin-antithrombin complexes, which results in a high risk of stroke and thromboembolism. AIM: To evaluate the anticoagulant effect of rivaroxaban by anti-Xa factor activity and its correlation with thrombin-antithrombin complexes, thrombin generation and prothrombin time in patients newly diagnosed with non-valvular AF. PATIENTS AND METHODS: Prospective study in patients with indication of anticoagulation. Demographic variables, cardiovascular risk factors, CHA2DS2-VASc and HAS-BLED scores were recorded. Blood samples were taken at baseline, at 3 and 24 hours after the administration of the drug and at 30 days. Rivaroxaban levels, anti-Xa activity, prothrombin time, thrombin generation and plasma levels of thrombin-antithrombin complexes were determined. RESULTS: We studied 20 patients aged 76.3 ± 8.0 years (60% female) with a CHA2DS2-VASc score > 2 points. The anti-Xa factor activity correlated with rivaroxaban plasma levels at 3 hours (r = 0.61, p < 0.01), at 24 hours (r = 0.85, p < 0.01) and at 30 days (r = 0.99, p < 0.01), with prothrombin time at 3 hours (r = -0.86, p = 0.019) and at 30 days (r = -0.63, p = 0.02) and with a sustained decrease in thrombin generation at 30 days of follow-up (r = -0.74, p < 0.01). There was no correlation with thrombin-antithrombin complexes (r = -0.02, p = 0.83). CONCLUSIONS: Rivaroxaban consistently inhibited the mild pro-coagulant state found in newly diagnosed non-valvular AF patients through the first 24 hours and this effect was maintained at 30 days. Plasma levels of the drug correlated with anti-Xa factor activity, thrombin generation and prothrombin time.


Assuntos
Antitrombina III/efeitos dos fármacos , Fibrilação Atrial/sangue , Inibidores do Fator Xa/farmacologia , Fator Xa/efeitos dos fármacos , Peptídeo Hidrolases/efeitos dos fármacos , Rivaroxabana/farmacologia , Trombina/efeitos dos fármacos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Fator Xa/metabolismo , Feminino , Humanos , Masculino , Estudos Prospectivos , Tempo de Protrombina , Trombina/metabolismo , Fatores de Tempo
11.
BMC Cancer ; 15: 290, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25886038

RESUMO

BACKGROUND: An increase in circulating platelets, or thrombocytosis, is recognized as an independent risk factor of bad prognosis and metastasis in patients with ovarian cancer; however the complex role of platelets in tumor progression has not been fully elucidated. Platelet activation has been associated with an epithelial to mesenchymal transition (EMT), while Tissue Factor (TF) protein expression by cancer cells has been shown to correlate with hypercoagulable state and metastasis. The aim of this work was to determine the effect of platelet-cancer cell interaction on TF and "Metastasis Initiating Cell (MIC)" marker levels and migration in ovarian cancer cell lines and cancer cells isolated from the ascetic fluid of ovarian cancer patients. METHODS: With informed patient consent, ascitic fluid isolated ovarian cancer cells, cell lines and ovarian cancer spheres were co-cultivated with human platelets. TF, EMT and stem cell marker levels were determined by Western blotting, flow cytometry and RT-PCR. Cancer cell migration was determined by Boyden chambers and the scratch assay. RESULTS: The co-culture of patient-derived ovarian cancer cells with platelets causes: 1) a phenotypic change in cancer cells, 2) chemoattraction and cancer cell migration, 3) induced MIC markers (EMT/stemness), 3) increased sphere formation and 4) increased TF protein levels and activity. CONCLUSIONS: We present the first evidence that platelets act as chemoattractants to cancer cells. Furthermore, platelets promote the formation of ovarian cancer spheres that express MIC markers and the metastatic protein TF. Our results suggest that platelet-cancer cell interaction plays a role in the formation of metastatic foci.


Assuntos
Plaquetas/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Tromboplastina/metabolismo , Biomarcadores , Comunicação Celular , Movimento Celular , Fatores Quimiotáticos/metabolismo , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Fenótipo , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Tromboplastina/genética , Células Tumorais Cultivadas
12.
Arterioscler Thromb Vasc Biol ; 34(11): 2439-48, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25234816

RESUMO

OBJECTIVE: Cocaine consumption is a risk factor for vascular ischemic complications. Although endothelial dysfunction and accelerated atherosclerosis have been observed in cocaine consumers, the mechanisms underlying their pathogenesis are not fully understood. This study aimed at identifying the effects of atorvastatin in relation to a proadhesive and prothrombotic phenotype induced by cocaine and plasma from chronic cocaine users on endothelial cells. APPROACH AND RESULTS: Human umbilical vein endothelial cells were exposed to either cocaine or platelet-free plasma (PFP) from chronic cocaine consumers in the presence or absence of 10 µmol/L of atorvastatin. Atorvastatin significantly reduced the enhanced platelet adhesion that was induced by cocaine and PFP from chronic cocaine consumers, as well as the release of the von Willebrand factor. Atorvastatin also avoided striking alterations on cell monolayer structure triggered by both stimuli and enhanced NO reduction because of cocaine stimulation through disrupting interactions between endothelial nitric oxide synthase (eNOS) and caveolin-1, thus increasing eNOS bioavailability. Cocaine-increased tissue factor-dependent procoagulant activity and reactive oxygen species generation were not counteracted by atorvastatin. Although monocyte chemoattractant protein-1 levels were not significantly higher than controls either under cocaine or PFP stimulation, atorvastatin completely avoided monocyte chemoattractant protein-1 release in both conditions. Platelets stimulated with cocaine or PFP did not express P-selectin, glycoprotein IIb/IIIa, or CD40L and failed to adhere to resting human umbilical vein endothelial cell. CONCLUSIONS: Cocaine and patient plasma equally induced a proadhesive and prothrombotic phenotype in endothelial cells, except for von Willebrand Factor release, which was only induced by PFP from chronic cocaine consumers. Atorvastatin improved endothelial cell function by reducing cocaine-induced and PFP from chronic cocaine consumer-induced effects on platelet adhesion, cell architecture, and NO production.


Assuntos
Adesão Celular/efeitos dos fármacos , Cocaína/farmacologia , Endotélio Vascular/patologia , Ácidos Heptanoicos/farmacologia , Fenótipo , Plasma , Pirróis/farmacologia , Trombose/patologia , Anticolesterolemiantes/farmacologia , Atorvastatina , Caveolina 1/metabolismo , Células Cultivadas , Transtornos Relacionados ao Uso de Cocaína/sangue , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Humanos , Técnicas In Vitro , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Trombose/metabolismo , Fator de von Willebrand/metabolismo
13.
Rev Med Chil ; 143(11): 1449-58, 2015 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-26757870

RESUMO

Sézary syndrome (SS) is an unusually aggressive T- cell lymphoma characterized by the triad of erythroderma, the presence of more than 1,000 Sézary cells in peripheral blood and lymphadenopathies. It is accompanied by generalized pruritus and poor quality of life. The management of SS depends on its stage, patient comorbidities, and treatment availability. Extracorporeal photopheresis (ECP) is the first line of treatment for patients with T-cell lymphomas in stage IVA1, IVA2 or SS. This treatment comprises three phases: leukapheresis, photoactivation and subsequent reinfusion of lymphocytes. As it is an immunomodulatory therapy it does not produce generalized immunosuppression. We report a 76 year-old male with SS stage IIIb initially treated with 12 sessions of ultraviolet phototherapy without response. After 10 well-tolerated sessions of ECP, itching and skin lesions eventually disappeared.


Assuntos
Fotoferese/métodos , Síndrome de Sézary/terapia , Neoplasias Cutâneas/terapia , Idoso , Biópsia , Fibroblastos/patologia , Citometria de Fluxo , Humanos , Masculino , Prurido/patologia , Indução de Remissão/métodos , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia
14.
Rev Med Chil ; 143(6): 697-706, 2015 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-26230552

RESUMO

BACKGROUND: Chronic cocaine users develop multiple potentially lethal ischemic vascular complications associated with accelerated atherosclerosis. AIM: To assess biochemical and lipid profiles among cocaine dependent subjects in recent abstinence. MATERIAL AND METHODS: A blood sample to measure blood count, biochemical and lipid profiles was obtained from 78 patients aged 19 to 53 years (78% males) who complied with DSM-IV criteria for cocaine dependency. Laboratory results were compared with a group of normal subjects. RESULTS: All cases had positive urinary cocaine, with a mean consumption lapse of 7.6 years. The frequency of smoking was higher in cases. Dependent males had higher body mass index than controls. Compared to controls, dependent females had significantly higher triglyceride (TG) levels and lower HDL cholesterol. Therefore the relation total/HDL cholesterol was higher (p = 0.0365). Dependent males had higher TG levels than their normal counterparts. Dependent subjects consuming cocaine base-paste had higher TG levels. Total proteins, albumin, urea and blood urea nitrogen were lower in dependent subjects. Among males, serum creatinine was lower and blood urea was positively correlated with the daily amount of cocaine use (p = 0.03). After a month of strict abstinence, lipid profile was repeated in 27 patients and remained unchanged. CONCLUSIONS: Chronic cocaine use was associated with higher TG in both genders and lower HDL cholesterol in women when compared with a group of healthy counterparts.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/sangue , Cocaína/efeitos adversos , Lipídeos/sangue , Adulto , Índice de Massa Corporal , Doenças Cardiovasculares , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Triglicerídeos/sangue , Adulto Jovem
15.
Clin Exp Med ; 23(3): 645-654, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35471714

RESUMO

Deep venous thrombosis is a frequent, multifactorial disease and a leading cause of morbidity and mortality. Most of the time deep venous thrombosis is triggered by the interaction between acquired risk factors, such as hip fracture, pregnancy, and immobility, and hereditary risk factors such as thrombophilias. The mechanisms underlying deep venous thrombosis are not fully elucidated; however, in recent years, important advances have shed light on the role of venous flow, endothelium, platelets, leukocytes, and the interaction between inflammation and hemostasis. It has been described that the alteration of venous blood flow produces endothelial activation, favoring the adhesion of platelets and leukocytes, which, through tissue factor expression and neutrophil extracellular traps formation, contribute to the activation of coagulation, trapping more cells, such as red blood cells. Thus, the concerted interaction of these phenomena allows the formation and growth of the thrombus. In this work, the main mechanisms involved in the pathophysiology of deep vein thrombosis will be described.


Assuntos
Trombose Venosa , Humanos , Trombose Venosa/metabolismo , Plaquetas , Coagulação Sanguínea , Leucócitos , Inflamação
16.
Res Pract Thromb Haemost ; 7(5): 102156, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37601022

RESUMO

Background: Mild secretion defects are the most frequent and challenging blood platelet disorders to diagnose. Most δ-granule secretion tests lack validation, are not quantitative, or have unreliable response to weak platelet agonists. Objectives: To compare platelet serotonin secretion by HPLC-electrochemical detection technique (HPLC-ECD) with the reference isotopic test (3H-5-HT), evaluating its performance in clinical laboratories. Methods: The assay validation followed STARD-2015 recommendations. HPLC-ECD measured the nonsecreted serotonin remaining in platelet pellets after aggregation, comparing it with the reference 3H-5-HT assay. We studied subjects with inherited and aspirin-induced blood platelet disorders and assessed the HPLC-ECD operation for routine clinical diagnosis. Results: Calibration curves were linear (R2 = 0.997), with SD for residuals of 3.91% and analytical sensitivity of 5ng/mL. Intra- and interassay imprecision bias ranged between -8.5% and 2.1% and -9% and 3.1%, respectively. Serotonin recovery and stability were >95%, and the variability range of measurements was -5.5% to 4.6%. Statistical differences detected between tests were biologically irrelevant, with bias of 1.48% (SD, 8.43) and CI agreement of -18% to 15%. Both assays distinctly detected platelet secretion induced by 10 µM epinephrine and 4 µmM adenosine diphosphate. However, HPLC-ECD is quantitative and more sensitive to low serotonin content in blood platelets. Reference cutoffs for each agonist were determined in 87 subjects. Initially, the HPLC-ECD requires relatively expensive equipment and trained operators but has remarkably cheap running costs and a turn-around time of 24-36 hours. We have used this diagnostic tool routinely for >8 years. Conclusion: HPLC-ECD assay for platelet serotonin secretion is highly accurate, has advantages over the reference 3H-5-HT test, and is suitable as a clinical laboratory technique.

17.
Blood Adv ; 7(13): 3005-3021, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-36929813

RESUMO

Implementation of international guidelines in Latin American settings requires additional considerations (ie, values and preferences, resources, accessibility, feasibility, and impact on health equity). The purpose of this guideline is to provide evidence-based recommendations about the diagnosis of venous thromboembolism (VTE) and its management in children and during pregnancy. We used the GRADE ADOLOPMENT method to adapt recommendations from 3 American Society of Hematology (ASH) VTE guidelines (diagnosis of VTE, VTE in pregnancy, and VTE in the pediatric population). ASH and 12 local hematology societies formed a guideline panel comprising medical professionals from 10 countries in Latin America. Panelists prioritized 10 questions about the diagnosis of VTE and 18 questions about its management in special populations that were relevant for the Latin American context. A knowledge synthesis team updated evidence reviews of health effects conducted for the original ASH guidelines and summarized information about factors specific to the Latin American context. In comparison with the original guideline, there were significant changes in 2 of 10 diagnostic recommendations (changes in the diagnostic algorithms) and in 9 of 18 management recommendations (4 changed direction and 5 changed strength). This guideline ADOLOPMENT project highlighted the importance of contextualizing recommendations in other settings based on differences in values, resources, feasibility, and health equity impact.


Assuntos
Hematologia , Tromboembolia Venosa , Feminino , Gravidez , Criança , Humanos , Estados Unidos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , América Latina , Medicina Baseada em Evidências/métodos
18.
Artigo em Inglês | MEDLINE | ID: mdl-22302636

RESUMO

C-reactive protein (CRP) is increased in patients with atrial fibrillation (AF) and it might predict the lack of sinus rhythm maintenance in the long term follow-up. Scarce data have been reported relating endothelial dysfunction and/or haemostatic or platelet markers to sinus rhythm maintenance in AF patients. We aimed to determine whether some biochemical markers including soluble thrombomodulin (sTM), soluble P-selectin, thrombin-antithrombin (TAT) complex and CRP levels could predict sinus rhythm maintenance at 1 year follow-up in non-valvular AF patients. 130 patients (70 males, mean age 67 ± 13 years) with newly diagnosed AF naïve of antithrombotic or antiplatelet therapy were studied. Baseline CRP, P-selectin, sTM and TAT levels were compared to those of 20 matched-healthy subjects in sinus rhythm. AF patients had significantly higher plasma CRP (10.5 ± 2.2 vs 3.25 ± 0.3 mg/l, p = 0.001), P-selectin (219 ± 141 vs 126 ng/ml, p = 0.01), and TAT (54 ± 237 vs 2.7 ± 3.3 ng/l, p = 0.001) levels compared with controls. Soluble TM levels, although higher than controls, did not reach statistical significance. Multivariate regression analyses showed that elevated CRP (OR = 4.8, p = 0.02) and sTM (OR = 1.05, p = 0.04) were the only two predictors of lack of sinus rhythm at 1 year follow-up. An altered inflammatory, haemostatic, endothelial and platelet environment exists in newly diagnosed AF patients. CRP and sTM levels might be used as biochemical markers to predict the status of cardiac rhythm at 1 year follow-up in some AF patients.

19.
Platelets ; 23(1): 36-44, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21787173

RESUMO

Fibrinolysis dysfunctions cause bleeding or predisposition to thrombosis. Platelets contain several factors of the fibrinolytic system, which could up or down regulate this process. However, the temporal relationship and relative contributions of plasma and platelet components in clot lysis are mostly unknown. We developed a clot lysis time (CLT) assay in platelet-rich plasma (PRP-CLT, with and without stimulation) and compared it to a similar one in platelet-free plasma (PFP) and to another previously reported test in platelet-poor plasma (PPP). We also studied the differential effects of a single dose of tranexamic acid (TXA) on these tests in healthy subjects. PFP- and PPP-CLT were significantly shorter than PRP-CLT, and the three assays were highly correlated (p < 0.0001). PFP- and PPP-, but more significantly PRP-CLT, were positively correlated with age and plasma PAI-1, von Willebrand factor, fibrinogen, LDL-cholesterol, and triglycerides (p < 0.001). All these CLT assays had no significant correlations with platelet aggregation/secretion, platelet counts, and pro-coagulant tests to explore factor X activation by platelets, PRP clotting time, and thrombin generation in PRP. Among all the studied variables, PFP-CLT was independently associated with plasma PAI-1, LDL-cholesterol, and triglycerides and, additionally, stimulated PRP-CLT was also independently associated with plasma fibrinogen. A single 1 g dose of TXA strikingly prolonged all three CLTs, but in contrast to the results without the drug, the lysis times were substantially shorter in non-stimulated or stimulated PRP than in PFP and PPP. This standardized PRP-CLT may become a useful tool to study the role of platelets in clot resistance and lysis. Our results suggest that initially, the platelets enmeshed in the clot slow down the fibrinolysis process. However, the increased clot resistance to lysis induced by TXA is overcome earlier in platelet-rich clots than in PFP or PPP clots. This is likely explained by the display of platelet pro-fibrinolytic effects. Focused research is needed to disclose the mechanisms for the relationship between CLT and plasma cholesterol and its potential pathophysiologic and clinical relevance.


Assuntos
Antifibrinolíticos/farmacologia , Plaquetas/metabolismo , Fibrinólise/efeitos dos fármacos , Plasma , Ácido Tranexâmico/farmacologia , Adolescente , Adulto , Fatores Etários , Idoso , Proteínas Sanguíneas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/métodos , Fatores de Tempo , Triglicerídeos/metabolismo
20.
Rev Med Chil ; 140(4): 507-11, 2012 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-22854698

RESUMO

BACKGROUND: Cocaine abuse is associated with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation and accelerated atherosclerosis are prominent findings. We report a 39-year-old male addicted to cocaine, who presented with three consecutive ischemic events characterized by an acute myocardial infarction and two ischemic strokes complicated by cardiac failure and severe neurological sequelae. The pathophysiology of cocaine-induce vascular damage and the management of the ischemic complications are discussed.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Infarto do Miocárdio/etiologia , Adulto , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Infarto do Miocárdio/diagnóstico , Fatores de Risco , Tomografia Computadorizada por Raios X
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