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Las prácticas funerarias del IV y III milenio cal ac se caracterizan en la mayor parte de la Península Ibérica por la generalización de la arquitectura megalítica, en paralelo a las importantes transformaciones sociales que tienen lugar a lo largo de la denominada Edad del Cobre. Al mismo tiempo, proliferan enterramientos colectivos en cuevas naturales en zonas montañosas del área meridional de Iberia, muchos de los cuales parecen compartir usos similares a los propios de cámaras ortostáticas. En este trabajo presentaremos el sorprendente caso del yacimiento de Peñacalera, en Obejo, provincia de Córdoba, una pequeña cavidad funeraria situada en un prominente afloramiento rocoso situado en el macizo de Sierra Morena descubierta en 2014. El contexto funerario comprende los restos óseos de al menos cinco individuos, asociados a elementos de ajuar como vasos cerámicos, y elementos de naturaleza orgánica en un notable estado de conservación, especialmente placas de corcho de alcornoque y algunos fragmentos textiles. El análisis de las dataciones radiocarbónicas efectuadas apunta a dos fases de uso diferenciadas, una en el tercer cuarto del iv y otra a mediados del III milenio cal AC.

Severe alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of emphysema. However, the clinical manifestations are very heterogeneous, and an individual prognosis is very difficult to establish. Intravenous augmentation therapy with alpha-1 antitrypsin (AAT) from pooled blood donors is the only specific treatment available, but it requires weekly or biweekly administration for life. Several guidelines provide the indication criteria for the initiation of AAT augmentation therapy. However, in clinical practice, there are situations in which the decision as to when to start treatment becomes uncertain and some studies have shown great variability in the indication of this treatment even among specialists. The usual dilemma is between initiating augmentation therapy in individuals who may not develop significant lung disease or in whom disease will not progress or delaying it in patients who may otherwise rapidly and irreversibly progress. We illustrate this dilemma with five clinical cases: from the case of a patient with normal lung function who requests initiation of therapy to a moderately stable patient without augmentation or a mild patient who, after several years of remaining stable without treatment, deterioration in lung function initiated and, consequently, augmentation therapy was begun. All the nuances associated with the indication of augmentation justify a personalised approach and the decision about initiating augmentation therapy must be made after careful consideration of the pros and cons with the patient in reference centres with experience in treatment. These reference centres can work in collaboration with local hospitals where patients can be closely followed and augmentation therapy can be administered to avoid unnecessary travelling, making periodical administrations more comfortable for the patient.

This study investigates NO adsorption on Pd-exchanged chabazite (Pd/H-CHA), a promising passive NOx adsorber (PNA) for capturing cold-start NOx emissions of gasoline- and diesel-powered vehicles. Temperature-programed desorption (TPD) and IR spectroscopy are combined with theoretical calculations to elucidate how and where NO is stored, and how water and O2 affect this process. NO adsorption on Pd/H-CHA produces two TPD features, around 423 and 753 K, and IR bands centered at 1860 and 1810 cm−1. Calculated NO stretching frequencies and maximum-desorption temperatures reveal that Pd2+ and Pd+ sites are responsible for these low- and high-temperature features, respectively, and that while the IR feature at 1810 cm−1 is due to NO adsorption on Pd+, the 1860 cm−1 feature contains contributions from both weakly-bound NO on Pd2+ and more strongly bound NO on Pd+, consistent with experimentally observed effects of water and O2.

Cation exchanged-zeolites are functional materials with a wide range of applications from catalysis to sorbents. They present a challenge for computational studies using density functional theory due to the numerous possible active sites. From Al configuration, to placement of extra framework cation(s), to potentially different oxidation states of the cation, accounting for all these possibilities is not trivial. To make the number of calculations more tractable, most studies focus on a few active sites. We attempt to go beyond these limitations by implementing a workflow for a high throughput screening, designed to systematize the problem and exhaustively search for feasible active sites. We use Pd-exchanged CHA and BEA to illustrate the approach. After conducting thousands of explicit DFT calculations, we identify the sites most favorable for the Pd cation and discuss the results in detail. The high throughput screening identifies many energetically favorable sites that are non-trivial. Lastly, we employ these results to examine NO adsorption in Pd-exchanged CHA, which is a promising passive NOx adsorbent (PNA) during the cold start of automobiles. The results shed light on critical active sites for NOx capture that were not previously studied.

Abstract Cation exchanged-zeolites are functional materials with a wide range of applications from catalysis to sorbents. They present a challenge for computational studies using density functional theory due to the numerous possible active sites. From Al configuration, to placement of extra framework cation(s), to potentially different oxidation states of the cation, accounting for all these possibilities is not trivial. To make the number of calculations more tractable, most studies focus on a few active sites. We attempt to go beyond these limitations by implementing a workflow for a high throughput screening, designed to systematize the problem and exhaustively search for feasible active sites. We use Pd-exchanged CHA and BEA to illustrate the approach. After conducting thousands of individual calculations, we identify the sites most favorable for the Pd cation and discuss the results in detail. The high throughput screening identifies many energetically favorable sites that are non-trivial. Lastly, we employ these results to examine NO adsorption in Pd-exchanged CHA, which is a promising passive NOx adsorbent (PNA) during the cold start of automobiles. The results shed light on critical active sites for NOx capture that were not previously studied.

Supported metal catalysts are extensively used in industrial and environmental applications. To improve their performance, it is crucial to identify the most active sites. This identification is, however, made challenging by the presence of a large number of potential surface structures that complicate such an assignment. Often, the active site is formed by an ensemble of atoms, thus introducing further complications in its identification. Being able to produce uniform structures and identify the ones that are responsible for the catalyst performance is a crucial goal. In this work, we utilize a combination of uniform Pd/Pt nanocrystal catalysts and theory to reveal the catalytic active-site ensemble in highly active propene combustion materials. Using colloidal chemistry to exquisitely control nanoparticle size, we find that intrinsic rates for propene combustion in the presence of water increase monotonically with particle size on Pt-rich catalysts, suggesting that the reaction is structure dependent. We also reveal that water has a near-zero or mildly positive reaction rate order over Pd/Pt catalysts. Theory insights allow us to determine that the interaction of water with extended terraces present in large particles leads to the formation of step sites on metallic surfaces. These specific step-edge sites are responsible for the efficient combustion of propene at low temperature. This work reveals an elusive geometric ensemble, thus clearly identifying the active site in alkene combustion catalysts. These insights demonstrate how the combination of uniform catalysts and theory can provide a much deeper understanding of active-site geometry for many applications.

Endometriosis-related neoplasms may arise within endometriotic cysts of organs of the female genital tract or other organ systems. Herein, we present a case of endometrioid adenocarcinoma arising within an endometriotic cyst in the mesosalpinx. A 27-year-old single female presented to the clinic with a history of right hypochondrial pain. Pelvic MRI revealed a bulky uterus with three intramural uterine fibroids and a complex cyst in the mesosalpinx. The excised cyst showed predominantly confluent growth of relatively well-defined glands resembling proliferative-phase endometrium in a background of endometriosis. The tumor was diagnosed as endometrioid adenocarcinoma within an endometriotic cyst, pathologic stage pT1a. She was referred to the oncology team, where a positron emission tomography scan showed unremarkable results. Although these neoplasms have been reported in various locations within the female genital tract, endometrioid adenocarcinoma arising from endometriosis in the mesosalpinx is seldom reported.

The identification of active sites in cation exchanged-zeolites is computationally highly demanding. Here the authors employ a DFT-based computational framework to identify the energetically most favorable adsorption sites in any zeolite using a systematic high-throughput approach.

While the search for catalysts capable of directly converting methane to higher value commodity chemicals and liquid fuels has been active for over a century, a viable industrial process for selective methane activation has yet to be developed. Electronic structure calculations are playing an increasingly relevant role in this search, but large-scale materials screening efforts are hindered by computationally expensive transition state barrier calculations. The purpose of the present letter is twofold. First, we show that, for the wide range of catalysts that proceed via a radical intermediate, a unifying framework for predicting C-H activation barriers using a single universal descriptor can be established. Second, we combine this scaling approach with a thermodynamic analysis of active site formation to provide a map of methane activation rates. Our model successfully rationalizes the available empirical data and lays the foundation for future catalyst design strategies that transcend different catalyst classes.

Abstract Background Acute kidney injury (AKI) occurs in 12–20% of multiple myeloma (MM) patients. Several studies have shown a reduction of free light chains (FLC) using hemodialysis with High-Cut-Off membranes. However, this technique entails albumin loss. Hemodiafiltration with ultrafiltrate regeneration is a technique that includes a process of adsorption. The aim of this study was to evaluate the effectiveness of hemodiafiltration with ultrafiltrate regeneration in reducing FLC levels without causing albumin loss. Methods This is an observational study (2012 to 2018) including nine patients with MM (5 kappa, 4 lambda) and AKI. All patients were treated with chemotherapy and hemodiafiltration with ultrafiltrate regeneration. Blood Samples (pre and post-dialysis) and ultrafiltrate were collected pre and post-resin at 5 min after initiation of the session and 5 min before the end of the procedure. Results The serum levels of kappa and lambda were reduced by a 57.6 ± 10% and 33.5 ± 25% respectively. Serum albumin concentration remained unchanged after the procedure. In the ultrafiltrate, the mean FLC reduction ratio shortly after initiation of the dialysis procedure was: 99.2 and 97.06% for kappa and lambda respectively, and only 0.7% for albumin; and at the end of the session the percent reduction was: 63.7 and 33.62% for kappa and lambda respectively, and 0.015% for albumin. Patients clinical outcome was: 33.3% recovered renal function, 22.2% died during the first year and 44.4% required maintenance dialysis. Conclusions Hemodiafiltration with ultrafiltrate regeneration reduces FLC levels without producing a significant loss of albumin; and, FLC removal is maintained throughout the session. Therefore, hemodiafiltration with ultrafiltrate regeneration may be considered an effective adjunctive therapy in patients with MM.

Long-term inappropriate proton pump inhibitors use (PPIs) is a matter of concern because of the risks associated with their long-term use in older patients with chronic conditions. The risk of PPI treatment in hemodialysis patients remains unexplored. Methods: We assessed the relationship between the use of PPIs and the risk of death in hemodialysis patients throughout a retrospective multicenter propensity score–matched study. Information about demographic, hemodialysis treatment, laboratory data, and concomitant medication was obtained from the EuCliD database (Fresenius Medical Care). We studied 1776 hemodialysis patients on PPI therapy compared to 466 patients not receiving PPIs. The resulting population comprising 2 groups of 410 matched patients was studied. Results: PPI use was associated with hypomagnesemia (Mg

BackgroundPatients with chronic kidney disease (CKD) show a chronic microinflammatory state that promotes premature aging of the vascular system. Currently, there is a growth interest in the search of novel biomarkers related to vascular aging to identify CKD patients at risk to develop cardiovascular complications.MethodsForty-five CKD patients were divided into three groups according to CKD-stages [predialysis (CKD4-5), hemodialysis (HD) and kidney transplantation (KT)]. In all these patients, we evaluated the quantitative changes in microRNAs (miRNAs), CD14+C16++ monocytes number, and microvesicles (MV) concentration [both total MV, and monocytes derived MV (CD14+Annexin V+CD16+)]. To understand the molecular mechanism involved in senescence and osteogenic transdifferentation of vascular smooth muscle cells (VSMC), these cells were stimulated with MV isolated from THP-1 monocytes treated with uremic toxins (txMV).ResultsA miRNA array was used to investigate serum miRNAs profile in CKD patients. Reduced expression levels of miRNAs-126-3p, -191-5p and -223-3p were observed in CKD4-5 and HD patients as compared to KT. This down-regulation disappeared after KT, even when lower glomerular filtration rates (eGFR) persisted. Moreover, HD patients had higher percentage of proinflammatory monocytes (CD14+CD16++) and MV derived of proinflammatory monocytes (CD14+Annexin V+CD16+) than the other groups. In vitro studies showed increased expression of osteogenic markers (BMP2 and miRNA-223-3p), expression of cyclin D1, β-galactosidase activity and VSMC size in those cells treated with txMV.ConclusionCKD patients present a specific circulating miRNAs expression profile associated with the microinflammatory state. Furthermore, microvesicles generated by monocytes treated with uremic toxins induce early senescence and osteogenic markers (BMP2 and miRNA-223-3p) in VSMC.

Abstract In chronic kidney disease (CKD), high serum phosphate concentration is associated with cardiovascular disease and deterioration in renal function. In early CKD, the serum phosphate concentration is normal due to increased fractional excretion of phosphate. Our premise was that high phosphate intake even in patients with early CKD would result in an excessive load of phosphate causing tubular injury and accelerating renal function deterioration. In CKD 2–3 patients, we evaluated whether increased phosphaturia accelerates CKD progression. To have a uniform group of patients with early CKD, 95 patients with metabolic syndrome without overt proteinuria were followed for 2.7 ± 1.6 years. The median decline in eGFR was 0.50 ml/min/1.73 m2/year. Patients with a more rapid decrease in eGFR had greater phosphaturia. Moreover, the rate of decrease in eGFR inversely correlated with the degree of phosphaturia. Additionally, phosphaturia independently predicted renal function deterioration. In heminephrectomized rats, a high phosphate diet increased phosphaturia resulting in renal tubular damage associated with inflammation, oxidative stress and low klotho expression. Moreover, in rats with hyperphosphatemia and metabolic syndrome antioxidant treatment resulted in attenuation of renal lesions. In HEK-293 cells, high phosphate promoted oxidative stress while melatonin administration reduced ROS generation. Our findings suggest that phosphate loading in early CKD, results in renal damage and a more rapid decrease in renal function due to renal tubular injury.

Abstract: We evaluated the impact of light chain type, lambda (λ) or kappa (κ), on disease features and outcomes in patients with immunoglobulin light chain (AL) amyloidosis receiving stem cell transplant at the Mayo Clinic between October 2002 and August 2016. Patients with λ AL amyloidosis had higher rates of renal and neurological involvement (λ 69% vs κ 57%, P = .02 and λ 16% vs κ 9%, P = .03, respectively). Patients with κ AL amyloidosis had more hepatic involvement (λ 7% vs κ 18%, P = .0003). Complete response rate was 43% for both groups and overall response rates were similar (λ 85% vs κ 91%, P = .12). Patients with κ light chain amyloidosis had better progression-free and overall survival (PFS: λ 74 months vs κ 101 months, P = .0064 and OS: λ 121 months vs κ not reached, P = .003). Mayo stage 2004 was more predictive of survival in the λ cohort (median OS of 143 months stage I vs 77 months stage II vs 33 months stage III, P < .0001) than in the κ cohort (median OS not reached for stage I and II and 102 months for stage III, P = .044). Conditioning dose predicted survival in the λ cohort only (median OS 149 months for melphalan 200 mg/m2 vs 50 months for melphalan

Introduction: Type iii extracapillary glomerulonephritis (PEGN) is a common cause of rapidly progressive glomerulonephritis and it is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Recent evidence points to complement activation as an important factor in the pathogenesis of PEGN.The aim of the present study was to assess the value of C3 deposits in the prognosis of PEGN. Methods: All patients diagnosed of PEGN from 1995 to 2015 (n = 72) were included in this study. Progression of renal disease in patients with positive staining for C3 by immunofluorescence was compared with those with negative staining. Mean follow up was 73 months. Progression to end-stage renal disease in relation to clinical and histological variables was analyzed. Results: Positive staining for C3 was observed in 22 out of the 72 patients (30.5%).At the time of diagnosis, patients with C3 deposits had higher serum creatinine concentration than those without C3 staining (5.00 vs. 3.85 mg/dl, p = 0.050). Renal survival at 10 years was 36.9% in patients with positive C3 staining vs. 64.4% in patients with negative staining (p = 0.005). Mortality at 10 years was higher in patients with C3 deposits than in patients without deposits (77 vs. 49.3%). Conclusions: Thus, our study shows that PEGN with deposits of C3 is associated with worse renal prognosis and greater mortality. These results would support the hypothesis that activation of the alternative pathway complement may play an important role in the generation of renal injury associated with PEGN. Resumen: Introducción: La glomerulonefritis extracapilar (GNEC) pauciinmune o de tipo iii es una de las causas más comunes de glomerulonefritis rápidamente progresiva y suele estar asociada con la presencia de anticuerpos antineutrófilos citoplasmáticos (ANCA). Están reportándose evidencias sobre la importancia de la activación del complemento en la patogénesis de la GNEC.El objetivo de nuestro estudio fue evaluar el papel pronóstico del depósito de C3 en las GNEC de tipo iii. Métodos: Se estudió a pacientes diagnosticados de GNEC de tipo iii entre 1995 y 2015 (n = 72). Comparamos a pacientes con tinción positiva para C3 en el estudio de inmunofluorescencia con aquellos con tinción negativa. Se analizaron variables clínicas e histológicas y se relacionaron con progresión a enfermedad renal terminal. Resultados: Se encontró tinción positiva para C3 en 22 pacientes de un total de 72 (30,5%).Basalmente los pacientes con depósitos de C3 tenían peor función renal que aquellos sin depósitos (creatinina sérica 5 vs. 3,85 mg/dl; p = 0,050). La supervivencia renal a los 10 años fue del 36,9% en los pacientes con tinción positiva para C3 frente al 64,4% en los pacientes con tinción negativa (p = 0,005). La supervivencia a los 10 años fue peor en los pacientes con depósitos de C3 (77 vs. 49,3%). Conclusiones: Nuestro estudio revela que la presencia de depósito de C3 en la GNEC de tipo iii se asocia a un peor pronóstico renal y de la supervivencia del paciente. Estos resultados son compatibles con la hipótesis de que la activación de la vía alternativa del complemento contribuye al daño renal asociado a la GNEC de tipo iii. Keywords: Complement, C3 deposits, Extracapillar glomerulonephritis, Crescents, Palabras clave: Complemento, Depósitos de C3, Glomerulonefritis extracapilar, Semilunas

Introducción: La glomerulonefritis extracapilar (GNEC) pauciinmune o de tipo iii es una de las causas más comunes de glomerulonefritis rápidamente progresiva y suele estar asociada con la presencia de anticuerpos antineutrófilos citoplasmáticos (ANCA). Están reportándose evidencias sobre la importancia de la activación del complemento en la patogénesis de la GNEC. El objetivo de nuestro estudio fue evaluar el papel pronóstico del depósito de C3 en las GNEC de tipo iii. Métodos: Se estudió a pacientes diagnosticados de GNEC de tipo iii entre 1995 y 2015 (n = 72). Comparamos a pacientes con tinción positiva para C3 en el estudio de inmunofluorescencia con aquellos con tinción negativa. Se analizaron variables clínicas e histológicas y se relacionaron con progresión a enfermedad renal terminal. Resultados: Se encontró tinción positiva para C3 en 22 pacientes de un total de 72 (30,5%). Basalmente los pacientes con depósitos de C3 tenían peor función renal que aquellos sin depósitos (creatinina sérica 5 vs. 3,85 mg/dl; p = 0,050). La supervivencia renal a los 10 años fue del 36,9% en los pacientes con tinción positiva para C3 frente al 64,4% en los pacientes con tinción negativa (p = 0,005). La supervivencia a los 10 años fue peor en los pacientes con depósitos de C3 (77 vs. 49,3%). Conclusiones: Nuestro estudio revela que la presencia de depósito de C3 en la GNEC de tipo iii se asocia a un peor pronóstico renal y de la supervivencia del paciente. Estos resultados son compatibles con la hipótesis de que la activación de la vía alternativa del complemento contribuye al daño renal asociado a la GNEC de tipo iii.

BACKGROUND: Vitamin D deficiency (VDD) is a major global health problem. In sickle cell disease (SCD), VDD is highly prevalent, reaching up to 96% of populations. VDD may contribute to many of the complications of SCD. OBJECTIVE: Estimate the 25-hydroxyvitamin D [25(OH)D] level and the frequency of VDD and insufficiency among among SCD patients by age group and disease status. DESIGN: Analytical cross-sectional. SETTING: Ministry of Health (MOH) secondary care hospital. PATIENTS AND METHODS: Non-probability purposive sampling was used to select SCD patients, aged 12 years and older, of both sexes, who had visited the hospital during a period of 5 years (2010-2014). Blood samples were processed by electrochemiluminescence technology. MAIN OUTCOME MEASURE(S): 25(OH)D levels by demographic data, and disease activity. SAMPLE SIZE: 640 patients. RESULTS: Of those, 82% (n=523) had suboptimal 25(OH)D (0-

Introduction: Patients on haemodialysis (HD) have a high prevalence of 25-OH-vitamin D (25-OH-D)deficiency. Secondary hyperparathyroidismis a common condition in these patients, which is very important to control. 25-OH-D is involved in regulating calcium homeostasis. As such, appropriate levels of this vitamin could help to control bone mineral metabolism. Objective: To evaluate the effect 25-OH-D repletion in HD patients with 25-OH-D deficiency ( 30 ng/ml and 4 between 20 and 30 ng/ml). Parathyroid hormone levels decreased in 32 of the 45 patients, 23 of which (51%) achieved a >30% decrease from baseline. In terms of concomitant treatment, we observed a significant reduction in the selective vitamin D receptor activator dose, but no changes in calcimimetic or phosphate binders administration. In terms of malnutrition–inflammation status, a decrease in C-reactive protein was noted, although other microinflammation parameters, such as activated monocytes (CD14+/CD16+ and CD 14++/CD16+) were unchanged. No changes were observed in the levels of FGF-23. Conclusions: Correcting 25-OH-D deficiency in HD patients is associated with better secondary hyperparathyroidism control with lower doses of vitamin D analogues, as well as an improvement in inflammatory status. Our results support the recommendation to determine 25-OH-D levels and correct its deficiency in these patients.

Introducción: El déficit de 25-OH-vitamina D (25-OH-D) es común en los pacientes en hemodiálisis (HD). Por otra parte, es bien conocida la elevada incidencia de hiperparatiroidismo secundario en este grupo de pacientes, y lo importante que es su adecuado control. La 25-OH-D está implicada en la regulación de la homeostasis del calcio, por lo que tener niveles adecuados puede contribuir en el control del metabolismo óseo-mineral. Objetivos: Evaluar el efecto de la repleción de 25-OH-D en pacientes en HD con déficit vitamínico (niveles 20 ng/ml (en 23 fueron > 30 ng/ml, y 4 entre 20-30 ng/ml). Las cifras de hormona paratiroidea descendieron en 32 de los 45 pacientes, alcanzando en 23 (51% de tratados) un descenso > 30% respecto al valor basal. En cuanto al tratamiento concomitante, se objetivó un descenso significativo de la dosis de activador selectivo del receptor de vitamina D; sin evidenciarse cambios en la dosis de calcimimético ni de quelantes. Respecto al estado de malnutrición-inflamación, destaca un descenso de la proteína C reactiva, aunque no se modificaron otros parámetros de microinflamación como los monocitos activados (CD14+/CD16+ y CD 14++/CD16+). Tampoco se observaron cambios en los niveles de FGF-23. Conclusiones: La corrección del déficit de 25-OH-D en pacientes en HD se asocia a un mejor control del hiperparatiroidismo secundario con menores dosis de análogos de vitamina D y a una mejoría en el estado inflamatorio de estos pacientes. Nuestros resultados apoyan la recomendación de determinar niveles de 25-OH-D y corregir el déficit en pacientes en HD.

Endothelial aging may be induced early in pathological situations. The uremic toxins indoxyl sulfate (IS) and p-cresol (PC) accumulate in the plasma of chronic kidney disease (CKD) patients, causing accelerated endothelial aging, increased cardiovascular events and mortality. However, the mechanisms by which uremic toxins exert their deleterious effects on endothelial aging are not yet fully known. Thus, the aim of the present study is to determine the effects of IS and PC on endothelial damage and early senescence in cultured human umbilical vein endothelial cells (HUVECs). Hence, we establish an in vitro model of endothelial damage mediated by different passages of HUVECs and stimulated with different concentrations of IS and PC to evaluate functional effects on the vascular endothelium. We observe that cell passage-induced senescence is associated with apoptosis, ROS production and decreased endothelial proliferative capacity. Similarly, we observe that IS and PC cause premature aging in a dose-dependent manner, altering HUVECs’ regenerative capacity, and decreasing their cell migration and potential to form vascular structures in vitro. In conclusion, IS and PC cause accelerated aging in HUVECs, thus contributing to endothelial dysfunction associated with CKD progression.

Although several studies suggest that the prognosis of hypertensive dialysis patients can be improved by using antihypertensive drug therapy, it is unknown whether the prescription of a particular class or combination of antihypertensive drugs is beneficial during hemodialysis. Methods: We performed a propensity score matching study to compare the effectiveness of various classes of antihypertensive drugs on cardiovascular (CV) mortality in 2518 incident hemodialysis patients in Spain. The patients had initially received antihypertensive therapy with a renin-angiotensin system (RAS) blocker (728 patients), a ß-blocker (679 patients), antihypertensive drugs other than a RAS blocker or a ß-blocker (787 patients), or the combination of a ß-blocker and a RAS inhibitor (324 patients). These patients were followed for a maximum of 5 years (median: 2.21 yr; range: 1.04–3.34 yr). Results: After adjustment for baseline CV risk covariates, no significant differences were observed in the risk of CV mortality between patients taking a RAS blocker and patients treated with ß-blocker–based antihypertensive therapy. The combination of a RAS blocker with a ß-blocker was associated with better CV survival than either agent alone (RAS blocker: hazard ratio [HR]: 1.68; 95% confidence interval [CI] 1.05–2.69; ß-blocker: HR: 1.59; 95% CI: 1.01–2.50; antihypertensive medication other than a RAS blocker or ß-blocker: HR: 1.67; 95% CI: 1.08–2.58). Discussion: Our data suggested that the combination of a RAS blocker and a ß-blocker could improve survival in hemodialysis patients. Further prospective randomized controlled trials are necessary to confirm the beneficial effects of this combination of antihypertensive drugs in patients undergoing hemodialysis.

Pancreatic autoantibodies (AAb) has been associated with a worse pancreas graft survival after simultaneous pancreas-kidney transplantation (SPK). However, due to the variable time for AAb to become positive and the lack of early biomarkers suggesting such autoimmune activation, the mechanisms leading ß-cell destruction remain uncertain. The present study aimed to evaluate the association between post-transplant AAb and the functional impairment of the pancreatic ß-cell and also the association of such AAb with inflammation after SPK. In a longitudinal study, we analyzed the impact of post-transplant glutamic acid decarboxylase (GAD-65) and the insulinoma-associated autoantigen 2 (IA-2) AAb on pancreas graft function. Serum Hb1Ac and C-peptide (C-pep) were longitudinally compared between a group with positive posttransplant AAb (AAb+; n = 40) and another matched group with negative AAb (AAb-; n = 40) until the fifth year following seroconversion. In the cross-sectional analysis, we further evaluated the systemic signatures of inflammation by measuring pro-inflammatory CD14+CD16+ monocytes by flow-cytometry and interleukin 17-A serum levels in 38 SPK recipients and ten healthy controls. In the longitudinal study, patients with AAb+ showed higher levels of Hb1Ac (p

Mohammed Al Ghobain,1,2 H Alhashemi,1,2 A Aljama,3 S Bin Salih,1,2 Z Assiri,4 A Alsomali,4 Gamal Mohamed5 1Department of Medicine, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, 2King Abdullah International Medical Research Centre, 3Department of Medicine, King Abdulaziz Medical City, 4College of Nursing, 5College of Public Health, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia Objectives: Nonadherence to antihypertensive medications has not been assessed in the Saudi population. The aim of this study was to address and evaluate the magnitude of nonadherence among hypertensive patients and the risk factors associated with it. Methods: A cross-sectional survey was conducted on hypertensive patients who attended the general internal medicine clinics at King Abdulaziz Medical City, Riyadh, Saudi Arabia, using a questionnaire that was modified after reviewing the literature. Hypertensive patients were labeled as nonadherent if they missed their medications for a total of 7 days during the previous month. Results: A total of 302 patients participated in the study, of whom 63% were females with a mean age of 64 years, and 64% were illiterate. The prevalence of nonadherence to medications among hypertensive patients was found to be 12.3%. Poor disease knowledge was reported in 80% of patients, while 66% of the patients had poor monitoring of their disease. Younger age (≤65 years), poor monitoring, and uncontrolled blood pressure (BP ≥140/90 mmHg) were the predictor factors associated with nonadherence (odds ratio [OR] =2.04, P=0.025; OR=2.39, P=0.004; and OR=2.86, P=0.003, respectively). Conclusion: Nonadherence to antihypertensive medications is lower than that previously reported in the literature. Younger age, uncontrolled BP, and poor monitoring are the main risk factors associated with nonadherence. Keywords: nonadherence, hypertension, Saudi Arabia, uncontrolled blood pressure

Background: As in the general population, in patients on haemodialysis (HD) hyponatraemia is associated with higher mortality risk. The objective of this article was to study the relationship between predialysis serum sodium (sNa) and mortality in an HD population. We also intended to define hyponatraemia and determine the characteristics of hyponatraemic patients in terms of anthropometric data, analytical features, dialysis measurements and hydration (bioimpedance). Methods: Observational, descriptive study of a cohort of HD incident patients. The independent variable was the mean of each patient's sNa analysed during their first 6 months on HD. Results: A total of 4153 patients were included in the study. Mean age was 64.7 years; 65.2% of the patients were male and 35% were diabetics. Mean follow-up time was 21.48 (SD) (1.31) months. sNa had a normal distribution, with a mean (SD) = 138.46 (2.7) mEq/l. Body weight, diabetes mellitus, systolic blood pressure, interdialytic weight gain, total ultrafiltration, serum glucose, albumin and creatinine, vascular access and haemodialysis type, acquire significant differences between sodium quartiles. Lean tissue index (LTI) in patients with low serum sodium, Q1 (135 mEq/l), was significantly lower than the LTI of patients from the other serum sodium quartiles. Patients with sNa

Introducción: Al igual que en la población general, en los pacientes en hemodiálisis (HD), la hiponatremia también se asocia a mayor riesgo de muerte. El objetivo de este trabajo es estudiar en la población en HD la relación entre natremia y mortalidad. Definir hiponatremia en HD y determinar qué peculiaridades tienen los pacientes hiponatrémicos en relación con aspectos antropométricos, analíticos, dialíticos y de hidratación, mediante bioimpedancia. Metodos: Estudio observacional, descriptivo, de una cohorte de pacientes incidentes en HD. La variable independiente fue la media de las natremias medidas en los 6 primeros meses en HD. Resultados: Se incluyó a 4.153 pacientes. La edad media era de 64,7 años y predominaban los hombres con un 64,2%. Un 34,8% eran diabéticos. El tiempo medio de seguimiento fue 21,48 (DE) (1,31) meses. Las natremias tenían una distribución normal, con una media (DE) de 138,46 (2,7) mEq/l. Las variables que presentan diferencias significativas en función de los cuartiles de natremia son: peso, diabetes, presión arterial sistólica, ganancia de peso interdialítica, ultrafiltración total, glucemia, albúmina y creatinina séricas y tipo de acceso vascular y de HD. El índice de masa magra (LTI) en los pacientes con hiponatremia, Q1 (135 mEq/l), fue significativamente más bajo que el del resto de pacientes. Los pacientes con una natremia menor de 136 mEq/l tienen un riesgo independiente de mortalidad mayor que el resto (OR = 1,62) (análisis de regresión de Cox). Conclusiones: Los pacientes en HD con hiponatremia tienen mal pronóstico y presentan desnutrición o sobrecarga de volumen.

The plasma cell proliferative index provides an insight into plasma cell biology in plasma cell disorders and is an important prognostic marker in myeloma and smoldering myeloma. We analyzed the prognostic impact of the plasma cell proliferative index in 513 patients with systemic immunoglobulin light chain (AL) amyloidosis undergoing stem cell transplantation at the Mayo Clinic between 1st January 2003 and 31st August 2016. Two cohorts were identified according to Low or Elevated plasma cell proliferative index. Patients with an Elevated plasma cell proliferative index had more cardiac involvement (56% vs. 44%; P=0.01), less renal involvement (55% vs. 70%; P=0.001), and were more likely to have 10% or over bone marrow plasma cells (58% vs. 32%; P

BACKGROUND:In hemodialysis patients, high levels of Fibroblast Growth Factor 23 (FGF23) predict mortality. Our study was designed to test whether the control of serum phosphate is associated with a reduction in serum FGF23 levels. Additionally other variables with a potential effect on FGF23 levels were evaluated. MATERIAL AND METHODS:The effect of sustained (40-weeks) control of serum phosphate on FGF23 levels (intact and c-terminal) was evaluated in 21 stable hemodialysis patients that were not receiving calcimimetics or active vitamin D. Patients received non-calcium phosphate binders to maintain serum phosphate below 4.5 mg/dl. In an additional analysis, values of intact-FGF23 (iFGF23) and c-terminal FGF23 (cFGF23) from 150 hemodialysis patients were correlated with parameters of mineral metabolism and inflammation. Linear mixed models and linear regression were performed to evaluate longitudinal trajectories of variables and the association between FGF23 and the other variables examined. RESULTS:During the 40-week treatment, 12 of 21 patients achieved the target of serum phosphate 4.5 mg, iFGF23 and cFGF23 increased two and four-fold respectively as compared with baseline. Furthermore, changes in serum phosphate correlated with changes in C-reactive protein (hs-CRP). In our 150 hemodialysis patients, those in the higher tertile of serum phosphate also showed increased hs-CRP, iPTH, iFGF23 and cFGF23. Multiple regression analysis revealed that iFGF23 levels directly correlated with both serum phosphate and calcium, whereas cFGF23 correlated with serum phosphate and hs-CRP but not with calcium. CONCLUSIONS:The control of serum phosphate reduced iFGF23. This reduction was also associated with a decreased in inflammatory parameters. Considering the entire cohort of hemodialysis patients, iFGF23 levels correlated directly with serum phosphate levels and also correlated inversely with serum calcium concentration. The levels of cFGF23 were closely related to serum phosphate and parameters of inflammation.

BACKGROUND:In pregnant women, the use of Mycophenolic acid (MPA) is associated with teratogenicity. Recently, the European Medicines Agency (EMEA) and the Spanish Agency of Medicine and Sanitary Products (AEMPS) warned about the potential teratogenic effects of MPA. These adverse events may occur even in children from males on treatment with MPA. However, evidence of malformations in offsprings of male kidney transplanted patients (KT) exposed to MPA is limited. Thus, the present study aimed to evaluate the incidence of offspring malformations in children of renal transplanted males under MPA. MATERIALS AND METHODS:We conducted a retrospective study in which we evaluated the incidence of malformations in descendants from male recipients that were exposed or not to MPA before and at the time of conception. Two groups of patients were evaluated. Those exposed to MPA (MPA group, n = 20) and the non-MPA group (n = 13) that included patients that did not receive AZA (n = 5) and eight that did receive AZA (n = 8) at the time of conception. RESULTS:A total of forty-nine post-transplant conceptions were identified from 33 different renal transplanted males. MPA was used as the immunosuppressant in 28 of the conceptions. Males from the non-MPA group fathered the other 21 children. Median time from grafting to conception was 6.1 (IQR 2.4-11.1) years, and it was similar between groups. There were eight miscarriage episodes, 2 in the non-MPA group and 6 in the MPA group although differences were not reached. After that, all patients had children without problems. No malformations were detected in any of the 49 regardless whether they were exposed or not to MPA. CONCLUSIONS:No evidence of MPA-associated malformations was observed in descendants of kidney transplanted males on treatment with MPA. Further research is warranted to confirm our findings to properly advice transplanted males keen to procreate.

The consolidation of single antigen beads (SAB-panIgG) assay in the detection of preformed anti-human leukocyte antigen (HLA) antibodies has improved transplantation success. However, its high sensitivity has limited the allograft allocation for sensitized patients, increasing their waiting time. A modification of the standard SAB-panIgG assay allows the detection of that subset of antibodies capable of binding C1q (SAB-C1q assay). However, the clinical usefulness of SAB-C1q assay for determining the unacceptable mismatches is under discussion. We retrospectively analyzed the impact of preformed donor-specific anti-HLA antibodies (DSA) according to the C1q-binding ability on allograft outcome, examining 389 single-kidney transplanted patients from deceased donors. Recipients with preformed C1q-binding DSA showed the lowest allograft survival up to 7 years (40.7%) compared to patients with preformed non-C1q-binding DSA (73.4%; p = 0.001) and without DSA (79.1%; p

Cardiovascular disease is a major cause of mortality in chronic kidney disease patients. Indoxyl sulfate (IS) is a typical protein-bound uremic toxin that cannot be effectively cleared by conventional dialysis. Increased IS is associated with the progression of chronic kidney disease and development of cardiovascular disease. After endothelial activation by IS, cells release endothelial microvesicles (EMV) that can induce endothelial dysfunction. We developed an in vitro model of endothelial damage mediated by IS to evaluate the functional effect of EMV on the endothelial repair process developed by endothelial progenitor cells (EPCs). EMV derived from IS-treated endothelial cells were isolated by ultracentrifugation and characterized for miRNAs content. The effects of EMV on healthy EPCs in culture were studied. We observed that IS activates endothelial cells and the generated microvesicles (IsEMV) can modulate the classic endothelial roles of progenitor cells as colony forming units and form new vessels in vitro. Moreover, 23 miRNAs were contained in IsEMV including four (miR-181a-5p, miR-4454, miR-150-5p, and hsa-let-7i-5p) that were upregulated in IsEMV compared with control endothelial microvesicles. Other authors have found that miR-181a-5p, miR-4454, and miR-150-5p are involved in promoting inflammation, apoptosis, and cellular senescence. Interestingly, we observed an increase in NFκB and p53, and a decrease in IκBα in EPCs treated with IsEMV. Our data suggest that IS is capable of inducing endothelial vesiculation with different membrane characteristics, miRNAs and other molecules, which makes maintaining of vascular homeostasis of EPCs not fully functional. These specific characteristics of EMV could be used as novel biomarkers for diagnosis and prognosis of vascular disease.

Objectives: The objective of the following study is to find out the effects of two different pushing techniques in the second stage of labor on postpartum maternal fatigue and APGAR score of neonates in Saudi females, as very few such studies are available in these patients. Hence this study was carried out in this population to see the results and to do a comparison with other studies in literature as well as to find out how we can make labor awareness in our females. Design: Quasi experimental study. Settings: It was carried out in two hospitals in the eastern province of Saudi Arabia from 1 January, 2011 up to 31 December, 2011. One hundred Saudi women who fulfilled criterion were included in the study. They were randomized and the results seen. Results: There was a significant difference in postpartum fatigue within 60 min and 24 h in two groups as P = 0.001, P < 0.001 respectively. There was a significant difference of APGAR score of newborn in both groups, i.e., P < 0.001. Conclusion: It is concluded that physiological pushing technique has a better outcome with regard to postpartum maternal fatigue and neonatal APGAR score when compared to directed pushing during the second stage of labor.

In this study, the linear method of extended partial directed coherence (ePDC) was applied to establish the temporal dynamic behavior of cardiovascular and cardiorespiratory interactions during orthostatic stress at a 70° head-up tilt (HUT) test on young age-matched healthy subjects and patients with orthostatic intolerance (OI), both male and female. Twenty 5-min windows were used to analyze the minute-wise progression of interactions from 5 min in a supine position (baseline, BL) until 18 min of the orthostatic phase (OP) without including pre-syncopal phases. Gender differences in controls were present in cardiorespiratory interactions during OP without compromised autonomic regulation. However in patients, analysis by ePDC revealed considerable dynamic alterations within cardiovascular and cardiorespiratory interactions over the temporal course during the HUT test. Considering the young female patients with OI, the information flow from heart rate to systolic blood pressure (mechanical modulation) was already increased before the tilt-up, the information flow from systolic blood pressure to heart rate (neural baroreflex) increased during OP, while the information flow from respiration to heart rate (respiratory sinus arrhythmia) decreased during the complete HUT test. Findings revealed impaired cardiovascular interactions in patients with orthostatic intolerance and confirmed the usefulness of ePDC for causality analysis.