Bisphenol A in chronic kidney disease

Phenols are uremic toxins of intestinal origin formed by bacteria during protein metabolism. Of these molecules, p-cresol is the most studied and has been associated with renal function impairment and vascular damage. Bisphenol A (BPA) is a molecule with structural similarity with phenols found in plastic food and beverage containers as well as in some dialyzers. BPA is considered an environmental toxicant based on animal and cell culture studies. Japanese authorities recently banned BPA use in baby bottles based on observational association studies in newborns. BPA is excreted in urine and uremic patients present higher serum levels, but there is insufficient evidence to set cut-off levels or to link BPA to any harmful effect in CKD. However, the renal elimination and potential exposure during dialysis warrant the monitoring of BPA exposure and the design of observational studies in which the potential health risks of BPA for end-stage renal disease patients are evaluated.This research was supported by a grant from ISCIII and FEDER funds PS09/00447, Sociedad Española de Nefrologia, ISCIII-RETICREDinREN/RD06/0016, RD12/0021/,Comunidad de Madrid/CIFRA/S2010/BMD-2378, and salary support was from ERA/EDTA to Usama Elewa and Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to Alberto Ortiz Arduán. ISC III (PI10/ 00072), RECAVA (RD06/0014/0038) and Lilly Foundation to Jesús Egido

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

Acessível em: www.ncbi.nlm.nih.gov/pmc/articles/PMC4423738/Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition

Impact of the COVID-19 pandemic on the organisation of stroke care. Madrid Stroke Care Plan

La sobrecarga asistencial y los cambios organizativos frente a la pandemia de COVID-19 podrían estar repercutiendo en la atención al ictus agudo en la Comunidad de Madrid. Métodos: Encuesta estructurada en bloques: características del hospital, cambios en infraestructura y recursos, circuitos de código ictus, pruebas diagnósticas, rehabilitación y atención ambulatoria. Análisis descriptivo según el nivel de complejidad en la atención del ictus (disponibilidad o no de unidad de ictus y de trombectomía mecánica). Resultados: De los 26 hospitales del SERMAS que atienden urgencias en adultos, 22 cumplimentaron la encuesta entre el 16 y 27 de abril. El 95% han cedido neurólogos para atender a pacientes afectados por la COVID-19. Se han reducido camas de neurología en el 89,4%, modificado los circuitos en urgencias para ictus en el 81%, con circuitos específicos para sospecha de infección por SARS-CoV2 en el 50%, y en el 42% de los hospitales los pacientes con ictus agudo positivos para SARS-CoV2 no ingresan en camas de neurología. Ha mejorado el acceso altratamiento, con trombectomía mecánica las 24 h en el propio hospital en 10 hospitales, y sehan reducido los traslados interhospitalarios secundarios. Se ha evitado el ingreso de pacientescon ataque isquémico transitorio o ictus leve (45%) y se han incorporado consultas telefónicaspara seguimiento en el 100%.Conclusiones: Los cambios organizativos de los hospitales de la Comunidad de Madrid frente ala pandemia por SARS-Co2 han modificado la dedicación de recursos humanos e infraestructurasde las unidades de neurología y los circuitos de atención del ictus, realización de pruebasdiagnósticas, ingreso de los pacientes y seguimientoThe overload of the healthcare system and the organisational changes made inresponse to the COVID-19 pandemic may be having an impact on acute stroke care in the Regionof Madrid.Methods: We conducted a survey with sections addressing hospital characteristics, changes ininfrastructure and resources, code stroke clinical pathways, diagnostic testing, rehabilitation,and outpatient care. We performed a descriptive analysis of results according to the level ofcomplexity of stroke care (availability of stroke units and mechanical thrombectomy).Results: The survey was completed by 22 of the 26 hospitals in the Madrid Regional HealthSystem that attend adult emergencies, between 16 and 27 April 2020. Ninety-five percent ofhospitals had reallocated neurologists to care for patients with COVID-19. The numbers of neuro-logy ward beds were reduced in 89.4% of hospitals; emergency department stroke care pathwayswere modified in 81%, with specific pathways for suspected SARS-CoV2 infection established in50% of hospitals; and SARS-CoV2-positive patients with acute stroke were not admitted to neu-rology wards in 42%. Twenty-four hour on-site availability of mechanical thrombectomy wasimproved in 10 hospitals, which resulted in a reduction in the number of secondary hospitaltransfers. The admission of patients with transient ischaemic attack or minor stroke was avoi-ded in 45% of hospitals, and follow-up through telephone consultations was implemented in100%.Conclusions: The organisational changes made in response to the SARS-Co2 pandemic in hos-pitals in the Region of Madrid have modified the allocation of neurology department staff andinfrastructure, stroke units and stroke care pathways, diagnostic testing, hospital admissions,and outpatient follow-u

Acute stroke care during the COVID-19 pandemic. Ictus Madrid Program recommendations

La pandemia por COVID-19 ha obligado a una reorganización de los sistemas sanitarios y ha comportado una saturación excepcional de sus recursos. En este contexto es vital asegurar la atención al ictus agudo y optimizar los procesos asistenciales del código ictus para reducir el riesgo de contagios y racionalizar el uso de recursos hospitalarios. Para ello, desde el Grupo Multidisciplinar Ictus Madrid proponemos una serie de recomendaciones. Métodos Revisión bibliográfica no sistemática de las publicaciones disponibles con los términos «stroke» y «COVID-19» o «coronavirus» o «SARS-CoV-2», así como otras conocidas por los autores. En base a esta se redacta un documento de recomendaciones que es sometido a consenso por el Grupo Multidisciplinar Ictus Madrid y su Comité de Neurología. Resultados Las recomendaciones se estructuran en cinco líneas fundamentales: 1) coordinar la actuación para garantizar el acceso a la asistencia hospitalaria de los pacientes con ictus; 2) reconocer a los pacientes con ictus potencialmente infectados por COVID-19, 3) organización adecuada para garantizar la protección de los profesionales sanitarios frente al riesgo de contagio por COVID-19, 4) en la realización de neuroimagen y otros procedimientos que conlleven contactos de riesgo de infección COVID-19 hay que procurar reducirlos y asegurar la protección, y 5) alta y seguimiento seguros procurando optimizar la ocupación hospitalaria. Resumimos el procedimiento de forma esquemática con el acrónimo CORONA (COordinar, Reconocer, Organizar, Neuroimagen, Alta). Conclusiones Estas recomendaciones pueden servir de apoyo para la organización del sistema sanitario en la atención al ictus agudo y la optimización de sus recursos, garantizando la protección de sus profesionalesThe COVID-19 pandemic has forced a reorganization of healthcare systems and an exceptional saturation of their resources. In this context, it is vital to ensure acute stroke care and optimize the care processes of the stroke code to reduce the risk of contagion and rationalize the use of hospital resources. To do this, the Ictus Madrid Multidisciplinary Group proposes a series of recommendations. Methods Non-systematic bibliographic review of the available publications with the terms «stroke» and «COVID-19» or «coronavirus» or «SARS-CoV-2», as well as other already known for the authors. We provide a document of recommendations as a result of the consensus of the Ictus Madrid Multidisciplinary Group and its Neurology Committee. Results Our recommendations are structured on five lines: (1) coordinate to guarantee the access to hospital care for stroke patients, (2) recognize potentially COVID-19 infected stroke patients, (3) organize to ensure the protection of healthcare professionals from COVID-19 infections, (4) neuroimaging and other procedures potentially associated to risks for COVID-19 infection should be reduced and secured to avoid contagion, and (5) at home as soon as possible and supported follow-up to optimize hospital occupancy. The procedure is shown summarized under the acronym CORONA (COordinate, Recognize, Organize, Neuroimaging, At home). Conclusions These recommendations can support the organization of healthcare services for acute stroke care and the optimization of their resources, guaranteeing the protection of healthcare professional

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento