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Oncolytic virus (OV) therapy is an emerging cancer treatment that uses replicating viruses to infect and kill tumor cells and incite anticancer immunity. While the approach shows promise, it currently fails most patients, indicating strategies to improve OV activity are needed. Developing these will require greater understanding of OV biology, particularly in the context of OV delivery and clearance, the infection process within a complex tumor microenvironment, and the modulation of anticancer immunity. To help achieve this, we have established a technique for high-resolution 4D imaging of OV-host interactions within intact tissues of live mice using intravital microscopy (IVM). We show that oncolytic vesicular stomatitis virus (VSV) directly labeled with Alexa Fluor dyes is easily visualized by single- or multiphoton microscopy while retaining bioactivity in vivo. The addition of fluorophore-tagged antibodies and genetically encoded reporter proteins to image target cells and the virus infection enables real-time imaging of dynamic interactions between VSV and host cells in blood, tumor, and visceral organs of live mice. The method has sufficient in vivo resolution to observe leukocytes in blood binding to and transporting VSV particles, foci of VSV infection spreading through a tumor, and antigen-presenting cells in the spleen interacting with and being infected by VSV. Visualizing OV-host interactions by IVM represents a powerful new tool for studying OV therapy. Keywords: oncolytic virus, intravital microscopy, virus-host interactions, tumor microenvironment, secondary lymphoid organs

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. Inclusion criteria: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). Exclusion criteria: underaged patients or not agreeing or not being capable of signing the IC. Results: 3470 patients were included, 63% males and with an average age of 67.9 ± 9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. Conclusions: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient. Resumen: El objetivo del estudio ha sido realizar un mapa descriptivo de la enfermedad de Fabry (EF) en la Comunidad de Madrid, así como realizar un despistaje de la EF a todo paciente incidente durante un período de 3 años. Criterios de inclusión: Pacientes mayores de 18 años, excluyendo aquellos diagnosticados de cualquier otra enfermedad hereditaria con afectación renal diferente de la EF, que firmaran el consentimiento informado. Criterios de exclusión: pacientes menores de edad, no estar de acuerdo o no ser capaces de firmar el consentimiento informado. Resultados: Se incluyeron 3.470 pacientes (63% hombres), con una edad media de 67,9 ± 9,7 años, de los cuales 2.357 eran pacientes prevalentes y 1.113 incidentes. En el caso de los pacientes prevalentes, el tiempo medio en hemodiálisis (HD) fue de 45,2 (DE 51,3) meses. En pacientes incidentes, la proteinuria estuvo presente en el 28,4%. No hubo diferencias estadísticamente significativas en la actividad plasmática de alfa-galactosidasa A o valores de Lyso-Gl3 al comparar las poblaciones de incidentes y de prevalentes, y tampoco entre hombres y mujeres. Se realizó estudio genético en 87 pacientes (2,5% de los pacientes): 60 varones con disminución de la actividad enzimática y 27 mujeres con una disminución de la actividad enzimática, aumento de los niveles de Lyso-Gl3 o ambos. Las variantes genéticas identificadas fueron: p.Asp313Tyr (4 pacientes), p.Arg220Gln (3 pacientes) y M290I (un paciente). Ninguna de las variantes identificadas fue patógena. Conclusiones: El 76% de los centros de HD de la Comunidad de Madrid participaron en el estudio. Este es el primer estudio epidemiológico prospectivo de EF en la población de HD de una región de España. También es la primera vez que se describen niveles de alfa-galactosidasa A y Lyso-Gl3 en HD, sin embargo, en este estudio no se han identificado pacientes con EF.

Conclusions: Future research should focus on the neuropathic characteristics of pain patients with OP, in order to better manage OP-related pain.

IntroductionThis randomized, controlled, single-blinded trial assessed the effect of magnesium (Mg)-Teadiola (Mg, vitamins B6, B9, B12, Rhodiola, and green tea/L-theanine) versus placebo on the brain response to stressful thermal stimulus in chronically stressed, but otherwise healthy subjects. Impacts on stress-related quality-of-life parameters (depression, anxiety, sleep, and perception of pain) were also explored.MethodsThe study recruited a total of 40 adults (20 per group), suffering from stress for more than 1 month and scaling ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire at the time of inclusion. Individuals received oral Mg-Teadiola or placebo for 28 days (D). fMRI analysis was used to visualize the interplay between stress and pain cerebral matrices, using thermal stress model, at baseline (D0) and after D28.ResultsBased on blood-oxygen-level-dependent (BOLD) signal variations during the stress stimulation (before pain perception), a significantly increased activation between D0 and D28 was observed for left and right frontal area (p = 0.001 and p = 0.002, respectively), left and right anterior cingulate cortex (ACC) (p = 0.035 and p = 0.04, respectively), and left and right insula (p = 0.034 and p = 0.0402, respectively) in Mg-Teadiola versus placebo group. During thermal pain stimulation, a significantly diminished activation of the pain matrix was observed between D0 and D28, for left and right prefrontal area (both p = 0.001), left and right insula (p = 0.008 and p = 0.019, respectively), and left and right ventral striatum (both p = 0.001) was observed in Mg-Teadiola versus placebo group. These results reinforce the clinical observations, showing a perceived benefit of Mg-Teadiola on several parameters. After 1 month of treatment, DASS-42 stress score significantly decreased in Mg-Teadiola group [effect size (ES) −0.46 (−0.91; −0.01), p = 0.048]. Similar reductions were observed on D14 (p = 0.011) and D56 (p = 0.008). Sensitivity to cold also improved from D0 to D28 for Mg-Teadiola versus placebo [ES 0.47 (0.02; 0.92) p = 0.042].ConclusionSupplementation with Mg-Teadiola reduced stress on D28 in chronically stressed but otherwise healthy individuals and modulated the stress and pain cerebral matrices during stressful thermal stimulus.

Safe and anti-inflammatory plant-based natural products present an increasing focus in the treatment of chronic inflammatory diseases such as osteoarthritis or inflammatory bowel diseases. Among them, saffron, a spice derived from the stigma of Crocus sativus, could have anti-inflammatory properties and would be therefore a promising therapeutic agent for the treatment of such conditions. However, the anti-inflammatory molecular mechanisms of saffron in humans are still understudied and unclear. In this study, combining human serum metabolites and cell cultures, we evaluated the effect of circulating metabolites from the consumption of a patented saffron extract (Safr’InsideTM) on the chondrocytes and colon epithelial cell responses to inflammatory stress. Parametric or non-parametric Analysis of Variance with post hoc tests was performed. We demonstrated that human serum containing metabolites from saffron intake attenuated IL-1β-stimulated production of PGE2 and MMP-13 in chondrocyte cells and limited the increase in ICAM-1, MCP-1, iNOS, and MMP-3 in human epithelial cells following combined IL-1β and TNF-α inflammatory stimulation. Altogether, these data provide new findings into the mechanisms underlying the beneficial effects of saffron on chondrocytes and enterocyte cells at the cellular level and in the context of chronic inflammatory disorders.

Kidney transplant recipients are at increased risk for infection, including coronavirus disease 2019 (COVID-19), given ongoing immunosuppression. In individuals with COVID-19, complications including thrombosis and endothelial dysfunction portend worse outcomes. In this report, we describe a kidney transplant recipient who developed severe thrombotic microangiopathy with a low platelet count (12 ×109/L), anemia (hemoglobin, 7.5 g/dL with 7% schistocytes on peripheral-blood smear), and severe acute kidney injury concurrent with COVID-19. The clinical course improved after plasma exchange. Given this presentation, we hypothesize that COVID-19 triggered thrombotic microangiopathy.

Resumen: Introducción: La hipotensión arterial intradiálisis (HAID) es una complicación frecuente que se asocia a una mayor morbimortalidad en hemodiálisis, aunque es una tarea pendiente la uniformidad de criterios respecto a su definición. El objetivo del estudio es analizar las características de distintas definiciones de hipotensión y su relación con la morbimortalidad en una cohorte de pacientes en hemodiálisis. Metodología: Estudio observacional, con un seguimiento de 30 meses, que incluye 68 pacientes prevalentes en hemodiálisis con al menos 6 meses de tratamiento. Se recogieron parámetros de diálisis, y distintas definiciones de hipotensión, de 18 sesiones no consecutivas (las primeras 3 sesiones de cada mes de un período de 6 meses). Se definió como evento positivo de HAID si ocurría cualquier definición en más del 25% de las sesiones estudiadas. Se analizó el poder predictivo para cada definición de hipotensión (Nadir90, Nadir100, Fall20, Fall30, Fall20Nadir90, Fall30Nadir90, KDOQI, HEMO) mediante un análisis de supervivencia. Se estimó la relación con los eventos cardiovasculares no fatales y la mortalidad global mediante distintos modelos proporcionales de Cox. Resultados: Encontramos definiciones de HAID que ocurrieron con una significativa mayor frecuencia (Nadir100: 339,8/1.000 sesiones; Nadir90: 172,3/1.000 sesiones) en comparación con otras (KDOQI: 98/1.000 sesiones; HEMO 129,9/1.000 sesiones). Con una media de seguimiento de 27,12 ± 6,84 meses se registraron 13 eventos mortales. Un mayor número de sesiones con HAID conforme a la definición Nadir90 fue un factor predictor de mortalidad (Log rank 5,02, p = 0,025), independiente según los modelos ajustados (HR: 3,23 [IC95%: 1,08-9,6], p = 0,035). Las definiciones Nadir100 (HR: 4,54 [IC95%: 1,25-16,4], p = 0,02) y Fall30Nadir90 (HR: 3,08 [IC95%: 1,07-8,8], p = 0,03) fueron predictores independientes de eventos cardiovasculares no fatales en los modelos ajustados. Conclusiones: La hipotensión intradiálisis, incluso asintomática, tiene poder predictivo de mortalidad y eventos cardiovasculares no fatales en pacientes prevalentes en hemodiálisis. Abstract: Introduction: Intradialytic hypotension (IDH) is a common complication and is associated with higher morbidity and mortality in patients on haemodialysis. However, there is a lack of uniformity in definitions of IDH. The main objective of this study is to analyse clinical and dialysis related factors with several IDH definitions, and its relationship with morbidity and mortality in a cohort of haemodialysis patients. Methodology: Observational study with a 30-month follow-up period that includes 68 prevalent patients on haemodialysis with at least six months of treatment. We analysed 18 non-consecutive dialysis sessions (first three of each month of a six-month period), and different definitions of IDH were recorded. A positive event of IDH was defined if any definition occurred in more than 25% of the sessions studied. Using survival analysis, we analysed the prediction capacity of each IDH definition (Nadir90, Nadir100, Fall20, Fall30, Fall20Nadir90, Fall30Nadir90, KDOQI, HEMO). The relationship with non-fatal cardiovascular disease and global mortality was estimated using different Cox proportional models. Results: We found IDH definitions that occurred significantly more frequently (Nadir100: 339.8/1,000 sessions, Nadir90: 172.3/1,000 sessions) than others (KDOQI: 98/1,000 sessions, HEMO 129.9/1,000 sessions). We registered 13 fatal events with a mean follow-up of 27.12 ± 6.84 months. A greater number of sessions with IDH according to the Nadir90 definition was a predictive factor of mortality (Log rank 5.02, p = 0.025), independent according to adjusted models (HR: 3.23 [95% CI: 1.08-9.6], p = 0.035). The definitions Nadir100 (HR: 4.54 [95% CI: 1.25-16.4], p = 0.02) and Fall30Nadir90 (HR: 3.08 [95% CI: 1.07-8.8], p = 0.03) were independent predictors of non-fatal cardiovascular disease in adjusted models. Conclusions: Intradialytic hypotension, even asymptomatic, is a predictor of mortality and non-fatal cardiovascular disease in prevalent patients on haemodialysis.

Introduction Although epidemiological studies associate the consumption of sugary beverages with adverse health effects, human experimental studies have demonstrated substantially different metabolic responses when 100% fruit juices are compared with artificial beverages. Fruit juices do not just provide sugars and associated calories, but they are also rich in bioactive compounds. Flavanones are bioactives specifically and abundantly found in citrus foods, with hesperidin as the major representative in sweet oranges. Flavanone intake has been associated with a lower incidence of mortality from cardiovascular disease (CVD). However, clinical evidence are too scarce to confirm the vasculoprotective effects of 100% orange juice (OJ) presumably mediated by flavanones and thereby do not allow firm conclusions to be drawn about their efficacy.Methods and analysis The HESPER-HEALTH study aims to assess the efficacy of OJ in improving vascular function and the contribution of hesperidin to these effects. This double-blind, randomised, controlled, crossover study will be carried out in 42 volunteers predisposed to CVD, based on age and on overweight. It includes three 6-week periods of consumption of 330 mL/d of OJ versus control drinks with and without hesperidin at a dose in agreement with a daily OJ serving (approx. 200–215 mg). The primary outcome is endothelial function, assessed by flow mediated dilation, with measurements performed at fasting and postprandially in response to a challenge meal. The secondary outcomes include bioavailability and metabolism of flavanones, changes in other markers of vascular function, systemic biomarkers of cardiovascular risk, endothelial dysfunction and inflammation, vitamin C and carotenoids status, anthropometry and body composition, gut microbiota composition, nutrigenomic response and in oxylipin profiling.Ethics and dissemination This ongoing study was approved by the Ethics committee Sud-Est III, Bron, France on 17 November 2020. The trial is registered on ClinicalTrials.gov. The results will be disseminated in peer-reviewed journals.Trial registration number NCT04731987; Pre-results.

Background and objective: Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyze the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF. Material and methods: Prospective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated hemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analyzed. Results: Age at baseline was 69.7 ± 13.6 years, 62.1% were male, 72.3 ± 13.9 kg, 1.78 ± 0.16 m2, with 48 (35.5–76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9 ± 2.9 L/session and follow-up period (time on OL-HDF) was 40.4 ± 26 months.A significant correlation was observed between mean substitution volume and the increase in HDL-c (r = 0.385, p = 0.039) and prealbumin levels (r = 0.404, p = 0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r = −0.531, p = 0.005), 2 years (r = −0.463, p = 0.046), and at the end of follow-up (r = −0.498, p = 0.007). Patients with mean substitution volume >26.9 L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with >26.9 L/session finished the study with higher HDL-c (48.1 ± 9.4 mg/dL vs. 41.2 ± 11.6 mg/dL, p = 0.025) and lower CRP levels (0.21 [0.1–2.22] mg/dL vs. 1.01 [0.15–6.96] mg/dL, p = 0.001), with no differences at baseline.Quarterly comparisons between substitution volume and laboratory changes [n = 271] showed a significant correlation with a reduction in HbA1c (r = −0.146, p = 0.021). Similar findings were obtained with annual comparisons [n = 72] (r = −0.237, p = 0.045). An annual mean substitution volume over 26.6 L/session (29.3 ± 1.7 L/session vs. 23.9 ± 1.9 L/session) was associated with a reduction in HbA1c (−0.51 ± 1.24% vs. 0.01 ± 0.88%, p = 0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters. Conclusion: There is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid. Resumen: Antecedentes y objetivo: La hemodiafiltración online (HDF-OL) con altos volúmenes de transporte convectivo mejora la supervivencia en los pacientes en hemodiálisis. Se ha propuesto limitar el volumen convectivo en los pacientes diabéticos por la carga de glucosa administrada con el líquido de sustitución. El objetivo del estudio fue analizar la influencia del volumen de sustitución en la evolución del perfil metabólico y la composición corporal de los pacientes diabéticos incidentes en HDF-OL. Material y métodos: Estudio observacional prospectivo en 29 pacientes diabéticos incidentes en HDF-OL posdilución. Basalmente se recogieron datos clínicos y demográficos, parámetros analíticos metabólicos, nutricionales e inflamatorios, y la composición corporal por bioimpedancia espectroscópica (BIS). Cada 4 meses se recogieron parámetros analíticos y el volumen de sustitución medio por sesión, y en 23 pacientes se realizó otra BIS al menos un año después. Se calcularon variaciones de hemoglobina glucosilada (HbA1c), triglicéridos, colesterol total, c-LDL, c-HDL, albúmina, prealbúmina y proteína C reactiva (PCR) al año, 2 años, 3 años y al final del seguimiento. Se calcularon las variaciones cuatrimestrales y anuales como periodos independientes, y se analizaron los cambios de composición corporal. Resultados: La edad al inicio fue a los 69,7 ± 13,6 años; el 62,1% eran varones, de 72,3 ± 13,9 kg, 1,78 ± 0,16 m2, y con 48 (35,5-76) meses en diálisis. El 81,5% recibía insulinoterapia, el 7,4% antidiabéticos y el 51,9% estatinas. El volumen de sustitución medio fue de 26,9 ± 2,9 L/sesión y el periodo de seguimiento (tiempo en HDF-OL) fue de 40,4 ± 26 meses.Se observó una correlación significativa entre el volumen de sustitución medio y un incremento de los niveles de c-HDL (r = 0,385, p = 0,039) y prealbúmina (r = 0,404, p = 0,003) a lo largo del seguimiento. El volumen convectivo se asoció a la reducción de los niveles de PCR al año (r = −0,531, p = 0,005), a los 2 años (r = −0,463, p = 0,046) y al final del seguimiento (r = −0,498, p = 0,007). Los pacientes con volumen de sustitución >26,9 L/sesión tuvieron mayor descenso en los niveles de triglicéridos y PCR, y un aumento de las cifras de c-HDL. Estos pacientes con >26,9 L/sesión finalizaron el estudio con niveles más altos de c-HDL (48,1 ± 9,4 mg/dL vs. 41,2 ± 11,6 mg/dL, p = 0,025) y más bajos de PCR (0,21 [0,1-2,22] mg/dL vs. 1,01 [0,15-6,96] mg/dL, p = 0,001), sin diferencias al inicio.Las comparaciones entre el volumen de sustitución y los cambios analíticos por periodos cuatrimestrales [n = 271] mostraron una correlación significativa con un descenso de HbA1c (r = −0,146, p = 0,021), al igual que las comparaciones por periodos anuales [n = 72] (r = −0,237, p = 0,045). Un volumen de sustitución medio anual >26,6 L/sesión (29,3 ± 1,7 L/sesión vs. 23,9 ± 1,9 L/sesión) se asoció a un descenso de HbA1c (−0,51 ± 1,24% vs. 0,01 ± 0,88%, p = 0,043). No se observó correlación entre el volumen de sustitución y las variaciones en el peso, IMC o parámetros de la BIS.Conclusión No existe suficiente evidencia para limitar el transporte convectivo en los pacientes diabéticos en HDF-OL por el contenido de glucosa del líquido de sustitución. Keywords: Haemodiafiltration, Online haemodiafiltration, Diabetes, Palabras clave: Hemodiafiltración, Hemodiafiltración online, Diabetes

Resumen: Antecedentes y objetivo: La hemodiafiltración online (HDF-OL) con altos volúmenes de transporte convectivo mejora la supervivencia en los pacientes en hemodiálisis. Se ha propuesto limitar el volumen convectivo en los pacientes diabéticos por la carga de glucosa administrada con el líquido de sustitución. El objetivo del estudio fue analizar la influencia del volumen de sustitución en la evolución del perfil metabólico y la composición corporal de los pacientes diabéticos incidentes en HDF-OL. Material y métodos: Estudio observacional prospectivo en 29 pacientes diabéticos incidentes en HDF-OL posdilución. Basalmente se recogieron datos clínicos y demográficos, parámetros analíticos metabólicos, nutricionales e inflamatorios, y la composición corporal por bioimpedancia espectroscópica (BIS). Cada 4 meses se recogieron parámetros analíticos y el volumen de sustitución medio por sesión, y en 23 pacientes se realizó otra BIS al menos un año después. Se calcularon variaciones de hemoglobina glucosilada (HbA1c), triglicéridos, colesterol total, c-LDL, c-HDL, albúmina, prealbúmina y proteína C reactiva (PCR) al año, 2 años, 3 años y al final del seguimiento. Se calcularon las variaciones cuatrimestrales y anuales como periodos independientes, y se analizaron los cambios de composición corporal. Resultados: La edad al inicio fue a los 69,7 ± 13,6 años; el 62,1% eran varones, de 72,3 ± 13,9 kg, 1,78 ± 0,16 m2, y con 48 (35,5-76) meses en diálisis. El 81,5% recibía insulinoterapia, el 7,4% antidiabéticos y el 51,9% estatinas. El volumen de sustitución medio fue de 26,9 ± 2,9 L/sesión y el periodo de seguimiento (tiempo en HDF-OL) fue de 40,4 ± 26 meses.Se observó una correlación significativa entre el volumen de sustitución medio y un incremento de los niveles de c-HDL (r = 0,385, p = 0,039) y prealbúmina (r = 0,404, p = 0,003) a lo largo del seguimiento. El volumen convectivo se asoció a la reducción de los niveles de PCR al año (r = −0,531, p = 0,005), a los 2 años (r = −0,463, p = 0,046) y al final del seguimiento (r = −0,498, p = 0,007). Los pacientes con volumen de sustitución > 26,9 L/sesión tuvieron mayor descenso en los niveles de triglicéridos y PCR, y un aumento de las cifras de c-HDL. Estos pacientes con > 26,9 L/sesión finalizaron el estudio con niveles más altos de c-HDL (48,1 ± 9,4 mg/dL vs. 41,2 ± 11,6 mg/dL, p = 0,025) y más bajos de PCR (0,21 [0,1-2,22] mg/dL vs. 1,01 [0,15-6,96] mg/dL, p = 0,001), sin diferencias al inicio.Las comparaciones entre el volumen de sustitución y los cambios analíticos por periodos cuatrimestrales [n = 271] mostraron una correlación significativa con un descenso de HbA1c (r = −0,146, p = 0,021), al igual que las comparaciones por periodos anuales [n=72] (r = −0,237, p = 0,045). Un volumen de sustitución medio anual > 26,6 L/sesión (29,3 ± 1,7 L/sesión vs. 23,9 ± 1,9 L/sesión) se asoció a un descenso de HbA1c (−0,51 ± 1,24% vs. 0,01 ± 0,88%, p = 0,043). No se observó correlación entre el volumen de sustitución y las variaciones en el peso, IMC o parámetros de la BIS.Conclusión No existe suficiente evidencia para limitar el transporte convectivo en los pacientes diabéticos en HDF-OL por el contenido de glucosa del líquido de sustitución. Abstract: Background and objective: Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF. Material and methods: Prospective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated haemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analysed. Results: Age at baseline was 69.7 ± 13.6 years, 62.1% were male, 72.3 ± 13.9 kg, 1.78 ± 0.16 m2, with 48 (35.5-76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9 ± 2.9 L/session and follow-up period (time on OL-HDF) was 40.4 ± 26 months.A significant correlation was observed between mean substitution volume and the increase in HDL-c (r = 0.385, p = 0.039) and prealbumin levels (r = 0.404, p = 0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r = –0.531, p = 0.005), 2 years (r = –0.463, p = 0.046), and at the end of follow-up (r = –0.498, p = 0.007). Patients with mean substitution volume > 26.9 L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with > 26.9 L/session finished the study with higher HDL-c (48.1 ± 9.4 mg/dL vs. 41.2 ± 11.6 mg/dL, p = 0.025) and lower CRP levels (0.21 [0.1-2.22] mg/dL vs. 1.01 [0.15-6.96] mg/dL, p = 0.001), with no differences at baseline.Quarterly comparisons between substitution volume and laboratory changes [n = 271] showed a significant correlation with a reduction in HbA1c (r = –0.146, p = 0.021). Similar findings were obtained with annual comparisons [n = 72] (r = –0.237, p = 0.045). An annual mean substitution volume over 26.6 L/session (29.3 ± 1.7 L/session vs. 23.9 ± 1.9 L/session) was associated with a reduction in HbA1c (–0.51 ± 1.24% vs. 0.01 ± 0.88%, p = 0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters. Conclusion: There is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid. Palabras clave: Hemodiafiltración, Hemodiafiltración online, Diabetes, Keywords: Haemodiafiltration, Online haemodiafiltration, Diabetes

Resumen: Antecedentes y objetivo: El abordaje multidisciplinar y el uso de ecografía doppler (ED) en la creación y vigilancia del acceso vascular (AV) puede mejorar la prevalencia y permeabilidad de las fístulas arteriovenosas (FAV) para hemodiálisis. El objetivo de este estudio es analizar el impacto de una nueva consulta multidisciplinar (CMD) de AV con ED de rutina. Material y métodos: Evaluamos los resultados de la consulta de AV en 2014 (pre-CMD) y 2015 (CMD), antes y después de la implantación de un equipo multidisciplinar (cirujano vascular/nefrólogo) con ED de rutina en mapeo prequirúrgico y FAV prevalente. Resultados: Se evaluaron 345 pacientes en 2014 (pre-CMD) y 364 pacientes en 2015 (CMD). En ambos periodos se realizó un número similar de cirugías, 172 vs. 198, p =0,289, con tendencia a aumentar las cirugías preventivas de reparación de FAV en el periodo CMD, 17 vs. 29 (p = 0,098). En FAV de nueva creación (155 vs. 169), disminuyó la tasa de fallo primario en el periodo CMD, 26,4 vs. 15,3%, p = 0,015 y aumentó de forma no significativa la realización de FAV radiocefálicas distales, 25,8 vs. 33,2% (n = 40 vs. 56), p = 0,159. También aumentó la concordancia entre la indicación quirúrgica en la consulta y la cirugía realizada (81,3 vs. 93,5%, p = 0,001). En el periodo CMD se solicitaron menos exploraciones radiológicas desde la consulta, 78 vs. 35 (p

Background: A multidisciplinary approach and Doppler ultrasound (DU) assessment for the creation and maintenance of arteriovenous fistulas (AVF) for haemodialysis can improve prevalence and patency. The aim of this study was to analyze the impact of a new multidisciplinary vascular access (VA) clinic with routine DU. Material and methods: We analyzed the VA clinic results from 2014 and 2015, before and after the implementation of a multidisciplinary team protocol (vascular surgeon/nephrologist) with routine DU in preoperative mapping and prevalent AVF. Results: We analyzed 345 and 364 patients from 2014 and 2015 respectively. The number of surgical interventions was similar in both periods (p = .289), with a trend toward an increase in preventive surgical repair of AVF in 2015 (17 vs. 29, p = .098). 155 vs. 169 new AVF were performed in 2014 and 2015, with a significantly lower primary failure rate in 2015 (26.4 vs. 15.3%, p = .015), and a non-significant increase in radiocephalic AVF, 25.8 vs. 33.2% (n = 40 vs. 56), p = .159. The concordance between the indication at the clinic and the surgery performed also increased (81.3 vs. 93.5%, p = .001). Throughout 2015 fewer complementary imaging test were requested from the clinic (78 vs. 35, p

Background and objectives: Hyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass. Design, setting, participants, & measurements: Retrospective study with a cohort of 324 patients with reduced renal mass from an outpatient basis, followed during 60 (36–98) months. Demographics variables, cardiovascular factors, concomitant medications, albuminuria and uric acid levels were recorded yearly. The primary endpoint was the annual fall of estimated glomerular filtration rate (eGFR) by MDRD-4. The sample was divided into three successive groups (A1: patients with fall of eGFR lower than median, A2: greater than median, B: without fall of eGFR). Factors associated and predictors of kidney function decline were analyzed. Results: One hundred and seventy out of 324 patients suffered a fall of eGFR (group A), (median of fall −1.6 ml/min/1.73 m2/year (−3.0, −0.7)). Male gender, albuminuria > 100 mg/day and higher pulse pressure were associated to progression in our cohort (group A). Hyperuricemia was more frequent among patients with higher kidney disease progression (group A2) (33% vs 49%, p = 0.04) when comparing to lower progression (group A1). Adjusted Cox regression models showed that hyperuricemia, pulse pressure and albuminuria were independent predictors of kidney disease progression (HR 1.67 (1.06–2.63), p = 0.023; 1.02 (1.01–1.03), p = 0.001 and HR: 2.14 (1.26–3.64), p = 0.005, respectively). Kidney disease progression was higher in patients with unilateral renal atrophy or agenesis than nephrectomy (log rank: 7.433, p = 0.006). Conclusions: Hyperuricemia is independently associated with kidney disease progression in patients with reduce functioning renal mass.

Hepatitis C virus (HCV) infection is highly prevalent among patients on haemodialysis and leads to a poorer prognosis compared to patients who do not have said infection. Treatment with interferon and ribavirin is poorly tolerated and there are limited data on the experience with new direct-acting antivirals (DAAs). The aim of this study is to retrospectively analyse the current prevalence of HCV infection and efficacy and safety results with different DAA regimens in the haemodialysis population of 2 hospital areas. This is a multicentre, retrospective and observational study in which HCV antibodies were analysed in 465 patients, with positive antibody findings in 54 of them (11.6%). Among these, 29 cases (53.7%) with genotypes 1 and 4 were treated with different DAA regimens, including combinations of paritaprevir/ritonavir, ombitasvir, dasabuvir, sofosbuvir, simeprevir, daclatasvir and ledipasvir, with/without ribavirin. Mean age was 53.3 ± 7.9 years, 72.4% of patients were male and the most important aetiology of chronic kidney disease involved glomerular abnormalities. In 100% of cases, a sustained viral response was achieved after 24 weeks, regardless of DAA regimen received. Adverse effects were not relevant and no case required stopping treatment. In 15 cases, ribavirin was combined with the DAA. In these cases, the most significant adverse effect was anaemic tendency, which was reflected in the increase of the dose of erythropoietin stimulating agents, although none required transfusions. In summary, we conclude that new DAAs for the treatment of HCV in haemodialysis patients are highly effective with minimal adverse effects; it is a very important advance in HCV management. These patients are therefore expected to have a much better prognosis than they have had until very recently.

La infección por el virus de la hepatitis C (VHC) es muy prevalente entre los pacientes en hemodiálisis y condiciona un peor pronóstico respecto a los que no la padecen. El tratamiento con interferón y ribavirina es mal tolerado y existen pocos datos sobre la experiencia con los nuevos antivirales de acción directa (AAD). El objetivo de este trabajo es estudiar retrospectivamente la prevalencia actual de la infección por el VHC y los resultados de eficacia y seguridad con distintas pautas de AAD en la población en hemodiálisis de 2 áreas hospitalarias. Estudio multicéntrico, retrospectivo y observacional en el que se analizan los anticuerpos frente al VHC en 465 pacientes, entre los que 54 de ellos eran positivos (11,6%). Entre estos, 29 casos (53,7%) con genotipos 1 y 4 fueron tratados con distintas pautas de AAD, que incluían combinaciones de paritaprevir/ritonavir, ombitasvir, dasabuvir, sofosbuvir, simeprevir, daclatasvir y ledipasvir, con/sin ribavirina. La edad media era de 53,3 + 7,9 años, el 72,4% eran varones y la causa más importante de la enfermedad renal crónica eran las alteraciones glomerulares. En el 100% de los casos se obtuvo una respuesta viral sostenida a las 24 semanas independientemente de la pauta de AAD recibida. Los efectos secundarios fueron poco relevantes y ningún caso precisó suspender el tratamiento. En 15 de ellos, se asoció ribavirina a los AAD. En estos casos, el efecto adverso más destacable fue la tendencia a la anemización, reflejada en el incremento de la dosis de agentes estimulantes de la eritropoyesis, aunque ninguno precisó transfusiones. En resumen, concluimos que los nuevos AAD para el tratamiento del VHC en pacientes en hemodiálisis presentan una gran eficacia, con mínimos efectos secundarios, y constituyen un avance muy importante en su manejo, con lo que cabe esperar un pronóstico mucho mejor que el que presentaban hasta muy recientemente.

Haematuria has been traditionally considered as a benign hallmark of some glomerular diseases; however new studies show that haematuria may decrease renal function.To determine the influence of haematuria on the rate of chronic kidney disease (CKD) progression in 71 proteinuric patients with advanced CKD (baseline eGFR 65 years (-1.2±6.8 (HP) vs. 1.5±7.7 (P) mL/min/1.73 m2/year). Furthermore, the harmful effect of haematuria on eGFR slope was found patients with proteinuria >0.5 g/24 h (-5.8±6.4 (HP) vs. -1.37± 7.9 (P) mL/min/1.73 m2/year, p