El colesterol sigue alto. ¿Y ahora qué hacemos? Tratamiento de la hipercolesteremia no controlada a lo largo de un año

ObjetivoConocer la efectividad sobre el control lipídico del tratamiento hipolipemiante, basado en la práctica clínica habitual en atención primaria, en pacientes con hipercolesteremia manifiesta.DiseñoIntervención semiexperimental, antes-después.EmplazamientoCentro de salud urbano. Participantes: 187 pacientes dislipémicos conocidos, con colesterol total o colesterol LDL (cLDL) > 270 o 190 mg/dl, respectivamente.IntervenciónPráctica clínica habitual durante 12 meses en 9 consultas de atención primaria.Mediciones principalesSe registró el perfil lipídico y el tratamiento hipolipemiante al inicio del estudio y al cabo de 12 meses. El control lipídico (en función del cLDL) se evaluó como óptimo, aceptable y deficiente en función del riesgo cardiovascular según los criterios de la Sociedad Española de Arteriosclerosis (1994).ResultadosEn un 27% de casos no se registró ninguna visita relacionada con la hipercolesteremia por su médico. El número de pacientes tratados con hipolipemiantes creció de 50 a 98 (27 frente a 52%; p < 0,005), fundamentalmente a expensas del uso de estatinas. Tras 12 meses, se observaron descensos significativos en la concentración plasmática del cLDL (12%; IC del 95%, 9–15%) y del porcentaje de pacientes con control deficiente, que descendió del 91% inicial al 61% (p < 0,005), aunque sólo un 16% alcanzó un control óptimo.ConclusionesTras un año, con las condiciones de práctica clínica habitual, se observó un incremento en el uso de hipolipemiantes y una mejoría en el control lipídico, aunque algo más de la mitad de los pacientes (61%) con hipercolesteremia manifiesta permanecen con concentraciones tributarias de tratamiento.ObjectiveTo find the effectiveness of lipid-lowering treatment, based on normal clinical practice in primary care, on lipid control of patients with clear hypercholesterolaemia (HC).DesignSemi-experimental before-and-after intervention study.SettingUrban health centre. Participants: 187 patients known to have lipaemia, with total or LDL cCholesterol (cLDL) above 270 and 190 mg/dl, respectivelyInterventionNormal clinical practice for twelve months in nine primary care clinicsMain measurementsThe lipid profile and lipid-lowering treatment were recorded at the start of the study and after twelve months. Lipid control (as a function of cLDL) was evaluated as optimal, acceptable or deficient, as a function of the cardiovascular risk, following the criteria of the Spanish Arteriosclerosis Society (1994)ResultsIn 27% of cases, no visit relating to HC was recorded by the patient´s doctor. The number of patients treated with lipid-lowering drugs grew from 50 to 98 (27 vs 52%, p < 0,005), fundamentally at the expense of statin treatment. After twelve months, there were significant drops in the plasma concentration of cLDL (12%, 95%CI, 9 to 15%) and in the percentage of patients with deficient control, which fell from the initial 91% to 61% (p < 0.005), although only 16% reached optimal control.ConclusionsAfter a year, under conditions of normal clinical practice, there was an increase in the use of lipid-lowering drugs and improvement in lipid control, though a bit over half the patients (61%) with clear hypercholesterolaemia maintained concentrations requiring treatment

Structures of T7 bacteriophage portal and tail suggest a viral DNA retention and ejection mechanism

Double-stranded DNA bacteriophages package their genome at high pressure inside a procapsid through the portal, an oligomeric ring protein located at a unique capsid vertex. Once the DNA has been packaged, the tail components assemble on the portal to render the mature infective virion. The tail tightly seals the ejection conduit until infection, when its interaction with the host membrane triggers the opening of the channel and the viral genome is delivered to the host cell. Using high-resolution cryo-electron microscopy and X-ray crystallography, here we describe various structures of the T7 bacteriophage portal and fiber-less tail complex, which suggest a possible mechanism for DNA retention and ejection: a portal closed conformation temporarily retains the genome before the tail is assembled, whereas an open portal is found in the tail. Moreover, a fold including a seven-bladed β-propeller domain is described for the nozzle tail protein.This work was supported by the Ministry of Science, Innovation and Universities of Spain, grants BFU 2014-54181 (to J.L.C.), BFU 2014-53550-P and BFU2017-83720-P (to M.C.), and contracts SEV-2013-0347 (to A.C.) and RYC-2011-09071 (to C.M.). We acknowledge institutional funding through the Spanish Government Centres and Units of Excellence Severo Ochoa and Maria de Maeztu awards to IRB Barcelona (SEV-2015-0500) and IBMB Structural Biology Unit (MDM-2014-0435), respectively, and from the CERCA Programme of the Catalan Government to the IRB Barcelona. This work has also been supported by the European Commission, Horizon 2020 program through iNEXT project (grant number 653706)

Patient Experience in Pancreas-Kidney Transplantation-A Methodological Approach Towards Innovation in an Established Program

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components

European Society for Organ Transplantation (ESOT) Consensus Statement on the Role of Pancreas Machine Perfusion to Increase the Donor Pool for Beta Cell Replacement Therapy

The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney’s and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating the effects of ischemia incurred during the retrieval process. Recent experimental models of pancreatic MP appear promising. Applications of MP to the pancreas, needs refinement regarding perfusion protocols and organ viability assessment criteria. To address the “Role of pancreas machine perfusion to increase the donor pool for beta cell replacement,” the European Society for Organ Transplantation (ESOT) assembled a dedicated working group comprising of experts to review literature pertaining to the role of MP as a method of improving donor pancreas quality as well as quantity available for transplant, and to develop guidelines founded on evidence-based reviews in experimental and clinical settings. These were subsequently refined during the Consensus Conference when this took place in Prague.</p

Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days old) Duroc breed females (n=21) either with a standard growth diet (3800 kcal/day) or one with a high-calorie content (5200 kcal/day) during 70 days. Computerized tomography, mass-spectrometry-based metabolomics and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake. Samples from a human cohort confirmed potential lipidomic markers. Compared to those fed a standard growth diet, pigs fed a high-calorie diet showed an increased weight gain (13%), much higher adiposity (53%), hypertriacylglyceridemia and hypercholesterolemia in parallel to insulin resistance. This diet induced marked changes in the circulating lipidome, particularly in phosphatidylethanolamine-type molecules. Also, circulating specific diacylglycerol and monoacylglycerol contents correlated with visceral fat and intrahepatic triacylglycerol concentrations. Specific lipids associated with obesity in swine (mainly belonging to glycerophospholipid, triacylglyceride and sterol classes) were also linked with obesity traits in the human cohort, reinforcing the usefulness of the chosen approach. Interestingly, no overt inflammation in plasma or adipose tissue was evident in this model. The presented model is useful as a preclinical surrogate of prepubertal obesity in order to ascertain the pathophysiology interactions between energy intake and obesity development.Supported by Centro para el Desarrollo Tecnológico e Industrial, Spain, Project reference: IPT-20111008, and Generalitat de Catalunya grants 2017SGR1719 and 2017SGR696. MJ is a "Serra Hunter" program fellow. Supported by Instituto de Salud Carlos III, Spain, Project reference: 17-00134, co-financed by FEDER Funds A way to make Europe

Influencia del octreótido sobre la secreción exocrina pancreática después de la duodenopancreatectomía

Trabajo presentado en la XIII Reunión del Club Español Pancreático, celebrada en Alicante, España, del 19 al 21 de septiembre de 2013Peer Reviewe

Using a partial atomic model from medium- resolution cryo-EM to solve a large crystal structure

Medium-resolution cryo-electron microscopy maps, in particular when they include a significant number of α-helices, may allow the building of partial models that are useful for molecular-replacement searches in large crystallo­graphic structures when the structures of homologs are not available and experimental phasing has failed. Here, as an example, the solution of the structure of a bacteriophage portal using a partial 30% model built into a 7.8 Å resolution cryo-EM map is shown. Inspection of the self-rotation function allowed the correct oligomerization state to be determined, and density-modification procedures using rotation matrices and a mask based on the cryo-EM structure were critical for solving the structure. A workflow is described that may be applicable to similar cases and this strategy is compared with direct use of the cryo-EM map for molecular replacement.The following funding is acknowledged: Ministry of Science, Innovation and Universities of Spain (grant Nos. BFU2014-53550-P and BFU2017-83720-P to Miquel Coll; grant No. BFU2014-54181 to Jose´ L. Carrascosa; contract No. SEV2013-0347 to Ana Cuervo; contract No. RYC-2011-09071 to Cristina Machon; award No. SEV-2015-0500 to IRB Barcelona; award No. MDM-2014-0435 to IBMB Structural Biology Unit); Catalan Government CERCA Programme (grant to IRB Barcelona)