RESUMO
COVID-19 is a worldwide health emergency, therapy for this disease is based on antiviral drugs and immunomodulators, however, there is no treatment to effectively reduce the COVID-19 mortality rate. Fucoidan is a polysaccharide obtained from marine brown algae, with anti-inflammatory, antiviral, and immune-enhancing properties, thus, fucoidan may be used as an alternative treatment (complementary to prescribed medical therapy) for the recovery of COVID-19. This work aimed to determine the effects of ex-vivo treatment with fucoidan on cytotoxicity, apoptosis, necrosis, and senescence, besides functional parameters of calcium flux and mitochondrial membrane potential (ΔΨm) on human peripheral blood mononuclear cells isolated from SARS-CoV-2 infected, recovered and healthy subjects. Data suggest that fucoidan does not exert cytotoxicity or senescence, however, it induces the increment of intracellular calcium flux. Additionally, fucoidan promotes recovery of ΔΨm in PBMCs from COVID-19 recovered females. Data suggest that fucoidan could ameliorate the immune response in COVID-19 patients.
Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Feminino , Humanos , Leucócitos Mononucleares , Cálcio , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêuticoRESUMO
OBJECTIVE: The aim of the study was to carry out an epidemiological analysis of patients with carbapenemase-producing Enterobacteriaceae (CPE) isolations in our hospital as well as to perform a description of the genotypic temporal evolution of CPE isolated. METHODS: An observational prospective cohort study was performed involving all patients with CPE isolates from clinical samples during November 2014 to November 2016 in a Spanish teaching hospital. Patients were clinically evaluated and classified either as infected or colonized. Information on the consumption of carbapenems in the hospital during the study period was also analyzed. PCR was used for identification of the carbapenemase genes blaKPC, blaVIM, and blaOXA-48. RESULTS: A total of 301 CPE isolates were obtained (107 in 2014, 89 in 2015 and 105 in 2016). Klebsiella pneumoniae (73.4%) was the most prevalent microorganism. Hundred and seventy (56.7%) of carbapenemases detected were blaOXA-48, 73 (24.3%) were blaKPC and 57 (19%) were blaVIM. In year 2014 KPC was predominant while in 2016 OXA-48 predominated. In 2014 we observed a significant association between the medical wards and the ICU with a higher prevalence of OXA-48 (OR 4.15; P<0.001) and VIM (OR 7.40; P<0.001) in the univariate analysis, in the following years there was no association. Regarding the clinical significance of microbiological results after assessing our patients, 60% of isolates represented infection and 40% behaved as colonizers. One third of hospitalized patients with CPE isolation died within 30 days, regardless of whether they were colonized or infected. CONCLUSIONS: We have observed an epidemiological change in the genotypes of our isolates along the study period. A thorough knowledge of the CPE's epidemiological distribution in each hospital is fundamental for optimizing antimicrobial chemotherapy.
Assuntos
Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , beta-Lactamases/metabolismo , Antibacterianos/uso terapêutico , Estudos de Coortes , Farmacorresistência Bacteriana , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Espanha/epidemiologia , Centros de Atenção TerciáriaRESUMO
PURPOSE: The present study evaluates the massive study of gene expression in metastatic breast carcinoma (MBC) patients using microarray gene expression profiling (MAGE) complemented with conventional sequencing, immunohistochemistry (IHC) and fluorescent "in situ" hybridization (FISH), seeking to optimize the treatment in a subset of heavily pretreated patients and with limited life expectancy. PATIENTS, MATERIAL AND METHODS: MBC patients in hormone therapy progression with survival expectancy of at least 3 months (m) have been included. The MAGE contains gene probes representing genes known to potentially interact with available drugs as cited in the literature. RESULTS: Thirty-nine procedures were performed from October 2010 to April 2016. Within the 30 evaluable procedures, considering all hormonal manipulations as a single line, the patients had received a median of 4 treatment lines prior to MAGE (range 1-7). Progression was observed in 6 cases, stable disease (SD) in 7 cases and partial response (PR) in 16 cases, which implies a clinical benefit rate (SD + PR) of 76%. Actuarial median progression-free survival (PFS) was 6 m (95% CI 2.5-9.5) in patients with clinical benefit. The median overall survival (OS) for the entire series was 11 m (95% CI 2.2-19.8). CONCLUSION: Data presented here indicate that the use of MAGE provides relevant information to establish personalized treatment in frail patients with limited life expectancy in which therapeutic futility is a particularly difficult burden to assume.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Medicina de Precisão , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/secundário , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Projetos Piloto , Prognóstico , Taxa de SobrevidaRESUMO
A high performance liquid chromatography method, coupled to diode-array and fluorescence detectors, with a previous solid-liquid extraction, has been developed for the simultaneous detection and quantification of polyphenolic compounds in table olives and in olive paste. The effects of extraction variables have been studied by response surface methodology. The best conditions were extraction with 100% methanol (2mM NaF) during 30min for table olives, and 91% methanol (2mM NaF) during 40min for olive paste. Chromatographic separation of 26 polyphenols from different families was optimized. This method provides high linearity, in all cases higher than 98.65%, and high sensitivity whose detection limits ranged between 0.08 and 1.11µg/mL. The validated method has been applied for the determination of polyphenols in table olive and olive paste samples. The intra-day and inter-day assay repeatability, in the analysis of real samples was less than 7.6 and 11%, respectively.
Assuntos
Olea , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Pomadas , PolifenóisRESUMO
No disponible
Assuntos
Humanos , Masculino , Técnicas de Diagnóstico Urológico/economia , Técnicas de Diagnóstico Urológico/tendências , Técnicas de Diagnóstico Urológico , Excisão de Linfonodo/métodos , Excisão de Linfonodo/tendências , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/cirurgia , Valor Preditivo dos Testes , Razão de ChancesRESUMO
Objetivos: evaluar la utilidad práctica en nuestro medio del índice revisado de área y severidad del lupus cutáneo (RCLASI). Correlacionar RCLASI con DLQI (índice de calidad de vida dermatológico). Materiales y Métodos: estudio observacional, descriptivo y transversal realizado en el Hospital General de Agudos José María Ramos Mejía, Ciudad Autónoma de Buenos Aires - Argentina - por dos grupos de observadores divididos según nivel de experiencia en dermatología. Se realizó RCLASI Y DLQI en 12 pacientes con Lupus Eritematoso Cutáneo (LEC). Se evaluó en RCLASI el tiempo requerido, la variabilidad inter-observador y la dificultad del método. Resultados: la media de actividad para el grupo de baja experiencia fue de 11,8 puntos (SD 8,1) y para el de moderada / alta experiencia 12,7 (SD 8). La media de daño para el primer grupo fue 4 (SD 4,7) y para el segundo 4,4 puntos (SD 5,4), respectivamente. El tiempo promedio para ambos grupos fue de 7,76 minutos, siendo para el grupo de baja experiencia 9,79 y para el de moderada / alta 5,73. El método resultó fácil en más del 50% de los casos, independientemente del nivel de experiencia. El 50% de los pacientes no mostró efecto sobre la calidad de vida, 16,5% pequeño efecto, 25% moderado efecto y 8,5% gran efecto. Conclusión: el RCLASI es un método práctico y útil para evaluar todas las formas de LEC. Resulta fácil y expeditivo, pero carece de escala de severidad, lo que fue una limitante para compararlo con DLQI.(AU)
Objectives: to assess the practical utility of Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) in our population. To correlate: RCLASI with DLQI (Dermatology Life Quality Index). Materials and Methods: observational, descriptive and transversal study that was performed in Hospital General de Agudos José María Ramos Mejía, Ciudad Autónoma de Buenos Aires - Argentina - by two groups of observers divided by their level of experience in dermatology. RCLASI and DLQI were assessed in 12 patients with Cutaneous Lupus Erythematosus (CLE). Time spent, inter observer variability and method´s levels of difficulty were evaluated. Results: the mean activity score for the group of low experience was 11,8 (SD 8,1) and for the group of moderate / high experience 12,7 (SD 8). The mean damage score for the former was 4 (SD 4,79) and for the later 4,4 (SD 5,4). The mean time spent by both groups was 7,76 minutes (9,79 minutes mean by the group of low experience and 5,73 by the group of moderate / high experience). The method was considered easy in more than 50% of the cases, independently of the observers´s level of experience. 50% of the patients did not show effect in their quality of life whereas 16,5% showed little effect, 25% mild effect, and 8,5% big effect. Conclusions: RCLASI is a useful and feasible method to evaluate all types of CLE. It’s easy and rapid, however it lacks a severity scale. This later limited its comparison with DLQI.(AU)
RESUMO
Objetivos: evaluar la utilidad práctica en nuestro medio del índice revisado de área y severidad del lupus cutáneo (RCLASI). Correlacionar RCLASI con DLQI (índice de calidad de vida dermatológico). Materiales y Métodos: estudio observacional, descriptivo y transversal realizado en el Hospital General de Agudos José María Ramos Mejía, Ciudad Autónoma de Buenos Aires - Argentina - por dos grupos de observadores divididos según nivel de experiencia en dermatología. Se realizó RCLASI Y DLQI en 12 pacientes con Lupus Eritematoso Cutáneo (LEC). Se evaluó en RCLASI el tiempo requerido, la variabilidad inter-observador y la dificultad del método. Resultados: la media de actividad para el grupo de baja experiencia fue de 11,8 puntos (SD 8,1) y para el de moderada / alta experiencia 12,7 (SD 8). La media de daño para el primer grupo fue 4 (SD 4,7) y para el segundo 4,4 puntos (SD 5,4), respectivamente. El tiempo promedio para ambos grupos fue de 7,76 minutos, siendo para el grupo de baja experiencia 9,79 y para el de moderada / alta 5,73. El método resultó fácil en más del 50% de los casos, independientemente del nivel de experiencia. El 50% de los pacientes no mostró efecto sobre la calidad de vida, 16,5% pequeño efecto, 25% moderado efecto y 8,5% gran efecto. Conclusión: el RCLASI es un método práctico y útil para evaluar todas las formas de LEC. Resulta fácil y expeditivo, pero carece de escala de severidad, lo que fue una limitante para compararlo con DLQI.
Objectives: to assess the practical utility of Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) in our population. To correlate: RCLASI with DLQI (Dermatology Life Quality Index). Materials and Methods: observational, descriptive and transversal study that was performed in Hospital General de Agudos José María Ramos Mejía, Ciudad Autónoma de Buenos Aires - Argentina - by two groups of observers divided by their level of experience in dermatology. RCLASI and DLQI were assessed in 12 patients with Cutaneous Lupus Erythematosus (CLE). Time spent, inter observer variability and method´s levels of difficulty were evaluated. Results: the mean activity score for the group of low experience was 11,8 (SD 8,1) and for the group of moderate / high experience 12,7 (SD 8). The mean damage score for the former was 4 (SD 4,79) and for the later 4,4 (SD 5,4). The mean time spent by both groups was 7,76 minutes (9,79 minutes mean by the group of low experience and 5,73 by the group of moderate / high experience). The method was considered easy in more than 50% of the cases, independently of the observers´s level of experience. 50% of the patients did not show effect in their quality of life whereas 16,5% showed little effect, 25% mild effect, and 8,5% big effect. Conclusions: RCLASI is a useful and feasible method to evaluate all types of CLE. It’s easy and rapid, however it lacks a severity scale. This later limited its comparison with DLQI.
RESUMO
BACKGROUND: Sedation might improve tolerability and adherence to endoscopic procedures in patients with eosinophilic esophagitis (EoE). Propofol administration is often contraindicated in patients with hypersensitivity to egg, soy, or peanut. OBJECTIVE: To investigate the safety of propofol administration for procedural sedation in EoE patients sensitized/allergic to egg, soy, peanut. METHODS: A retrospective observational study in adult EoE patients undergoing esophagogastroduodenoscopy with propofol sedation was conducted between January 2009 and March 2013. Food-specific serum IgE and skin prick tests for egg, soy, peanut, and cross-reactant foods were performed in all patients. RESULTS: Sixty EoE adult patients, mostly on food elimination diets (91%), were evaluated (age: 28 years (14-56), male gender (90%)). Atopy was present in 88% of patients, being the most prevalent comorbidities rhinoconjunctivitis (78%) and asthma (67%). Fifty-two patients (86%) were sensitized to either egg, soy, or peanut. Eighteen patients (28%) had a history of allergic reactions to egg, legumes, and nuts and strictly avoided these foods. A total of 404 upper endoscopies were performed under propofol sedation. No allergic adverse events were reported, except a transient bronchospasm after orotracheal intubation in an asthmatic adolescent receiving multiple drugs for anesthesia, in whom no sensitization to either propofol or its lipid vehicle was confirmed. CONCLUSIONS: Propofol was safely administered for procedural sedation in a large series of adult EoE patients multisensitized to egg, soy, peanut, showing one-third clinical allergy to these foods.
Assuntos
Hipersensibilidade a Drogas/complicações , Hipersensibilidade a Drogas/imunologia , Esofagite Eosinofílica/complicações , Hipersensibilidade Alimentar/complicações , Alimentos/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Propofol/efeitos adversos , Adolescente , Adulto , Arachis/efeitos adversos , Ovos/efeitos adversos , Esofagite Eosinofílica/imunologia , Feminino , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Humanos , Hipnóticos e Sedativos/administração & dosagem , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Propofol/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Glycine max/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: To evaluate the influence of genetic polymorphism in UGT1A1, UGT1A7 and UGT1A9 on the population pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38G. METHODS: Plasma concentrations of irinotecan, SN-38 and SN- 38G from 72 patients were pooled to develop a population pharmacokinetic model using NONMEM VII. M3 method was used to account for plasma concentrations below the limit quantification. The effect of age, sex, body surface area, total bilirubin, co-medication, tumor type, and UGT1A1, UGT1A7 and UGT1A9 genotypes on the model parameters was evaluated. The model was internally validated using normalized visual predictive check (NVPC) and normalized predictive distribution errors (NPDE). RESULTS: The typical values (between-subject variability; %) of the irinotecan, SN-38 and SN-38G clearances were 42,9 L/h (56,4%), 1340 L/h (76,8%) and 188 L/h (70,1%), respectively. The presence of UGT1A1*28, UGT1A7*3, UGT1A9*22 genotypes decreases SN-38 clearance between 20 and 36%. Internal validation confirms the population pharmacokinetic model describe the time course of irinotecan, SN-38 and SN-38G plasma concentration and their associated variability in cancer patients. CONCLUSION: The inclusion of pharmacokinetic-pharmacogenomic information can add value to the individualized dose adjustment of irinotecan, because it will let quantitatively handle dose reductions in patients with iatrogenic toxicity due to UGT1A1 genetic polymorphisms.
Objetivo: Evaluar la influencia de los polimorfismos genéticos en UGT1A1, UGT1A7 y UGT1A9 sobre la farmacocinética poblacional de irinotecán y sus metabolitos, SN-38 y SN-38G. Metodología: Las concentraciones plasmáticas de irinotecán, SN-38 y SN-38G determinadas en 72 pacientes se utilizaron para desarrollar un modelo farmacocinético poblacional en el programa NONMEM VII. Se empleó el método M3 para incluir en el análisis las concentraciones por debajo del límite de cuantificación de la técnica analítica. Se evaluó el efecto de la edad, sexo, superficie corporal, bilirrubina total, medicación concomitante, tipo de tumor y polimorfismos genéticos en UGT1A1, UGT1A7 y UGT1A9 sobre los parámetros farmacocineticos del modelo. La validación interna del modelo farmacocinético se realizó mediante normalized visual predictive check (NVPC) y normalized predictive distribution error (NPDE). Resultados: El valor medio (variabilidad interpaciente, %) del aclaramiento de irinotecán, SN-38 y SN-38G ha sido 42,9 (56,4%), 1340 (76,8%) y 188 L/h (70,1%), respectivamente. La presencia de alelos con baja actividad enzimática (UGT1A1*28, UGT1A7*3 y UGT1A9*22) redujo el aclaramiento de SN-38 entre un 20 y un 36%. La validación interna ha confirmado que el modelo farmacocinético poblacional resulta adecuado para describir la evolución temporal de las concentraciones plasmáticas de irinotecán, SN-38 y SN-38G y su variabilidad en pacientes oncológicos. Conclusión: La inclusión de información farmacocinética-farmacogenética puede añadir valor a la personalización de la dosificación de irinotecán por cuanto que permitirá manejar cuantitativamente las reducciones de dosis en pacientes con toxicidad iatrogénica debido a los polimorfismos genéticos en UGT1A1.
Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Camptotecina/análogos & derivados , Glucuronatos/farmacocinética , Glucuronosiltransferase/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/sangue , Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/sangue , Camptotecina/farmacocinética , Camptotecina/uso terapêutico , Feminino , Glucuronatos/sangue , Glucuronatos/uso terapêutico , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/genética , UDP-Glucuronosiltransferase 1ARESUMO
Objetivo: Evaluar la influencia de los polimorfismos genéticos en UGT1A1, UGT1A7 y UGT1A9 sobre la farmacocinética poblacional de irinotecán y sus metabolitos, SN-38 y SN-38G. Metodología: Las concentraciones plasmáticas de irinotecán, SN-38 y SN-38G determinadas en 72 pacientes se utilizaron para desarrollar un modelo farmacocinético poblacional en el programa NONMEM VII. Se empleó el método M3 para incluir en el análisis las concentraciones por debajo del límite de cuantificación de la técnica analítica. Se evaluó el efecto de la edad, sexo, superficie corporal, bilirrubina total, medicación concomitante, tipo de tumor y polimorfismos genéticos en UGT1A1, UGT1A7 y UGT1A9 sobre los parámetros farmacocineticos del modelo. La validación interna del modelo farmacocinético se realizó mediante normalized visual predictive check(NVPC) y normalized predictive distribution error (NPDE). Resultados: El valor medio (variabilidad interpaciente, %) del aclaramiento de irinotecán, SN-38 y SN-38G ha sido 42,9 (56,4%), 1340 (76,8%) y 188 L/h (70,1%), respectivamente. La presencia de alelos con baja actividad enzimática (UGT1A1*28, UGT1A7*3 y UGT1A9*22) redujo el aclaramiento de SN-38 entre un 20 y un 36%. La validación interna ha confirmado que el modelo farmacocinético poblacional resulta adecuado para describir la evolución temporal de las concentraciones plasmáticas de irinotecán, SN-38 y SN-38G y su variabilidad en pacientes oncológicos. Conclusión: La inclusión de información farmacocinética-farmacogenética puede añadir valor a la personalización de la dosificación de irinotecán por cuanto que permitirá manejar cuantitativamente las reducciones de dosis en pacientes con toxicidad iatrogénica debido a los polimorfismos genéticos en UGT1A1 (AU)
Objective: To evaluate the Influence of genetic polymorphism in UGT1A1, UGT1A7 and UGT1A9 on the population pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38G. Methods: Plasma concentrations of irinotecan, SN-38 and SN-38G from 72 patients were pooled to develop a population pharmacokinetic model using NONMEM VII. M3 method was used to account for plasma concentrations below the limit quantification. The effect of age, sex, body surface area, total bilirubin, comedication, tumor type, and UGT1A1, UGT1A7 and UGT1A9 genotypes on the model parameters was evaluated. The model was internally validated using normalized visual predictive check (NVPC) and normalized predictive distribution errors (NPDE). Results: The typical values (between-subject variability; %) of the irinotecan, SN-38 and SN-38G clearances were 42,9 L/h (56,4%), 1340 L/h (76,8%) and 188 L/h (70,1%), respectively. The presence of UGT1A1*28, UGT1A7*3, UGT1A9*22 genotypes decreases SN-38 clearance between 20 and 36%. Internal validation confirms the population pharmacokinetic model describe the time course of irinotecan, SN-38 and SN-38G plasma concentration and their associated variability in cancer patients. Conclusion: The inclusion of pharmacokinetic-pharmacogenomic information can add value to the individualized dose adjustment of irinotecan, because it will let quantitatively handle dose reductions in patients with iatrogenic toxicity due to UGTIAVs genetic polymorphisms (AU)
Assuntos
Humanos , Inibidores da Topoisomerase I/farmacocinética , /genética , Marcadores Genéticos , Polimorfismo Genético , Técnicas de Genotipagem/métodosRESUMO
Cell migration and proliferation has been modelled in the literature as a process similar to diffusion. However, using diffusion models to simulate the proliferation and migration of cells tends to create a homogeneous distribution in the cell density that does not correlate to empirical observations. In fact, the mechanism of cell dispersal is not diffusion. Cells disperse by crawling or proliferation, or are transported in a moving ï¬uid. The use of cellular automata, particle models or cell-based models can overcome this limitation. This paper presents a stochastic cellular automata model to simulate the proliferation, migration and differentiation of cells. These processes are considered as completely stochastic as well as discrete. The model developed was applied to predict the behaviour of in vitro cell cultures performed with adult muscle satellite cells. Moreover, non homogeneous distribution of cells has been observed inside the culture well and, using the above mentioned stochastic cellular automata model, we have been able to predict this heterogeneous cell distribution and compute accurate quantitative results. Differentiation was also incorporated into the computational simulation. The results predicted the myotube formation that typically occurs with adult muscle satellite cells. In conclusion, we have shown how a stochastic cellular automata model can be implemented and is capable of reproducing the in vitro behaviour of adult muscle satellite cells.
Assuntos
Diferenciação Celular , Movimento Celular , Modelos Biológicos , Células Satélites de Músculo Esquelético/citologia , Algoritmos , Animais , Proliferação de Células , Células Cultivadas , Humanos , Camundongos , Camundongos Transgênicos , Reprodutibilidade dos Testes , Processos EstocásticosRESUMO
INTRODUCTION Epidermal growth factor receptor (EGFR) mutation related to tyrosine kinase inhibitors' (TKIs) responsiveness in non-small cell lung cancer (NSCLC) has become an important issue for therapeutic decision-making in NSCLC patients. MATERIAL AND METHODS Sixty-nine Caucasian NSCLC patients were screened for mutations in the tyrosine kinase (TK) domain of EGFR by direct sequencing from December 2005 to September 2010. RESULTS Activating mutations in the EGFR TK domain were found in 8 of 69 (11.6%) (7 deletions in exon 19 and one L858R mutation in exon 21). Seven of those mutations were found in adenocarcinoma and one mutation in bronchiolo-alveolar carcinoma; five of them in females (one smoker) and three of them in males (one smoker). All patients carrying activating mutations in the TK domain of EGFR were treated with TKIs. Ten patients not carrying an activating mutation in EGFR, who progressed after chemotherapy, were also treated with compassionate use of EGFR-specific TKIs (gefitinib or erlotinib). An objective response (partial response) was observed in all patients carrying an activating mutation in EGFR that received TKIs. Median overall survival for these patients has not been reached, however mean survival has been estimated at 39.5 months (95% CI, 22-57). CONCLUSIONS As previously reported, EGFR TK mutational analysis was a predictive test for response to targeted therapy with EGFR TKIs. The early identification of these patients consistently attains disease response and clearly improves outcomes.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Cloridrato de Erlotinib , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Masculino , Pessoa de Meia-Idade , Quinazolinas/uso terapêutico , Análise de SobrevidaRESUMO
INTRODUCTION Epidermal growth factor receptor (EGFR) mutation related to tyrosine kinase inhibitors' (TKIs) responsiveness in non-small cell lung cancer (NSCLC) has become an important issue for therapeutic decision-making in NSCLC patients. MATERIAL AND METHODS Sixty-nine Caucasian NSCLC patients were screened for mutations in the tyrosine kinase (TK) domain of EGFR by direct sequencing from December 2005 to September 2010. RESULTS Activating mutations in the EGFR TK domain were found in 8 of 69 (11.6%) (7 deletions in exon 19 and one L858R mutation in exon 21). Seven of those mutations were found in adenocarcinoma and one mutation in bronchiolo-alveolar carcinoma; five of them in females (one smoker) and three of them in males (one smoker). All patients carrying activating mutations in the TK domain of EGFR were treated with TKIs. Ten patients not carrying an activating mutation in EGFR, who progressed after chemotherapy, were also treated with compassionate use of EGFR-specific TKIs (gefitinib or erlotinib). An objective response (partial response) was observed in all patients carrying an activating mutation in EGFR that received TKIs. Median overall survival for these patients has not been reached, however mean survival has been estimated at 39.5 months (95% CI, 22-57). CONCLUSIONS As previously reported, EGFR TK mutational analysis was a predictive test for response to targeted therapy with EGFR TKIs. The early identification of these patients consistently attains disease response and clearly improves outcomes (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Mutação , Quinazolinas/uso terapêutico , Análise de SobrevidaRESUMO
Endotracheal tube fire during laryngeal surgery is a rare complication but one that has serious consequences. Surgeons, anesthesiologists and others involved with this type of surgery should become familiar with how to manage this difficult situation, which should be considered a sentinel event requiring prompt analysis of the root cause and surrounding circumstances. Measures to improve management should be implemented and training provided in order to prevent the recurrence of a similar unfortunate event. We report a case in which a patient's airway caught fire during use of an electrocautery device. The patient died as a result of the lesions sustained. We report the results of the investigation and the protocols for prevention and response implemented in our surgical department, in the hope that the experience will be of interest to others working in similar settings.
Assuntos
Queimaduras por Inalação/etiologia , Eletrocirurgia/instrumentação , Falha de Equipamento , Incêndios , Complicações Intraoperatórias/etiologia , Intubação Intratraqueal , Laringectomia , Salas Cirúrgicas , Idoso , Traumatismos Faciais/etiologia , Evolução Fatal , Incêndios/prevenção & controle , Humanos , Neoplasias Laríngeas/cirurgia , Laringe/lesões , Masculino , Boca/lesões , Insuficiência de Múltiplos Órgãos/etiologia , Faringe/lesões , Complicações Pós-Operatórias/etiologiaRESUMO
El riesgo de fuego asociado a ignición del tubo endotraquealdurante cirugía laríngea es una complicaciónpoco frecuente pero de graves consecuencias. Cirujanos,anestesiólogos y otros profesionales implicados en elmanejo de estos pacientes deben de estar formados yfamiliarizados con esta difícil situación. Se trata de unacomplicación que debe ser considerada como un eventocentinela y se debe realizar de forma inmediata un análisiscausa-raíz que permita investigar las circunstanciasen las que se produce, implementar medidas de mejoray formación que impidan que se dé este desgraciadoaccidente. Presentamos el caso clínico de un paciente quedurante cirugía laríngea sufrió una combustión de la víaaérea con el empleo de electrobisturí y que como resultadode las lesiones falleció. Aportamos la investigaciónrealizada y los protocolos de prevención y actuaciónimplantados en nuestra área quirúrgica considerandoque pueda ser de interés para otros profesionales denuestro ámbito(AU)
Endotracheal tube fire during laryngeal surgery is arare complication but one that has serious consequences.Surgeons, anesthesiologists and others involved with thistype of surgery should become familiar with how tomanage this difficult situation, which should beconsidered a sentinel event requiring prompt analysis ofthe root cause and surrounding circumstances. Measuresto improve management should be implemented andtraining provided in order to prevent the recurrence of asimilar unfortunate event. We report a case in which apatients airway caught fire during use of anelectrocautery device. The patient died as a result of thelesions sustained. We report the results of theinvestigation and the protocols for prevention andresponse implemented in our surgical department, in thehope that the experience will be of interest to othersworking in similar settings(AU)
Assuntos
Humanos , Masculino , Idoso , 35456 , Intubação Intratraqueal/efeitos adversos , Laringe/cirurgia , Terapia a Laser/efeitos adversos , 32408RESUMO
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Assuntos
Animais , Camundongos , Células-Tronco/imunologia , Esclerose Lateral Amiotrófica/fisiopatologia , Células Satélites de Músculo Esquelético/imunologia , Modelos Animais de DoençasRESUMO
Most of the somatic epidermal growth factor receptor (EGFR) mutations described to date in non-smallcell lung cancer (NSCLC) patients are located in the kinase domain and are considered activating mutations. Some of these mutations are associated with response to specific EGFR tyrosine kinase inhibitors (TKI) such as gefitinib and erlotinib. Here we report a case of a previously undescribed EGFR nonsense mutation in a lung adenocarcinoma patient who did not derive any clinical benefit with combination chemotherapy and erlotinib. To the best of our knowledge this is the second report in the literature describing an EGFR nonsense mutation in lung cancer patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sequência de Bases , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Códon sem Sentido , Cloridrato de Erlotinib , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-IdadeRESUMO
Most of the somatic epidermal growth factor receptor (EGFR) mutations described to date in non-smallcell lung cancer (NSCLC) patients are located in the kinase domain and are considered activating mutations. Some of these mutations are associated with response to specific EGFR tyrosine kinase inhibitors (TKI) such as gefitinib and erlotinib. Here we report a case of a previously undescribed EGFR nonsense mutation in a lung adenocarcinoma patient who did not derive any clinical benefit with combination chemotherapy and erlotinib. To the best of our knowledge this is the second report in the literature describing an EGFR nonsense mutation in lung cancer patients (AU)
No disponible