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1.
Br J Haematol ; 204(2): 525-533, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37905734

RESUMEN

Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL). Forty-five patients with NHL were treated. Cytokine release syndrome (any grade) occurred in 84% of patients (4% grade ≥3) and neurotoxicity in 7% (2% grade ≥3). The objective response rate was 73% at Day +100, and the 3-year duration of response was 56%. The 3-year progression-free and overall survival were 40% and 52% respectively. High lactate dehydrogenase was the only covariate with an impact on progression-free survival. The 3-year incidence of B-cell recovery was lower in patients with NHL compared to ALL (25% vs. 60%). In conclusion, in patients with NHL, the toxicity of var-cel was manageable, while B-cell recovery was significantly prolonged compared to ALL. This trial was registered as NCT03144583.


Asunto(s)
Linfoma de Células B , Linfoma no Hodgkin , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos , Humanos , Sistemas de Atención de Punto , Linfoma de Células B/terapia , Linfoma no Hodgkin/terapia , Inmunoterapia Adoptiva/efectos adversos , Anticuerpos , Antígenos CD19 , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfocitos T
2.
Artículo en Inglés | MEDLINE | ID: mdl-38381397

RESUMEN

BACKGROUND AND OBJECTIVE: The prevalence of food allergy (FA) has increased significantly, and the risk of developing anaphylaxis is unpredictable. Thus, discriminating between sensitized patients and those at risk of having a severe reaction is of utmost interest. To explore mast cell activation pattern and T follicular helper (TFH) 13 presence in sensitized and food anaphylaxis patients. METHODS: Patients sensitized to Lipid transfer protein (LTP) were classified as anaphylaxis or sensitized depending on the symptoms elicited by LTP-containing food. CD34+-derived MCs from patients and controls were obtained, sensitized with pooled sera, and challenged with Pru p 3 (peach LTP). Degranulation, PGD2, and cytokine/chemokine release were measured. The TFH13 population was examined by flow cytometry in the peripheral blood of all groups. In parallel, LAD2 cells were activated similarly to patients' MCs. RESULTS: A distinguishable pattern of mast cell activation was found in anaphylaxis compared to sensitized patients. Robust degranulation, PGD2, and IL-8 and GM-CSF secretion were higher in anaphylaxis, whereas TFG- and CCL2 secretion increased in sensitized patients. Concomitantly, anaphylaxis patients had a larger TFH13 population. MC activation profile was dependent on the sera rather than the MC source. In agreement with that, LAD2 cells reproduce the same pattern as MCs from anaphylactic and sensitized patients. CONCLUSION: The distinct profile of mast cell activation allows to discriminate between anaphylaxis and sensitized patients. Pooled sera may determine mast cell activation independently of mast cell origin. Besides, the presence of TFH13 cells in anaphylaxis patients points to an essential role of IgE affinity.

3.
Public Health ; 234: 158-163, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39013237

RESUMEN

OBJECTIVES: Several countries in different global regions are implementing lung cancer (LC) screening programmes. This study aimed to estimate the proportion of the Chilean population ≥15 years who are at high risk of developing LC. STUDY DESIGN: Cross-sectional study. METHODS: Data from the Chilean National Health Survey were used in this study. Information on age and history of tobacco consumption were retrieved to estimate national and regional proportions of the Chilean population ≥15 years who are at high risk of developing LC, according to the inclusion criteria in the NELSON trial, NLST trial and USPSTF2021 recommendations. Stratified analyses were performed by sex and quartiles of monthly household income. RESULTS: An estimated 292,158 (2.2%; 95% confidence interval [CI] 1.6-2.8), 174,196 (1.3%; 95% CI 0.9-1.7) and 404,751 (3.1%; 95% CI 2.4-3.8) of Chileans are at high risk of LC according to NELSON and NLST trial inclusion criteria and USPSTF2021 recommendations, respectively. Proportions of males who are at high risk were higher in comparison to females. The highest proportion of people who are at high risk was found in the lowest household income quartile. Regionally, the lowest percentage of Chileans who are at high risk was found in La Araucanía and the highest in Magallanes y Antártica. CONCLUSIONS: There is a relevant number of Chileans who are at high risk of developing LC. Policymakers in Chile should enhance tobacco control efforts to reduce the prevalence of tobacco smoking and also explore the implementation of LC screening programmes to reduce the burden of LC.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiología , Masculino , Femenino , Chile/epidemiología , Persona de Mediana Edad , Estudios Transversales , Adulto , Anciano , Detección Precoz del Cáncer/estadística & datos numéricos , Adolescente , Adulto Joven , Factores de Riesgo , Encuestas Epidemiológicas , Fumar/epidemiología
4.
BMC Nurs ; 23(1): 439, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926730

RESUMEN

BACKGROUND: Advanced practice nursing has emerged as a result of the evolution of healthcare systems, the changing needs of the population and the academic development of nursing, as well as sociodemographic and epidemiological changes. The aim of this study is to describe the professional experiences of Spanish advanced practice nurses in specific positions within the healthcare system in order to better understand the development and characteristics of this specialised nursing role. METHODS: A descriptive qualitative study was conducted. Fourteen advanced practice nurses from healthcare centres participated. Semi-structured interviews were carried out. Braun and Clarke's method for reflexive thematic analysis was followed. The Atlas. Ti version 22 program was used for technological support. The COREQ checklist was used to optimise the reporting of this qualitative study. RESULTS: From the analysis of the data collected, three themes and six subthemes were extracted: 1) Advanced practice nursing on the rise: (a) The driving forces in the development of advanced practice nursing, (b) Barriers to the development of advanced practice nursing; 2) Advanced practice nurses as a response to the population's needs: (a) The development of a new professional nursing role, (b) The patient at the centre of care in advanced practice nursing; 3) Training as the foundation for advanced practice nursing: (a) Expert nurses in a specific context, (b) Differences in the level of training depending on the context. CONCLUSION: Advanced practice nurses have faced countless barriers and difficulties that have impeded them from demonstrating their importance and effectiveness within the healthcare system. A stable regulatory framework for the functions of advanced practice nurses is required to promote care, training and research in the field of advanced practice nursing. Health institutions need to promote the role of advanced practice nurses, facilitate the employment of new professionals, and establish new areas of practice. TRIAL REGISTRATION: Not applicable.

5.
Trop Anim Health Prod ; 55(5): 288, 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37578575

RESUMEN

During the dry and rainy seasons of the Northeastern Zone of Peru, a chemical characterization of five species of bamboo prevalent in the area (Guadua lynnclarkiae, G. takahashiae, Bambusa vulgaris, G. weberbaueri, and Dendrocalamus asper) was conducted. Then, the effect of supplementing bamboo leaves (0, 20, and 40% inclusion of D. asper) on the intake and live weight gain of 18 Gyr × Holstein heifers was evaluated for 28 days. Among the species evaluated, D. asper has the greatest crude protein (CP) concentration (158-166 g/kg Dry matter- DM), post-ruminal CP supply (127 g/kg DM), and in vitro organic matter digestibility (444-456 g/kg DM) but similar concentrations of crude ash (124 g/kg DM), calcium (2.4-2.8 mg/g), phosphorus (0.7-2.1 mg/g), protein fractions A, B1, B2, B3, C (45, 5, 35, 56, and 17g/kg DM, respectively), rumen-undegraded CP (31% CP), neutral detergent fiber (NDF, 685g/kg DM), and acid detergent fiber (ADF, 357 g/kg DM) than the other species evaluated. Dry matter intake was higher in the control treatment and in the 20% bamboo leaf inclusion treatment than in the 40% bamboo inclusion treatment. Intake of CP and NDF decreased with the increase in bamboo inclusion. Despite the differences in DM, CP, and NDF intake, the live weight gain remained similar across treatments. However, there was a greater feed conversion in the 20% bamboo leaf inclusion treatment. During the dry season, bamboo leaves can be used as an alternative supplement at a maximum inclusion of 20% without affecting the live weight gain.


Asunto(s)
Fibras de la Dieta , Digestión , Bovinos , Animales , Femenino , Perú , Fibras de la Dieta/metabolismo , Alimentación Animal/análisis , Detergentes/metabolismo , Aumento de Peso , Dieta/veterinaria , Rumen/metabolismo , Fermentación
6.
Int Orthop ; 46(8): 1873-1880, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35608676

RESUMEN

PURPOSE: The incidence of hip fractures is increasing exponentially due to an aging Brazilian population. Older people had significant comorbidities which increases the risk of post-operative mortality. Our purpose was to examine the association between pre-operative infections and comorbidities on the risk of post-operative in-hospital mortality after proximal femur fracture surgery's, beyond that, to evaluate the association between comorbidities and time to surgery. METHODS: This is a population-based cohort retrospective study, using medical records of all six year consecutive surgical procedures for correction of hip fracture in a tertiary teaching Hospital in Brazil. The exclusion criteria aimed to exclusively allocate patients who had their first hip fracture secondary to low-energy trauma. Multivariate logistical regression was performed and receiver operating characteristic (ROC) curve with area under curve (AUC) to evaluate the sensitivity and specificity of the model. p-value < 0.05 was considered significant. RESULTS: Final sample was composed by 856 consecutive patients with 81 years of median and 164 patients were excluded. The median length of hospital say was five days with - l mortality at 3.6%. Significant variables for increased mortality included the presence of pre-operative infection (odds ratio (OR): 3.9(1.12-8.54), chronic obstructive pulmonary disease (COPD) (OR: 3.83(1.36-10.82)), and systemic arterial hypertension (SAH) (OR: 4.1(1.18-14.25)). Development of pre-operative infection was associated with a delay to surgery (OR: 1.1 (1.08-1.13)). CONCLUSIONS: In older people with proximal femur fracture, the presence of pre-operative infection, COPD and SAH were the strongest risk factor for post-operative in-hospital mortality. Pre-operative infection was associated with statistically significant delay to surgery.


Asunto(s)
Fracturas de Cadera , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Brasil/epidemiología , Fracturas de Cadera/complicaciones , Fracturas de Cadera/cirugía , Mortalidad Hospitalaria , Humanos , Complicaciones Posoperatorias/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria
7.
Clin Immunol ; 230: 108821, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34391937

RESUMEN

BACKGROUND: Information regarding inborn error of immunity (IEI) as a risk factor for severe COVID-19 is scarce. We aimed to determine if paediatric patients with moderate/severe IEI got COVID-19 at the same level as the general population, and to describe COVID-19 expression. MATERIAL AND METHODS: We included patients with moderate/severe IEI aged 0-21 years old: cross-sectional study (June2020) to determine the prevalence of COVID-19; prospective study (January2020-January2021) including IEI patients with COVID-19. Assays used: nasopharyngeal swab SARS-CoV-2 PCR and SARS-CoV-2-specific immunoglobulins. RESULTS: Seven from sixty-five patients tested positive (prevalence: 10.7% (7%-13%)) after the first SARS-COV-2 wave and 13/15 patients diagnosed with COVID-19 had an asymptomatic/mild course. CONCLUSIONS: In our area, prevalence of COVID-19 in moderate/severe IEI paediatric patients after the first wave was slightly higher than in the general population. The majority of patients presented a benign course, suggesting a possible protective factor related with age despite IEI.


Asunto(s)
COVID-19/complicaciones , Enfermedades de Inmunodeficiencia Primaria/complicaciones , SARS-CoV-2 , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Prevalencia , Adulto Joven
8.
Anaesthesia ; 76(2): 199-208, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32803791

RESUMEN

The effect of intra-operative intravenous methadone on quality of postoperative recovery was compared with morphine after laparoscopic gastroplasty. We included 137 adult patients with a body mass index > 35 kg.m-2 who underwent bariatric surgery. Patients were allocated at random to receive either intra-operative methadone (n = 69) or morphine (n = 68). All patients received the same postoperative care and analgesia. The primary outcome of postoperative quality of recovery was assessed using the Quality of Recovery-40 questionnaire total score 24 h after surgery. Secondary outcomes were assessed in the post-anaesthesia care unit the night of the day of surgery (T1), in the morning after surgery (T2); and at night on the day following surgery (T3). The median (IQR [range]) total Quality of Recovery-40 questionnaire score of 194 (190-197 [165-200]) was higher (p < 0.0001) in the methadone group compared with the score of 181 (174-185.5 [121-200]) in the morphine group. In the post-anaesthesia care unit, the pain burden; incidence of nausea and vomiting; rescue morphine dose; and time to discharge, were significantly lower in the methadone group. On the ward, the methadone group had a lower: incidence of rescue morphine requests at T1 (5.8 vs. 54.4%, p < 0.0001) and T2 (0 vs. 20.1%, p < 0.0001); and incidence of nausea (21.7 vs. 41.2%, p = 0.014), compared with the morphine group. We conclude that intra-operative intravenous methadone improved quality of recovery in patients who underwent laparoscopic gastroplasty, compared with intra-operative morphine. Methadone also reduced postoperative pain, postoperative opioid consumption and the incidence of opioid-related adverse events.


Asunto(s)
Analgésicos Opioides/uso terapéutico , Gastroplastia/métodos , Laparoscopía/métodos , Metadona/uso terapéutico , Morfina/uso terapéutico , Adulto , Analgesia Controlada por el Paciente , Analgésicos Opioides/efectos adversos , Periodo de Recuperación de la Anestesia , Método Doble Ciego , Femenino , Humanos , Periodo Intraoperatorio , Masculino , Metadona/efectos adversos , Persona de Mediana Edad , Morfina/efectos adversos , Manejo del Dolor , Dimensión del Dolor/efectos de los fármacos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/epidemiología , Náusea y Vómito Posoperatorios/epidemiología , Resultado del Tratamiento
9.
J Biomed Inform ; 107: 103421, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32407878

RESUMEN

The value of robust and responsible data sharing in clinical research and healthcare is recognized by patients, patient advocacy groups, researchers, journal editors, and the healthcare industry globally. Privacy and security concerns acknowledged, the act of exchanging data (interoperability) along with its meaning (semantic interoperability) across studies and between partners has been difficult, if not elusive. For shared data to retain its value, a recommendation has been made to follow the Findable, Accessible, Interoperable, Reusable (FAIR) principles. Without applying appropriate data exchange standards with domain-relevant content standards and accessible rich metadata that uses applicable terminologies, interoperability is burdened by the need for transformation and/or mapping. These obstacles to interoperability limit the findability, accessibility and reusability of data, thus diminishing its value and making it impossible to adhere to FAIR principles. One effort to standardize data collection has been through common data elements (CDEs). CDEs are data collection units comprising one or more questions together with a set of valid values. Some CDEs contain standardized terminology concepts that define the meaning of the data, and others include links to unique terminology concept identifiers and unique identifiers for each CDE; however, usually CDEs are defined for specific projects or collaborations and lack traceable or machine readable semantics. While the name implies that these are 'common', this has not necessarily been a requirement, and many CDEs have not been commonly used. The National Institutes of Health (NIH) CDEs are, in fact, a conglomerate of CDEs developed in silos by various NIH institutes. Therefore, CDEs have not brought the anticipated benefit to the industry through widescale interoperability, nor is there widespread reuse of CDEs. Certain institutes in the NIH recommend, albeit do not enforce, institute-specific preferred CDEs; however, at the NIH level a preponderance of choice and a lack of any overarching harmonization of CDEs or consistency in linking them to controlled terminology or common identifiers create confusion for researchers in their efforts to identify the best CDEs for their protocol. The problem of comparing data among studies is exacerbated when researchers select different CDEs for the same variable or data collection field. This manuscript explores reasons for the disappointingly low adoption of CDEs and the inability of CDEs or other clinical research standards to broadly solve the interoperability and data sharing problems. Recommendations are offered for rectifying this situation to enable responsible data sharing that will help in adherence to FAIR principles and the realization of Learning Health Systems for the sake of all of us as patients.


Asunto(s)
Investigación Biomédica , Salud Poblacional , Elementos de Datos Comunes , Humanos , Difusión de la Información , Metadatos
10.
Brain Behav Immun ; 81: 608-616, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31344493

RESUMEN

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder with an etiopathophysiology that seems to include immune alterations. Previous studies have suggested that variations in the levels of circulating T cell subpopulations may be involved in psychiatric diseases. However, the role of these cells in OCD remains unexplored. Hence, the present study aimed to examine the levels of T helper 1 (Th1), Th2, Th17 and regulatory T (Treg) cells in patients with early-onset OCD and healthy controls. METHODS: The assessment was performed in 99 children and adolescents with OCD and 46 control subjects. The percentages of circulating Th1, Th2, Th17 and Treg cells were evaluated using flow cytometry. RESULTS: OCD patients had significantly higher levels of Th17 cells and lower percentages of Treg cells than healthy controls (p = 0.001 and p = 0.005, respectively). Furthermore, levels of Th17 cells progressively increased with the duration (p = 0.005) and severity of OCD (p = 0.008), whereas the percentages of Treg cells significantly declined with the duration of the disorder (p = 1.8 × 10-5). CONCLUSIONS: These results provide more evidence of the involvement of immune dysregulation, specifically an imbalance in the levels of circulating T helper and regulatory T cells, in the pathophysiology of early-onset OCD.


Asunto(s)
Trastorno Obsesivo Compulsivo/inmunología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Adolescente , Citocinas/inmunología , Femenino , Citometría de Flujo/métodos , Humanos , Masculino , Trastorno Obsesivo Compulsivo/metabolismo , Linfocitos T Reguladores/metabolismo , Células TH1/inmunología , Células Th17/metabolismo , Células Th2/inmunología
11.
Environ Sci Technol ; 52(4): 2071-2080, 2018 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-29320848

RESUMEN

A thorough understanding of spatial and temporal emission and immission patterns of air pollutants in urban areas is challenged by the low number of air-quality monitoring stations available. Plants are promising low-cost biomonitoring tools. However, source identification of the trace metals incorporated in plant tissues (i.e., natural vs anthropogenic) and the identification of the best plant to use remain fundamental challenges. To this end, Nerium oleander L. collected in the city of Zaragoza (NE Spain) has been investigated as a biomonitoring tool for assessing the spatial immission patterns of airborne metals (Pb, Cu, Cr, Ni, Ce, and Zn). N. oleander leaves were sampled at 118 locations across the city, including the city center, industrial hotspots, ring-roads, and outskirts. Metal concentrations were generally higher within a 4 km radius around the city center. Calculated enrichment factors relative to upper continental crust suggest an anthropogenic origin for Cr, Cu, Ni, Pb, and Zn. Zinc isotopes showed significant variability that likely reflects different pollution sources. Plants closer to industrial hotspots showed heavier isotopic compositions (δ66ZnLyon up to +0.70‰), indicating significant contributions of fly ash particles, while those far away were isotopically light (up to -0.95‰), indicating significant contributions from exhaust emissions and flue gas. We suggest that this information is applied for improving the environmental and human risk assessment related to the exposure to air pollution in urban areas.


Asunto(s)
Metales Pesados , Nerium , Ciudades , Monitoreo del Ambiente , Humanos , Hojas de la Planta , España , Isótopos de Zinc
12.
Scand J Med Sci Sports ; 28(3): 760-771, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28452070

RESUMEN

The main objective was to systematically review the scientific literature about the effects of exergame-based interventions on musculoskeletal pain, as well as to provide directions for the clinical practice. A systematic search was conducted in four electronic databases following PRISMA guidelines. The inclusion criteria were as follows: (a) the subjects were suffering musculoskeletal pain, (b) the study was randomized controlled trial (RCT), (c) intervention was based on exergames, (d) the article was written in English, and (e) the article was not an abstract or summary presented in a congress or conference. Risk of bias and quality of evidence were evaluated using the PEDro Scale and GRADE approach, respectively. A meta-analysis was carried out to determine effect sizes. Seven studies were selected in the systematic review. The meta-analysis included those six articles which reported means and SD before and after treatment and used a visual analog scale or a Numeric Pain Rating Scale. Four of the seven articles reported significant reduction in pain while the rest did not found any significant change in pain after the intervention. The overall effect size for pain was -0.51 (95% CI from -1.25 to 0.23) with large heterogeneity. Although four of the seven articles reported significant within-group differences, zero was included in the CI of the overall effect size. Therefore, up-to-date there is not enough evidence to conclude that exergames improve musculoskeletal pain.


Asunto(s)
Terapia por Ejercicio , Dolor Musculoesquelético/terapia , Juegos Recreacionales , Humanos , Dimensión del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto
13.
J Neuroinflammation ; 14(1): 261, 2017 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-29284508

RESUMEN

BACKGROUND: Although the exact etiology of obsessive-compulsive disorder (OCD) is unknown, there is growing evidence of a role for immune dysregulation in the pathophysiology of the disease, especially in the innate immune system including the microglia. To test this hypothesis, we studied inflammatory markers in monocytes from pediatric patients with OCD and from healthy controls. METHODS: We determined the percentages of total monocytes, CD16+ monocytes, and classical (CD14highCD16-), intermediate (CD14highCD16low), and non-classical (CD14lowCD16high) monocyte subsets in 102 patients with early-onset OCD and in 47 healthy controls. Moreover, proinflammatory cytokine production (GM-CSF, IL-1ß, IL-6, IL-8, and TNF-α) was measured by multiplex Luminex analysis in isolated monocyte cultures, in basal conditions, after exposure to lipopolysaccharide (LPS) to stimulate immune response or after exposure to LPS and the immunosuppressant dexamethasone. RESULTS: OCD patients had significantly higher percentages of total monocytes and CD16+ monocytes than healthy controls, mainly due to an increase in the intermediate subset but also in the non-classical monocytes. Monocytes from OCD patients released higher amounts of GM-CSF, IL-1ß, IL-6, IL-8, and TNF-α than healthy controls after exposure to LPS. However, there were no significant differences in basal cytokine production or the sensitivity of monocytes to dexamethasone treatment between both groups. Based on monocyte subset distribution and cytokine production after LPS stimulation, patients receiving psychoactive medications seem to have an intermediate inflammatory profile, that is, lower than non-medicated OCD individuals and higher than healthy controls. CONCLUSIONS: These results strongly support the involvement of an enhanced proinflammatory innate immune response in the etiopathogenesis of early-onset OCD.


Asunto(s)
Citocinas/metabolismo , Inflamación/metabolismo , Monocitos/metabolismo , Trastorno Obsesivo Compulsivo/metabolismo , Adolescente , Niño , Dexametasona/farmacología , Femenino , Glucocorticoides/farmacología , Humanos , Lipopolisacáridos/farmacología , Masculino , Monocitos/efectos de los fármacos , Adulto Joven
14.
Tumour Biol ; 39(6): 1010428317705509, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28621236

RESUMEN

Despite initial responsiveness, acquired resistance to both bevacizumab and chemotherapy in metastatic colorectal cancer is universal. We have recently published that in vitro, chronically oxaliplatin resistance upregulates soluble vascular endothelial growth factor receptor 1, downregulates vascular endothelial growth factor, and also promotes c-MET, b-catenin/transcription factor 4, and AKT activation. We tested whether variation in three serum biomarkers such as the natural c-MET ligand (hepatocyte growth factor), soluble vascular endothelial growth factor receptor 1, and vascular endothelial growth factor-A was associated with efficacy in metastatic colorectal cancer patients treated in the prospective BECOX study. Serum levels of vascular endothelial growth factor-A165, soluble vascular endothelial growth factor receptor 1, and hepatocyte growth factor were assessed by enzyme-linked immunosorbent assay method basally and every 3 cycles (at the time of computed tomography evaluation) in a preplanned translational study in the first-line BECOX trial in metastatic colorectal cancer patients treated with CAPOX plus bevacizumab. Response was evaluated by routine contrast-enhanced computed tomography by RECIST 1.1 by investigator assessment and by three blinded independent radiologists. Ratios between soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A and hepatocyte growth factor/vascular endothelial growth factor-A were established and variations through time were related to RECIST 1.1 by investigator assessment and independent radiologist. The BECOX trial included 68 patients, and 27 patients were analyzed in the translational trial. A total of 80 RECIST 1.1 evaluations were done by investigator assessment and 56 by independent radiologist. We found that a 3.22-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by investigator assessment and a 3.06-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by independent radiologist from previous determination were associated with responses compared with 1.38-fold increase by investigator assessment and 1.59 by independent radiologist in non-responders (p = 0.0009 and p = 0.03, respectively). Responders had a 3.36-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A from previous determination by investigator assessment and 3.66-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A by independent radiologist compared with 1.43-fold increase by investigator assessment and 1.53 by independent radiologist for non-responders (p = 0.002 and 0.003, respectively). In conclusion, a decrease in vascular endothelial growth factor-A and an increase in soluble vascular endothelial growth factor receptor 1 during chemotherapy and bevacizumab exposure can contribute to both chemotherapy (due to c-MET/b-catenin activation) and bevacizumab (due to low vascular endothelial growth factor requirements) resistance. Because hepatocyte growth factor levels decrease also during acquired resistance, alternative strategies to hepatocyte growth factor-ligand inhibition should be investigated.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Factor de Crecimiento de Hepatocito/sangre , Neovascularización Patológica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/sangre , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangre , Adulto , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Patológica/sangre , Neovascularización Patológica/patología , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino
15.
Neurochem Res ; 42(2): 347-359, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27747481

RESUMEN

Lectins are proteins that bind cellular glycans and can modulate various neuronal functions. We have evaluated the neuroprotective effect of ConBr, a lectin purified from the seeds of Canavalia brasiliensis in a model of rat organotypic hippocampal cultures (OHCs) exposed to oxygen and glucose deprivation (OGD). OGD for 15 min followed by 24 h re-oxygenation significantly increased cell death, caused mitochondrial depolarization and increased reactive oxygen species (ROS) in CA1 region of OHCs. ConBr (0.1 µg/mL) added during the re-oxygenation period counteracted cell death, mitochondrial depolarization and overproduction of ROS induced by OGD. Moreover, ConBr restored the levels of Akt and ERK1 phosphorylation that were reduced by OGD. Modulation of intracellular Ca2+ by ConBr was evaluated in isolated hippocampal neurons loaded with the fluorescent calcium dye Fluo-4/AM. ConBr (0.1 and 1 µg/mL) reduced by 25-30 % the Ca2+ increment induced by 70 mM K+. A sub effective concentration of ConBr (0.01 µg/mL) together with a sub effective concentration of the L-type calcium channel antagonist nifedipine (0.3 µM) conferred a synergic neuroprotective effect in OHCs subjected to OGD. In conclusion, ConBr provides OHCs neuroprotection against OGD. The mechanism was not fully addressed but it may involve modulation of L-type voltage-gated Ca2+ channels by ConBr.


Asunto(s)
Isquemia Encefálica/metabolismo , Canales de Calcio/metabolismo , Canavalia , Hipocampo/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Lectinas de Plantas/uso terapéutico , Animales , Isquemia Encefálica/prevención & control , Células Cultivadas , Relación Dosis-Respuesta a Droga , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Técnicas de Cultivo de Órganos , Lectinas de Plantas/aislamiento & purificación , Lectinas de Plantas/farmacología , Ratas , Ratas Sprague-Dawley , Semillas
16.
Nutr Metab Cardiovasc Dis ; 27(2): 183-189, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28017525

RESUMEN

BACKGROUND AND AIMS: The concern over the weight gain problem continues to grow among both the international scientific community and public health authorities, since overweight and obesity prevalence rates continue to increase worldwide. In Chile, two out of three people are overweight, whereas 25% of the adult population is obese. Abdominal fat, has been linked to the development of a number of metabolic disorders. Waist circumference (WC) and the waist:height ratio (WHtR) have recently been evidenced as good predictors of metabolic risk for both adults and children. Thus, the present work aims at establishing smoothed centile charts and LMS tables for WC and WHtR for Chilean adults based on data from the National Health Survey-ENS, in order to have reliable information for identifying groups at risk. METHODS AND RESULTS: A sample of 4788 subjects aged 15-75 years old (mean age 46 ± 18 years old) was considered. Body weight, height, and WC were measured and Body Mass Index (BMI) and WHtR were also determined. Percentiles were calculated using the L (curve Box-Cox), M (curve median), S (curve coefficient of variation) method. In the obese group the WC cutoff values were 99.75 cm and 92.35 cm for men and women, respectively. The cutoff point for WHtR was 0.59 for both obese men and women. CONCLUSION: The study shows, for the first time, reference values for WC and WHtR for Chilean adults.


Asunto(s)
Estatura , Obesidad/diagnóstico , Circunferencia de la Cintura , Relación Cintura-Estatura , Adolescente , Adulto , Distribución por Edad , Anciano , Área Bajo la Curva , Chile/epidemiología , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/fisiopatología , Valor Predictivo de las Pruebas , Curva ROC , Valores de Referencia , Medición de Riesgo , Factores de Riesgo , Distribución por Sexo , Adulto Joven
17.
Anesth Analg ; 124(5): 1674-1677, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28431427

RESUMEN

Intrathecal local anesthetic maldistribution is a well-known cause of spinal anesthesia failure (SAF). This could potentially result in sensory blockade restricted to the sacral dermatomes. We sought to determine the overall incidence of SAF and the role of sacral dermatomes in differentiating between total and partial failures. Of the 3111 spinals prospectively examined, 194 (6.2%) were classified as failures. Of the 72 presumed total failures based on the initial assessment, evaluation of the sacral dermatomes revealed sensory blockade in 32 (44%; 95% confidence interval, 32.7%-56.6%). Sacral dermatome assessment after SAF may be important in safely guiding subsequent anesthetic management.


Asunto(s)
Anestesia Raquidea/efectos adversos , Anestésicos Locales/efectos adversos , Bupivacaína/efectos adversos , Actividad Motora/efectos de los fármacos , Sacro/efectos de los fármacos , Umbral Sensorial/efectos de los fármacos , Adulto , Anestésicos Locales/administración & dosificación , Bupivacaína/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico , Umbral del Dolor/efectos de los fármacos , Estudios Prospectivos , Sacro/fisiología , Sensación Térmica/efectos de los fármacos , Insuficiencia del Tratamiento
18.
Anaesthesia ; 72(4): 496-503, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27987218

RESUMEN

We studied the effects of tracheal tube cuffs filled with air, saline or alkalinised lidocaine on haemodynamic changes during tracheal extubation and postoperative laryngotracheal morbidity in children. We randomly allocated 164 children aged 3-13 years undergoing general anaesthesia to one of four groups; tracheal tube cuffs filled with air (n = 41); saline (n = 41); alkalinised lidocaine 0.5% (n = 41); or alkalinised lidocaine 1% (n = 41). Intracuff pressure was monitored and maintained below 20 cmH2 O. The mean (SD) increases in systolic blood pressure after tracheal extubation compared with before extubation were 10.9 (10.8) mmHg, 7.3 (17.7) mmHg, 4.1 (10.5) mmHg and 1.9 (9.5) mmHg in the air, saline, 0.5% and 1% alkalinised lidocaine groups, respectively (p = 0.021). The mean (SD) increases in diastolic blood pressure after tracheal extubation compared with before extubation were 3.9 (9.7) mmHg, 7.9 (14.6) mmHg, 0.7 (10.4) mmHg and 3.6 (6.9) mmHg in the air, saline, 0.5% and 1% alkalinised lidocaine groups, respectively (p = 0.019). The mean (SD) increases in heart rate after tracheal extubation compared with before extubation were 14.2 (7.6) beats.min-1 , 15.5 (13.1) beats.min-1 , 5.2 (9.6) beats.min-1 and 4.1 (6.6) beats.min-1 in the air, saline, 0.5% and 1% alkalinised lidocaine groups, respectively (p < 0.001). The incidence of sore throat 8 h after tracheal extubation was 22.0% in the air-filled group, 9.8% in the saline group, 4.9% in the 0.5% alkalinised lidocaine group and 2.4% in the 1% alkalinised lidocaine group, p = 0.015. We conclude that filling the tracheal tube cuff with alkalinised lidocaine-filled reduces the haemodynamic response to tracheal extubation and postoperative laryngotracheal morbidity in children.


Asunto(s)
Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/métodos , Laringe/lesiones , Tráquea/lesiones , Adolescente , Aire , Extubación Traqueal , Álcalis , Presión Sanguínea , Niño , Preescolar , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Lidocaína , Masculino , Faringitis/epidemiología , Faringitis/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Presión , Estudios Prospectivos , Solución Salina
20.
Neurologia ; 31(3): 183-94, 2016 Apr.
Artículo en Inglés, Español | MEDLINE | ID: mdl-26383062

RESUMEN

INTRODUCTION: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. DEVELOPMENT: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. CONCLUSION: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue.


Asunto(s)
Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Cognición , Pruebas Neuropsicológicas , Anciano , Anciano de 80 o más Años , Demencia/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados
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