Infective endocarditis after transcatheter aortic valve replacement : new insights into incidence, clinical characteristics, management, and outcomes

L'endocardite infectieuse (EI) est une complication rare mais potentiellement mortelle du remplacement valvulaire aortique percutané (TAVR). Le TAVR a révolutionné le traitement de la sténose aortique sévère et est récemment devenu une option thérapeutique pour les patients plus jeunes avec un risque chirurgical faible. Par conséquent, le nombre de patients à risque de développer cette complication grave augmente de façon exponentielle. Il existe peu de données sur l'EI après le TAVR et plusieurs questions restent sans réponse. Tout d'abord, au cours des dernières années, il y a eu un intérêt croissant pour limiter les gestes invasifs péri-procéduraux au cours des TAVR. De plus, la simplification des procédures a permis un rétablissement plus rapide des patients, de réduire la durée d'hospitalisation et de réduire le risque d'infection nosocomiale. Cependant, l'impact de la combinaison de ces améliorations et du profil clinique contemporain des patients bénéficiant d'un TAVR sur l'incidence et les conséquences des EI post-TAVR reste à ce jour incertain. Deuxièmement, une EI causée par un Staphylococcus aureus ainsi que la survenue d'une accident vasculaire cérébral pendant l'hospitalisation pour EI sont classiquement associées à un pronostic sombre chez les patients présentant une EI sur valve native ou prothétique. Cependant, il existe peu de données sur l'incidence, la prise en charge et l'évolution de ces deux situations particulières dans le cadre des IE-TAVR. Ensuite, de nouvelles techniques d'imagerie sont apparues comme étant un outil prometteur en vue d'un diagnostic plus précis de l'IE post-TAVR. Au sein des valves prothétiques chirurgicales, une légère absorption des radio-traceurs dans la zone périvalvulaire peut se produire en l'absence d'infection. Cependant, les preuves de l'existence d'un tel phénomène au sein des prothèses TAVR font défaut, et les normes permettant de distinguer une répartition normale d'une répartition anormale du traceur radioactif n'ont pas encore été établies. Enfin, bien que la chirurgie soit un traitement efficace et bien établi chez les patients présentant une EI sur valve prothétique, le traitement optimal de l'EI après le TAVR reste indéterminé. Les principaux objectifs de ce projet de doctorat sont: (i) de déterminer les tendances temporelles de l'incidence, des caractéristiques cliniques, de la prise en charge et des résultats de l'EI post-TAVR, (ii) d'évaluer l'incidence et les résultats de l'EI post-TAVR dans certains sous-groupes spécifiques de patients, (iii) de déterminer le rôle des nouvelles techniques d'imagerie pour le diagnostic de l'EI après le TAVR et (iv) d'évaluer les caractéristiques et les résultats des patients non sélectionnés atteints d'EI après le TAVR traités par chirurgie cardiaque comparés aux patients traités uniquement par antibiotiques.Infective endocarditis (IE) is a rare but life-threatening complication following transcatheter aortic valve replacement (TAVR). TAVR has revolutionized the treatment of severe aortic stenosis and is currently expanding toward the treatment of younger patients with lower surgical risks. Consequently, the number of patients at risk of developing this serious complication is growing exponentially. Despite this, there is a paucity of data on IE following TAVR, and several questions remain unanswered. Firstly, there has recently been an increase in interest in simplifying the TAVR procedure. This would allow for more rapid patient recovery, a shorter length of hospital stay, and a lower risk of nosocomial infections. However, it is unknown whether this minimalist approach, combined with the contemporary clinical profile of TAVR patients, has influenced the incidence and outcomes of IE. Secondly, two specific subgroups of patients (those with IE caused by Staphylococcus aureus, and those with TAVR-IE complicated by stroke during the index hospitalization) have typically been associated with a worse prognosis in native and prosthetic valve IE. However, there is a scarcity of data on the incidence, management, and outcomes of these patients in the TAVR-IE population. Thirdly, novel imaging techniques have emerged as promising tools for improving diagnostic accuracy in patients with TAVR-IE. In surgical prosthetic valves, mild radiotracer uptake may be identified in the perivalvular area in the absence of infection. However, there is no evidence of this phenomenon in TAVR devices, and the standards for distinguishing normal and abnormal uptake patterns have not yet been described. Finally, although surgery is an effective and well-established treatment for prosthetic valve endocarditis in some clinical scenarios, the optimal management of TAVR-IE remains uncertain. The main objectives of this Ph.D. research project are to: (i) determine temporal trends in the incidence, clinical characteristics, management, and outcomes of IE post TAVR; (ii) assess the incidence and outcomes of TAVR-IE in specific patient subgroups;(iii) determine the role of novel imaging techniques for the diagnosis of TAVR-IE; and (iv) evaluate the characteristics and outcomes of patients with IE following TAVR who were treated with cardiac surgery, compared with those treated with antibiotics alone

La inversión Matuyama-Brunhes en la secuencia de terrazas del río Jarama entre Velilla de San Antonio y Altos de la Mejorada, al SE de Madrid (España)

Al Este de la ciudad de Madrid, en el valle del río Jarama y entre Mejorada del Campo y Velilla de San Antonio se han estudiado las propiedades paleomagnéticas de una secuencia de terrazas comprendidas entre El Rasillo y Altos de la Mejorada, a lo largo de la autopista M-203 de reciente construcción. La cartografía geomorfológica realizada permitió separar además de la llanura aluvial a +4-5 m, terrazas a +20 m, +30-35 m, +60-65 m, +85-90 m, +105-110 m y +125-130 m. De ellas se muestrearon 5 niveles, a excepción de la de +20 m, en taludes frescos de la autovía que permiten situar a las terrazas con altitudes relativas igual o mayores a +60-65 m en el Chron Matuyama, mientras que las terrazas a +20 m y +30-35 m pertenecerían al Chron Brunhes (< 0.780 Ma). Dataciones por ESR en terrazas del valle del río Arlanzón en Burgos (Moreno et al., 2012), sugieren que en el valle del Jarama la inversión Matuyama-Brunhes podría establecerse entre el final de la sedimentación de la terraza a +60-65 m y el encajamiento de la terraza a +50-55 m subsiguiente, representada aguas arriba de Mejorada del Campo, en Marchamalo (Pérez-González, 1994)

Tratamiento de la hipercolesterolemia con inhibidores de la PCSK9 en receptores de trasplante cardiaco: primera experiencia en España

Carta científic

Interatrial Shunting for Treating Acute and Chronic Left Heart Failure

The creation of an interatrial shunt has emerged as a new therapy to decompress the left atrium in patients with acute and chronic left heart failure (HF). Current data support the safety of this therapy, and promising preliminary efficacy results have been reported in patients who are refractory to optimal medical/device therapy. This article aims to provide an updated overview and clinical perspective on interatrial shunting for treating different HF conditions, and highlights the potential challenges and future directions of this therapy

Rapid start-up and stable maintenance of the mainstream nitritation process based on the accumulation of free nitrous acid in a pilot-scale two-stage nitritation-anammox system

Two-stage partial nitritation (PN) and anammox (AMX) systems showed promising results for applying autotrophic nitrogen removal under mainstream conditions. In this study, a pilot-scale (600 L per reactor) two-stage PN/AMX system was installed in a municipal wastewater treatment plant (WWTP) provided with a high-rate activated sludge (HRAS) system for organic carbon removal. The PN/AMX system was operated without temperature control (ranging from 11 to 28 °C) and was subjected to the same variations in wastewater characteristics as the WWTP (22 to 63 mg NH4+- N/L). The developed strategy is simple, does not require the addition of chemicals and is characterised by short start-up periods. The PN process was established by applying a high hydraulic load and maintained by in situ accumulated free nitrous acid (FNA) of 0.015–0.2 mg HNO2-N/L. Based on pH value, a controlled aeration strategy was applied to achieve the target nitrite to ammonium ratio in the effluent (1.1 g NO2–-N/g NH4+-N) to feed the AMX reactor. Although NOB were not fully washed out from the system, nitrite accumulation remained (>99 %) stable with no evidence of NOB activity. In the AMX reactor, an overall nitrogen removal efficiency of 80 % was achieved. Regarding effluent quality, 12 ± 3 mg TN/L was obtained, but 5 mg NO3–-N/L was already in the HRAS effluent. The relative abundance of NOB showed a strong negative correlation with the FNA concentration, providing a good strategy for establishing PN under mainstream conditionsThis work has been financed by the European Commission (EU) through the LIFE project ZERO WASTE WATER (LIFE19 ENV/ES/000631), the Waterworks 2014 Cofounded Call (Water JPI/Horizon) through the Pioneer_STP (PCIN-2015-022 MINECO(AEI)/ID 199 (UE)) and by the Spanish Government (AEI) through GRANDSEA (CTM2014-55397-JIN), TREASURE (CTQ2017-83225-C2-1-R) and ECOPOLYVER (PID2020-112550RB-C21 and PID2020-112550RB-C22) projects. Alba Pedrouso also acknowledges the Xunta de Galicia (Spain) for her postdoctoral fellowship (ED481B-2021-041). Authors from the USC belong to the Galician Competitive Research Group (GRC D431C-2021/37)S

Reassessing the role of carnivores in the formation of FLK North 3 (Olduvai Gorge, Tanzania): A pilot taphonomic analysis using Artificial Intelligence tools

FLK North (FLK N) (Bed I, Olduvai Gorge, Tanzania) is one of the best examples of a palimpsest where felids, hyenids and hominins made use of the same space without or with minimal interaction between hominins and the other two carnivores. Felids have been interpreted as the main accumulators and carcass consumers followed by frequent hyenid intervention. The presence of hominins at this site has been documented through the discovery of stone tools. Here, we test previous taphonomic interpretations of this site through the application of Artificial Intelligence (AI) tools (computer vision applied to bidimensional images of tooth pits) to taxonomically discriminate carnivore-made tooth marks. The bones we analyzed constitute a small sample, being a preliminary study of bone surface modifications (BSM) through the application of AI to a sample of the FLK N archaeofaunal assemblage (mostly to Level 3 fossils), pending access to the larger excavated collections. The results obtained in the present study show that the marks analyzed have been generated both by hyenids and felids. The slight predominance of hyena tooth marks is expected, since the bone sample used is dominated by long limb bones, and hyenas are the most likely agent causing long bone breakage, although felids also break bones of carcasses smaller than 150 kg as documented in the site. Felid impact, in at least three cases, is documented with tooth marks imprinted by felids and hyenas occurring on the same specimens. Felid-hyenid interaction is, thus, documented though the deep learning methods applied. The limited number of specimens where both agents are documented suggest that both hyenids and felids were independently breaking a substantial part of the bones at FLK N. This preliminarily modifies previous interpretations that attributed most long bone fragmentation exclusively to hyenas

Claudin-3 Loss of Expression Is a Prognostic Marker in Castration-Resistant Prostate Cancer

Castration-resistant prostate cancer (CRPC) development is the foremost concern after treatment of patients with high risk with locally advanced or metastatic prostate cancer. Androgen receptor (AR) is the main driver of CRPC development, through its interaction with epigenetic modifier genes, placing epigenetics modifications in the forefront of CRPC development. Comparing the DNA methylation and expression profile of androgen-sensitive and -refractory prostate cancer cells, we describe the epigenetic silencing of claudin-3 (CLDN3) in AR positive cells resistant to androgen deprivation (LNCaP-abl). CLDN3 silencing was associated with DNA methylation, loss of histone acetylation and H3K27 methylation, and was re-expressed by the combined treatment with the epigenetic modulators Aza and SAHA. From a functional point of view, CLDN3 loss was associated with increased cellular invasion. Immunohistochemical analysis showed decreased CLDN3 expression in samples from CRPC patients. Interestingly, CLDN3 expression was significantly decreased in samples from patients with high total Gleason score (>= 8) and locally advanced tumors. Finally, CLDN3 loss of expression was associated with worse disease-free survival and time to clinical progression. In conclusion, our findings strongly indicate that epigenetic silencing of CLDN3 is a common event in CRPC that could be useful as a molecular marker for the prognosis of prostate cancer patients and to discriminate aggressive from indolent prostate tumors

Polyhydroxyalkanoates (PHAs) Production: A Feasible Economic Option for the Treatment of Sewage Sludge in Municipal Wastewater Treatment Plants?

Sludge is a by-product of municipal wastewater treatment plants (WWTPs) and its management contributes significantly to the operating costs. Large WWTPs usually have anaerobic sludge digesters to valorize sludge as methane and to reduce its mass. However, the low methane market price opens the possibility for generating other high value-added products from the organic matter in sludge, such as polyhydroxyalkanoates (PHAs). In this work, the economic feasibility of retrofitting two types of WWTPs to convert them into biofactories of crude PHAs was studied. Two cases were analyzed: (a) a large WWTP with anaerobic sludge digestion; and (b) a small WWTP where sludge is only dewatered. In a two-stage PHA-production system (biomass enrichment plus PHAs accumulation), the minimum PHAs cost would be 1.26 and 2.26 US$/kg PHA-crude for the large and small WWTPs, respectively. In a single-stage process, where a fraction of the secondary sludge (25%) is directly used to accumulate PHAs, the production costs would decrease by around 15.9% (small WWTPs) and 19.0% (large WWTPs), since capital costs associated with bioreactors decrease. Sensitivity analysis showed that the PHA/COD (Chemical Oxygen Demand) yield is the most crucial parameter affecting the production costs. The energy, methane, and sludge management prices also have an essential effect on the production costs, and their effect depends on the WWTP’s sizeThis research was funded by the Chilean Government through the Projects FONDECYT 1200850 and CRHIAM Centre grant number ANID/FONDAP/15130015. This research was also supported by the Spanish Government (AEI) through the TREASURE project (CTQ2017-83225-C2-1-R). Authors from USC belong to the Galician Competitive Research Group ED431C 2017/29. All these programs are co-funded by FEDER (EU)S