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PURPOSE: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors radically changed the treatment paradigm for breast cancer. Similar to estrogen receptor in breast cancer, androgen receptor signaling activates cyclin D-CDK4/6, driving proliferation and resistance to hormonal manipulation in prostate cancer. This study was designed to detect signals of clinical activity for abemaciclib in treatment-refractory metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Eligible patients had progressive mCRPC, measurable disease, and previously received ≥1 novel hormonal agent(s) and 2 lines of taxane chemotherapy. Abemaciclib 200 mg twice daily was administered on a continuous dosing schedule. Primary endpoint was objective response rate (ORR) without concurrent bone progression. This study was designed to detect a minimum ORR of 12.5%. RESULTS: At trial entry, 40 (90.9%) of 44 patients had objective radiographic disease progression, 4 (9.1%) had prostate-specific antigen (PSA)-only progression, and 20 (46.5%) had visceral metastases (of these, 60% had liver metastases). Efficacy analyses are as follows: ORR without concurrent bone progression: 6.8%; disease control rate: 45.5%; median time to PSA progression: 6.5 months [95% confidence interval (CI), 3.2-NA]; median radiographic PFS; 2.7 months (95% CI, 1.9-3.7); and median OS, 8.4 months (95% CI, 5.6-12.7). Most frequent grade ≥3 treatment-emergent adverse events (AE) were neutropenia (25.0%), anemia, and fatigue (11.4% each). No grade 4 or 5 AEs were related to abemaciclib. CONCLUSIONS: Abemaciclib monotherapy was well tolerated and showed clinical activity in this heavily pretreated population, nearly half with visceral metastases. This study is considered preliminary proof-of-concept and designates CDK4/6 as a valid therapeutic target in prostate cancer.
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Aminopiridinas , Bencimidazoles , Neoplasias de la Próstata Resistentes a la Castración , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Aminopiridinas/administración & dosificación , Aminopiridinas/uso terapéutico , Aminopiridinas/efectos adversos , Bencimidazoles/administración & dosificación , Bencimidazoles/efectos adversos , Bencimidazoles/uso terapéutico , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Metástasis de la Neoplasia , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Resultado del TratamientoRESUMEN
Objetivos: evaluar la efectividad de la combinación de la estimulación eléctrica funcional y terapia en espejo en la recuperación de la función de la extremidad superior en personas con un accidente cerebro vascular. Métodos: estudio de caso pre- post en una persona con accidente cerebro vascular. Para la recogida de datos se han empleado diversas escalas como: Functional Independence Measure, Motor Activity Log, Box & Blocks Test o Abilhand entre otras. La intervención duró 8 semanas en las que se realizaron 3 sesiones semanales, sumando un total de 24 sesiones. Las evaluaciones se hicieron pre- y post-tratamiento. Discusión: la combinación de estas técnicas o abordajes ha demostrado ser eficaz, mejorando la funcionalidad de la extremidad superior y, consecuentemente, su calidad de vida e independencia de una persona que sufrió un accidente cerebro vascular.(AU)
Objective: Effectiveness evaluation of the combination of functional electrical stimulation and mirror therapy in the recovery of the upper limb function in people with stroke. Methods: Pre- post case study in a person with stroke. Various scales were used for data collection, such as: Functional Independence Measure, Motor Activity Log, Box & Blocks Test or Abilhand, among others. The intervention lasted 8 weeks in which 3 weekly sessions were held, making a total of 24 sessions. The assessments were done pre- and post-treatment. Discussion: The combination of these techniques or approaches has proven to be effective, improving the functionality of the upper extremity and, consequently, the quality of life and Independence of a person with stroke.(AU)
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Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular , Rehabilitación de Accidente Cerebrovascular , Estimulación Eléctrica , Extremidad Superior , Rehabilitación Neurológica , Examen Físico , Pacientes Internos , Evaluación de Síntomas , Terapia OcupacionalRESUMEN
Background: The prognosis of patients with synchronous metastatic renal cell carcinoma (mRCC) is poor. Whereas single-agent tyrosine kinase inhibition (TKI) is clearly insufficient, the effects can be enhanced by combinations with immune checkpoint inhibitors. Innovative treatment options combining TKI and other immune-stimulating agents could prove beneficial. Objective: To evaluate the clinical effects on metastatic disease when two doses of allogeneic monocyte-derived dendritic cells (ilixadencel) are administrated intratumorally followed by nephrectomy and treatment with sunitinib compared with nephrectomy and sunitinib monotherapy, in patients with synchronous mRCC. Design setting and participants: A randomized (2:1) phase 2 multicenter trial enrolled 88 patients with newly diagnosed mRCC to treatment with the combination ilixadencel/sunitinib (ILIXA/SUN; 58 patients) or sunitinib alone (SUN; 30 patients). Outcome measurements and statistical analysis: The primary endpoints were 18-mo survival rate and overall survival (OS). A secondary endpoint was objective response rate (ORR) assessed up to 18 mo after enrollment. Statistic evaluations included Kaplan-Meier estimates, log-rank tests, Cox regression, and stratified Cochran-Mantel-Haenszel tests. Results and limitations: The median OS was 35.6 mo in the ILIXA/SUN arm versus 25.3 mo in the SUN arm (hazard ratio 0.73, 95% confidence interval 0.42-1.27; p = 0.25), while the 18-mo OS rates were 63% and 66% in the ILIXA/SUN and SUN arms, respectively. The confirmed ORR in the ILIXA/SUN arm were 42.2% (19/45), including three patients with complete response, versus 24.0% (six/25) in the SUN arm (p = 0.13) without complete responses. The study was not adequately powered to detect modest differences in survival. Conclusions: The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher, nonsignificant, confirmed response rate, including complete responses, compared with sunitinib monotherapy. Patient summary: We studied the effects of intratumoral vaccination with ilixadencel followed by sunitinib versus sunitinib only in a randomized phase 2 study. The combination treatment showed numerically higher numbers of confirmed responses, suggesting an immunologic effect.
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BACKGROUND: Renal dysfunction in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) indicates a poor long-term prognosis. However, the prognostic value of the improvement or stabilisation of renal function during follow-up has not yet been assessed. This study aimed to investigate the long-term predictive impact of the improvement or stabilisation of renal function after one year of follow-up in patients with STEMI undergoing pPCI with renal dysfunction at discharge. METHODS: This prospective, single-centre cohort study included 2170 consecutive patients with STEMI who underwent pPCI. The glomerular filtration rate (GFR) was determined at hospital discharge and one-year follow-up. The median clinical follow-up was 72 months. RESULTS: Among the 2004 patients, 393 (19.6%) had a GFR <60 ml/min, and 1611 (80.4%) had a GFR ≥ 60 ml/min at discharge. Among patients with GFR <60 ml/min, data at one-year follow-up were available for 342. Of these patients, 127 (32%) showed improvement in renal function (defined as improvement in the Kidney Disease Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) classification), 47 (12%) showed worsening of renal function (defined as worsening of the KDIGO CKD classification), and 168 (43%) showed no category changes. Improvement or stabilisation of GFR at one year of follow-up was associated with a reduction of major adverse cardiovascular events (MACE) [HR 0.51, 95% CI: 0.35-0.75, p = 0.001] and all-cause mortality [HR 0.54, 95% CI: 0.34-0.84, p = 0.007] during follow-up. CONCLUSIONS: The improvement or stabilisation of renal function at one-year follow-up in patients with STEMI and renal dysfunction is associated with a better long-term prognosis.
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Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Infarto del Miocardio con Elevación del ST , Estudios de Cohortes , Humanos , Riñón/fisiología , Intervención Coronaria Percutánea/efectos adversos , Pronóstico , Estudios Prospectivos , Sistema de Registros , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/cirugíaRESUMEN
AIMS: There are insufficient data regarding risk scores validation in patients with diabetes mellitus and non-ST elevation acute coronary syndrome (NSTEACS). We performed a diabetes mellitus-specific analysis of cardiovascular outcomes after NSTEACS. We tested the predictive power of the Global Registry of Acute Coronary Events (GRACE) and PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti-Platelet Therapy (PRECISE-DAPT) scores. METHODS: This work is a retrospective analysis that included 7,415 consecutive NSTEACS patients from two Spanish Universitarian hospitals between the years 2003 and 2017. The area under the ROC curve among with and without diabetes mellitus patients was calculated, to evaluate the predictive power of both scores. RESULTS: Among the study participants, 2124 patients (28.0%) were diabetic. The median follow-up was 54,3 months (IQR 24,7-80,0 months). Diabetic patients were more women (30.5% vs. 25.7%) and older (70.0 ± 10.8 vs. 65.3 ± 13.2 years old); they had higher GRACE (146 ± 36 vs. 137 ± 36), PRECISE-DAPT (15 ± 7 vs. 18 ± 9) at admission. Early invasive coronary angiography (≤ 24 h after admission) was performed more frequently in non-diabetic. We tested the predictive power of the GRACE and PRECISE-DAPT risk scores among diabetic and non-diabetic. PRECISE-DAPT risk score showed a good predictive power for all-cause mortality, cardiovascular mortality and MACE in diabetic admitted with NSTEACS, without differences compared to non-diabetic. CONCLUSIONS: PRECISE-DAPT risk score has an appropriate predictive power in diabetic patients admitted with NSTEACS compared to non-diabetic NSTEACS. However, GRACE would be predictive worse in diabetic during long-term follow-up in a large contemporary registry.
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Síndrome Coronario Agudo , Diabetes Mellitus , Intervención Coronaria Percutánea , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/diagnóstico , Anciano , Diabetes Mellitus/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Previous studies have shown that men with HIV and germ cell cancer (HIV-GCC) have inferior overall survival (OS) in comparison with their HIV-negative counterparts. However, little information is available on treatments and outcomes of HIV-GCC in the era of combination antiretroviral therapy (cART). METHODS: This study examined men living with HIV who were 18 years old or older and had a diagnosis of histologically proven germ cell cancer (GCC). The primary outcomes were OS and progression-free survival (PFS). RESULTS: Data for 89 men with a total of 92 HIV-GCCs (2 synchronous GCCs and 1 metachronous bilateral GCC) were analyzed; among them were 64 seminomas (70%) and 28 nonseminomas (30%). The median age was 36 years, the median CD4 T-cell count at GCC diagnosis was 420 cells/µL, and 77% of the patients on cART had an HIV RNA load < 500 copies/mL. Stage I disease was found in 44 of 79 gonadal GCCs (56%). Among 45 cases with primary disseminated GCC, 78%, 18%, and 4% were assigned to the good-, intermediate-, and poor-prognosis groups, respectively, of the International Germ Cell Cancer Collaborative Group. Relapses occurred in 14 patients. Overall, 12 of 89 patients (13%) died. The causes of death were refractory GCC (n = 5), an AIDS-defining illness (n = 3), and other causes (n = 4). After a median follow-up of 6.5 years, the 5- and 10-year PFS rates were 81% and 73%, respectively, and the 5- and 10-year OS rates were 91% and 85%, respectively. CONCLUSIONS: The 5- and 10-year PFS and OS rates of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients. LAY SUMMARY: Men living with HIV are at increased risk for germ cell cancer (GCC). Previous studies have shown that the survival of men with HIV-associated germ cell cancer (HIV-GCC) is poorer than the survival of their HIV-negative counterparts. This study examined the characteristics, treatments, and outcomes of 89 men with HIV-GCC in the era of effective combination antiretroviral therapies. The long-term outcomes of men with HIV-GCC were similar to those reported for men with HIV-negative GCC. Patients with HIV-GCC should be managed identically to HIV-negative patients.
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Infecciones por VIH , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Adolescente , Adulto , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Recurrencia Local de Neoplasia , Seminoma/patología , Neoplasias Testiculares/patologíaRESUMEN
Resumen El presente estudio tiene como objetivo argumentar que la recurrencia es una herramienta en la valoración del juez al momento de imponer la medida de detención preventiva en establecimiento carcelario. Para ello, se aplicó una metodología mixta frente a dos ejes: primero, se empleó la correlación de Spearman en el examen cuantitativo de la relación estadística entre las capturas por hurto en todas sus modalidades, lesiones personales y homicidio, y los comportamientos contrarios a la convivencia que ponen en riesgo la vida e integridad de las personas, contemplados en los numerales 1, 2, 3, 6 y 7 del Código Nacional de Seguridad y Convivencia Ciudadana (Ley 1801 de 2016, art. 27), haciendo uso de datos oficiales registrados en Colombia, en el Sistema de Información Estadístico, Delincuencial, Contravencional y Operativo de la Policía Nacional, entre los años 2017 y 2019. Segundo, se realizó un análisis cualitativo que compara los dos casos más relevantes de capturas recurrentes ocurridos en Colombia durante los años 2017 y 2019. Los resultados revelan que existe una relación estadística significativa no causal entre dichos comportamientos y las capturas por los delitos mencionados; esta relación tiende a fortalecerse en el tiempo. Además, se encuentra que los individuos con más capturas recurrentes actúan de acuerdo con un aprendizaje criminológico que les permite desarrollar estrategias para disminuir al máximo el riesgo de obtener una medida de detención restrictiva de la libertad. Como conclusión, se tiene que la recurrencia puede aportar información importante en la valoración de la instauración de la medida de detención preventiva en establecimiento carcelario, lo que fortalece dicha evaluación.
Abstract The aim of this study is to affirm that recurrence is a tool in the judge's assessment at the time of imposing the measure of Pretrial detention in prison. To this end, a mixed methodology was applied to two axes: first, the Spearman correlation was used in the quantitative examination of the statistical relationship between arrests for theft in all its forms, personal injury and homicide, and behaviors contrary to coexistence (CCC) that put at risk the life and integrity of people, contemplated in numerals 1, 2, 3, 6, 7 of the National Code of Security and Citizen Coexistence (CNSCC) (Law 1801, 2016, art. 27), making use of official data registered in Colombia, in the Statistical, Criminal, Contraventional and Operational Information System of the National Police (SIEDCO), between 2017 and 2019. Secondly, a qualitative analysis was carried out that compares the two most relevant cases of recurrent catches that occurred in Colombia during the years 2017 and 2019. The results reveal that there is a significant non-causal statistical relationship between such behaviour and arrests for the aforementioned offences; this relationship tends to strengthen over time. In addition, it is found that individuals with more recurrent captures act according to a criminological learning that allows them to develop strategies to minimize the risk of obtaining a measure of detention restrictive of liberty. In conclusion, it is found that the recurrence can provide relevant information in the assessment of the establishment of the preventive detention measure in prison, which allows this evaluation to be strengthened.
Resumo O presente estudo tem como objetivo afirmar que a reincidência é uma ferramenta na avaliação do Juiz no momento da imposição da medida de prisão preventiva em estabelecimento prisional. Para isso, foi aplicada uma metodologia mista a dois eixos: primeiro, a correlação de Spearman foi utilizada no exame quantitativo da relação estatística entre prisões por roubo em todas as suas formas, lesões pessoais e homicídio, e comportamentos contrários à convivência (CCC) que colocavam em risco a vida e a integridade das pessoas, contemplados nos numerais 1, 2, 3, 6, 7 do Código Nacional de Segurança e Convivência Cidadã (CNSCC) (Lei 1801, de 2016, art. 27), fazendo uso de dados oficiais registrados na Colômbia, no Sistema de Informações Estatísticas, Criminais, Contrariacionais e Operacionais da Polícia Nacional (SIEDCO), entre 2017 e 2019. Em segundo lugar, foi realizada uma análise qualitativa que compara os dois casos mais relevantes de capturas recorrentes ocorridos na Colômbia durante os anos de 2017 e 2019. Os resultados revelam que há uma relação estatística não causal significativa entre tal comportamento e prisões pelos crimes supracitados; essa relação tende a se fortalecer com o tempo. Além disso, constatase que indivíduos com capturas mais recorrentes atuam de acordo com uma aprendizagem criminológica que lhes permite desenvolver estratégias para minimizar o risco de obtenção de medida de detenção restritiva à liberdade. Em conclusão, constatase que a recorrência pode fornecer informações relevantes na avaliação do estabelecimento da medida de prisão preventiva, o que permite que essa avaliação seja reforçada.
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AIMS: Left ventricular ejection fraction (LVEF) recovery after an ST-segment elevation myocardial infarction (STEMI) identifies a group of patients with a better prognosis. However, the association between long-term outcomes and LVEF recovery among patients with STEMI undergoing primary percutaneous coronary intervention (PCI) has not yet been well investigated. Our study aims to detect differences in long-term all-cause and cardiovascular mortality between patients who recover LVEF at 1-year post-PCI and those who do not, and search for predictors of LVEF recovery. METHODS AND RESULTS: This is a retrospective, single-centre study of 2170 consecutive patients admitted for STEMI in which primary PCI is performed. LVEF was determined at admission and at 1-year follow-up. The primary outcomes were long-term all-cause and cardiovascular mortality. Among the 2168 patients with baseline LVEF data, 822 (38%) had a LVEF < 50% and 1346 (62%) ≥ 50%. Among those with LVEF < 50%, LVEF data at 1-year were available in 554, and 299 (54.0%) presented with complete recovery (LVEF ≥ 50%). LVEF recovery was associated with a reduction in long-term all-cause and cardiovascular mortality (P < 0.0001). Female sex, treatment with ACEIs, lower creatinine levels, infarct-related artery different from the left main or left anterior descendent artery, and absence of prior ischaemic heart disease were independently associated with LVEF recovery. CONCLUSIONS: Nearly 40% of patients with STEMI undergoing primary PCI presented with LVEF depression at hospital admission. Among them, LVEF recovery at 1-year occurred in more than 50% and was independently associated with a significant decrease in long-term all-cause and cardiovascular mortality.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Femenino , Humanos , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/cirugía , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
RESUMEN: Los Adultos Mayores en Chile son el sector de la población con más daño en su salud oral, encontrándose un porcentaje de ellos institucionalizados y al resguardo de cuidadores, muchas veces sin capacitación. Propósito: Determinar el nivel de conocimientos sobre higiene oral en cuidadores de Adultos Mayores institucionalizados en ELEAM de Valparaíso. Materiales y Métodos: Estudio descriptivo transversal, con una muestra de 75 cuidadores voluntarios que cumplieron los criterios de inclusión. Se aplicó una encuesta validada para determinar su nivel de conocimiento. Se analizaron mediante frecuencias, prueba exacta de Fisher y coeficiente de correlación. Resultados: Los cuidadores presentan un nivel de conocimientos medio, sin relación con su edad, experiencia o capacitación. Muestran un alto nivel de conocimiento en frecuencia del cepillado y cuidados protésico dental, y un bajo nivel en la técnica y recambio del cepillo. No se aprecian diferencias estadísticamente significativas entre el nivel de conocimiento y años de experiencia, educación formal o capacitación. Conclusión: Los cuidadores requieren mayor conocimiento de las características del cepillo, uso de coadyuvantes y frecuencia de control odontológico. La mayoría del conocimiento es empírico, basado en su experiencia y percepción del tema. Es fundamental una capacitación formal y constantes actualizaciones sobre el tema.
ABSTRACT: Older adults are the age group with worst oral health in Chile, a large percentage of them being institutionalized and often under the care of untrained or unqualified personnel. Purpose: To determine the level of knowledge in caregivers on oral hygiene in elderly residents, institutionalized in the ELEAM of Valparaíso. Materials and methods: A cross-sectional descriptive study with a sample of 75 volunteer caregivers who met the inclusion criteria. A validated survey was applied to determine their level of knowledge. They were analyzed using frequency measures, Fisher's exact test and Pearson correlation coefficient. Results: Caregivers have a mid-level of expertise, unrelated to age, experience or training. They have a high level of knowledge regarding brushing frequency, dental prosthesis care, and low level in technique and toothbrush replacement. No statistically significant differences were found between the level of knowledge and years of experience, formal education or training. Conclusion: Caregivers require greater knowledge on toothbrush characteristics, use of adjuvants and frequency of dental visits. Most of the knowledge demonstrated is empirical, based on their experience and perception on the subject. Training and constant updates on the topic are essential.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Higiene Bucal , Salud Bucal , Cuidadores , Hogares para Ancianos , Epidemiología DescriptivaRESUMEN
Remote vehicle monitoring is a field that has recently attracted the attention of both academia and industry. With the dawn of the Internet of Things (IoT) paradigm, the possibilities for performing this task have multiplied, due to the emergence of low-cost and multi-purpose monitoring devices and the evolution of wireless transmission technologies. Low Power-Wide Area Network (LPWAN) encompasses a set of IoT communication technologies that are gaining momentum, due to their highly valued features regarding transmission distance and end-device energy consumption. For that reason, in this work we present a vehicular monitoring platform enabled by LPWAN-based technology, namely Long Range Wide Area Network (LoRaWAN). Concretely, we explore the end-to-end architecture considering vehicle data retrieving by using an On-Board Diagnostics II (OBD-II) interface, their compression with a novel IETF compression scheme in order to transmit them over the constrained LoRaWAN link, and information visualization through a data server hosted in the cloud, by means of a web-based dashboard. A key advance of the proposal is the design and development of a UNIX-based network interface for LPWAN communications. The whole system has been tested in a university campus environment, showing its capabilities to remotely track vehicle status in real-time. The conducted performance evaluation also shows high levels of reliability in the transmission link, with packet delivery ratios over 95%. The platform boosts the process of monitoring vehicles, enabling a variety of services such as mechanical failure prediction and detection, fleet management, and traffic monitoring, and is extensible to light vehicles with severe power constraints.
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Painful bone metastases are common in prostate cancer, with current treatments including non-steroidal analgesics and opiates, surgery, external beam radiotherapy and bone-targeting ß-emitting radiopharmaceuticals. The α-emitting isotope 223Ra-dichloride (Ra-223) has been associated with improved overall survival and increased time to first skeletal-related events in patients with castration-resistant prostate cancer (CRPC) presenting with symptomatic bone metastases. The current study reports the case of a 70-year-old male patient, who was diagnosed with prostate cancer in 1999 upon presentation with increased prostate-specific antigen (PSA) levels and painful bone metastases in the context of CRPC. In November 2010, subsequent to undergoing hormonal blockage, the patient was treated with ketoconazole (200 mg/8 h) followed by 10 cycles of docetaxel (75 mg/m2 every 3 weeks). Following disease progression, the patient received 6 doses of Ra-223 (50 kBq/kg; 1 dose/4 weeks). During this treatment period, an improvement in the patient's symptoms, and levels of bone alkaline phosphatase (BAP) and PSA were noted. Furthermore, Ra-223 was well-tolerated without any relevant bone marrow toxicity. However, 2 months after the administration of the final dose of Ra-223, PSA and BAP levels increased again, and bone pain deteriorated. A bone scan showed stable disease in the previously observed metastatic lesions; however, new lesions simultaneously appeared in different locations, indicating progressive disease.
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UNLABELLED: The aim of this study is to describe the results obtained after growth hormone (GH) treatment and neurorehabilitation in a young man that suffered a very grave traumatic brain injury (TBI) after a plane crash. METHODS: Fifteen months after the accident, the patient was treated with GH, 1 mg/day, at three-month intervals, followed by one-month resting, together with daily neurorehabilitation. Blood analysis at admission showed that no pituitary deficits existed. At admission, the patient presented: spastic tetraplegia, dysarthria, dysphagia, very severe cognitive deficits and joint deformities. Computerized tomography scanners (CT-Scans) revealed the practical loss of the right brain hemisphere and important injuries in the left one. Clinical and blood analysis assessments were performed every three months for three years. Feet surgery was needed because of irreducible equinovarus. RESULTS: Clinical and kinesitherapy assessments revealed a prompt improvement in cognitive functions, dysarthria and dysphagia disappeared and three years later the patient was able to live a practically normal life, walking alone and coming back to his studies. No adverse effects were observed during and after GH administration. CONCLUSIONS: These results, together with previous results from our group, indicate that GH treatment is safe and effective for helping neurorehabilitation in TBI patients, once the acute phase is resolved, regardless of whether or not they have GH-deficiency (GHD).
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Accidentes de Aviación , Lesiones Encefálicas/tratamiento farmacológico , Hormona del Crecimiento/uso terapéutico , Adolescente , Lesiones Encefálicas/etiología , Lesiones Encefálicas/rehabilitación , Hormona del Crecimiento/administración & dosificación , Humanos , Quinesiología Aplicada , MasculinoRESUMEN
Objetivo: El propósito de éste estudio in vitro fue comparar la resistencia a la tensión entre dos materiales para la fabricación de bases protésicas acrílicas (Veracril® de New Stetic y SR Triplex Hot® de Ivoclar Vivadent), y conocer las propiedades mecá-nicas de los materiales a estudiar que tienen repercusiones a nivel clínico. Materiales y métodos: Bajo la norma téc-nica de ASTM Internacional # D 638 03 se realizaron las pruebas de laboratorio para evaluar las dos resinas acrílicas para bases protésicas, procesadas mediante mu-fla prensada clásica. Las observaciones se hicieron por medio de la máquina universal de ensayos marca Tinius Olsen® H50KS, para analizar las propiedades tensionales, como el módulo de elasticidad, elongación, límite elástico, fuerza máxima, energía, esfuerzo y estrés tensil entre los dos mate-riales evaluados. Resultados: Para el esfuerzo, la fuerza máxima y el módulo de elasticidad, la resi-na acrílica de alto impacto SR Triplex Hot® mostró valores mayores. En cuanto a las características de desplazamiento máximo antes de la ruptura, elongación y la energía, la resina acrílica convencional mostró va-lores más altos. La única característica que presentó una diferencia significativa entre los dos grupos de resinas acrílicas de termo curado fue el módulo de elasticidad donde la de alto impacto obtuvo un valor mucho mayor que la resina acrílica convencional. Conclusiones: La resina acrílica SR Tri-plex Hot® presenta valores mayores en algunas propiedades tensiles, mientras que el Veracril® muestra mejores valores en otras. La única característica que presentó una diferencia significativa entre las dos re-sinas acrílicas fue el módulo de elasticidad. Palabras clave: Bases protésicas de resinas acrílicas, propiedades tensionales, resinas acrílicas de alto impacto.
Objective: The purpose of this in vitro study was to compare the tensile strength bet-ween two materials for the manufacture of acrylic denture bases (Veracril® from New Stetic and SR Triplex Hot® from Ivoclar Vivadent), and to know the mechanical properties of materials to study that have clinical implications. Methods: Laboratory tests were conducted under the technical standard of ASTM International # D 638-03 to evaluate the two acrylic resin materials for denture bases, processed by pressed moulding. The observations were made using the univer-sal testing machine Tinius Olsen® brand H50KS to analyze the tensile properties such as modulus of elasticity, elongation, yield strength, maximum strength, energy, effort and tensile stress between the two materials evaluated. Results: For the effort, maximum strength and modulus of elasticity, high-impact acrylic resin SR Triplex Hot® showed higher values. With regard to the cha-racteristics of maximum displacement before the fracture, elongation and energy, conventional acrylic resin showed higher values. The only characteristic that showed a significant difference between the two groups of thermo-cured acrylic resin was the modulus of elasticity where the high-impact acrylic resin obtained a much higher value than conventional acrylic resin. Conclusions: The acrylic resin SR Triplex Hot® presents higher values in some ten-sile properties, while the Veracril® shows better in others. The only characteristic that showed a significant difference between the two acrylic resins was the modulus of elasticity.
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Odontología , Operatoria Dental , Rehabilitación Bucal , Medicina Oral , Preparación del Diente , Modelos Dentales , Estética DentalRESUMEN
AIMS: Our aim was to evaluate first-line treatment of metastatic renal cell carcinoma (mRCC) with sorafenib in patients unwilling to receive immunotherapy or with early intolerance to immunotherapy. PATIENTS AND METHODS: Patients had clear-cell mRCC with good or intermediate risk status, were unsuited to cytokine therapy due to preference or intolerance (based on <4 weeks prior immunotherapy) and had not received antiangiogenic agents. Patients received sorafenib 400 mg twice daily until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Twenty-six evaluable patients were enrolled at six centres between March and July 2006. The most common metastatic sites were lung and bone; nine patients had one or two metastatic lesions. Median PFS was 7.5 months (95% confidence interval [CI] 5.1-17.5) and overall survival (OS) 15.4 months (95% CI 12.9-17.4). Among 21 patients evaluable for response, 19 (90.5%) experienced disease control (including one complete response; four partial responses; 14 stable disease). The majority of adverse events were grade 1-2 (87.3%). The most common were asthenia (53.0%) and diarrhoea (50.0%). CONCLUSION: In patients with mRCC who were unwilling to receive or intolerant to immunotherapy, treatment with sorafenib led to a high rate of disease control with toxicities that were generally mild and manageable. The PFS achieved in this essentially treatment-naïve population compares favourably with that obtained in the randomised first-line phase II study.
Asunto(s)
Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Piridinas/uso terapéutico , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Femenino , Humanos , Inmunoterapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Inducción de Remisión , SorafenibRESUMEN
A 35-year-old woman presented with a 12-cm right renal mass with retroperitoneal lymph node involvement and pulmonary and bone metastases. Renal mass biopsy revealed an unclassified high-grade non-clear cell renal cell carcinoma (RCC) with eosinophilic cells. Due to the extent of the disease, neoadjuvant temsirolimus was initiated. After 6 wk of treatment, a significant downstaging of the disease and complete disappearance of the metastases were noticed on computed tomography scan. Three months later, a laparoscopic radical nephrectomy and lymphadenectomy was performed. Final pathology confirmed a high-grade non-clear cell RCC, with necrotic changes on lymph node specimens, pT1bN0Mx.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Sirolimus/análogos & derivados , Adulto , Femenino , Humanos , Terapia Neoadyuvante , Estadificación de Neoplasias , Sirolimus/uso terapéuticoRESUMEN
The neurotoxin MPTP reproduces most of the biochemical and pathological hallmarks of Parkinson's disease. In addition to reactive oxygen species (ROS) generated as a consequence of mitochondrial complex I inhibition, microglial NADPH-derived ROS play major roles in the toxicity of MPTP. However, the exact mechanism regulating this microglial response remains to be clarified. The peptide angiotensin II (AII), via type 1 receptors (AT1), is one of the most important inflammation and oxidative stress inducers, and produces ROS by activation of the NADPH-oxidase complex. Brain possesses a local angiotensin system, which modulates striatal dopamine (DA) release. However, it is not known if AII plays a major role in microglia-derived oxidative stress and DA degeneration. The present study indicates that in primary mesencephalic cultures, DA degeneration induced by the neurotoxin MPTP/MPP(+) is amplified by AII and inhibited by AT1 receptor antagonists, and that protein kinase C, NADPH-complex activation and microglial activation are involved in this effect. In mice, AT1 receptor antagonists inhibited both DA degeneration and early microglial and NADPH activation. The brain angiotensin system may play a key role in the self-propelling mechanism of Parkinson's disease and constitutes an unexplored target for neuroprotection, as previously reported for vascular diseases.
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Angiotensinas/fisiología , Encéfalo/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Mediadores de Inflamación/fisiología , Intoxicación por MPTP/metabolismo , Enfermedad de Parkinson Secundaria/metabolismo , Enfermedad de Parkinson Secundaria/patología , Angiotensinas/toxicidad , Animales , Células Cultivadas , Progresión de la Enfermedad , Mediadores de Inflamación/toxicidad , Intoxicación por MPTP/patología , Masculino , Ratones , Ratones Endogámicos C57BL , RatasRESUMEN
BACKGROUND/OBJECTIVE: Improved understanding of renal cell carcinomas (RCC) and recent contributions in the field of RCC biology led to the development of a novel class of drugs, i.e. multiple-kinase inhibitors, targeting growth factor receptors (e.g. sorafenib). Sorafenib has proven significant benefit in terms of progression-free survival in a phase II trial in RCC patients. A subsequent randomized phase III study (Treatment Approaches in Renal Cancer Global Evaluation Trial) confirmed the significantly prolonged progression-free survival and improvement in the quality of life compared to patients receiving placebo. In the USA and Europe, sorafenib has been approved for the treatment of advanced RCC. PATIENTS: Two RCC patients on chronic hemodialysis were treated with sorafenib. RESULTS: Both patients responded to sorafenib treatment. Apart from high blood pressure, a major adverse effect of sorafenib treatment, treatment was well tolerated, in agreement with previous results. CONCLUSION: The results of our study confirm the beneficial effect of sorafenib in the treatment of RCC in our 2 patients on dialysis.
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Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Diálisis Renal , Adulto , Carcinoma de Células Renales/secundario , Humanos , Neoplasias Renales/patología , Neoplasias Pulmonares/secundario , Masculino , Nefrectomía , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , SorafenibRESUMEN
The unilateral and intrastriatal injection of 6-hydroxydopamine is commonly used to provide a partial lesion model of Parkinson's disease in the investigation of the molecular mechanisms involved in its pathogenesis and to assess new neuroprotective treatments. Its capacity to induce neurodegeneration has been related to its ability to undergo autoxidation in the presence of oxygen and consequently to generate oxidative stress. The aim of the present study was to investigate the time course of brain oxidative damage induced by 6-hydroxydopamine (6 microg in 5 microl of sterile saline containing 0.2% ascorbic acid) injection in the right striatum of the rat. The results of this study show that the indices of both lipid peroxidation (TBARS) and protein oxidation (carbonyl and free thiol contents) increase simultaneously in the ipsilateral striatum and ventral midbrain, reaching a peak value at 48-h post-injection for both TBARS and protein carbonyl content, and at 24 h for protein free thiol content. A lower but significant increase was also observed in the contralateral side (striatum and ventral midbrain). The indices of oxidative stress returned to values close to those found in controls at 7-day post-injection. These data show that the oxidative stress is a possible triggering factor for the neurodegenerative process and the retrograde neurodegeneration observed after 1-week post-injection is a consequence of the cell damage caused during the first days post-injection. The optimal time to assess brain indices of oxidative stress in this model is 48-h post-injection.
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Estrés Oxidativo/efectos de los fármacos , Oxidopamina/toxicidad , Trastornos Parkinsonianos/fisiopatología , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Cetonas/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Mesencéfalo/efectos de los fármacos , Mesencéfalo/metabolismo , Oxidopamina/administración & dosificación , Proteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Compuestos de Sulfhidrilo/análisis , Compuestos de Sulfhidrilo/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
There is growing evidence indicating that oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. The brain, and particularly the basal ganglia, possesses a local rennin-angiotensin system. Angiotensin activates NAD(P)H-dependent oxidases, which are a major intracellular source of superoxide, and angiotensin converting enzyme inhibitors (ACEIs) have shown antioxidant properties. We treated mice with MPTP and the ACEI captopril to study the possible neuroprotective and antioxidant effects of the latter on the dopaminergic system. Pre-treatment with captopril induced a significant reduction in the MPTP-induced loss of dopaminergic neurons in the substantia nigra and a significant reduction in the loss of dopaminergic terminals in the striatum. Furthermore, captopril reduced the MPTP-induced increase in the levels of major oxidative stress indicators (i.e. lipid peroxidation and protein oxidation) in the ventral midbrain and the striatum. Captopril did not reduce striatal MPP(+) levels, MAO-B activity or dopamine transporter activity, which may reduce MPTP neurotoxicity. Our results suggest that angiotensin-converting enzyme inhibitors may be useful for treatment of Parkinson's disease, and that further investigation should focus on the neuroprotective capacity of these compounds.