Dietary modulation of gut microbiota in patients with colorectal cancer undergoing surgery: A review.

Colorectal cancer (CRC) is the third most frequent malignancy and the second cause of cancer death worldwide. Several factors have been postulated to be involved in CRC pathophysiology, including physical inactivity, unhealthy dietary habits, obesity, and the gut microbiota. Emerging data suggest that the microbiome may play a key role in CRC prognosis and derived complications in patients undergoing colorectal surgery. On the other hand, dietary intervention has been demonstrated to be able to induce significant changes in the gut microbiota and related metabolites in different conditions; therefore, the manipulation of gut microbiota through dietary intervention may constitute a useful approach to improve perioperative dysbiosis and post-surgical outcomes in patients with CRC. In this article, we review the role of the gut microbiota in CRC surgery complications and the potential therapeutic modulation of gut microbiome through nutritional intervention in patients with CRC undergoing surgery.

Spirulina extract improves age-induced vascular dysfunction.

CONTEXT: Vascular dysfunction is considered a hallmark of ageing that has been associated with altered vasomotor responses, in which nitric oxide (NO) and reactive oxygen species participate. The consumption of Spirulina extracts, with antioxidant properties, increased recently. OBJECTIVE: This study investigates the effect of Spirulina aqueous extract (SAE) on the vascular function of the aorta from aged rats. MATERIALS AND METHODS: Aortic segments from aged male Sprague-Dawley rats (20-22 months old) were exposed to SAE (0.1% w/v, for 3 h) to analyse: (i) the vasodilator response induced by acetylcholine (ACh), by the NO donor sodium nitroprusside (SNP), by the carbon monoxide releasing molecule (CORM) and by the KATP channel opener, cromakalim (CK); (ii) the vasoconstrictor response induced by KCl and noradrenaline (NA); (iii) the production of NO and superoxide anion, and (iv) the expression of the p-eNOS and HO-1 proteins. RESULTS: Incubation with SAE increased the expression of p-eNOS (1.6-fold) and HO-1 (2.0-fold), enhanced NO release (1.4-fold in basal and 1.9-fold in ACh-stimulated conditions) while decreased the production of superoxide (0.7-fold). SAE also increased the sensitivity (measured as pEC50) to ACh (control: -7.06 ± 0.11; SAE: -8.16 ± 0.21), SNP (control: -7.96 ± 0.16; SAE: -9.11 ± 0.14) and CK (control: -7.05 ± 0.39; SAE: -8.29 ± 0.53), and potentiated the response to KCl (1.3-fold) and to NA (1.7-fold). CONCLUSION: The antioxidant properties of SAE improved the vasomotor responses of aorta from aged rats. These results may support the use of Spirulina as a protection against vascular dysfunction.

Effect of CLA supplementation on factors related to vascular dysfunction in arteries of orchidectomized rats.

The vascular endothelium is a monolayer of flat epithelial cells located between the circulating blood and the underlying connective tissue. It conveys key functions that when impaired, lead to endothelial dysfunction. This condition is responsible for the pathogenesis of vascular diseases. The cardioprotective effect of sex hormones is widely known; hence, a murine orchidectomized model has been employed to study the effects caused by their deficiency. In the search for approaches to maintain vascular health, the effect of dietary fatty acids as CLA on cardiovascular diseases has been studied. Some proven beneficial properties of CLA are antioxidant, antiatherogenic and anti-inflammatory. Our objective was to evaluate the effect of a diet supplemented with 1.8 % (w/w) of CLA, administered during eight weeks, on the amount of cholesterol oxidation products (COPs) produced by orchidectomy and on factors related to vascular dysfunction in the aorta and the mesenteric arteries. The diet with CLA prevented the increase in prostanoids formation and maintained the normal physiological conditions of NO and antioxidant activity. In addition, it prevented the increase in cholesterol and COPs at the vascular wall. CLA-supplemented diet prevented the orchidectomy-induced alterations on prostanoids, NO and COPs and also improved the antioxidant activity. These findings could contribute to understand the mechanisms of actions of CLA involved in the prevention of cardiovascular diseases.

Long-term antibiotic therapy in patients with surgery-indicated not undergoing surgery infective endocarditis.

BACKGROUND: To date, there is little information regarding management of patients with infective endocarditis (IE) that did not undergo an indicated surgery. Therefore, we aimed to evaluate prognosis of these patients treated with a long-term antibiotic treatment strategy, including oral long term suppressive antibiotic treatment in five referral centres with a multidisciplinary endocarditis team. METHODS: This retrospective, multicenter study retrieved individual patient-level data from five referral centres in Spain. Among a total of 1797, 32 consecutive patients with IE were examined (median age 72 years; 78% males) who had not undergone an indicated surgery, but received long-term antibiotic treatment (LTAT) and were followed by a multidisciplinary endocarditis team, between 2011 and 2019. Primary outcomes were infection relapse and mortality during follow-up. RESULTS: Among 32 patients, 21 had IE associated with prostheses. Of the latter, 8 had an ascending aorta prosthetic graft. In 24 patients, a switch to long-term oral suppressive antibiotic treatment (LOSAT) was considered. The median duration of LOSAT was 277 days. Four patients experienced a relapse during follow-up. One patient died within 60 days, and 12 patients died between 60 days and 3 years. However, only 4 deaths were related to IE. CONCLUSIONS: The present study results suggest that a LTAT strategy, including LOSAT, might be considered for patients with IE that cannot undergo an indicated surgery. After hospitalization, they should be followed by a multidisciplinary endocarditis team.

Androgen Deprivation Therapy in Patients With Prostate Cancer Increases Serum Levels of Thromboxane A2: Cardiovascular Implications.

Introduction: Androgens have been described as important players in the regulation of vascular function/structure through their action on the release and effect of vasoactive factors, such as prostanoids. Patients with prostate cancer (PCa) under androgen deprivation therapies (ADTs) present increased risk of cardiovascular mortality. Since thromboxane A2 (TXA2) is one of the most studied prostanoids and its involvement in different cardiovascular diseases has been described, the aim of this study was to investigate: (i) the effect of ADT on the serum levels of TXA2 in PCa patients and its possible link to the redox status and (ii) the effect of the non-hydrolyzable TXA2 analog U-46619 on the function of the aorta of male rats. Methods: The levels of TXA2 and total antioxidant status in 50 healthy subjects, 54 PCa patients, and 57 PCa under ADT were evaluated. These determinations were accompanied by levels of testosterone and C-reactive protein as an inflammation marker. In aortic segments from male rats, the U46619-induced effects on: (i) the vasomotor responses to acetylcholine (ACh), to the NO donor sodium nitroprusside (SNP), to the carbon monoxide-releasing molecule-3 (CORM-3), and to noradrenaline (NA) and (ii) the expression of cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), and phosphorylated ERK1/2 were analyzed. Results: The serum level of TXA2 in patients with PCa was increased with respect to healthy subjects, which was further increased by ADT. There was no modification in the total antioxidant status among the three experimental groups. In aortic segments from male rats, the TXA2 analog decreased the endothelium-dependent relaxation and the sensitivity of smooth muscle cells to NO, while it increased the vasoconstriction induced by NA; the expression of COX-2, HO-1, and pERK1/2 was also increased. Conclusions: ADT increased, along with other inflammatory/oxidative markers, the serum levels of TXA2. The fact that TXA2 negatively impacts the vascular function of the aorta of healthy male rats suggests that inhibition of TXA2-mediated events could be considered a potential strategy to protect the cardiovascular system.

Vasomotor action of androgens in the mesenteric artery of hypertensive rats. Role of perivascular innervation.

Androgens may exert cardiovascular protective actions by regulating the release and function of different vascular factors. In addition, testosterone (TES) and its 5-reduced metabolites, 5α- and 5ß-dihydrotestosterone (5α- and 5ß-DHT) induce vasorelaxant and hypotensive effects. Furthermore, hypertension has been reported to alter the release and function of the neurotransmitters nitric oxide (NO), calcitonin gene-related peptide (CGRP) and noradrenaline (NA). Since the mesenteric arteries possess a dense perivascular innervation and significantly regulate total peripheral vascular resistance, the objective of this study was to analyze the effect of TES, 5α- and 5ß-DHT on the neurogenic release and vasomotor function of NO, CGRP and NA. For this purpose, the superior mesenteric artery from male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to analyze: (i) the effect of androgens (10 nM, incubated for 30 min) on the neurogenic release of NO, CGRP and NA and (ii) the vasoconstrictor-response to NA and the vasodilator responses to the NO donor, sodium nitroprusside (SNP) and exogenous CGRP. The results showed that TES, 5α- or 5ß-DHT did not modify the release of NO, CGRP or NA induced by electrical field stimulation (EFS) in the arteries of SHR; however, in the arteries of WKY rats androgens only caused an increase in EFS-induced NO release. Moreover, TES, and especially 5ß-DHT, increased the vasodilator response induced by SNP and CGRP in the arteries of SHR. These findings could be contributing to the hypotensive/antihypertensive efficacy of 5ß-DHT previously described in conscious SHR and WKY rats, pointing to 5ß- DHT as a potential drug for the treatment of hypertension.

Defining persistent Staphylococcus aureus bacteraemia: secondary analysis of a prospective cohort study.

BACKGROUND: Staphylococcus aureus persistent bacteraemia is only vaguely defined and the effect of different durations of bacteraemia on mortality is not well established. Our primary aim was to analyse mortality according to duration of bacteraemia and to derive a clinically relevant definition for persistent bacteraemia. METHODS: We did a secondary analysis of a prospective observational cohort study at 17 European centres (nine in the UK, six in Spain, and two in Germany), with recruitment between Jan 1, 2013, and April 30, 2015. Adult patients who were consecutively hospitalised with monomicrobial S aureus bacteraemia were included. Patients were excluded if no follow-up blood culture was taken, if the first follow-up blood-culture was after 7 days, or if active antibiotic therapy was started more than 3 days after first blood culture. The primary outcome was 90-day mortality. Univariable and time-dependent multivariable Cox regression analysis were used to assess predictors of mortality. Duration of bacteraemia was defined as bacteraemic days under active antibiotic therapy counting the first day as day 1. FINDINGS: Of 1588 individuals assessed for eligibility, 987 were included (median age 65 years [IQR 51-75]; 625 [63%] male). Death within 90 days occurred in 273 (28%) patients. Patients with more than 1 day of bacteraemia (315 [32%]) had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture. Crude 90-day mortality increased from 22% (148 of 672) with 1 day of bacteraemia, to 39% (85 of 218) with 2-4 days, 43% (30 of 69) with 5-7 days, and 36% (10 of 28) with more than 7 days of bacteraemia. Metastatic infections developed in 39 (6%) of 672 patients with 1 day of bacteraemia versus 40 (13%) of 315 patients if bacteraemia lasted for at least 2 days. The second day of bacteraemia had the highest HR and earliest cutoff significantly associated with mortality (adjusted hazard ratio 1·93, 95% CI 1·51-2·46; p<0·0001). INTERPRETATION: We suggest redefining the cutoff duration for persistent bacteraemia as 2 days or more despite active antibiotic therapy. Our results favour follow-up blood cultures after 24 h for early identification of all patients with increased risk of death and metastatic infection. FUNDING: None.

RISK FACTORS FOR HYPOGLYCEMIA IN INPATIENTS WITH TOTAL PARENTERAL NUTRITION AND TYPE 2 DIABETES: A POST HOC ANALYSIS OF THE INSUPAR STUDY.

Objective: Treatment of hyperglycemia with insulin is associated with increased risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients receiving total parenteral nutrition (TPN). The aim of this study was to determine the predictors of hypoglycemia in hospitalized T2DM patients receiving TPN. Methods: Post hoc analysis of the INSUPAR study, which is a prospective, open-label, multicenter clinical trial of adult inpatients with T2DM in a noncritical setting with indication for TPN. Results: The study included 161 patients; 31 patients (19.3%) had hypoglycemic events, but none of them was severe. In univariate analysis, hypoglycemia was significantly associated with the presence of diabetes with end-organ damage, duration of diabetes, use of insulin prior to admission, glycemic variability (GV), belonging to the glargine insulin group in the INSUPAR trial, mean daily grams of lipids in TPN, mean insulin per 10 grams of carbohydrates, duration of TPN, and increase in urea during TPN. Multiple logistic regression analysis showed that the presence of diabetes with end-organ damage, GV, use of glargine insulin, and TPN duration were risk factors for hypoglycemia. Conclusion: The presence of T2DM with end-organ damage complications, longer TPN duration, belonging to the glargine insulin group, and greater GV are factors associated with the risk of hypoglycemia in diabetic noncritically ill inpatients with parenteral nutrition. Abbreviations: ADA = American Diabetes Association; BMI = body mass index; CV% = coefficient of variation; DM = diabetes mellitus; GI = glargine insulin; GV = glycemic variability; ICU = intensive care unit; RI = regular insulin; T2DM = type 2 diabetes mellitus; TPN = total parenteral nutrition.

Gonadal function protects against organ culture-induced vascular damage. Involvement of prostanoids.

Androgen deprivation induces vascular dysfunction in which altered release and action of prostanoids has been extensively studied. On the other hand, the vascular organ-culture system has been reported as a valid model for phenotypic changes that occur in several cardiovascular pathologies. Since there are no studies analyzing the impact of androgenic loss on vascular vulnerability during induced vascular damage, the objective of this study was to analyze the possible preventive role of male sex hormones on the organ culture-induced vascular damage in rat aorta. The link to possible changes in gross structure was also analyzed. For this purpose, fresh and 20 h-cultured aortic arterial segments from intact and orchidectomized rats were used to analyze: (i) the release and vasomotor effect of the thromboxane A2 (TXA2), prostaglandin (PG) E2, PGF2α and PGI2; (ii) the vasodilator response induced by acetylcholine (ACh) as well as the involvement of prostanoids, in particular TXA2, in the ACh-induced response; (iii) the effect of activation of thromboxane/prostaglandin (TP) receptors on the ACh-induced response; and (iv) the vascular structure. The results showed that organ culture: i) increased production of prostanoids; ii) increased prostanoids-induced vasomotor responses; iii) decreased ACh-induced relaxation after incubation with indomethacin, a blocker of cyclooxygenases; iv) increased the ACh-induced relaxation after incubation with the TXA2 synthase inhibitor, furegrelate, more in arteries from orchidectomized rats than in those of intact rats; v) diminished ACh-induced relaxation after U-46619 incubation only in arteries from orchidectomized rats; and vi) preserved the integrity of the different vascular layers. These results showed the protective role of male sex hormones against the induced vascular damage, since a decreased deleterious effect of prostanoids, in particular that of TXA2, was observed in arteries from rats with intact gonadal function.

Analysis of Quality of Life and Nutritional Status in Elderly Patients with Dysphagia in Order to Prevent Hospital Admissions in a COVID-19 Pandemic.

(1) Background: Oropharyngeal dysphagia (OD) is currently recognized as one of the geriatric syndromes due to its high frequency in older people and its associated complications, which have a direct impact on quality of life. The main objective is to determine the effectiveness of telehealth consultation for the re-evaluation of nutritional status and quality of life assessment in older people diagnosed with OD associated with active use of thickeners to prevent hospital admissions in a COVID-19 pandemic. (2) Methods: an observational, descriptive, and longitudinal study that included a sample of 33 subjects with age equal or superior to 65 years diagnosed with OD with conserved cognitive capacity. The nutritional status was evaluated through the Mini-Nutritional Assessment (MNA) questionnaire and biochemical parameters and, the quality of life was determined through the Swallowing Quality of Life (SWAL-QOL) questionnaire. (3) Results: Thirty-three older patients with OD were recruited (54.5% women), with a mean age of 83.5 ± 7.6 years. The main cause of OD in the study population was neurodegenerative disease (51.5%), followed by cerebrovascular disease (33.3%), and other causes (15.2%). Sixty point six percent of patients were found to be at risk of malnutrition. The MNA score was significantly correlated to albumin (r: 0.600, p < 0.001) and total proteins (r: 0.435, p = 0.015), but not to total cholesterol (r: -0.116, p = 0.534) or lymphocytes (r: -0.056, p = 0.758). The mean total score of the SWAL-QOL was 75.1 ± 16.4 points. (4) Conclusions: the quality of life of the subjects related to the use of a thickener is good. Although the body mass index (BMI) and average biochemical, nutritional parameters of the subjects are within the range of normality, the MNA has detected a high percentage of subjects with the risk of malnutrition, which suggests the need for continuous re-evaluation in these patients, demonstrating the viability of the telematic route in this research.

Beneficial Effects of Spirulina Aqueous Extract on Vasodilator Function of Arteries from Hypertensive Rats.

Hypertension is a multifactorial disorder considered one of the major causes of premature death worldwide. This pathology is associated with vascular functional/structural alterations in which nitric oxide (NO) and oxygen reactive species participate. On the other hand, the use of microalgae extracts in the treatment of cardiovascular diseases is increasing. Based on the antioxidant and antihypertensive properties of Spirulina, this study aims to investigate the effect of an aqueous extract of Spirulina on the vasodilator function of the aorta from spontaneously hypertensive rats (SHR), analyzing the functional role of NO. For this, aortic segments from male SHR were divided into two groups, one control and the other exposed to an Spirulina aqueous extract (0.1% w/v, for 3 hours), to analyze (i) the production of NO, superoxide anion, and hydrogen peroxide; (ii) the vasodilator response induced by acetylcholine (ACh), by the NO donor and sodium nitroprusside (SNP), and by the KATP channel opener and pinacidil; and (iii) the expression of the p-Akt, p-eNOS, and HO-1 proteins. The results showed that the aqueous Spirulina extract (i) increased the production of NO, did not significantly modify that of superoxide, while decreased that of hydrogen peroxide; (ii) increased the vasodilatory responses induced by ACh, NPS, and pinacidil; and (iii) increased the expression of p-Akt and HO-1. These results suggest that incubation with the aqueous Spirulina extract improves the vascular function of arteries from SHR by increasing the release/bioavailability/function of NO. Increased KATP channel activation and expression of pAkt and HO-1 appear to be participating in these actions.

Regular insulin added to total parenteral nutrition vs subcutaneous glargine in non-critically ill diabetic inpatients, a multicenter randomized clinical trial: INSUPAR trial.

BACKGROUND: There is no established insulin regimen in T2DM patients receiving parenteral nutrition. AIMS: To compare the effectiveness (metabolic control) and safety of two insulin regimens in patients with diabetes receiving TPN. DESIGN: Prospective, open-label, multicenter, clinical trial on adult inpatients with type 2 diabetes on a non-critical setting with indication for TPN. Patients were randomized on one of these two regimens: 100% of RI on TPN or 50% of Regular insulin added to TPN bag and 50% subcutaneous GI. Data were analyzed according to intention-to-treat principle. RESULTS: 81 patients were on RI and 80 on GI. No differences were observed in neither average total daily dose of insulin, programmed or correction, nor in capillary mean blood glucose during TPN infusion (165.3 ± 35.4 in RI vs 172.5 ± 43.6 mg/dL in GI; p = 0.25). Mean capillary glucose was significantly lower in the GI group within two days after TPN interruption (160.3 ± 45.1 in RI vs 141.7 ± 43.8 mg/dL in GI; p = 0.024). The percentage of capillary glucose above 180 mg/dL was similar in both groups. The rate of capillary glucose ≤70 mg/dL, the number of hypoglycemic episodes per 100 days of TPN, and the percentage of patients with non-severe hypoglycemia were significantly higher on GI group. No severe hypoglycemia was detected. No differences were observed in length of stay, infectious complications, or hospital mortality. CONCLUSION: Effectiveness of both regimens was similar. GI group achieved better metabolic control after TPN interruption but non-severe hypoglycemia rate was higher in the GI group. CLINICAL TRIAL REGISTRY: This trial is registered at clinicaltrials.gov as NCT02706119.

Nutrición enteral domiciliaria en el paciente con patología neurológica de un área de salud del sureste español / Home enteral nutrition in patients with neurological disease in an area of the southeast of Spain

Introducción: la desnutrición en el paciente neurológico presenta una alta prevalencia, aumentando las complicaciones y disminuyendo la calidad de vida. La nutrición artificial minimiza el riesgo de malnutrición. En los últimos años, en Murcia, se pone en marcha una vía clínica de adecuación a la Guía Nacional de Nutrición Enteral Domiciliaria (NED) para optimizar este recurso y reducir la variabilidad de prescripción. Objetivo: analizar las características de la NED en el paciente neurológico, de un área de salud de Murcia, antes y después de la adecuación a las directrices nacionales. Método: diseño observacional de corte transversal. Análisis y comparación de las muestras NED de adultos del Área 1 de salud de Murcia, en 2010 y 2014. Resultados: la patología más asociada a las prescripciones de NED fue la neurológica. La vía de administración más utilizada fue la oral, aunque desciende en la muestra de 2014 a favor de la sonda de nutrición y ostomía. El tipo de fórmula más usado en 2010 fue la no específica. Tras la vía clínica se reduce el uso de fórmulas específicas, disminuyendo especialmente las fórmulas hiperproteicas y/o hipercalóricas. Conclusiones: la implementación de una vía clínica de adecuación a la Guía Nacional NED ha provocado un cambio en la realidad de este tipo de nutrición artificial en el Área 1 de salud del Servicio Murciano de Salud, consiguiendo normalizar su uso bajo criterios unificados y profesionales especializados. Finalmente, estos logros se han generalizado a toda la región

Introduction: malnutrition in patients with neurological disease is very prevalent, worsening their complications and diminishing their quality of life. For that reason, nutritional support can provide a reduction in comorbidities. Over the past years, in Murcia (southeast of Spain), a clinical pathway has been stablished in accordance to the National Home Enteral Nutrition guide (HEN) to optimize this resource and reduce the prescription gap. Objective: to analyze the HEN characteristics in neurological patients in an area of Murcia, before and after the adequacy of the national recommendations. Method: observational cross-sectional study. Analysis and comparison of HEN in health area no. 1 in Murcia in 2010 and 2014. Results: the most prevalent cause for HEN was neurological disease. In 2010, oral nutrition was the most used way compared with 2014, when it had changed to enteral nutrition through feeding tube or ostomy. Non-specific formula was the most frequently used in 2010. However, after the establishment of the clinical pathway there was a reduction in specific enteral formula use, specially hypercaloric and hyperproteic. Conclusions: the implementation of a clinical pathway according to the National HEN guide has caused a change in the reality of artificial nutrition in health area no. 1 in Murcia (Spain), which means a standardization of its use under unified criteria made by specialized professionals. Finally, due to these results, this clinical pathway has been generalized to the rest of the region

Análisis de la vía clínica de nutrición enteral domiciliaria de la Región de Murcia. Consumo y gastos asociados y adecuación a la Guía del Sistema Nacional de Salud / Analysis of a clinical pathway for home enteral nutrition in the Region of Murcia. Consumption and associated expenses and adaptation to the National Health System Guide

Objetivo: Analizar la adecuación a la Guía de Nutrición Enteral Domiciliaria (NED) en el Sistema Nacional de Salud (SNS), de las prescripciones realizadas en el Área 1 de Salud de la Región de Murcia, antes y después de implementar una Vía Clínica basada en dicha guía; así como examinar la evolución del coste sanitario en los años 2007-2014 en los Sistemas Murciano y Nacional de Salud en producto dietoterápico. Método: Estudio descriptivo de cuantificación de criterios de adecuación a la Guía NED en el SNS. Se analizaron los principales criterios de adecuación en el año 2010 (antes de la implementación de la Vía Clínica) y en 2013-2014 (después). Finalmente, se analizó la evolución del gasto y consumo sanitario durante el período 2007-2014. Resultados: Tras la implementación de la Vía Clínica se observa una mejora del cumplimiento de todos los indicadores de adecuación a la Guía NED nacional. Además, la Región de Murcia se coloca en uno de los últimos lugares en gasto y consumo de envases por habitantes, por debajo de la media española. Conclusión: La Vía Clínica implementada mejora la adecuación, a la Guía NED nacional, de la prescripción en los pacientes subsidiarios de NED en la Región de Murcia, al igual que contiene el gasto y el consumo, haciendo más sostenible la indicación de este recurso nutricional

Objective: To analyze the compliance with the Guide for home enteral nutrition (HEN) of the Spanish national health system of the prescriptions made in a specific area (Health Area I of the Region of Murcia) before and after implementation of a clinical pathway based on that guide, and to compare the changes in healthcare costs of diet therapy during the 2007-2014 period in the Regional and National Health system. Method: A descriptive study to quantify compliance with the main criteria of the HEN guide before (2010) and after (2013-2014) implementation of the clinical pathway. Changes in health expenditure and consumption during the 2007-2014 period were also analyzed. Results: All markers of compliance with the national HEN guide improved after implementation of the clinical pathway. In addition, Murcia has one of the Spanish lowest expenditures per population, below the national average. Conclusion: The clinical pathway implemented improves compliance with the national guide of prescriptions to patients in the Region of Murcia while containing health resources expenditure and consumption, thus making diet therapy prescription more sustainable

Analysis of a clinical pathway for home enteral nutrition in the Region of Murcia. Consumption and associated expenses and adaptation to the National Health System Guide. / Análisis de la vía clínica de nutrición enteral domiciliaria de la Región de Murcia. Consumo y gastos asociados y adecuación a la Guía del Sistema Nacional de Salud.

OBJECTIVE: To analyze the compliance with the Guide for home enteral nutrition (HEN) of the Spanish national health system of the prescriptions made in a specific area (Health Area I of the Region of Murcia) before and after implementation of a clinical pathway based on that guide, and to compare the changes in healthcare costs of diet therapy during the 2007-2014 period in the Regional and National Health system. METHOD: A descriptive study to quantify compliance with the main criteria of the HEN guide before (2010) and after (2013-2014) implementation of the clinical pathway. Changes in health expenditure and consumption during the 2007-2014 period were also analyzed. RESULTS: All markers of compliance with the national HEN guide improved after implementation of the clinical pathway. In addition, Murcia has one of the Spanish lowest expenditures per population, below the national average. CONCLUSION: The clinical pathway implemented improves compliance with the national guide of prescriptions to patients in the Region of Murcia while containing health resources expenditure and consumption, thus making diet therapy prescription more sustainable.

Vasoactive androgens: Vasorelaxing effects and their potential regulation of blood pressure.

BACKGROUND: Testosterone, 5α- and 5ß-dihydrotestosterone (-DHT) induce an acute in vitro vasorelaxation and in vivo vasodepressor, hypotensive and antihypertensive responses. Our aim was to study whether androgen-induced blood pressure (BP) reduction is involved with a blockade of Ca2+ influx through L-type voltage-operated calcium channels (L-VOCCs) and/or the signaling pathways of α1-adrenoceptors to induce vasoconstriction, which are one of the major mechanisms of BP maintenance. MATERIALS AND METHODS: The relaxing potency and efficacy of each androgen in large conduit (thoracic aorta) and resistance (mesenteric) arteries from male hypertensive (SHR) and normotensive (WKY) rats were established. Blood vessels were isometrically recorded and precontracted with KCl or phenylephrine (Phe). RESULTS: Androgens induced concentration-dependent vasorelaxation in precontracted arteries from SHR and WKY rats. 5ß-DHT was always the most potent vasorelaxant in arteries from SHR. The KCl-induced contraction resulted significantly more sensitive to androgen-induced vasorelaxation than the Phe-induced contraction. On Phe-induced contraction, 5ß-DHT was more potent in the mesenteric artery than in the thoracic aorta. CONCLUSIONS: The vasorelaxation induced by androgens is mainly mediated by blocking L-VOCCs and in lesser extent by the blockade of multiple signaling pathways operative during α-adrenoceptor-induced vasoconstriction. 5ß-DHT regulates vascular resistance and BP by mainly acting in the mesenteric arterial bed, which may explain its outstanding antihypertensive response previously reported.

Defective p27 phosphorylation at serine 10 affects vascular reactivity and increases abdominal aortic aneurysm development via Cox-2 activation.

Phosphorylation at serine 10 (S10) is the major posttranslational modification of the tumor suppressor p27, and is reduced in both human and mouse atherosclerosis. Moreover, a lack of p27-phospho-S10 in apolipoprotein E-null mice (apoE-/-) leads to increased high-fat diet-induced atherosclerosis associated with endothelial dysfunction and augmented leukocyte recruitment. In this study, we analyzed whether p27-phospho-S10 modulates additional endothelial functions and associated pathologies. Defective p27-phospho-S10 increases COX-2 activity in mouse aortic endothelial cells without affecting other key regulators of vascular reactivity, reduces endothelium-dependent dilation, and increases arterial contractility. Lack of p27-phospho-S10 also elevates aortic COX-2 expression and thromboxane A2 production, increases aortic lumen diameter, and aggravates angiotensin II-induced abdominal aortic aneurysm development in apoE-/- mice. All these abnormal responses linked to defective p27-phospho-S10 are blunted by pharmacological inhibition of COX-2. These results demonstrate that defective p27-phospho-S10 modifies endothelial behavior and promotes aneurysm formation via COX-2 activation.

Patients' and professionals' preferences in terms of the attributes of home enteral nutrition products in Spain. A discrete choice experiment.

BACKGROUND/OBJECTIVES: To elicit and compare preferences in terms of the attributes of home enteral nutrition (HEN) among patients and physicians, using a discrete choice experiment (DCE). SUBJECTS/METHODS: A DCE comprising eight choice scenarios, with six HEN attributes (tolerability, adaptation to comorbidities, nutrition and calories, handling, connections and information; two levels each) was designed. The Relative Importance (RI) for patients and physicians of each attribute was estimated. Sociodemographic and clinical variables, as well as additional questions (n = 8) were compiled to analyze possible explanatory variables and other preferences. RESULTS: A total of 148 HEN patients (71 needing caregivers to answer on their behalf) and 114 physicians completed the DCE. The most important attributes for patients were adaptation to comorbidities (33% RI), tolerability (33% RI), and nutrition and calories (26% RI). Significantly, younger patients had stronger preferences for tolerability whereas elderly ones (≥75 years) were more concerned about handling. In comparison, physicians gave a higher RI to tolerability, and nutrition and calories compared to patients (p = 0.002). Overall, a higher percentage of physicians answered that HEN characteristics such as easy-handling bags (85.1 vs. 64.9%; p = 0.001), container material (69.3 vs. 57.1%; p = 0.003) or reusable containers (79.8 vs. 70.3%; p = 0.01) were "important" or "very important" compared to patients. CONCLUSIONS: Our findings showed that although patients and physicians have a similar perception about the relevance of different HEN attributes, the relative weight given to each one varies between them. Therefore, both points of view should be considered when choosing a HEN product in order to improve patients' satisfaction and clinical outcomes.

[Preferences for the attributes of home enteral nutrition (HEN) in Spain. Do caregivers know their patients' preferences?] / Preferencias por los atributos de la nutrición enteral domiciliaria (NED) en España. ¿Conocen los cuidadores las preferencias de los pacientes?

INTRODUCTION: Establishing a home enteral nutrition (HEN) that is adapted to the patient's needs and preferences can improve their quality of life and adherence, contributing to a higher treatment efficiency, better prognosis and cost reduction. As in most cases, patients need total or partial help from their caregivers, and there is a need for evaluating how well do caregivers know their patients' priorities. OBJECTIVES: Exploring patients' preferences for HEN characteristics in Spain, and the concordance between patients and caregivers. METHODS: A cross-sectional observational study based on the discrete choice experiment methodology. A set of eight choice scenarios generated from six attributes with two levels each was presented along with an ad hoc questionnaire on the importance and satisfaction with HEN. The relative importance (RI) of each attribute and the patient-caregiver concordance was estimated in every question. RESULTS: One hundred and forty-eight patients participated, and in 77 cases both the patient and the caregiver took the survey. The most important attributes (RI) for HEN were adaptation to comorbidities (33%), tolerability (33%), nutrients and calories (26%) and package characteristics (8%). Patients showed a high degree of satisfaction with the assistance received. Concordance between patient and caregiver was found in every question, being it moderate to good. CONCLUSIONS: According to patients, an ideal HEN product would be adaptable to comorbidities, easy to tolerate, providing the necessary nutrients and calories, with an easy to handle package. Caregivers know well their patients' preferences.

Dietary docosahexaenoic acid supplementation prevents the formation of cholesterol oxidation products in arteries from orchidectomized rats.

Testosterone deficiency has been correlated with increased cardiovascular diseases, which in turn has been associated with increased oxidative stress. Several studies have considered cholesterol oxidation products (COPs) as oxidative stress biomarkers, since some of them play pro-oxidant and pro-inflammatory roles. We have previously described the cardioprotective effects of a dosahexaenoic acid (DHA) supplemented diet on the aortic and mesenteric artery function of orchidectomized rats. The aim of this study was to investigate whether impaired gonadal function alters the formation of COPs, as well as the potential preventive role of a DHA-supplemented diet on that effect. For this purpose, aortic and mesenteric artery segments obtained from control and orchidectomized rats, fed with a standard or supplemented with DHA, were used. The content of the following COPs: 7α-hydroxycholesterol, 7ß-hydroxycholesterol, 7-ketocholesterol, 5,6α-epoxycholesterol, 5,6ß-epoxycholesterol, cholestanetriol and 25-hydroxycholesterol, were analyzed by gas chromatography. The results showed that orchidectomy increased the formation of COPs in arteries from orchidectomized rats, which may participate in the orchidectomy-induced structural and functional vascular alterations already reported. The fact that the DHA-supplemented diet prevented the orchidectomy-induced COPs increase confirms the cardiovascular protective actions of DHA, which could be of special relevance in mesenteric arterial bed, since it importantly controls the systemic vascular resistance.