The proteasome inhibitor carfilzomib exerts anti-inflammatory and antithrombotic effects on the endothelium.

BACKGROUND: Carfilzomib (CFZ) is a second-generation proteasome inhibitor used to treat multiple myeloma. Potent inhibition of the proteasome results in chronic proteotoxic endoplasmic reticulum (ER) stress, leading to apoptosis. While CFZ has improved survival rates in multiple myeloma, it is associated with an increased risk of cardiovascular adverse effects. While this has been putatively linked to cardiotoxicity, CFZ could potentially also exhibit adverse effects on the endothelium. OBJECTIVES: To investigate the effects of CFZ on the endothelium. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with CFZ, and expression of relevant markers of ER stress, inflammation, and thrombosis was measured and functionally assessed. RESULTS: CFZ failed to induce ER stress in HUVECs but induced the expression of Kruppel-like factor 4, endothelial nitric oxide synthase, tissue plasminogen activator, and thrombomodulin and reduced tumor necrosis factor alpha (TNFα)-mediated intercellular adhesion molecule 1 and tissue factor expression, suggesting a potential protective effect on the endothelium. Consistent with these observations, CFZ reduced leukocyte adhesion under shear stress and reduced factor Xa generation and fibrin clot formation on the endothelium following TNFα treatment and inhibited von Willebrand factor (VWF) and angiopoietin-2 exocytosis from Weibel-Palade bodies. Subsequently, CFZ inhibited the formation of VWF-platelet strings, and moreover, media derived from myeloma cell lines induced VWF release, a process also inhibited by CFZ. CONCLUSION: These data demonstrate that CFZ is unable to induce ER stress in confluent resting endothelial cells and can conversely attenuate the prothrombotic effects of TNFα on the endothelium. This study suggests that CFZ does not negatively alter HUVECs, and proteasome inhibition of the endothelium may offer a potential way to prevent thrombosis.

Analysis of Regional Palliative Care Strategies: Do Health Policies Influence the Development of Assistance Coverage?

In Spain, health competencies are decentralized, and each autonomous community implements its own plans. Our aim is to determine if the existence of regional palliative care plans implies an improvement in health care coverage. We reviewed regional palliative care plans published in Spain and analyzed the following variables: number and profile of palliative care resources, guidelines and objectives of implementation of resources of these plans, and compliance with European standards. The publication of regional plans is associated with an increase in specific resources in the following years. From 2004 to 2009, the implementation of plans in 6 autonomous communities was associated with an increase in palliative care resources compared to those without a strategy (odds ratio: 1.58, P = .02) or with a settled plan (odds ratio: 1.40, P = .07). The same phenomenon was observed between 2009 and 2015 in 4 autonomous communities and 2 autonomous cities compared with those without a strategy (odds ratio: 2.49, P = .001) and those that implemented a plan before 2009 (odds ratio: 2.62, P < .001). Updating and evaluating these regional plans are also associated with the growth of palliative care resources.

Crisis de opioides: ¿nos afecta? / Opioid crisis: does it affect us?

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Relación de la hiperuricemia con las alteraciones metabólicas y factores de riesgo cardiovascular en jóvenes mexicanos.

INTRODUCTION: Hyperuricemia is a risk factor for cardiovascular disease, but its impact has not been properly documented. OBJECTIVE: To assess the impact of hyperuricemia on metabolic parameters and cardiovascular risk factors (CRF) in apparently healthy Mexicans. METHOD: Cross-sectional study of 768 young adults. Association of hyperuricemia with alterations in metabolic parameters and CRF (hypertension, mixed dyslipidemia, metabolic syndrome) was sought. Log-linear and regression models were used to determine the influence of hyperuricemia. A multivariate analysis of variance was applied to observe the interaction of hyperuricemia and overweight or obesity with changes in metabolic parameters. RESULTS: Metabolic parameters were higher in patients with hyperuricemia than with normal uric acid (all < 0.05). Hyperuricemia was significantly associated with hypertension (OR=6.8, 95 % CI: 1.1-46), dyslipidemia (OR=2.5, 95% CI: 1.3-4.7) and metabolic syndrome (OR=2.3, 95% CI: 1.1-4.6). Hyperuricemia and overweight or obesity significantly predict changes in cardiovascular risk metabolic parameters (Wilks' l=0.91, F (6.175)=3.1, p=0.007). CONCLUSIONS: Hyperuricemia is significantly associated with metabolic alterations and different CRF.

INTRODUCCIÓN: La hiperuricemia es un factor de riesgo para enfermedad cardiovascular, pero su impacto no ha sido bien documentado. OBJETIVO: Evaluar el impacto de la hiperuricemia en los parámetros metabólicos y los factores de riesgo cardiovascular en mexicanos aparentemente sanos. MÉTODO: Estudio trasversal de 768 adultos jóvenes. Se buscó asociación de la hiperuricemia con alteraciones de los parámetros metabólicos y factores de riesgo cardiovascular (hipertensión, dislipidemia mixta y síndrome metabólico). Se aplicaron modelos loglineales y de regresión para determinar la influencia de la hiperuricemia. Se aplicó análisis multivariado de varianza para observar la interacción de la hiperuricemia y el sobrepeso u obesidad en los cambios de los parámetros metabólicos. RESULTADOS: Los parámetros metabólicos fueron mayores en los individuos con hiperuricemia que con ácido úrico normal (< 0.05). La hiperuricemia se asoció significativamente con hipertensión (RM = 6.8, IC 95 % = 1.1-46), dislipidemia (RM = 2.5, IC 95 % = 1.3-4.7) y síndrome metabólico (RM = 2.3, IC 95 % = 1.1-4.6). La hiperuricemia y el sobrepeso u obesidad predicen significativamente los cambios en los parámetros metabólicos de riesgo cardiovascular (l de Wilks = 0.91, F [6.175] = 3.1, p = 0.007). CONCLUSIONES: La hiperuricemia está asociada significativamente con las alteraciones metabólicas y los distintos factores de riesgo cardiovascular.

Estrategias regionales de cuidados paliativos en España: estudio descriptivo / Regional approaches to palliative care in Spain: a descriptive study

OBJETIVOS: Los cuidados paliativos (CP) forman parte de las transferencias de salud que asumieron las comunidades autónomas (CCAA). Nos planteamos describir las características principales de las estrategias regionales de CP que se han publicado hasta la fecha. MÉTODO: Revisión de los planes, programas o estrategias de CP de las CCAA y las ciudades autónomas de Ceuta y Melilla publicadas desde 2002 a 2018. La búsqueda se ha llevado a cabo en los sitios web de las consejerías y planes de salud de las CCAA y se ha complementado con el Observatorio de CP de Castilla y León. Variables analizadas: fechas y versiones, cronograma, perfil de los redactores, estructura del plan, objetivos, líneas estratégicas, evaluación y organización. RESULTADOS: Hasta enero de 2018 son 15 las CCAA que han publicado su Plan Estratégico de CP, además del de Ceuta y Melilla. Cuatro han editado una actualización del Plan y en la actualidad solo están en vigor tres de las estrategias de las que definían un cronograma o periodo de aplicación. Solo dos han presentado datos de evaluación. La proporción de profesionales de CP en la composición del grupo redactor varía mucho. La estructura general de los documentos es similar y el objetivo principal es común: la mejora de la calidad de vida de los pacientes terminales y sus familias. Casi todos los planes asumen varias de las líneas estratégicas propuestas por los Planes Nacionales de 2001 y 2007. Seis CCAA incluyen también la mejora de los sistemas de información y registro y la participación de la comunidad. El modo de plantear la organización de la atención en CP presenta una gran variabilidad. Aunque la mayor parte de las CCAA diferencia equipos hospitalarios y de atención domiciliaria, se aprecia una tendencia a integrar estos recursos. CONCLUSIONES: Los objetivos generales de los planes son similares y responden a las líneas del Plan Nacional. Sin embargo, hay heterogeneidad en el diseño, planteamiento y organización de los programas de CP. Se aprecian carencias en la actualización y evaluación de los planes

OBJECTIVES: Palliative care (PC) has been taken on by the Spanish Autonomous Communities (ACs) as part of the central government's transfer of healthcare competencies to regional institutions. We describe the main characteristics of the PC strategies reported by ACs to this day. METHOD: A review of all PC plans, programs and strategies reported from 2002 through 2018 by the Spanish ACs and autonomous cities of Ceuta and Melilla. A search was performed of the websites of AC ministries and health plans, supplemented by the PC Observatory of Castilla y León. Assessed variables included: dates and versions, chronogram, author profiles, structure, objectives, strategic lines, evaluation, and organization. RESULTS: Through January 2018, 15 ACs published their PC Strategic Plans, in addition to Ceuta and Melilla. Four ACs have published updates of their Plans, and to date only three of those with a predefined period for implementation are active. Only two have reported evaluation data. The proportion of PC professionals in the composition of the drafting groups varies. The documents have similar structures and a common primary objective: improving quality of life for terminal patients and their families. Almost all Plans endorse several of the strategic lines proposed by the National Plans for 2001 and 2007. Six ACs also contemplate improvements in their information and recording systems, as well as in community participation. Organizational designs vary extensively regarding PC; while most ACs differentiate between hospital and home care teams, there is a tendency to integrate these resources. CONCLUSIONS: The primary objectives of AC Plans are similar and aligned with the National Plan. However, there is heterogeneity in the design, planning and organization of PC programs. Deficiencies in the updating and evaluation of these Plans also exist

Relación de la hiperuricemia con las alteraciones metabólicas y factores de riesgo cardiovascular en jóvenes mexicanos / Relationship of hyperuricemia with metabolic alterations and cardiovascular risk factors in young Mexicans

Resumen Introducción: La hiperuricemia es un factor de riesgo para enfermedad cardiovascular, pero su impacto no ha sido bien documentado. Objetivo: Evaluar el impacto de la hiperuricemia en los parámetros metabólicos y los factores de riesgo cardiovascular en mexicanos aparentemente sanos. Método: Estudio trasversal de 768 adultos jóvenes. Se buscó asociación de la hiperuricemia con alteraciones de los parámetros metabólicos y factores de riesgo cardiovascular (hipertensión, dislipidemia mixta y síndrome metabólico). Se aplicaron modelos loglineales y de regresión para determinar la influencia de la hiperuricemia. Se aplicó análisis multivariado de varianza para observar la interacción de la hiperuricemia y el sobrepeso u obesidad en los cambios de los parámetros metabólicos. Resultados: Los parámetros metabólicos fueron mayores en los individuos con hiperuricemia que con ácido úrico normal (< 0.05). La hiperuricemia se asoció significativamente con hipertensión (RM = 6.8, IC 95 % = 1.1-46), dislipidemia (RM = 2.5, IC 95 % = 1.3-4.7) y síndrome metabólico (RM = 2.3, IC 95 % = 1.1-4.6). La hiperuricemia y el sobrepeso u obesidad predicen significativamente los cambios en los parámetros metabólicos de riesgo cardiovascular (l de Wilks = 0.91, F [6.175] = 3.1, p = 0.007). Conclusiones: La hiperuricemia está asociada significativamente con las alteraciones metabólicas y los distintos factores de riesgo cardiovascular.

Abstract Introduction: Hyperuricemia is a risk factor for cardiovascular disease, but its impact has not been properly documented. Objective: To assess the impact of hyperuricemia on metabolic parameters and cardiovascular risk factors (CRF) in apparently healthy Mexicans. Method: Cross-sectional study of 768 young adults. Association of hyperuricemia with alterations in metabolic parameters and CRF (hypertension, mixed dyslipidemia, metabolic syndrome) was sought. Log-linear and regression models were used to determine the influence of hyperuricemia. A multivariate analysis of variance was applied to observe the interaction of hyperuricemia and overweight or obesity with changes in metabolic parameters. Results: Metabolic parameters were higher in patients with hyperuricemia than with normal uric acid (all < 0.05). Hyperuricemia was significantly associated with hypertension (OR=6.8, 95 % CI: 1.1-46), dyslipidemia (OR=2.5, 95% CI: 1.3-4.7) and metabolic syndrome (OR=2.3, 95% CI: 1.1-4.6). Hyperuricemia and overweight or obesity significantly predict changes in cardiovascular risk metabolic parameters (Wilks’ l=0.91, F (6.175)=3.1, p=0.007). Conclusions: Hyperuricemia is significantly associated with metabolic alterations and different CRF.

Choriocarcinoma Syndrome as an Initial Presentation of Testicular Cancer.

Choriocarcinoma syndrome (CS) is a rare clinical entity within the spectrum of nonseminomatous germ-cell tumors (NSGCT). It is characterized by the abrupt establishment of rapidly progressive and hemorrhagic tumors associated with very high levels of the beta fraction of human chorionic gonadotropin (ß-hCG) and with a very poor prognosis, particularly in patients with ß-hCG values above 50,000 IU/L. We present the case of a 17-year-old man with a sudden onset nonmassive hemoptysis. Physical examination revealed a right testicular mass. Imaging studies showed metastatic lung, bone, and retroperitoneal disease. ß-hCG serum levels were 222,493.21 IU/L, AFP 1.56 ng/mL, and DHL 457 IU/L. Histopathological study after right radical orchiectomy showed a mixed germ-cell tumor. Based on poor-risk characteristics, chemotherapy was started with an adequate clinical response. Physicians should be aware of the potential complications of CS in the treatment of testicular cancer with high ß-hCG levels since they could be associated with a rapidly progressive and high-volume disease. Patients in this category should be referred to the centers experienced in the treatment of advanced germ-cell tumors. Due to the severity of the presentation, hemodynamic monitoring, ideally in an intensive care unit, is essential as well as timely administration of cytotoxic treatment.

Successful Angiojet® aortic thrombectomy of extracorporeal membrane oxygenation-related thrombus in a newborn.

Thrombosis and systemic embolization are important complications of extracorporeal membrane oxygenation (ECMO). We present a 2.5 kg neonate born at 37.4 weeks with hypoplastic left heart supported on ECMO that developed an acute, occlusive distal aortic thrombus that was emergently managed by transcatheter Angiojet® (Boston Scientific, Boston, MA) thrombectomy. The procedure successfully restored perfusion to the lower extremities with sustained result upon 1-week follow-up. This case highlights the Angiojet® thrombectomy as a treatment option for limb- or organ-threatening acute thrombus in even the most complex ECMO patients.

Índice cintura-talla: prueba para valoración de riesgo cardiovascular y diagnóstico del síndrome metabólico / Waist-Length Index: Test for Cardiovascular Risk Assessment and Diagnosis of Metabolic Syndrome

Introducción: la presencia de síndrome metabólico y enfermedad cardiovascular está vinculada fisiopatológicamente con el sobrepeso y obesidad. Objetivo: evaluar la utilidad y precisión del Índice cintura-talla en la valoración de riesgo y diagnóstico del síndrome metabólico y otras alteraciones cardiometabólicas. Métodos: se evaluaron a adultos jóvenes aparentemente sanos para su implementación como una prueba diagnóstica o tamiz diagnóstico de rutina en los niveles primarios de atención en salud. Se realizó un estudio transversal con una muestra de 369 adultos jóvenes con edad de 18-22 años del primer año de la licenciatura de medicina en la Benemérita Universidad Autónoma de Puebla. Se determinaron parámetros bioquímicos y antropométricos para la presencia de síndrome metabólico y otras alteraciones cardiovasculares, se calculó el Índice cintura-talla y se generaron cuartiles para proponer un punto de corte con el cual se pueda valorar el riesgo y la utilidad diagnóstica. Resultados: el Índice cintura-talla mostró ser una prueba diagnóstica bastante sensible (91 por ciento, 70 por ciento y 52 por ciento) y específica (78 por ciento, 78 por ciento, 76 por ciento) en la detección de síndrome metabólico, alteraciones cardiovasculares y aterogénicas respectivamente. Los valores predictivos muestran la probabilidad del 81 por ciento de tener síndrome metabólico si el individuo cuenta con un Índice cintura-talla elevado y una probabilidad 90 por ciento de no tener síndrome metabólico si el Índice cintura-talla es normal. Conclusiones: la precisión diagnóstica del Índice cintura-talla es muy elevada, por lo que puede usarse como un tamiz diagnóstico de síndrome metabólico o de alteraciones metabólicas en adultos jóvenes aparentemente sanos(AU)

Introduction: The presence of metabolic syndrome (MS) and cadiovascular disease (CVD) is physiopathologically linked to overweight and obesity. Objective: Evaluate the usefulness and accuracy of the waist-length index (CTI) in the assessment of risk and diagnosis of the metabolic syndrome and other cardiometabolic disorders. Methods: Apparently healthy young adults were evaluated for their implementation as a diagnostic test or screening routine at the primary levels of health care. A cross-sectional study was conducted with a sample of 369 young adults aged 18-22 years of the first year of the medical degree at the Benemérita Autonomous University of Puebla (BUAP). Biochemical and anthropometric parameters were determined for the presence of metabolic syndrome and other cardiovascular alterations, the waist-height index was calculated and quartiles were generated to propose a cut-off point with which the risk and diagnostic utility could be assessed. Results: The waist-height index showed to be a very sensitive (91 percent, 70 percent and 52 percent) and specific (78 percent, 76 percent) diagnostic test in the detection of metabolic syndrome, cardiovascular and atherogenic alterations, respectively. The predictive values showed 81 percent probability of having metabolic syndrome if the subject has a high waist-height index and 90 percent chance of not having metabolic syndrome if the waist-height index is normal. Conclusions: The diagnostic accuracy of the waist-length index is very high, so it can be used as a diagnostic screen for metabolic syndrome or metabolic alterations in apparently healthy young adults(AU)

Índice cintura-talla: prueba para valoración de riesgo cardiovascular y diagnóstico del síndrome metabólico / Waist-Length Index: Test for Cardiovascular Risk Assessment and Diagnosis of Metabolic Syndrome

Introducción: la presencia de síndrome metabólico y enfermedad cardiovascular está vinculada fisiopatológicamente con el sobrepeso y obesidad. Objetivo: evaluar la utilidad y precisión del Índice cintura-talla en la valoración de riesgo y diagnóstico del síndrome metabólico y otras alteraciones cardiometabólicas. Métodos: se evaluaron a adultos jóvenes aparentemente sanos para su implementación como una prueba diagnóstica o tamiz diagnóstico de rutina en los niveles primarios de atención en salud. Se realizó un estudio transversal con una muestra de 369 adultos jóvenes con edad de 18-22 años del primer año de la licenciatura de medicina en la Benemérita Universidad Autónoma de Puebla. Se determinaron parámetros bioquímicos y antropométricos para la presencia de síndrome metabólico y otras alteraciones cardiovasculares, se calculó el Índice cintura-talla y se generaron cuartiles para proponer un punto de corte con el cual se pueda valorar el riesgo y la utilidad diagnóstica. Resultados: el Índice cintura-talla mostró ser una prueba diagnóstica bastante sensible (91 por ciento, 70 por ciento y 52 por ciento) y específica (78 por ciento, 78 por ciento, 76 por ciento) en la detección de síndrome metabólico, alteraciones cardiovasculares y aterogénicas respectivamente. Los valores predictivos muestran la probabilidad del 81 por ciento de tener síndrome metabólico si el individuo cuenta con un Índice cintura-talla elevado y una probabilidad 90 por ciento de no tener síndrome metabólico si el Índice cintura-talla es normal. Conclusiones: la precisión diagnóstica del Índice cintura-talla es muy elevada, por lo que puede usarse como un tamiz diagnóstico de síndrome metabólico o de alteraciones metabólicas en adultos jóvenes aparentemente sanos(AU)

Introduction: The presence of metabolic syndrome (MS) and cadiovascular disease (CVD) is physiopathologically linked to overweight and obesity. Objective: Evaluate the usefulness and accuracy of the waist-length index (CTI) in the assessment of risk and diagnosis of the metabolic syndrome and other cardiometabolic disorders. Methods: Apparently healthy young adults were evaluated for their implementation as a diagnostic test or screening routine at the primary levels of health care. A cross-sectional study was conducted with a sample of 369 young adults aged 18-22 years of the first year of the medical degree at the Benemérita Autonomous University of Puebla (BUAP). Biochemical and anthropometric parameters were determined for the presence of metabolic syndrome and other cardiovascular alterations, the waist-height index was calculated and quartiles were generated to propose a cut-off point with which the risk and diagnostic utility could be assessed. Results: The waist-height index showed to be a very sensitive (91 percent, 70 percent and 52 percent) and specific (78 percent, 76 percent) diagnostic test in the detection of metabolic syndrome, cardiovascular and atherogenic alterations, respectively. The predictive values showed 81 percent probability of having metabolic syndrome if the subject has a high waist-height index and 90 percent chance of not having metabolic syndrome if the waist-height index is normal. Conclusions: The diagnostic accuracy of the waist-length index is very high, so it can be used as a diagnostic screen for metabolic syndrome or metabolic alterations in apparently healthy young adults(AU)

Use of magnesium sulfate for treatment of pre-eclampsia and eclampsia in Mexico.

OBJECTIVE: To establish a baseline of magnesium sulfate utilization prior to publication of the updated 2006 technical guidelines on pre-eclampsia and eclampsia in Mexico, and to examine barriers to treating pregnant women with magnesium sulfate as perceived by maternal health experts. METHODS: In collaboration with the Federal Ministry of Health, medical charts were reviewed for 87 maternal deaths due to hypertensive disorders that occurred in Mexico in 2005. Evidence was gathered on whether magnesium sulfate had been indicated or administered. In-depth interviews with experts were conducted to identify barriers to treatment utilization. RESULTS: Magnesium sulfate had been used in 37.5% of severe pre-eclampsia and 47.7% of eclampsia cases. Thematic analysis of expert interview data revealed 4 primary barriers to the implementation of evidence-based guidelines and use of magnesium sulfate: lack of knowledge of magnesium sulfate, lack of acceptance, drug-related barriers, and insufficient monitoring or supervision. It was found that magnesium sulfate was not the treatment used for Mexican women who died of pregnancy-related hypertensive disorders in public facilities, and there was suboptimal implementation of evidence-based practices and official guidelines. CONCLUSION: The results highlight barriers to magnesium sulfate use, which constitutes a significant gap in treating women with eclampsia in Mexico.

Changing climate and endangered high mountain ecosystems in Colombia.

High mountain ecosystems are among the most sensitive environments to changes in climatic conditions occurring on global, regional and local scales. The article describes the changing conditions observed over recent years in the high mountain basin of the Claro River, on the west flank of the Colombian Andean Central mountain range. Local ground truth data gathered at 4150 m, regional data available at nearby weather stations, and satellite info were used to analyze changes in the mean and the variance, and significant trends in climatic time series. Records included minimum, mean and maximum temperatures, relative humidity, rainfall, sunshine, and cloud characteristics. In high levels, minimum and maximum temperatures during the coldest days increased at a rate of about 0.6 degrees C/decade, whereas maximum temperatures during the warmest days increased at a rate of about 1.3 degrees C/decade. Rates of increase in maximum, mean and minimum diurnal temperature range reached 0.6, 0.7, and 0.5 degrees C/decade. Maximum, mean and minimum relative humidity records showed reductions of about 1.8, 3.9 and 6.6%/decade. The total number of sunny days per month increased in almost 2.1 days. The headwaters exhibited no changes in rainfall totals, but evidenced an increased occurrence of unusually heavy rainfall events. Reductions in the amount of all cloud types over the area reached 1.9%/decade. In low levels changes in mean monthly temperatures and monthly rainfall totals exceeded + 0.2 degrees C and - 4% per decade, respectively. These striking changes might have contributed to the retreat of glacier icecaps and to the disappearance of high altitude water bodies, as well as to the occurrence and rapid spread of natural and man-induced forest fires. Significant reductions in water supply, important disruptions of the integrity of high mountain ecosystems, and dramatic losses of biodiversity are now a steady menu of the severe climatic conditions experienced by these fragile tropical environments.