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1.
J Neurooncol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630385

RESUMO

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

3.
J Neurooncol ; 166(3): 407-415, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38153582

RESUMO

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Estudos Prospectivos , Dacarbazina/efeitos adversos , Intervalo Livre de Doença , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Antineoplásicos Alquilantes/efeitos adversos
4.
Rehabilitación (Madr., Ed. impr.) ; 57(4): [100804], Oct-Dic, 2023. tab
Artigo em Inglês | IBECS | ID: ibc-228349

RESUMO

Introduction: Dysphagia is a common post-stroke complication, which may result in serious pulmonary sequelae. Early detection of dysphagia and aspiration risk can reduce morbidity, mortality and length of hospitalization. Objectives: This study aims to identify association between dysphagia and acute cerebrovascular disease, and evaluate the prevalence and impact of pulmonary complications on readmissions and mortality. Material and methods: Retrospective observational study based on 250 clinical records of patients with acute cerebrovascular disease: clinical history, neurological examination, imaging and Gugging Swallowing Screen in the first 48h. Patients were followed for 3 months via medical records to estimate 3-month mortality and readmissions. Results: Out of 250 clinical records analyzed, 102 (40.8%) were evaluated for dysphagia. The prevalence of dysphagia was 32.4%. The risk was higher in older patients (p<0.001), in severe stroke (p<0.001) and in the hemorrhagic subtype (p=0.008). An association was found with dysarthria and aphasia (p=0.003; p=0.017). Respiratory tract infections occurred in 14.4% of all patients (GUSS group 11.8% versus no GUSS group 16.2%), and in 75% of those with severe dysphagia (p<0.001). Mortality at 3 months was 24.2% in dysphagic patients, especially high in the severe dysphagia group (75%, p<0.001). Conclusions: The type of cerebrovascular disease, NIHSS and GCS scores, age, dysarthria, and aphasia were significant associated factors to dysphagia. The prevalence of respiratory tract infections was higher in patients with no GUSS record, and no statistical significance was observed in related readmissions. Mortality at 3 months was superior in the severe dysphagia group.(AU)


Introducción: La disfagia es una complicación frecuente posterior a un evento cerebrovascular, que puede provocar graves secuelas pulmonares. La detección temprana de la disfagia y el riesgo de aspiración puede reducir la morbilidad, la mortalidad y la duración de la hospitalización. Objetivos: Este estudio pretende identificar asociaciones entre la disfagia y la enfermedad cerebrovascular aguda, y evaluar la prevalencia y el impacto de las complicaciones pulmonares en los reingresos y en la mortalidad. Material y método: Estudio observacional retrospectivo basado en 250 historias clínicas de pacientes con enfermedad cerebrovascular aguda: historia clínica, examen neurológico, pruebas de imagen y Gugging Swallowing Screen (GUSS) en las primeras 48h. Los pacientes fueron seguidos durante 3 meses a través de las historias clínicas para estimar la mortalidad a los 3 meses y los reingresos. Resultados: De las 250 historias clínicas analizadas, 102 (40,8%) fueron evaluados por disfagia. La prevalencia de disfagia fue del 32,4%. El riesgo fue mayor en los pacientes de mayor edad (p<0,001), en el ictus grave (p<0,001) y en el subtipo hemorrágico (p=0,008). Se encontró asociación con la disartria y la afasia (p=0,003; p=0,017). Las infecciones del tracto respiratorio se produjeron en el 14,4% de todos los pacientes (grupo GUSS 11,8% vs. grupo sin GUSS 16,2%), y en el 75% de los que tenían disfagia grave (p<0,001). La mortalidad a los 3 meses fue del 24,2% en pacientes disfágicos, especialmente alta en el grupo de disfagia grave (75%; p<0,001). Conclusiones: El tipo de enfermedad cerebrovascular, las puntuaciones NIHSS y GCS, edad, disartria y afasia fueron factores asociados de forma significativa a la disfagia. La prevalencia de infecciones del tracto respiratorio fue mayor en los pacientes sin registro GUSS, y no se observó significación estadística en los reingresos relacionados. La mortalidad a los 3 meses fue superior en el grupo de disfagia grave.(AU)


Assuntos
Humanos , Masculino , Feminino , Transtornos de Deglutição , Acidente Vascular Cerebral , Reabilitação do Acidente Vascular Cerebral , Afasia/complicações , Infecções Respiratórias/complicações , Estudos Retrospectivos , Reabilitação
5.
Rehabilitacion (Madr) ; 57(4): 100804, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37399640

RESUMO

INTRODUCTION: Dysphagia is a common post-stroke complication, which may result in serious pulmonary sequelae. Early detection of dysphagia and aspiration risk can reduce morbidity, mortality and length of hospitalization. OBJECTIVES: This study aims to identify association between dysphagia and acute cerebrovascular disease, and evaluate the prevalence and impact of pulmonary complications on readmissions and mortality. MATERIAL AND METHODS: Retrospective observational study based on 250 clinical records of patients with acute cerebrovascular disease: clinical history, neurological examination, imaging and Gugging Swallowing Screen in the first 48h. Patients were followed for 3 months via medical records to estimate 3-month mortality and readmissions. RESULTS: Out of 250 clinical records analyzed, 102 (40.8%) were evaluated for dysphagia. The prevalence of dysphagia was 32.4%. The risk was higher in older patients (p<0.001), in severe stroke (p<0.001) and in the hemorrhagic subtype (p=0.008). An association was found with dysarthria and aphasia (p=0.003; p=0.017). Respiratory tract infections occurred in 14.4% of all patients (GUSS group 11.8% versus no GUSS group 16.2%), and in 75% of those with severe dysphagia (p<0.001). Mortality at 3 months was 24.2% in dysphagic patients, especially high in the severe dysphagia group (75%, p<0.001). CONCLUSIONS: The type of cerebrovascular disease, NIHSS and GCS scores, age, dysarthria, and aphasia were significant associated factors to dysphagia. The prevalence of respiratory tract infections was higher in patients with no GUSS record, and no statistical significance was observed in related readmissions. Mortality at 3 months was superior in the severe dysphagia group.


Assuntos
Afasia , Transtornos de Deglutição , Infecções Respiratórias , Acidente Vascular Cerebral , Humanos , Idoso , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/diagnóstico , Disartria/complicações , Acidente Vascular Cerebral/complicações , Afasia/etiologia , Afasia/complicações , Infecções Respiratórias/complicações
6.
Int J Drug Policy ; 72: 189-194, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31160156

RESUMO

BACKGROUND: Prisoners and other high-risk patients who show a sustained virological response (SVR) after treatment for hepatitis C virus (HCV) can become reinfected. We aimed to calculate the rate of HCV reinfection in a large cohort of inmates with SVR and to determine factors that predict reinfection. METHODS: We included all inmates treated for hepatitis C in Catalonia (Spain) from January 2002 to December 2016 who achieved SVR and in whom viral load was subsequently determined. The incidence rate was calculated per 100 person-years (100 py) of follow up. Risk factors associated with reinfection were evaluated by bivariate log-rank test and multivariate Cox regression. Hazard ratio (HR) and their 95% confidence intervals (CI) were calculated. RESULTS: 602 patients were included, with a mean age of 37.9 years: 95% were men, 74.1% had a history of intravenous drug use (IDU) and 28.7% were HIV-infected. Patients were followed for a total of 2154.9 years (average 3.58 ± 3.1 years). 63 (10.5%) had HCV reinfection. 41 (65.1%) presented different genotype/subgenotype, 8 the initial genotype/subgenotype, and in 14 (22.2%) the genotype could not be determined. Of the 21 reinfected patients who were interviewed, 20 (95.2%) reported IDU after antiviral treatment, and 7 (33.3%) during treatment. The overall incidence of reinfection was 2.9 cases per 100 py. All reinfections occurred in patients with IDU history. At multivariate level, HIV infection was associated with reinfection (HR = 3.03; CI:1.82-5.04). CONCLUSION: In HIV-infected inmates with IDU history, the rate of reinfection of HCV post-SVR is very high. Prisons play a key role in the detection and treatment of infection and reinfection by HCV and in the post-treatment monitoring in these patients, which should be combined with counseling and the optimization of the harm reduction programs. Effective control of these vulnerable groups favours the elimination of the HCV infection.


Assuntos
Antivirais/administração & dosagem , Infecções por HIV/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Prisioneiros , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Hepatite C Crônica/epidemiologia , Humanos , Incidência , Masculino , Prisões , Recidiva , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Resposta Viral Sustentada
7.
Rev. andal. med. deporte ; 11(3): 0-0, sept. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-181205

RESUMO

Objective: To evaluate the effect of hyperventilation during a repeated sprint training on a cycle ergometer. Method: Seven cyclists performed two training sessions (10 maximal sprints of 10 s, with 60 s of rest), one with free ventilatory frequency and another one with hyperventilation (the participants breathed 60 cycles per minute during the last 30 s of recovery). Power, fatigue index and blood lactate concentration were analyzed. Results: The lactate concentrations pre- and post-training did not differ between trainings. Regarding to the maximum absolute and relative power, no differences were found between sprints in the hyperventilation condition, however, the values obtained in the first four sprints were higher than the latter two (p < 0.05) in the normal condition. In relation to the mean absolute and relative power, differences were found between sprints in both conditions. In the hyperventilation condition the value of the first sprint was higher than the penultimate (p < 0.05), while in the normal condition, the value of the first sprint was greater than the last four (p < 0.05) and the value of the second sprint exceeded the last two ones (p < 0.05). For the fatigue index, both protocols showed differences from the first to the eighth sprint (p < 0.05). Conclusion: Despite the absence of differences in lactate concentration between normal condition and hyperventilation condition, hyperventilation between efforts during a repeated sprint training could reduce the decrease in power output on a cycle ergometer


Objetivo: Evaluar el efecto de la hiperventilación durante una sesión de entrenamiento con esfuerzos repetidos en cicloergómetro. Método: Siete ciclistas realizaron dos entrenamientos (10 sprints máximos de 10 s con 60 s de recuperación), uno con frecuencia de respiración normal y otro con hiperventilación (los participantes respiraron a 60 ciclos por minuto durante los últimos 30 s de recuperación). Se analizaron la potencia, el índice de fatiga y la concentración sanguínea de lactato. Resultados: La concentración de lactato pre y postentrenamiento no difirió entre los entrenamientos. En relación con los valores de potencia máxima absoluta y relativa, no se encontraron diferencias entre los sprints en la condición de hiperventilación; sin embargo, en la condición normal, los valores obtenidos en los cuatro primeros sprints fueron superiores a los dos últimos (p < 0.05). En relación con los valores de potencia media absoluta y relativa, se encontraron diferencias entre los sprints en las dos condiciones (p < 0.001). En la condición de hiperventilación, el valor del primer sprint fue superior al penúltimo (p < 0.05), mientras que en la condición normal el valor del primer sprint fue superior a los últimos cuatro (p < 0.05) y el valor del segundo fue mayor que los dos últimos (p < 0.05). Para el índice de fatiga, ambos protocolos presentaron diferencias desde el primer hasta el octavo sprint (p < 0.05). Conclusión: Hiperventilación entre esfuerzos máximos repetidos puede reducir la disminución de potencia en cicloergómetro


Objetivo: Avaliar o efeito da hiperventilação durante um treinamento de sprints repetidos em um cicloergômetro. Método: Sete ciclistas executaram duas sessões de treinamento (10 sprints máximos de 10s, com 60s de descanso), sendo um com frequência ventilatória livre e outro com hiperventilação (o participante respirava 60 ciclos por minuto, durante os 30s de recuperação). Potência, índice de fadiga e as concentrações séricas de lactato foram analisadas. Resultados: As concentrações de lactato pré- e pós-treinamento não diferiram entre os treinamentos. Em relação à potência máxima e relativa, não foram encontradas diferenças entre os sprints na condição de hiperventilação, entretanto, os valores obtidos nos quatro primeiros sprints foram maiores que os dois últimos (p < 0.05) executados em condições normais. Quanto à média da potência absoluta e relativa, foram encontradas diferenças entre ambas as condições. Na condição de hiperventilação, o valor do primeiro sprint foi maior que o penúltimo (p < 0.05), enquanto que em condição normal, o valor do primeiro sprint foi maior que os quatro últimos (p < 0.05) e o valor do segundo sprint excedeu os dois últimos (p < 0.05). O índice de fadiga demonstrou diferenças do primeiro ao oitavo sprint (p < 0.05) em ambos os protocolos. Conclusão: Apesar da ausência de diferenças nas concentrações de lactato entre as condições estudadas, a execução da hiperventilação entre os sprints pode reduzir o decréscimo da potência em um treinamento de sprints repetidos em cicloergômetro


Assuntos
Humanos , Masculino , Adulto Jovem , Adulto , Hiperventilação/fisiopatologia , Desempenho Atlético/estatística & dados numéricos , Exercício Físico/fisiologia , Fadiga Muscular/fisiologia , Treinamento de Força/estatística & dados numéricos , Ergometria/estatística & dados numéricos , Teste de Esforço/estatística & dados numéricos , Ciclismo/estatística & dados numéricos , Ácido Láctico/metabolismo , Acidose Láctica/fisiopatologia
8.
Crit Rev Food Sci Nutr ; 58(9): 1526-1537, 2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28125279

RESUMO

The development of packaging materials with new functionalities and lower environmental impact is now an urgent need of our society. On one hand, the shelf-life extension of packaged products can be an answer to the exponential increase of worldwide demand for food. On the other hand, uncertainty of crude oil prices and reserves has imposed the necessity to find raw materials to replace oil-derived polymers. Additionally, consumers' awareness toward environmental issues increasingly pushes industries to look with renewed interest to "green" solutions. In response to these issues, numerous polymers have been exploited to develop biodegradable food packaging materials. Although the use of biopolymers has been limited due to their poor mechanical and barrier properties, these can be enhanced by adding reinforcing nanosized components to form nanocomposites. Cellulose is probably the most used and well-known renewable and sustainable raw material. The mechanical properties, reinforcing capabilities, abundance, low density, and biodegradability of nanosized cellulose make it an ideal candidate for polymer nanocomposites processing. Here we review the potential applications of cellulose based nanocomposites in food packaging materials, highlighting the several types of biopolymers with nanocellulose fillers that have been used to form bio-nanocomposite materials. The trends in nanocellulose packaging applications are also addressed.


Assuntos
Celulose/química , Embalagem de Alimentos , Nanocompostos/química , Biodegradação Ambiental , Biopolímeros/química , Fenômenos Químicos
9.
Ann Burns Fire Disasters ; 31(3): 233-237, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30863259

RESUMO

Despite the wide and growing use of microsurgery, its application in primary burn reconstruction is not very frequent as it faces a number of additional challenges in this setting. A retrospective analysis of the clinical records of all patients submitted to microvascular free tissue transfer for primary burn reconstruction over an 8-year period (from January 2009 to December 2016) was performed. An evaluation of the indications, timing, principles of flap selection, complications and outcomes of free tissue transfer in primary burn reconstruction was made. Fourteen patients required 18 microsurgical flaps for acute soft tissue reconstruction (1.1% of all patients admitted). 64.3% of the patients were male. The mean age was 59.64 years, and mean TBSA was 10.5%. The majority of the injuries were caused by flames (71.4%), followed by electrical contact (21.4%). The primary indication for microsurgical reconstruction was tissue deficit with exposure of tendons, nerves, vessels, bone and/or joints after debridement. The procedure was more often performed in the early period after injury (between the 5th and 22nd day). The most frequently used flaps were the Latissimus dorsi and the anterolateral thigh flap. Major complications included 2 total flap failures (11.1%) and a partial flap failure that required reconstruction with another free flap. Microsurgical free flaps have a valuable role in primary burn reconstruction. Despite the reported higher complication rate in this specific clinical scenario, their use may reduce the total number of surgeries needed to achieve wound closure.


Bien que de plus en plus utilisée, la microchirurgie est rarement utilisée dans la prise en charge initiale des brûlés, et doit faire face à plusieurs difficultés supplémentaires dans cette indication. Nous avons effectué une analyse rétrospective des dossiers de tous les patients brûlés entre janvier 2009 et décembre 2016 ayant bénéficié au stade d'un lambeau libre (LL). Nous avons évalué l'indication, le délai, la sélection du site donneur, les complications et l'évolution du lambeau. Quatorze patients (1,1% du total) dont 64,5% d'hommes ont bénéficié de 18 LL. L'âge moyen était de 59,64 ans, la surface brûlée de 10,5%. La majorité des brûlures (71,4%) étaient dues à une flamme, 21,4% à l'électricité. L'indication principale était l'exposition ostéo-articulaire ou d'éléments nobles (tendons, nerfs, vaisseaux) après excision. La réalisation du LL était précoce (J5-J22). Les sites donneurs étaient Latissimus dorsi et la région antéro-latérale de cuisse. Deux lambeaux ont totalement nécrosé, un partiellement, ce qui a nécessité la réalisation d'un second LL. Les LL ont une place dans la prise en charge initiale des brûlés. Bien de grevés d'un taux de complications plus élevé dans cette indication, ils peuvent permettre de diminuer le nombre d'interventions nécessaires à la cicatrisation.

10.
Arq. bras. med. vet. zootec. (Online) ; 69(6): 1551-1559, nov.-dez. 2017. ilus, graf
Artigo em Português | LILACS, VETINDEX | ID: biblio-910563

RESUMO

O objetivo deste estudo foi utilizar a sonda uretral flexível como método alternativo para aferição da pressão intracraniana em coelhos com trauma cranioencefálico induzido pelo cateter de Fogarty 4 Fr (balão epidural) e comparar os dados obtidos com o método convencional de cateter de ventriculostomia. Foram utilizados 12 coelhos, machos, adultos, distribuídos aleatoriamente em dois grupos, denominados de G1: mensuração da PIC com cateter de ventriculostomia (n=6) e G2: mensuração com sonda uretral (n=6). Foram realizadas duas craniotomias na região parietal direita e esquerda para a implantação do cateter de ventriculostomia ou sonda uretral flexível e o balão epidural, respectivamente. A PAM, a PPC, a FC, a FR e a TR foram mensurados antes e após a craniotomia. A PIC foi avaliada após a craniotomia e a cada 10 minutos depois do preenchimento do balonete com 0,3mL de NaCl 0,9%, durante 40 minutos, e com 0,6mL, pelo mesmo período de tempo, totalizando 80 minutos. A PIC aumentou em ambos os grupos, sendo menores os valores registrados com a sonda uretral flexível. Foi possível reproduzir o aumento da PIC com o modelo experimental de TCE utilizando o cateter de Fogarty 4 Fr na região epidural e, embora haja a necessidade de outros estudos, a sonda uretral flexível demonstra ser um método alternativo de mensuração da PIC em coelhos com trauma cranioencefálico.(AU)


The aim of this study was to evaluate the use of flexible urethral catheter as an alternative method for measuring intracranial pressure in rabbits with head trauma induced by 4 F Fogarty catheter (epidural balloon) and compare the data obtained with the conventional method of ventriculostomy catheter. In this study, New Zealand rabbits were randomly distributed into two groups, G1: measuring the ICP with ventriculostomy catheter (n=6) and G2: measuring the ICP with urethral catheter (n=6). Two craniotomies were performed in the right and left parietal region for the implantation of a ventriculostomy catheter and/or flexible urethral catheter and epidural 4 Fr Fogarty arterial embolectomy catheter, respectively. MAP, CPP, HR, RF and RT values were measured before and after of the craniotomy. The ICP value was measured after craniotomy, every five minutes during 40 minutes after the balloon was inflated with 0.3 ml with NaCl and further 40 minutes after the balloon was inflated with 0.6 ml. The ICP value increased in both groups; however, the ICP values were lower in the flexible urethral catheter. The flexible urethral catheter can be used as an alternative method to measure ICP values in rabbits with head injury.(AU)


Assuntos
Animais , Coelhos , Pressão Intracraniana , Equipamentos de Medição de Riscos , Cateterismo Urinário/estatística & dados numéricos , Cateterismo Urinário/veterinária , Traumatismos Craniocerebrais/diagnóstico , Ventriculostomia/veterinária
11.
Ann Oncol ; 28(12): 2994-2999, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29045512

RESUMO

BACKGROUND: Patients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. Fas cell surface death receptor and mammalian target of rapamycin pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients. PATIENTS AND METHODS: A multicenter, single-arm phase II trial was sponsored by the Spanish Group for Research on Sarcoma. Osteosarcoma patients, relapsed or progressing after standard chemotherapy and unsuitable for metastasectomy received gemcitabine and rapamycin p.o. 5 mg/day except for the same day of gemcitabine administration, and the day before. The main end point was 4-month progression-free survival rate (PFSR), with the assumption that rates higher than 40% would be considered as an active regimen. Translational research aimed to correlate biomarkers with the clinical outcome. RESULTS: Thirty-five patients were enrolled and received at least one cycle. PFSR at 4 months was 44%, and after central radiologic assessment, 2 partial responses and 14 stabilizations (48.5%) were reported from 33 assessable patients. The most frequent grade 3-4 adverse events were: neutropenia (37%), thrombocytopenia (20%), anemia (23%), and fatigue (15%); however, only three patients had febrile neutropenia. Positive protein expression of RRM1 significantly correlated with worse PFS and overall survival, while positivity of P-ERK1/2 was correlated with significant better overall survival. CONCLUSION: Gemcitabine plus sirolimus exhibits satisfactory antitumor activity and safety in this osteosarcoma population, exceeding the prespecified 40% of 4-month PFSR. The significant correlation of biomarkers with clinical outcome encourages further prospective investigation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/patologia , Recidiva , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Adulto Jovem , Gencitabina
12.
Br J Cancer ; 117(6): 767-774, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28787430

RESUMO

BACKGROUND: First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients. METHODS: This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR patients (metastatic, axial-pelvic primaries or bone marrow micrometastasis) received 2 window cycles of G/D. Patients with an objective response (OR) to G/D received 12 monthly cycles of G/D after completion of mP6. The primary end point was the OR rate to the G/D window phase and the event-free survival (EFS) and overall survival (OS) for all patients. The study is registered at ClinicalTrials.gov (identifier: NCT00006734). RESULTS: Forty-three patients were enroled, median age 17 years (range, 3-40). After a median follow-up of 43.4 months, the 5-year OS rate is 55.0% (95% CI, 41-74%) with an EFS of 50.0% (95% CI, 36-68%). The 5-year OS and EFS rates for standard risk (SR) patients was 76.0% (95% CI, 57-100%) and 71.0% (CI, 54-94%); for HR 36.0% (CI, 20-65%) and 29.0% (CI, 15-56%). Twelve of 17 (70.6%) high-risk (HR) patients showed an OR (7 PR and 5 SD) to G/D window therapy. The 5-year OS rate for patients ⩽18 years of age was 74.0% (CI, 56-97%) and 31.0% for >18 years (95% CI, 15-66%), P<0.001. Grade 4 adverse events during mP6 occurred in 28/39 of patients (72%) and did not correlate with age. Multivariate survival analyses with <18 vs ⩾18 and risk groups significant differences, P<0.00001. Using a Cox model for OS, both age and risk group were statistically significant (P=0.0011 and P=0.0065, respectively). CONCLUSIONS: Age at diagnosis is an independent prognostic factor superior to the presence of metastases with 18 years as the strongest cut-off. The mP6 regimen provided survival curves that plateau at 3 years and G/D produced significant responses in HR-ES that is worth further exploring.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Sarcoma de Ewing/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel , Humanos , Estimativa de Kaplan-Meier , Razão de Chances , Prognóstico , Estudos Prospectivos , Sarcoma de Ewing/mortalidade , Espanha , Taxa de Sobrevida , Taxoides/administração & dosagem , Gencitabina
13.
Am J Emerg Med ; 35(4): 628-631, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28040382

RESUMO

INTRODUCTION: Clinicians still face significant challenge in predicting intra-abdominal injuries in patients admitted to an emergency department for blunt abdominal trauma. This study was thus designed to investigate the value of dipstick urinalysis in patients with blunt abdominal trauma. METHODS: We performed a retrospective, multicenter, cohort study involving patients admitted to the emergency department for abdominal traumas, examined by means of urinary dipstick and abdominal CT scan. The primary endpoint was the correlation between microscopic hematuria detected via dipstick urinalysis (defined by the presence of blood on the dipstick urinalysis but without gross hematuria) and abdominal injury, as evidenced on CT scan. RESULTS: Of the 100 included patients, 56 experienced microscopic hematuria, 17 gross hematuria, and 44 no hematuria. Patients with abdominal injury were more likely to present with hypovolemic shock (odds ratio [OR]: 8.4; 95% confidence interval [CI]: 2.7-26), abdominal wall hematoma (OR: 3.1; 95% CI: 1.2-7.9), abdominal defense (OR: 5.2; 95% CI: 1.8-14.5), or anemia (OR: 3.6; 95% CI: 1.2-10.3). Moreover, dipstick urinalysis was less likely to predict injury, with just 72.2% sensitivity (95% CI: 54.8-85.8), 53.1% specificity (95% CI: 40.2-65.7), and positive and negative predictive values of 46.4% (95% CI: 33.0-60.3) and 77.3% (95% CI: 62.2-88.5), respectively. CONCLUSION: Dipstick urinalysis was neither adequately specific nor sensitive for predicting abdominal injury and should thus not be used as a key assessment component in patients suffering from blunt abdominal trauma, with physical exam and vital sign assessment the preferred choice.


Assuntos
Traumatismos Abdominais/urina , Hematúria/diagnóstico , Sistema Urinário/lesões , Ferimentos não Penetrantes/urina , Traumatismos Abdominais/complicações , Traumatismos Abdominais/diagnóstico por imagem , Acidentes por Quedas , Acidentes de Trânsito , Adulto , Idoso , Anemia/etiologia , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hematúria/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Choque/etiologia , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico por imagem
14.
Ann Burns Fire Disasters ; 30(4): 268-271, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-29983679

RESUMO

Although electrical burns have a rather low incidence, they are considered one of the most devastating injuries. The aim of this retrospective study was to analyse specific aspects of electrical injuries and to delineate a prevention strategy. A retrospective analysis of medical records of all the patients admitted to our Unit with electrical burns over a 10-year period (2006/01/01-2015/12/31) was undertaken. Demographic data, mechanism of injury and electric current voltage, total burn surface area (TBSA), location and depth of burns, acute complications, surgical interventions and length of hospital stay (LOS) were analysed. Out of 1695 burn patients admitted to our Unit, 99 subjects (5.84%) suffered electrical burns. 97% of these patients were male. The mean age was 38.3±13.7years and mean TBSA was 11.9%±13.2%. The mechanism of injury was occupational in 75 cases. Injuries were classified as low-voltage burns (24.2%), highvoltage burns (30.3%) and flash burns (45.5%). TBSA (p=0.014), mean LOS (p=0.002) and serum creatinine kinase levels (p<0.001) were significantly higher in patients with high-voltage injury in comparison to low-voltage injury, as well as the incidence of escharotomy/ fasciotomy (p=0.049) and flap surgeries (p=0.004). Although there was a higher incidence of amputations in this group (16.7% vs. 12.5%), the difference was not statistically significant (p=0.487). The high prevalence of electrical burns in males and workers emphasizes the need to review occupational safety regulations. Educational efforts regarding potential hazards of electricity and reinforcing compliance with safety measures are essential to avoid these injuri.


Bien que plutôt rares, les brûlures électriques sont considérées comme les plus délabrants des accidents. Le but de cette étude était d'analyser les aspects spécifiques des brûlures électriques et de définir une stratégie de prévention. Elle a consister en l'analyse des dossiers de tous les patients admis pour brûlure électrique entre le 1er janvier 2006 et les 31 décembre 2015. Les données démographiques, le mécanisme exact de l'accident, le voltage, la surface brûlée (SB), la localisation, la profondeur, les complications initiales, les interventions chirurgicales et la durée moyenne de séjour (DMS) ont été analysées. Quatre vingt dix neuf (5,84%) des 1 695 patients hospitalisés pour brûlure avaient subi un accident électrique, 97% d'entre eux étaient des hommes. Leur âge moyen était de 38,3 +/- 13,7 ans, la surface brûlée de 11,9 +/- 13,2%. Soixante quinze accidents étaient survenus au travail. On recensait 24,2% de brûlures électrothermiques par bas voltage, 30,3% par haut voltage et 45,5% de flashes. La surface brûlés (p=0,014), la DMS (p=0,002), le niveau de CPK sanguine (p<0,001), l'incidence des incisions de décharge et aponévrotomies (p=0,049) et de lambeaux (p=0,004) était plus élevés en cas d'atteinte par haut voltage. Bien que plus élevée chez ces patients (16,7% VS 12,5%), l'incidence des amputation n'était pas statistiquement significative (p=0,487). L'incidence élevée des accidents électriques chez les hommes au travail est une indication à revoir la législation. Des efforts de formation et de contrôle de l'application de la législation sont nécessaires pour éviter ces accidents.

15.
Arq. bras. med. vet. zootec ; 68(3): 695-701, tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: lil-785707

RESUMO

The common marmoset is an important Neotropical primate for biomedical research. With the intention of providing pelvimetric values that allow the selection of animals with better characteristics for reproduction, we studied the X-ray of the pelvis, in ventro-dorsal projection of 12 adult animals, six males and six females, belonging to the National Center of Primates - CENP. The measurements were made to right diagonal diameters (RDD), left diagonal diameter (LDD), bi-iliac middle diameter (BIMD), bi-iliac upper diameter (BIUD), bi-iliac lower diameter (BILD), sacrum-pubic diameter (SPD), and the input area of the pelvis (IAP), which were compared in relation to sex and bodily correlated with the biometrics. The results of the means and standard deviations regarding pelvimetry (cm) were: for the RDD in males of 1.91±0.14 and in the females of 2.05±0.08; LDD in males of 1.85±0.16 and in females of 2.03± 0.08; BIMD in males of 1.46±0.12 and in the females of 1.5±0; BIUD showed in males 1.3±0.1 and in females of 1.3±0.06; BILD in males of 1.35±0.15 and in females of 1.25±0.08; SPD in males of 1.68±0.09 and in females of 1.93±0.13; IAP in males of 1.9±0.26 and in the females of 2.23±0.13. It was concluded that the pelvis of Callithrix jacchus could be classified as dolicopelvic type, there is sexual dimorphism in relation to the pelvis of adult animals and that the bodily measurements have low positive correlation with pelvic measurements.(AU)


O sagui-de-tufo-branco se destaca como um importante primata neotropical para as pesquisas biomédicas. Com o intuito de fornecer valores pelvimétricos que permitam a seleção de animais com melhores características para a reprodução, estudaram-se radiografias da pelve, em projeção ventrodorsal, de 12 animais, sendo seis machos e seis fêmeas, adultos, pertencentes ao Centro Nacional de Primatas - CENP. As mensurações realizadas foram referentes aos diâmetros diagonal direito (DDD), diagonal esquerdo (DDE), bi-ilíaco médio (DBIM), bi-ilíaco superior (DBIS), bi-ilíaco inferior (DBII), sacropúbico (DSP), além da área de entrada da pelve (AEP), os quais foram comparados em relação ao sexo e correlacionados com a biometria corpórea. Os resultados de médias e desvios-padrão com relação à pelvimetria (cm) foram: para o DDD nos machos de 1,91±0,14 e nas fêmeas de 2,05±0,08; DDE nos machos de 1,85±0,16 e nas fêmeas de 2,03±0,08; DBIM nos machos de 1,46±0,12 e nas fêmeas de 1,5±0; DBIS nos machos de 1,3±0,1 e nas fêmeas de 1,3±0,06; DBII nos machos de 1,35±0,15 e nas fêmeas de 1,25±0,08; DSP nos machos de 1,68±0,09 e nas fêmeas de 1,93±0,13; AEP nos machos de 1,9±0,26 e nas fêmeas de 2,23±0,13. Concluiu-se que a pelve de Callithrix jacchus pode ser classificada como do tipo dolicopélvica, existe dimorfismo sexual em relação às pelves de animais adultos e que as medidas corpóreas apresentam baixa correlação positiva com as medidas pélvicas.(AU)


Assuntos
Animais , Callitrichinae , Pelvimetria/veterinária , Pelve , Primatas , Radiografia/veterinária , Biometria/métodos , Caracteres Sexuais
16.
Clin Transl Oncol ; 18(8): 805-12, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26542177

RESUMO

PURPOSE: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. METHODS/PATIENTS: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. RESULTS: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. CONCLUSION: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos de Nitrosoureia/uso terapêutico , Compostos Organofosforados/uso terapêutico , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Feminino , Glioma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Genes Immun ; 15(5): 265-74, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24739497

RESUMO

The tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-tube (QFTGIT) are adjunctive tests used in the diagnosis of pediatric tuberculosis (TB). Neither test can rule out TB; however, a positive test usually triggers preventive treatment in TB contacts aged <5 years. TST and QFTGIT can give divergent results and it is unclear how discordant results should be interpreted in terms of TB risk and preventive treatment. To understand the immune processes underlying concordant or discordant TST and QFTGIT results, we analyzed immune responses in children from Palamaner Taluk in India (a TB-endemic region with routine neonatal BCG vaccination) who were referred to a TB case verification ward on suspicion of TB. Two hundred and ten children aged <3 years were classified according to their TST and QFTGIT results, and their immune responses analyzed by dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification, using a panel of 45 genes and a 10-plex antigen-specific enzyme-linked immunosorbent assay. We show that immune biomarkers FPR1, TNFRSF1A and interferon (IFN)-γ are upregulated (all P<0.05) in concordant test-positive children, whereas BPI is downregulated (P<0.05). In contrast, SEC14L1 (P=0.034) and Interferon gamma-induced protein 10 (IP-10) (P=0.001) are differentially expressed between the TST+QFTGIT- /TST-QFTGIT+ groups. Known TB exposure was more frequent in concordant positive children and results were consistent with elevated expression of genes associated with inflammatory responses. Children with discordant test results displayed a mixed profile with activation of both pro- and anti-inflammatory markers. TST and/or QFTGIT positivity appears to reflect distinct but overlapping aspects of host immunity.


Assuntos
Teste Tuberculínico/normas , Tuberculose/diagnóstico , Adolescente , Adulto , Biomarcadores/sangue , Proteínas de Transporte/sangue , Feminino , Humanos , Índia , Lactente , Recém-Nascido , Interferon gama/sangue , Estudos Longitudinais , Masculino , Reação em Cadeia da Polimerase Multiplex/normas , Estudos Prospectivos , Receptores de Formil Peptídeo/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Sensibilidade e Especificidade , Tuberculose/imunologia , Regulação para Cima
20.
Int J Sports Med ; 35(1): 41-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23771835

RESUMO

The aim was to investigate the effects of the intra-session exercise order during water-based concurrent training on the neuromuscular adaptations in young women. 26 women (25.1±2.9 years) were placed into 2 groups: resistance prior to (RA) or after (AR) aerobic training. Subjects performed resistance (sets at maximal effort) and aerobic training (exercises at heart rate corresponding to the second ventilatory threshold) twice a week over 12 weeks, performing both exercise types in the same training session. Upper (elbow flexion) and lower-body (knee extension) one-repetition maximum test (1RM) and peak torque (PT) were evaluated. The muscle thickness (MT) of upper (sum of MT of biceps brachii and brachialis) and lower-body (sum of MT of vastus lateralis, vastus medialis, vastus intermedius, and rectus femoris) was determined by ultrasonography. Moreover, the maximal electromyographic activity (EMG) of upper (biceps brachii) and lower-body (sum of EMG of vastus lateralis and rectus femoris) was measured. Both RA and AR groups increased the upper and lower-body 1RM and PT, while the lower-body 1RM increases observed in the RA was greater than AR (43.58±14.00 vs. 27.01±18.05%). RA and AR showed MT increases in all muscles evaluated, while the lower-body MT increases observed in the RA were also greater than AR (10.24±3.11 vs. 5.76±1.88%). There were increases in the maximal EMG of upper and lower-body in both RA and AR, with no differences between groups. Performing resistance prior to aerobic exercise during water-based concurrent training seems to optimize the lower-body strength and hypertrophy.


Assuntos
Adaptação Fisiológica/fisiologia , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Água , Adulto , Eletromiografia , Feminino , Voluntários Saudáveis , Humanos , Contração Isométrica/fisiologia , Perna (Membro)/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/crescimento & desenvolvimento , Consumo de Oxigênio , Treinamento de Força/métodos , Torque , Ultrassonografia
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