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1.
Front Bioeng Biotechnol ; 12: 1373473, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38600947

RESUMEN

This study analyzes Paraguay's biotechnology regulatory framework and its alignment with international standards amid biotechnological advancements. It also identifies areas of improvement for enhancing framework effectiveness. Through this work, we aim to provide a resource for policymakers, stakeholders, and researchers navigating Paraguay's biotechnology regulation.

2.
Ther Adv Med Oncol ; 16: 17588359241248328, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38665845

RESUMEN

Background: Olaparib is an inhibitor of the human poly-(ADP-ribose)-polymerase enzymes (PARP1/2) needed to repair single-strand DNA breaks. It is used in breast, ovarian, prostate and pancreatic cancer. Objectives: This work aimed to describe the pharmacokinetics/pharmacodynamics (PK/PD) relationship between olaparib plasma concentrations and common adverse effects (i.e. anaemia and hypercreatininaemia), in a real-life setting, to propose a target concentration for therapeutic drug monitoring. Methods: Two PK/PD models describing the evolution of haemoglobinaemia and creatininaemia as a function of time were developed, based on data from, respectively, 38 and 37 patients receiving olaparib. The final model estimates were used to calculate the incidence of anaemia and creatinine increase according to plasma trough concentrations for 1000 virtual subjects to define target exposure. Results: The final models correctly described the temporal evolution of haemoglobinaemia and creatininaemia for all patients. The haemoglobinaemia PK/PD model is inspired by Friberg's model, and the creatininaemia PK/PD model is an indirect response model. Model parameters were in agreement with physiological values and close to literature values for similar models. The mean (population) plasma haemoglobin concentration at treatment initiation, as estimated by the model, was 11.62 g/dL, while creatinine concentration was 71.91 µmol/L. Using simulations, we have identified a target trough concentration of 3500-4000 ng/mL, above which more than 20% of patients would report grade ≥3 anaemia. Conclusion: Based on real-world data, we were able to properly describe the time course of haemoglobinaemia and plasma creatininaemia during olaparib treatment.

3.
J Clin Oncol ; 41(28): 4478-4485, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37603816

RESUMEN

PURPOSE: The Atezo-Brain study evaluated atezolizumab combined with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) with untreated brain metastases, a population traditionally excluded from trials. METHODS: This single-arm phase II clinical trial enrolled patients with advanced nonsquamous NSCLC with untreated brain metastases without neurologic symptoms or asymptomatic with medical treatment. Dexamethasone was allowed up to 4 mg once daily. Atezolizumab plus carboplatin and pemetrexed was given for four to six cycles followed by atezolizumab plus pemetrexed until progression for a maximum of 2 years. The primary end points were to determine the progression-free survival (PFS) rate at 12 weeks and the incidence of grade ≥3 adverse events during the first 9 weeks. Intracranial outcomes were assessed using response assessment in neuro-oncology brain metastases criteria. RESULTS: Forty patients were enrolled and 22 (55%) were receiving corticosteroids at baseline. The overall 12-week PFS rate was 62.2% (95% credibility interval [CrI], 47.1 to 76.2). The rate of grade 3/4 adverse events during the first 9 weeks was 27.5%. Most neurologic events were grade 1 and 2 but five patients (12.5%) experienced grade 3-4 neurologic events. With a median follow-up of 31 months, intracranial median PFS was 6.9 months and response rate was 42.7% (95% CrI, 28.1 to 57.9). Systemic median PFS was 8.9 months and response rate was 45% (95% CrI, 28.1 to 57.9). The median overall survival (OS) was 11.8 months (95% CI, 7.6 to 16.9) and the 2-year OS rate was 27.5% (95% CI, 16.6 to 45.5). CONCLUSION: Atezolizumab plus carboplatin and pemetrexed demonstrates activity in patients with advanced nonsquamous NSCLC with untreated brain metastases with an acceptable safety profile.


Asunto(s)
Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carboplatino , Pemetrexed/uso terapéutico , Neoplasias Pulmonares/patología , Neoplasias Encefálicas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Encéfalo/patología
4.
J Cardiothorac Vasc Anesth ; 37(10): 1938-1945, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37453808

RESUMEN

OBJECTIVES: The aim of this analysis was to compare the effect of extubating in the operating room (OR) versus and the intensive care unit (ICU) among patients undergoing coronary artery bypass grafting (CABG). DESIGN: A retrospective cohort analysis. SETTING: Ten cardiac referral hospitals in Latin America; participants of the São Paulo Registry of Cardiovascular Surgery II (REPLICCAR II). PARTICIPANTS: The database included a total of 4,015 patients who underwent primary and isolated CABG surgery and were ≥18 years old, of whom 205 patients were extubated in the OR. INTERVENTIONS: The analysis was made after a propensity score matching (PSM) adjustment in the population sample of patients extubated in the OR and ICU by the following variables: sex, age, body mass index, smoking, type of surgery, chronic obstructive pulmonary disease, preoperative atrial fibrillation, cardiopulmonary bypass time, preoperative creatinine, and preoperative left ventricular ejection fraction. MEASUREMENTS AND MAIN RESULTS: This study focused on the analysis of the ICU and hospital length of stay, need for reintubation, morbidity, and mortality. After PSM, 402 patients were analyzed. Both groups had similar baseline characteristics, such as age (p = 0.132), sex (p = 1.00), and estimated risk of prolonged ventilation (>24 hours, p = 0.168); however, the median ventilation time was significantly shorter in the group extubated in the OR compared to the ICU group (5.67 hours v 17.55 hours, p < 0.001). The group of patients extubated in the ICU had a longer postoperative stay (7.54 ± 3.40 days v 6.41 ± 2.91 days, p < 0.001) and longer total hospitalization time (11.49 ± 5.70 days v 10.36 ± 5.72, p = 0.013) compared to those extubated in the OR. The authors did not observe a significant difference in the need for reintubation, morbidity, or mortality rates among the evaluated groups. CONCLUSIONS: In the REPLICCAR II database, extubation performed in the OR was associated with a reduced length of postoperative and total hospital stays compared to extubation in the ICU.


Asunto(s)
Extubación Traqueal , Quirófanos , Humanos , Adolescente , Tiempo de Internación , Estudios Retrospectivos , Volumen Sistólico , Brasil , Función Ventricular Izquierda , Puente de Arteria Coronaria/efectos adversos
5.
Acta Med Port ; 36(2): 105-112, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36738190

RESUMEN

INTRODUCTION: A growing number of countries have legalized the process of hastening death. At a time when laws decriminalizing hastened death have been passed in the Portuguese Parliament, the development of research related with decision making regarding this issue is of crucial importance. This study seeks to evaluate, in a sample of Portuguese doctors, whether the presentation of clinical vignettes changes the agreement with the practice of hastened death compared with general scenarios. MATERIAL AND METHODS: A questionnaire was distributed among academic physicians from medical schools across Portugal to assess their level of agreement or disagreement with the practice of hastened death. The questionnaire included eight standard cases and eight clinical vignettes framed under conditions defined by law for the practice of hastened death. Differences were analyzed using the t-Student test for paired samples. RESULTS: There were statistically significant differences in five scenarios (t = 3.46; p < 0.05; t = 2.47; p < 0.05; t = 4.28; p < 0.05; t = 3.38; p < 0.05; t = 3.66; p < 0.05) with greater agreement concerning the clinical vignettes. The highest acceptance was found in the requests made by adults with terminal and incurable illnesses. CONCLUSION: Agreement increased when the clinical vignette was presented in comparison with the respective standard for most of the cases of hastened death presented.


Asunto(s)
Médicos , Adulto , Humanos , Portugal , Estudios Transversales , Encuestas y Cuestionarios
6.
SICOT J ; 8: 31, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35969122

RESUMEN

Ruptures of the extensor apparatus can have different etiologies and be complicated by underlying situations. Direct repair is not always possible, and reconstruction procedures can be insufficient, which leads to the appearance of multiple augmentation techniques to improve the strength of these constructs. Despite the proven results of these techniques, numerous procedures are described without any gold standard. We present our augmentation method for repairing the knee extensor apparatus with a vascular prosthesis that facilitates healing, does not interfere with the primary procedure, has no donor morbidity or rejection risk, and allows earlier mobilization and rehabilitation. The technique was used in different cases with multiple etiologies that needed reinforcement, with promising results.

7.
J Geriatr Cardiol ; 19(5): 377-392, 2022 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-35722032

RESUMEN

In recent decades, life expectancy has been increasing significantly. In this scenario, health interventions are necessary to improve prognosis and quality of life of elderly with cardiovascular risk factors and cardiovascular disease. However, the number of elderly patients included in clinical trials is low, thus current clinical practice guidelines do not include specific recommendations. This document aims to review prevention recommendations focused in patients ≥ 75 years with high or very high cardiovascular risk, regarding objectives, medical treatment options and also including physical exercise and their inclusion in cardiac rehabilitation programs. Also, we will show why geriatric syndromes such as frailty, dependence, cognitive impairment, and nutritional status, as well as comorbidities, ought to be considered in this population regarding their important prognostic impact.

8.
J Clin Oncol ; 40(25): 2924-2933, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35576508

RESUMEN

PURPOSE: Neoadjuvant chemotherapy plus nivolumab has been shown to be effective in resectable non-small-cell lung cancer (NSCLC) in the NADIM trial (ClinicalTrials.gov identifier: NCT03081689). The 3-year overall survival (OS) and circulating tumor DNA (ctDNA) analysis have not been reported. METHODS: This was an open-label, multicenter, single-arm, phase II trial in which patients with stage IIIA NSCLC, who were deemed to be surgically resectable, were treated with neoadjuvant paclitaxel (200 mg/m2 once a day) and carboplatin (area under curve 6) plus nivolumab (360 mg) once on day 1 of each 21-day cycle, for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The 3-year OS and ctDNA analysis were secondary objectives of the trial. RESULTS: OS at 36 months was 81.9% (95% CI, 66.8 to 90.6) in the intention-to-treat population, rising to 91.0% (95% CI, 74.2 to 97.0) in the per-protocol population. Neither tumor mutation burden nor programmed cell death ligand-1 staining was predictive of survival. Conversely, low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and OS (hazard ratio [HR], 0.20; 95% CI, 0.06 to 0.63, and HR, 0.07; 95% CI, 0.01 to 0.39, respectively). Clinical responses according to RECIST v1.1 criteria did not predict survival outcomes. However, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and OS (HR, 0.26; 95% CI, 0.07 to 0.93, and HR, 0.04; 95% CI, 0.00 to 0.55, respectively). The C-index to predict OS for ctDNA levels after neoadjuvant treatment (0.82) was superior to that of RECIST criteria (0.72). CONCLUSION: The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3-year OS. ctDNA levels were significantly associated with OS and outperformed radiologic assessments in the prediction of survival.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Terapia Neoadyuvante/métodos , Nivolumab/uso terapéutico
9.
Am J Hum Genet ; 109(5): 909-927, 2022 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-35390279

RESUMEN

Pontocerebellar hypoplasias (PCHs) are congenital disorders characterized by hypoplasia or early atrophy of the cerebellum and brainstem, leading to a very limited motor and cognitive development. Although over 20 genes have been shown to be mutated in PCHs, a large proportion of affected individuals remains undiagnosed. We describe four families with children presenting with severe neonatal brainstem dysfunction and pronounced deficits in cognitive and motor development associated with four different bi-allelic mutations in PRDM13, including homozygous truncating variants in the most severely affected individuals. Brain MRI and fetopathological examination revealed a PCH-like phenotype, associated with major hypoplasia of inferior olive nuclei and dysplasia of the dentate nucleus. Notably, histopathological examinations highlighted a sparse and disorganized Purkinje cell layer in the cerebellum. PRDM13 encodes a transcriptional repressor known to be critical for neuronal subtypes specification in the mouse retina and spinal cord but had not been implicated, so far, in hindbrain development. snRNA-seq data mining and in situ hybridization in humans show that PRDM13 is expressed at early stages in the progenitors of the cerebellar ventricular zone, which gives rise to cerebellar GABAergic neurons, including Purkinje cells. We also show that loss of function of prdm13 in zebrafish leads to a reduction in Purkinje cells numbers and a complete absence of the inferior olive nuclei. Altogether our data identified bi-allelic mutations in PRDM13 as causing a olivopontocerebellar hypoplasia syndrome and suggest that early deregulations of the transcriptional control of neuronal fate specification could contribute to a significant number of cases.


Asunto(s)
Encefalopatías , Pez Cebra , Animales , Encefalopatías/patología , Tronco Encefálico , Cerebelo/anomalías , Cerebelo/patología , Discapacidades del Desarrollo , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Ratones , Mutación/genética , Malformaciones del Sistema Nervioso , Neurogénesis/genética , Células de Purkinje/metabolismo , Factores de Transcripción/genética , Pez Cebra/metabolismo
10.
Case Rep Orthop ; 2021: 6633690, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33954000

RESUMEN

Shoulder hemiarthroplasty is a viable option in young patients with an intact rotator cuff in order to preserve the native glenoid. To avoid the dreaded and expected wear of the glenoid in very active shoulders, implants with humeral head coated with a high resistant and elastic material-pyrolytic carbon-are now an option. The authors present the first pyrocarbon coated hemishoulder arthroplasty performed at our Orthopedic Department in a patient with osteonecrosis of the humeral head. At three years of follow-up, the patient is pain free and without limitations in his daily work. The Constant score was applied pre- and postoperatively, and an improvement of 32 points was reported. Larger cohorts with long-term follow-up are required to confirm our promising results.

11.
Transl Lung Cancer Res ; 10(4): 1761-1772, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34012791

RESUMEN

BACKGROUND: The Spanish Customized Adjuvant Therapy (SCAT) trial assessed the role of individualized adjuvant therapy in clinical N0 incidental pN1 and/or N2 non-small cell lung cancer (NSCLC) completely resected. We assessed surgical topics with an in-depth analysis of quality of lymphadenectomy based on International Association for the Study of Lung Cancer (IASLC) recommendations. METHODS: Patients with information about lymphadenectomy available were included (N=451). Prospectively collected data about tumor, type of resection, and postoperative morbidity and quality of lymph node dissection (LND) were retrospectively evaluated. Role of lymph node assessment on survival was analyzed using Kaplan-Meier curves, using regression models to identify prognostic factors. RESULTS: In 33.7%, 17.7% and 49.9% of cases, regions 7, 10 and 11 respectively were not assessed. In 21.1% of patients, less than three lymph node regions were biopsied, while in 19.6% of patients less than six lymph nodes were assessed. In 53,4% of patients only one N1 region was evaluated. From patients with positive N2, 8.9% had no N1 regions biopsied. Twenty-nine percent of patients with at least one N2 lymph node resected shown the highest region involved. Thirty-day postoperative mortality was unknown. Five-year overall survival (OS) was 61.7% (95% CI: 55.4-67.4%), 51.5% (95% CI: 39.2-62.4%) and 42.3% (95% CI: 32.1-52.2%) for patients with N1, N2 and N1+N2 disease, respectively (P<0.01). Both number of lymph nodes resected and number of lymph nodes involved by tumor were significantly related to prognosis. CONCLUSIONS: IASLC recommendations for surgical resections were not followed in a high proportion of surgical procedures. Hilar and mediastinal lymph node assessment and involvement showed to impact prognosis. Surgical issues such as postoperative mortality could not be evaluated owing to trial design.

12.
Lancet Oncol ; 21(11): 1413-1422, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32979984

RESUMEN

BACKGROUND: Non-small-cell lung cancer (NSCLC) is terminal in most patients with locally advanced stage disease. We aimed to assess the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage IIIA NSCLC. METHODS: This was an open-label, multicentre, single-arm phase 2 trial done at 18 hospitals in Spain. Eligible patients were aged 18 years or older with histologically or cytologically documented treatment-naive American Joint Committee on Cancer-defined stage IIIA NSCLC that was deemed locally to be surgically resectable by a multidisciplinary clinical team, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received neoadjuvant treatment with intravenous paclitaxel (200 mg/m2) and carboplatin (area under curve 6; 6 mg/mL per min) plus nivolumab (360 mg) on day 1 of each 21-day cycle, for three cycles before surgical resection, followed by adjuvant intravenous nivolumab monotherapy for 1 year (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was progression-free survival at 24 months, assessed in the modified intention-to-treat population, which included all patients who received neoadjuvant treatment, and in the per-protocol population, which included all patients who had tumour resection and received at least one cycle of adjuvant treatment. Safety was assessed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03081689, and is ongoing but no longer recruiting patients. FINDINGS: Between April 26, 2017, and Aug 25, 2018, we screened 51 patients for eligibility, of whom 46 patients were enrolled and received neoadjuvant treatment. At the time of data cutoff (Jan 31, 2020), the median duration of follow-up was 24·0 months (IQR 21·4-28·1) and 35 of 41 patients who had tumour resection were progression free. At 24 months, progression-free survival was 77·1% (95% CI 59·9-87·7). 43 (93%) of 46 patients had treatment-related adverse events during neoadjuvant treatment, and 14 (30%) had treatment-related adverse events of grade 3 or worse; however, none of the adverse events were associated with surgery delays or deaths. The most common grade 3 or worse treatment-related adverse events were increased lipase (three [7%]) and febrile neutropenia (three [7%]). INTERPRETATION: Our results support the addition of neoadjuvant nivolumab to platinum-based chemotherapy in patients with resectable stage IIIA NSCLC. Neoadjuvant chemoimmunotherapy could change the perception of locally advanced lung cancer as a potentially lethal disease to one that is curable. FUNDING: Bristol-Myers Squibb, Instituto de Salud Carlos III, European Union's Horizon 2020 research and innovation programme.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Nivolumab/administración & dosificación , Anciano , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Estadificación de Neoplasias , Nivolumab/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Supervivencia sin Progresión , España/epidemiología , Resultado del Tratamiento
13.
Rev. esp. cardiol. Supl. (Ed. impresa) ; 20(supl.C): 3-12, jun. 2020. ilus, tab, graf
Artículo en Español | IBECS | ID: ibc-197033

RESUMEN

La insuficiencia cardiaca es una enfermedad que precisa un tratamiento multidisciplinario, dadas la diversidad de causas y entornos clínicos implicados que las tratan y las diferentes estrategias terapéuticas que precisan la participación indispensable de diversas disciplinas. La presencia en los servicios de cardiología de unidades de insuficiencia cardiaca centradas en el tratamiento de los pacientes con esta afección y unidades de rehabilitación cardiaca que, entre sus indicaciones para la reducción de la morbimortalidad, también están implicadas en la atención de esos mismos pacientes puede causar dificultades de coordinación y pérdida de una atención integral centrada en el paciente. Por estos motivos, en el presente documento se plantea una estrategia de coordinación entre las diferentes unidades implicadas en el tratamiento de los pacientes dentro de los servicios de cardiología y la continuidad asistencial con atención primaria, tanto tras haber conseguido la estabilidad como la interrelación para una coordinación posterior más efectiva


Heart failure is a condition that requires a multidisciplinary approach to treatment because of the wide range of causes and clinical contexts that may be involved and because the diverse treatment strategies used necessitate the participation of multiple disciplines. In cardiology departments, the presence of both heart failure units that focus on the treatment of affected patients and cardiac rehabilitation units that, as well as targeting reductions in morbidity and mortality, are also involved in caring for the same patients can create difficulties for coordination and can result in the loss of comprehensive patient-centered care. For these reasons, this paper presents a strategy for coordinating the different units involved in patient management in cardiology departments and for ensuring continuity of care in primary care, both immediately after achieving stabilization and subsequently, when these interactions are important for effective coordination


Asunto(s)
Humanos , Grupo de Atención al Paciente/organización & administración , Continuidad de la Atención al Paciente/organización & administración , Insuficiencia Cardíaca/rehabilitación , Rehabilitación Cardiaca/métodos , Terapia por Ejercicio/métodos , Consenso , Alta del Paciente/normas , Atención Primaria de Salud/organización & administración , Atención Integral de Salud/organización & administración , Tolerancia al Ejercicio , Atención de Enfermería/organización & administración
15.
J Thorac Oncol ; 14(7): 1266-1276, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30978502

RESUMEN

INTRODUCTION: ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS). PATIENTS AND METHODS: The trial was a multicenter, single-arm phase II trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria included patients who were 18 years of age or older with advanced/metastatic lung cancer and centrally confirmed ROS1-rearranged lung cancer (fluorescence-in situ hybridization). Treatment included 250 mg crizotinib twice daily. The primary endpoint was investigator-assessed objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors, version 1.1). Key secondary endpoints were progression-free survival (PFS), overall survival, efficacy by independent radiologic review, safety, health-related quality of life, and molecular characterization of tumor tissue. RESULTS: Thirty-four patients received treatment. Four patients were excluded from efficacy analysis. Investigator ORR was 70% (95% confidence interval [CI]: 51-85; 21 of 30 patients) and median PFS was 20.0 months (95% CI: 10.1-not reached). Two patients with ROS1 wild-type sequences assessed by DNA sequencing had progression as best response. CD74-ROS1-positive patients had a trend towards a higher ORR and longer median PFS. TP53-co-mutant patients had a significantly shorter median PFS than wild-type patients (7.0 months, 95% CI: 1.7-20.0 versus 24.1 months, 95% CI: 10.1-not reached; p = 0.022). Treatment-related adverse events were documented in 33 of 34 patients (97%). CONCLUSIONS: Crizotinib is highly effective and safe in patients with ROS1-rearranged lung cancer. ROS1-/TP53-co-aberrant patients had a significantly worse outcome compared to TP53 wild-type patients.


Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Crizotinib/uso terapéutico , Reordenamiento Génico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tasa de Supervivencia
17.
Endocrinology ; 154(12): 4757-67, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24064358

RESUMEN

Nesfatin-1, a satiety-inducing peptide identified in hypothalamic regions that regulate energy balance, is an integral regulator of energy homeostasis and a putative glucose-dependent insulin coadjuvant. We investigated its production by human cardiomyocytes and its effects on glucose uptake, in the main cardiac glucose transporter GLUT-4 and in intracellular signaling. Quantitative RT-PCR, Western blots, confocal immunofluorescence microscopy, and ELISA of human and murine cardiomyocytes and/or cardiac tissue showed that cardiomyocytes can synthesize and secrete nesfatin-1. Confocal microscopy of cultured cardiomyocytes after GLUT-4 labeling showed that nesfatin-1 mobilizes this glucose transporter to cell peripherals. The rate of 2-deoxy-D-[(3)H]glucose incorporation demonstrated that nesfatin-1 induces glucose uptake by HL-1 cells and cultured cardiomyocytes. Nesfatin-1 induced dose- and time-dependent increases in the phosphorylation of ERK1/2, AKT, and AS160. In murine and human cardiac tissue, nesfatin-1 levels varied with diet and coronary health. In conclusion, human and murine cardiomyocytes can synthesize and secrete nesfatin-1, which is able to induce glucose uptake and the mobilization of the glucose transporter GLUT-4 in these cells. Nesfatin-1 cardiac levels are regulated by diet and coronary health.


Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al ADN/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Alimentación Animal/análisis , Animales , Proteínas de Unión al Calcio/genética , Células Cultivadas , Proteínas de Unión al ADN/genética , Dieta , Grasas de la Dieta/farmacología , Femenino , Regulación de la Expresión Génica/fisiología , Glucosa/metabolismo , Transportador de Glucosa de Tipo 4/genética , Humanos , Masculino , Ratones , Proteínas del Tejido Nervioso/genética , Nucleobindinas , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley
18.
Ann Bot ; 108(1): 177-83, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21624960

RESUMEN

BACKGROUND AND AIMS: A meta-analysis of global change experiments in arctic tundra sites suggests that plant productivity and the cover of shrubs, grasses and dead plant material (i.e. litter) will increase and the cover of bryophytes will decrease in response to higher air temperatures. However, little is known about which effects these changes in vegetation structure will have on seedling recruitment of species and invasibility of arctic ecosystems. METHODS: A field experiment was done in a bryophyte-dominated, species-rich subarctic heath by manipulating the cover of bryophytes and litter in a factorial design. Three phases of seedling recruitment (seedling emergence, summer seedling survival, first-year recruitment) of the grass Anthoxanthum alpinum and the shrub Betula nana were analysed after they were sown into the experimental plots. KEY RESULTS: Bryophyte and litter removal significantly increased seedling emergence of both species but the effects of manipulations of vegetation structure varied strongly for the later phases of recruitment. Summer survival and first-year recruitment were significantly higher in Anthoxanthum. Although bryophyte removal generally increased summer survival and recruitment, seedlings of Betula showed high mortality in early August on plots where bryophytes had been removed. CONCLUSIONS: Large species-specific variation and significant effects of experimental manipulations on seedling recruitment suggest that changes in vegetation structure as a consequence of global warming will affect the abundance of grasses and shrubs, the species composition and the susceptibility to invasion of subarctic heath vegetation.


Asunto(s)
Betula/fisiología , Briófitas/fisiología , Germinación/fisiología , Poaceae/fisiología , Semillas/fisiología , Adaptación Fisiológica , Regiones Árticas , Betula/crecimiento & desarrollo , Briófitas/crecimiento & desarrollo , Ecosistema , Calentamiento Global , Poaceae/crecimiento & desarrollo , Estaciones del Año , Plantones/crecimiento & desarrollo , Semillas/crecimiento & desarrollo , Especificidad de la Especie , Suecia , Temperatura
19.
Rev. cienc. med. Pinar Rio ; 11(4): 341-351, oct.-nov. 2007.
Artículo en Español | LILACS | ID: lil-739517

RESUMEN

Los medios de enseñanza reducen considerablemente el tiempo dedicado al aprendizaje, el trabajo con estos estimula la auto-actividad creadora. La simulación obliga al alumno a demostrar lo aprendido. La pérdida de dientes existe desde tiempos remotos por lo que se han buscado procedimientos, como la prótesis inmediata, para reponerlos y restablecer la estética y la función. Por ello y con la intención de lograr prótesis inmediatas estéticas y con una adecuada adaptación sobre la cirugía recién realizada en el paciente, nos propusimos como objetivo lograr el desarrollo de conocimientos y habilidades en los estudiantes de cuarto año de Estomatología con la confección en el laboratorio de los diferentes pasos de la prótesis inmediata, haciendo énfasis en la preparación de los alvéolos artificiales en yeso. Los estudiantes tuvieron una gran participación, utilizando variado instrumental y materiales. Para ello se tomó de forma aleatoria una población de 40 alumnos de cuarto año y de ellos una muestra de 11 alumnos. Se incluyeron alumnos de ambos sexos, la muestra fue escogida de las clínicas estomatológicas de San Juan y Martínez "Hermanos Saíz" y "Antonio Briones Montoto" de Pinar del Río. Se logró que los estudiantes, durante la conferencia, se apropiaran de los conocimientos teóricos con mayor facilidad a través del medio de enseñanza y sirvió además de guía para la obtención de habilidades necesarias no sólo en esta edad académica, sino en su formación como futuros profesionales que tributan a la atención primaria de salud.


Teaching aids reduce considerably time dedicated to teaching activities, working with them auto-creative activity is stimulated. The simulation compels students to demonstrate what they have learned. Loss of teeth has always existed , thus procedures such as the immediate dental protheses to replace and re-establish their esthetic and function are followed. Aimed at developing knowledge, skills and training of the students enrolled in 4th academic year of dentistry specialty, in laboratories where immediate prostheses are made and putting emphasis on the preparation of artificial alveolus in plaster Students participated in these activities using varied tools and materials. To carry out this work 11 students of both sexes were selected at random out of 40 enrolled in 4th academic year at " Hermanos Saiz" Clinic in San Juan y Martinez municipality and at " Antonio Briones Montoto" Clinic respectively. By means of the lectures taught and the teaching aids made , students achieved theoretical knowledge easily using them as a guide to obtain the necessary skills not only for this academic age but also in the formation of future professionals that will work in primary health care.

20.
Rev cienc méd pinar río ; 11(2/3)mar. 2007. ilus
Artículo en Español | CUMED | ID: cum-35944

RESUMEN

Los medios de enseñanza reducen considerablemente el tiempo dedicado al aprendizaje, el trabajo con estos estimula la auto-actividad creadora. La simulación obliga al alumno a demostrar lo aprendido. La pérdida de dientes existe desde tiempos remotos por lo que se han buscado procedimientos, como la prótesis inmediata, para reponerlos y restablecer la estética y la función. Por ello y con la intención de lograr prótesis inmediatas estéticas y con una adecuada adaptación sobre la cirugía recién realizada en el paciente, nos propusimos como objetivo lograr el desarrollo de conocimientos y habilidades en los estudiantes de cuarto año de Estomatología con la confección en el laboratorio de los diferentes pasos de la prótesis inmediata, haciendo énfasis en la preparación de los alvéolos artificiales en yeso. Los estudiantes tuvieron una gran participación, utilizando variado instrumental y materiales. Para ello se tomó de forma aleatoria una población de 40 alumnos de cuarto año y de ellos una muestra de 11 alumnos. Se incluyeron alumnos de ambos sexos, la muestra fue escogida de las clínicas estomatológicas de San Juan y Martínez “Hermanos Saíz” y “Antonio Briones Montoto” de Pinar del Río. Se logró que los estudiantes, durante la conferencia, se apropiaran de los conocimientos teóricos con mayor facilidad a través del medio de enseñanza y sirvió además de guía para la obtención de habilidades necesarias no sólo en esta edad académica, sino en su formación como futuros profesionales que tributan a la atención primaria de salud (AU)


Teaching aids reduce considerably time dedicated to teaching activities, working with them auto-creative activity is stimulated. The simulation compels students to demonstrate what they have learned. Loss of teeth has always existed , thus procedures such as the immediate dental protheses to replace and re-establish their esthetic and function are followed. Aimed at developing knowledge, skills and training of the students enrolled in 4th academic year of dentistry specialty, in laboratories where immediate prostheses are made and putting emphasis on the preparation of artificial alveolus in plaster Students participated in these activities using varied tools and materials. To carry out this work 11 students of both sexes were selected at random out of 40 enrolled in 4th academic year at “ Hermanos Saiz” Clinic in San Juan y Martinez municipality and at “ Antonio Briones Montoto” Clinic respectively. By means of the lectures taught and the teaching aids made , students achieved theoretical knowledge easily using them as a guide to obtain the necessary skills not only for this academic age but also in the formation of future professionals that will work in primary health care (AU)


Asunto(s)
Estudiantes de Odontología , Materiales de Enseñanza , Prótesis Dental
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