Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure.

BACKGROUND AND OBJECTIVE: Adequate serum phosphorus levels in patients with chronic kidney disease is essential for their clinical management. However, the control of hyperphosphatemia is difficult because is normally associated with increases in serum PTH. In the present study, the effects of hyperphosphatemia, in the presence of elevated and normal PTH, on cardiac inflammation, hypertrophy and fibrosis in an experimental renal failure model were analyzed. MATERIALS AND METHODS: 4 groups of rats were formed. Two groups underwent total parathyroidectomy (PTx). Rats with Ca <7.5 mg/dL and PTH < 50 pg/mL underwent 7/8 nephrectomy (CRF) and a subcutaneous pellet was placed that releases PTH 1-34 (5 µg/kg/day). One group received a diet with normal P (NP) (CRF + PTx + rPTH + NP group) and another with a high P diet (0.9% - HP) (CRF + PTx + rPTH + HP group). Other 2 groups that only had CRF received NP (CRF + NP) and HP (CRF + HP) diet. A SHAM group for nephrectomy and parathyroidectomy was also added. After 14 weeks the rats were sacrificed. RESULTS: The groups with a diet high in phosphorus (CRF + H A and CRF + PTx + rPTH + HP) had a significant reduction in creatinine clearance and also in body weight with an increase in serum phosphorus regardless of parathyroidectomy, but not serum levels of calcium, FGF23 and calcitriol that were 2-3 times higher in the group with secondary hyperparathyroidism (CRF + HP). The diameter of the cardiomyocytes was greater in the CRF + HP group, while parathyroidectomy (CRF + PTx + rPTH + HP) significantly reduced them, despite the high and similar serum phosphorus values. TNF-α, Adam17 and cardiac fibrosis at the histological and molecular level showed a similar pattern with increases in the group with severe secondary hyperparathyroidism (CRF + HP). CONCLUSIONS: Hyperphosphatemia confirmed its importance in the genesis of secondary hyperparathyroidism, but also of kidney damage that was independent of PTH levels. However, inflammation, fibrosis, and cardiomyocyte growth were more closely related to PTH levels, since in the presence of similar severe hyperphosphatemia, parathyroidectomy reduced the values ​​of inflammatory parameters, cardiac hypertrophy, and fibrosis.

Distinguishing the region-of-origin of roasted coffee beans with trace element ratios.

Determining coffee region-of-origin is most appropriately addressed through analyses of the product available to the consumer. We analyzed the concentrations of 44 trace elements in 53 samples of roasted Arabica coffee beans (Coffea arabica) from 21 different countries. Variations in absolute elemental concentrations of coffee beans arise through varying degrees of roasting (from green through dark roasts). Since trace elements are not volatilized at roasting temperatures, we conducted analyses of element ratios to evaluate concentration-related differences among beans of different origins. We used kernel density estimates to compare the distributions of 1892 element ratios for each of these countries with the combined distribution of coffee samples from the other countries. Using this quantitative approach, we demonstrated that many of the world's coffee-producing regions can be distinguished from other regions of the world on the basis of element ratios.

Single- versus double-injection costoclavicular block: a randomized comparison.

BACKGROUND: The costoclavicular approach targets the brachial plexus in the proximal infraclavicular fossa, where the lateral, medial, and posterior cords are tightly bundled together. This randomized trial compared single- and double-injection ultrasound-guided costoclavicular blocks. We selected onset time as the primary outcome and hypothesized that, compared with its single-injection counterpart, the double-injection technique would result in a swifter onset. METHODS: Ninety patients undergoing upper limb surgery (at or below the elbow joint) were randomly allocated to receive a single- (n=45) or double-injection (n=45) ultrasound-guided costoclavicular block. The local anesthetic agent (35 mL of lidocaine 1%-bupivacaine 0.25%with epinephrine 5 µg/mL and 2 mg of preservative-free dexamethasone) was identical in all subjects. In the single-injection group, the entire volume of local anesthetic was injected between the three cords of the brachial plexus. In the double-injection group, the first half of the volume was administered in this location; the second half was deposited between the medial cord and the subclavian artery. After the performance of the block, a blinded observer recorded the onset time (defined as the time required to achieve a minimal sensorimotor composite score of 14 out of 16 points), success rate (surgical anesthesia) and block-related pain scores. Performance time and the number of needle passes were also recorded during the performance of the block. The total anesthesia-related time was defined as the sum of the performance and onset times. RESULTS: Compared with its single-injection counterpart, the double-injection technique displayed shorter onset time (16.6 (6.4) vs 23.4 (6.9) min; p<0.001; 95% CI for difference 3.9 to 9.7) and total anesthesia-related time (22.5 (6.7) vs 28.9 (7.6) min; p<0.001). No intergroup differences were found in terms of success and technical execution (ie, performance time/procedural pain). The double-injection group required more needle passes than the single-injection group (2 (1-4) vs 1 (1-3); p<0.001). CONCLUSION: Compared with its single-injection counterpart, double-injection costoclavicular block results in shorter onset and total anesthesia-related times. Further investigation is required to determine if a triple-injection technique (with targeted local anesthetic injection around each cord of the brachial plexus) could further decrease the onset time. TRIAL REGISTRATION NUMBER: NCT03595514.

The use of a binary chelate formulation: Could gadolinium based linear contrast agents be rescued by the addition of zinc selective chelates?

Tissue and bone retention of gadolinium based contrast agents (GBCAs) has become a clinical concern because of the potential short and long term toxic effects of free gadolinium. This is a critical problem for most open-chain agents that more readily transmetallate in vivo, in comparison to macrocyclic compounds. Gadolinium diethylene tri-aminepentaacetic acid bis-glucosamide (Gd-DTPA-BIGA) is an experimental, open-chain contrast agent which has a significantly increased relaxivity coefficient in comparison to other GBCAs. This results in greater signal intensity and improved contrast enhancement. These superior imaging qualities initiated a search for a solution to the transmetallation of this agent. Plasma zinc is a well-known GBCA transmettalation agent. Since the base chelate of Gadodiamide (Gd-DPTA-Bis-Methylamide or Omniscan), DTPA-Bis-Methylamide (DTPA-BMA), readily transmettalates with and binds serum zinc, we hypothesized that a plasma "zinc sink," may significantly reduce transmetallation of linear agents. 5% DTPA-BMA was added to a formulation of Gd-DTPA-BIGA, which was tested against the original formulation of Gd-DTPA-BIGA with 0.2% of the base chelate DTPA-BIGA. These formulations, including gadodiamide, were labeled with 153GdCl3 followed by infusion into cohorts of Sprague Dawley rats which were sacrificed at 1, 30 and 60 days. Internal organs were harvested, along with blood, skin and femur, and analyzed for residual gadolinium. A subset of tissues were also interrogated with ICP-MS. Labeled Gadodiamide and saline where used as controls. Conclusion: The addition of 5% DTPA-BMA, as a zinc binding agent, reduced the transmetallation of the linear agent Gd-DTPA-BIGA, in comparison to its original formulation supplemented with 0.2% BIGA. This result indicates that supplementing linear GBCAs with ancillary chelates may hold promise for reducing, or eliminating the biological archiving of gadolinium in tissues. In addition, this paper provides valuable animal data on the long term retention of gadolinium from linear based contrast agents.

Light Affects Mood and Learning through Distinct Retina-Brain Pathways.

Light exerts a range of powerful biological effects beyond image vision, including mood and learning regulation. While the source of photic information affecting mood and cognitive functions is well established, viz. intrinsically photosensitive retinal ganglion cells (ipRGCs), the central mediators are unknown. Here, we reveal that the direct effects of light on learning and mood utilize distinct ipRGC output streams. ipRGCs that project to the suprachiasmatic nucleus (SCN) mediate the effects of light on learning, independently of the SCN's pacemaker function. Mood regulation by light, on the other hand, requires an SCN-independent pathway linking ipRGCs to a previously unrecognized thalamic region, termed perihabenular nucleus (PHb). The PHb is integrated in a distinctive circuitry with mood-regulating centers and is both necessary and sufficient for driving the effects of light on affective behavior. Together, these results provide new insights into the neural basis required for light to influence mood and learning.

Proceso INFORNUT®; mejora de la accesibilidad del paciente hospitalizado desnutrido a su diagnóstico y soporte nutricional; repercusión en indicadores de gestión; dos años de evaluación / Infornut® process; improves accessibility to diagnosis and nutritional support for the malnourished hospitalized patient; impact on management indicators; two-year assessment

Introducción: La alta prevalencia de desnutrición hospitalaria relacionada con la enfermedad justifica la necesidad de herramientas de cribado y detección precoz de los pacientes en riesgo de desnutrición, seguido de una valoración encaminada a su diagnóstico y tratamiento. Existe asimismo una manifiesta infracodificación de los diagnósticos de desnutrición y los procedimientos para revertirla. Objetivos: Describir el programa/proceso INFORNUT® y su desarrollo como sistema de información. Cuantificar el rendimiento en sus diferentes fases. Citar otras herramientas utilizadas como fuente de codificación. Calcular las tasas de codificación de diagnósticos de desnutrición y procedimientos relacionados. Mostrar su relación con Estancia Media, Tasas de Mortalidad y Reingreso urgente; así como cuantificar su impacto en el Índice de Complejidad hospitalario y su efecto en justificación de Costes de Hospitalización. Material y métodos: El proceso INFORNUT® se basa en un programa de cribado automatizado de detección sistemática e identificación precoz de pacientes desnutridos al ingreso hospitalario, así como de su valoración, diagnóstico, documentación e informe. Sobre el total de ingresos con estancias mayores de tres días habidos en los años 2008 y 2010, se contabilizaron pacientes objeto de cribado analítico con alerta de riesgo medio o alto de desnutrición, así como el subgrupo de pacientes a los que se les pudo completar en su totalidad el proceso INFORNUT® llegando al informe por paciente. Se citan otras fuentes documentales de codificación. Del Conjunto Mínimo de la Base de Datos se analizaron los códigos definidos en consenso SENPE-SEDOM. Los datos se procesaron con el programa Alcor-GRD. Se calcularon las tasas en % altas dadas para los años 2009 y 2010 de diagnósticos de desnutrición, procedimientos y diagnósticos asociados a procedimientos. Se compararon dichas tasas con las tasas medias de la comunidad andaluza. Se estimó la contribución de dichos códigos en el Índice de Complejidad y, a partir de los datos de contabilidad analítica, se estimó la fracción del coste de hospitalización que se ve justificada por esta actividad. Resultados: Resumimos aquí un resultado para ambos años estudiados. En cuanto al rendimiento del proceso, más de 3.600 pacientes por año (30% de los ingresos con estancia > 3 días) fueron objeto de cribado analítico. La mitad de ellos resultaron de riesgo medio o alto, de los cuales al 55 % se les completó una valoración nutricional mediante INFORNUT®, obteniéndose unos 1.000 informes/año. Nuestras tasas de codificación superaron a las tasas medias de Andalucía, siendo 3,5 veces superior en diagnósticos (35 %); 2,5 veces en procedimientos (50 %) y quintuplicando la tasa de diagnósticos asociados a procedimientos en el mismo paciente (25 %). La Estancia Media de los pacientes codificados al alta de desnutrición fue de 31,7 días, frente a los 9,5 de global hospitalaria. La Tasa de Mortalidad para los mismos (21,8 %) fue casi cinco veces superior a la media y la de Reingresos «urgentes» (5,5 %) resultó 1,9 veces superior. El impacto de dicha codificación en el Índice de Complejidad hospitalario fue de cuatro centésimas (de 2,08 a 2,12 en 2009 y de 2,15 a 2,19 en 2010). Esto se traduce en una justificación de costes de hospitalización por 2.000.000 euros; cinco a seis veces el coste de la nutrición artificial. Conclusiones: El proceso ha facilitado el acceso al diagnóstico de la desnutrición o al conocimiento del riesgo de padecerla, así como a la prescripción de los procedimientos y/o suplementos para remediarla. La coordinación interdisciplinar del equipo, lo participativo del proceso y las herramientas utilizadas mejoran las tasas de codificación hasta resultados muy por encima de la media andaluza. Estos resultados contribuyen a ajustar al alza el IC hospitalario, así como a la justificación de costes de hospitalización (AU)

Introduction: The high prevalence of disease-related hospital malnutrition justifies the need for screening tools and early detection in patients at risk for malnutrition, followed by an assessment targeted towards diagnosis and treatment. At the same time there is clear undercoding of malnutrition diagnoses and the procedures to correct it. Objectives: To describe the INFORNUT program/ process and its development as an information system. To quantify performance in its different phases. To cite other tools used as a coding source. To calculate the coding rates for malnutrition diagnoses and related procedures. To show the relationship to Mean Stay, Mortality Rate and Urgent Readmission; as well as to quantify its impact on the hospital Complexity Index and its effect on the justification of Hospitalization Costs. Material and methods: The INFORNUT® process is based on an automated screening program of systematic detection and early identification of malnourished patients on hospital admission, as well as their assessment, diagnoses, documentation and reporting. Of total readmissions with stays longer than three days incurred in 2008 and 2010, we recorded patients who underwent analytical screening with an alert for a medium or high risk of malnutrition, as well as the subgroup of patients in whom we were able to administer the complete INFORNUT® process, generating a report for each. Other documentary coding sources are cited. From the Minimum Basic Data Set, codes defined in the SEDOM-SENPE consensus were analyzed. The data were processed with the Alcor-DRG program. Rates in % of discharges for 2009 and 2010 of diagnoses of malnutrition, procedure and procedures-related diagnoses were calculated. These rates were compared with the mean rates in Andalusia. The contribution of these codes to the Complexity Index was estimated and, from the cost accounting data, the fraction of the hospitalization cost seen as justified by this activity was estimated. Results: Results are summarized for both study years. With respect to process performance, more than 3,600 patients per year (30% of admissions with a stay > 3 days) underwent analytical screening. Half of these patients were at medium or high risk and a nutritional assessment using INFORNUT® was completed for 55% of them, generating approximately 1,000 reports/year. Our coding rates exceeded the mean rates in Andalusia, being 3.5 times higher for diagnoses (35%); 2.5 times higher for procedures (50%) and five times the rate of procedure-related diagnoses in the same patient (25%). The Mean Stay of patients coded with malnutrition at discharge was 31.7 days, compared to 9.5 for the overall hospital stay. The Mortality Rate for the same patients (21.8%) was almost five times higher than the mean and Urgent Readmissions (5.5%) were 1.9 times higher. The impact of this coding on the hospital Complexity Index was four hundredths (from 2.08 to 2.12 in 2009 and 2.15 to 2.19 in 2010). This translates into a hospitalization cost justification of 2,000,000 euros; five to six times the cost of artificial nutrition. Conclusions: The process facilitated access to the diagnosis of malnutrition and to understanding the risk of developing it, as well as to the prescription of procedures and/or supplements to correct it. The interdisciplinary team coordination, the participatory process and the tools used improved coding rates to give results far above the Andalusian mean. These results help to upwardly adjust the hospital Complexity Index or Case Mix-, as well as to explain hospitalization costs (AU)

[Contribution of the new oral anticoagulants to the treatment of acute coronary syndrome]. / Aportación de los nuevos anticoagulantes orales al tratamiento del síndrome coronario agudo.

Acute coronary syndrome (ACS) occurs as a result of atherosclerotic plaque rupture and subsequent platelet activation and coagulation leading to thrombus formation and coronary occlusion. Thrombin and activated factor X (FXa) are key elements in the coagulation cascade. The use of anticoagulants in ACS, both in the acute phase and in the long term, has improved prognosis by reducing thrombotic events, but is associated with an increased risk of bleeding. In recent years, new oral anticoagulants have been developed that do not require monitoring and produce a lower risk of bleeding. Rivaroxaban is the only drug with a favorable risk-benefit profile in patients with ACS. The ATLAS ACS TIMI 2-51 is the first phase III trial demonstrating that the addition of low-dose rivaroxaban to optimal antiplatelet therapy reduces mortality, cardiovascular mortality, infarct or stroke without significantly increasing fatal bleeding.