Timing of P2Y12 Inhibitor Administration in Patients With STEMI Undergoing Primary PCI.

BACKGROUND: The optimal timing of P2Y12 inhibitor administration in patients with ST-segment elevation myocardial infarction (STEMI) has not been completely elucidating. OBJECTIVES: This analysis from a prospective multicenter registry sought to assess the safety and effectiveness of P2Y12 inhibitor pretreatment in patients transferred for primary percutaneous coronary intervention (PCI) within a regional STEMI network. METHODS: Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography. Endpoints were major adverse cardiac events (MACE), major bleeding, and net adverse clinical events, a composite of MACE or major bleeding, within 30 days of index admission. Association of P2Y12 inhibitor pretreatment with outcomes was modeled using doubly robust weighted estimators based on propensity score analysis. RESULTS: Of 1,624 patients included, 1,033 received P2Y12 inhibitors before angiography and 591 in the catheterization laboratory (cath lab). The non-pretreated cohort more often had history of coronary artery disease and were more likely to receive antiplatelet therapy before the index admission. After adjustment for confounding and dependent censoring, pretreatment with P2Y12 inhibitors predicted lower risk of MACE (adjusted HR: 0.53; 95% CI: 0.37-0.76), without increasing bleeding risk (adjusted HR: 0.62; 95% CI: 0.36-1.05), resulting in superior net clinical benefit (adjusted HR: 0.47; 95% CI: 0.26-0.86) compared with in-cath lab administration of P2Y12 inhibitors. There was a significant treatment-by-time interaction for MACE risk, whereby the observed benefits of pretreatment only became apparent when time between P2Y12 inhibitor administration and PCI was longer than 80 minutes. CONCLUSIONS: In contemporary patients with STEMI transferred for primary PCI, pretreatment with P2Y12 inhibitors was associated with a significant time-dependent reduction of 30-day MACE without increasing bleeding risk.

Distributed electrified heating for efficient hydrogen production.

This study introduces a distributed electrified heating approach that is able to innovate chemical engineering involving endothermic reactions. It enables rapid and uniform heating of gaseous reactants, facilitating efficient conversion and high product selectivity at specific equilibrium. Demonstrated in catalyst-free CH4 pyrolysis, this approach achieves stable production of H2 (530 g h-1 L reactor -1) and carbon nanotube/fibers through 100% conversion of high-throughput CH4 at 1150 °C, surpassing the results obtained from many complex metal catalysts and high-temperature technologies. Additionally, in catalytic CH4 dry reforming, the distributed electrified heating using metallic monolith with unmodified Ni/MgO catalyst washcoat showcased excellent CH4 and CO2 conversion rates, and syngas production capacity. This innovative heating approach eliminates the need for elongated reactor tubes and external furnaces, promising an energy-concentrated and ultra-compact reactor design significantly smaller than traditional industrial systems, marking a significant advance towards more sustainable and efficient chemical engineering society.

Transcriptomic analysis identifies dysregulated pathways and therapeutic targets in PMM2-CDG.

PMM2-CDG (MIM # 212065), the most common congenital disorder of glycosylation, is caused by the deficiency of phosphomannomutase 2 (PMM2). It is a multisystemic disease of variable severity that particularly affects the nervous system; however, its molecular pathophysiology remains poorly understood. Currently, there is no effective treatment. We performed an RNA-seq based transcriptomic study using patient-derived fibroblasts to gain insight into the mechanisms underlying the clinical symptomatology and to identify druggable targets. Systems biology methods were used to identify cellular pathways potentially affected by PMM2 deficiency, including Senescence, Bone regulation, Cell adhesion and Extracellular Matrix (ECM) and Response to cytokines. Functional validation assays using patients' fibroblasts revealed defects related to cell proliferation, cell cycle, the composition of the ECM and cell migration, and showed a potential role of the inflammatory response in the pathophysiology of the disease. Furthermore, treatment with a previously described pharmacological chaperone reverted the differential expression of some of the dysregulated genes. The results presented from transcriptomic data might serve as a platform for identifying therapeutic targets for PMM2-CDG, as well as for monitoring the effectiveness of therapeutic strategies, including pharmacological candidates and mannose-1-P, drug repurposing.

Exploring miRNA-target gene pair detection in disease with coRmiT.

A wide range of approaches can be used to detect micro RNA (miRNA)-target gene pairs (mTPs) from expression data, differing in the ways the gene and miRNA expression profiles are calculated, combined and correlated. However, there is no clear consensus on which is the best approach across all datasets. Here, we have implemented multiple strategies and applied them to three distinct rare disease datasets that comprise smallRNA-Seq and RNA-Seq data obtained from the same samples, obtaining mTPs related to the disease pathology. All datasets were preprocessed using a standardized, freely available computational workflow, DEG_workflow. This workflow includes coRmiT, a method to compare multiple strategies for mTP detection. We used it to investigate the overlap of the detected mTPs with predicted and validated mTPs from 11 different databases. Results show that there is no clear best strategy for mTP detection applicable to all situations. We therefore propose the integration of the results of the different strategies by selecting the one with the highest odds ratio for each miRNA, as the optimal way to integrate the results. We applied this selection-integration method to the datasets and showed it to be robust to changes in the predicted and validated mTP databases. Our findings have important implications for miRNA analysis. coRmiT is implemented as part of the ExpHunterSuite Bioconductor package available from https://bioconductor.org/packages/ExpHunterSuite.

Falta de adherencia a ticagrelor frente a clopidogrel y riesgo de eventos en pacientes con SCA. Resultados del registro CREA-ARIAM / Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry

Introduction and objectives Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). Methods We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. Results Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,−0.99-1.24). Conclusions In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor (AU)

Introducción y objetivos Una baja adherencia al tratamiento antiagregante plaquetario doble (TAPD) condiciona peor pronóstico tras un síndrome coronario agudo (SCA). Se analizó si el riesgo de eventos adversos cardiovasculares mayores (MACE) tras la interrupción prematura del TAPD varía según el inhibidor del P2Y12. Métodos Análisis preespecificado de pacientes con SCA tratados con ticagrelor o clopidogrel entre 2015 y 2019 dentro de un registro prospectivo multicéntrico. Se categorizó la suspensión prematura como indicada por el médico o como interrupción por hemorragia, efectos secundarios o incumplimiento del paciente. La asociación entre la suspensión del TAPD y los MACE se analizó mediante modelos multivariantes de Cox dependientes del tiempo, con estimadores robustos ponderados por probabilidad inversa de censura. Resultados De 2.180 pacientes, 174 (8,3%) suspendieron el TAPD precozmente (126 por indicación médica y 48 por disrupción). Los pacientes incumplidores tenían más edad y más comorbilidad que los adherentes. Frente a la suspensión indicada por el médico, la disrupción del TAPD fue más precoz y frecuente con el ticagrelor que con el clopidogrel. La suspensión del TAPD condicionó mayor riesgo de MACE (HRajustada=1,32; IC95%, 1,10-1,76), principalmente en caso de la disrupción (HRajustada=1,47; IC95%, 1,22-1,73). Este riesgo aumentó exponencialmente en los 90 días posteriores al SCA y fue más evidente con ticagrelor (pinteracción<0,001). Tras considerar la duración del TAPD, esta interacción no resultó significativa en la escala aditiva (exceso de riesgo debido a interacción=0,12; IC95%, –0,99 a 1,24)(AU)

Tumor de Buschke-Löwenstein en el embarazo adolescente / Buschke-Löwenstein Tumor in Adolescent Pregnancy

Resumen El tumor de Buschke-Löwenstein, también denominado condiloma acuminado gigante, es una entidad rara causada por el virus del papiloma humano (VPH), con una incidencia de 0.01% en la población en general y solo 6 casos reportados en embarazadas. No existe un consenso con respecto al tratamiento; sin embargo, la cirugía es la técnica más descrita. Caso clínico: Paciente primigesta de 14 años, con un embarazo de 21 semanas de gestación, quien ingresó a urgencias por una masa dolorosa en región perineal de 5 meses de evolución. A la exploración física se encontraron en región perineal 2 lesiones exofíticas, coliformes, irregulares, ulceradas de aproximadamente 20 × 10 cm con presencia de secreción amarillenta fétida. Se realizó escisión del tumor con amplios márgenes quirúrgicos y cierre por segunda intención. Por parte de patología se reportó un condiloma acuminado gigante sin lesión en borde quirúrgico. La prueba por PCR detectó el genotipo 53 del virus de papiloma humano. Después de 12 semanas se presentó epitelización completa, sin complicaciones. Conclusión: El tumor de Buschke-Löwenstein es considerado como benigno, no obstante, representa cierto grado de malignidad y tiende a recurrir después del tratamiento, por lo que es importante reforzar las medidas de tamizaje y prevención del Virus del Papiloma Humano.

Abstract Buschke-Löwenstein tumor also called giant condyloma acuminatum is a rare condition due to the human papillomavirus with an incidence of 0.01% and just 6 cases reported in pregnancy. There is no consensus on the treatment, although surgery has been the most reported. Clinical case: A 14 year-old primigravid patient with a 21- week pregnancy who was admitted to the Emergency Department due to a perineal painful tumor which appeared 5 months before. On physical examination two irregular exophytic, cauliflower-like and ulcerated lesions of 20 × 10 cm of size each one with malodorous discharge were found on her perineal region suggestive of giant condyloma acuminatum. We decided to resect the tumor with tumor-free margin control and healing per secundam. The pathology report showed a giant condyloma acuminatum with tumor-free margin. The PCR analysis revealed human papillomavirus genotype 53. Complete epithelialization was noted at 12 weeks with no complications noted. Conclusion: Buschke-Löwenstein tumor is considered as a benign tumor, but it carries a risk of malignant transformation and it can appear after treatment, which makes important to strengthen the prevention and screening of human papillomavirus.

Application of real-time PCR for the identification of the endangered species Galemys pyrenaicus through faecal samples.

BACKGROUND: Currently, many micromammals are important targets for study. The endangered Galemys pyrenaicus is an outstanding example. Globally, their populations have suffered a substantial decline in last 20 years. In the surveyed area, the capture of desman is legally forbidden due to the high conservation concerns. Reason by non-invasive sampling through faeces is proposed for its monitoring. Furthermore, the confusion between faeces from desman and Mediterranean water shrews must be considered. Thus, the aim of this study was focused on developing RT-PCR assays to determine the presence of Galemys pyrenaicus and N. a. anomalus from non-invasive samples. METHODS AND RESULTS: The study was conducted in the mountains of the System Central of Extremadura (Spain). A total of 186 samples were collected from 2018 to 2021 by experts where historically reported and/or our previous studies confirmed their presence. RT-PCR assays using hydrolysis probes were designed to detect genetic material from both desman and Mediterranean water shrews and its specificity was confirmed. The reliability of the method was further assessed by PCR sequencing of mitochondrial Cyb and d-loop, resulting fully compatible with the RT-PCR approach. Intraspecific phylogenetic relationship was reported to improve knowledge about mtDNA variability in the desman from the Central System. CONCLUSIONS: We demonstrated that RT-PCR gives a gold opportunity to further map the species using faeces which minimizes disturbance and reports both population status and individual presence. Cost-effective RT-PCR combined with field-collected faeces allows us to better investigate the full range of occurrence of the species.

Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis.

Efferocytic clearance of apoptotic cells in general, and T cells in particular, is required for tissue and immune homeostasis. Transmembrane mucins are extended glycoproteins highly expressed in the cell glycocalyx that function as a barrier to phagocytosis. Whether and how mucins may be regulated during cell death to facilitate efferocytic corpse clearance is not well understood. Here we show that normal and transformed human T cells express a subset of mucins which are rapidly and selectively removed from the cell surface during apoptosis. This process is mediated by the ADAM10 sheddase, the activity of which is associated with XKR8-catalyzed flipping of phosphatidylserine to the outer leaflet of the plasma membrane. Mucin clearance enhances uptake of apoptotic T cells by macrophages, confirming mucins as an enzymatically-modulatable barrier to efferocytosis. Together these findings demonstrate a glycocalyx regulatory pathway with implications for therapeutic intervention in the clearance of normal and transformed apoptotic T cells.

Kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test in older adults with heart failure with preserved ejection fraction.

AIMS: This paper aims to assess kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test (6MWT) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: A cross-sectional study was conducted in which adults 70 years or older with HFpEF were voluntarily recruited between April 2019 and March 2020. An inertial sensor was placed at the L3-L4 level and another on the sternum to assess kinematic parameters. The 6MWT was divided into two 3-min phases. Leg fatigue and breathlessness, assessed by the Borg scale, the heart rate (HR), and the oxygen saturation (SpO2), were measured at the beginning and the end of the 6MWT. The difference in kinematic parameters between the 6MWT two 3-min phases was also calculated. Bivariate Pearson correlations and subsequent multivariate linear regression analysis were performed. Seventy older adults with HFpEF (mean = 80.74 years old) were included. Kinematic parameters explained 81.00% of the functional capacity, 45.50% of the leg fatigue and 66.10% of the breathlessness variance. Moreover, kinematic parameters could explain 30.90% of the SpO2 variance at the end of the 6MWT. Kinematic parameters also explained 33.10% of the SpO2 difference between the beginning and end of 6MWT. Kinematic parameters explained neither the HR variance at the end of 6MWT nor the HR difference between the beginning and end. CONCLUSION: Gait kinematics from L3-L4 and sternum explain a part of the variance in subjective outcomes, assessed by the Borg scale, and objective outcomes such as functional capacity and SpO2. The kinematic assessment allows clinicians to quantify fatigue and breathlessness through objective parameters related to the patient's functional capacity. REGISTRATION: ClinicalTrials.gov NCT03909919.

Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry.

INTRODUCTION AND OBJECTIVES: Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). METHODS: We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. RESULTS: Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,-0.99-1.24). CONCLUSIONS: In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor. Clinical trial registered at ClinicalTrials.gov (Identifier: NCT02500290).

Integrating differential expression, co-expression and gene network analysis for the identification of common genes associated with tumor angiogenesis deregulation.

Angiogenesis is essential for tumor growth and cancer metastasis. Identifying the molecular pathways involved in this process is the first step in the rational design of new therapeutic strategies to improve cancer treatment. In recent years, RNA-seq data analysis has helped to determine the genetic and molecular factors associated with different types of cancer. In this work we performed integrative analysis using RNA-seq data from human umbilical vein endothelial cells (HUVEC) and patients with angiogenesis-dependent diseases to find genes that serve as potential candidates to improve the prognosis of tumor angiogenesis deregulation and understand how this process is orchestrated at the genetic and molecular level. We downloaded four RNA-seq datasets (including cellular models of tumor angiogenesis and ischaemic heart disease) from the Sequence Read Archive. Our integrative analysis includes a first step to determine differentially and co-expressed genes. For this, we used the ExpHunter Suite, an R package that performs differential expression, co-expression and functional analysis of RNA-seq data. We used both differentially and co-expressed genes to explore the human gene interaction network and determine which genes were found in the different datasets that may be key for the angiogenesis deregulation. Finally, we performed drug repositioning analysis to find potential targets related to angiogenesis inhibition. We found that that among the transcriptional alterations identified, SEMA3D and IL33 genes are deregulated in all datasets. Microenvironment remodeling, cell cycle, lipid metabolism and vesicular transport are the main molecular pathways affected. In addition to this, interacting genes are involved in intracellular signaling pathways, especially in immune system and semaphorins, respiratory electron transport and fatty acid metabolism. The methodology presented here can be used for finding common transcriptional alterations in other genetically-based diseases.

Textbook Outcome in Bariatric Surgery: Evolution During 15 Years in a Referral Center.

BACKGROUND: Textbook outcome (TO) is a multidimensional measure used to assess the quality of care. It is the "ideal" surgical result, based on a series of established indicators. In the field of bariatric surgery (BS), only one publication on TO is available. OBJECTIVES: To determine TO in our BS unit and identify the factors linked to TO. SETTING: University public hospital in Alicante (Spain). METHODS: Retrospective observational study of all primary BS was performed. TO for BS was defined in relation to the following features: no major postoperative complications (Clavien-Dindo >II), hospital stay <75th percentile, and no mortality or readmissions within 30 days of surgery. Comparative analysis of the characteristics of the TO and non-TO groups was performed, as well as univariate and multivariate logistic regressions, to identify the independent factors associated with obtaining TO. RESULTS: In 970 patients, TO was achieved in 71.5%. The hospital stay was the one that most affected achievement of TO. Analysis according to the type of procedure (sleeve gastrectomy and gastric bypass) did not reveal any differences between both procedures in terms of obtaining TO (71.5 vs 71.26%). Logistic regression identified smoking, heart disease, operative time, and upper gastrointestinal bleeding as independent factors associated with obtaining TO (p<0.05). Analysis of the annual evolution of TO reveals a progressive increase in its achievement (7.7-86.4%). CONCLUSION: In our series, TO was obtained in 71.5% of patients. The standardization of the technique and the experience gained over the years has improved our TO results.

Non-Invasive Wildlife Disease Surveillance Using Real Time PCR Assays: The Case of the Endangered Galemys pyrenaicus Populations from the Central System Mountains (Extremadura, Spain).

The Iberian desman (Galemys pyrenaicus) is a small semi-aquatic mammal that inhabits mountainous areas from the centre to the north of the Iberian Peninsula and the Pyrenees and is listed as endangered because it has suffered a serious decline. Since 1960, only three species of digeneans (Omphalometra flexuosa, Maritrema pyrenaica and Mathovius galemydis) and two nematodes (Aonchotheca galemydis and Paracuaria hispanica) have been reported from the desman, but no further information on health status and no data from Extremadura has been available. The aim of our study was to characterise the diversity and distribution of parasites and microbiomes of desmans in different areas of the Central System of Extremadura. Between 2019 and 2021 we collected 238 fecal samples and one tissue (intestine) sample that was obtained from a dead desman. DNA templates were processed by commercial or customised real-time PCR using TaqMan probes. Representative data were obtained for Cryptosporidium spp., Omphalometra spp., Eimeria spp., Salmonella spp., Staphylococcus spp. and Leptospira spp. Omphalometra spp. was studied using a newly developed PCR test. The screening of the dead desman allowed us to obtain, for the first time, a partial sequence of the 18SrDNA. This study is the most complete study of the desman, allowing us to identify parasites and the microbiome in populations of G. pyrenaicus using non-invasive sampling.

Role of microRNAs in arrhythmogenic cardiomyopathy: translation as biomarkers into clinical practice.

Arrhythmogenic cardiomyopathy is a rare inherited entity, characterized by a progressive fibro-fatty replacement of the myocardium. It leads to malignant arrhythmias and a high risk of sudden cardiac death. Incomplete penetrance and variable expressivity are hallmarks of this arrhythmogenic cardiac disease, where the first manifestation may be syncope and sudden cardiac death, often triggered by physical exercise. Early identification of individuals at risk is crucial to adopt protective and ideally personalized measures to prevent lethal episodes. The genetic analysis identifies deleterious rare variants in nearly 70% of cases, mostly in genes encoding proteins of the desmosome. However, other factors may modulate the phenotype onset and outcome of disease, such as microRNAs. These small noncoding RNAs play a key role in gene expression regulation and the network of cellular processes. In recent years, data focused on the role of microRNAs as potential biomarkers in arrhythmogenic cardiomyopathy have progressively increased. A better understanding of the functions and interactions of microRNAs will likely have clinical implications. Herein, we propose an exhaustive review of the literature regarding these noncoding RNAs, their versatile mechanisms of gene regulation and present novel targets in arrhythmogenic cardiomyopathy.

FaMYB123 interacts with FabHLH3 to regulate the late steps of anthocyanin and flavonol biosynthesis during ripening.

In this work, we identified and functionally characterized the strawberry (Fragaria × ananassa) R2R3 MYB transcription factor FaMYB123. As in most genes associated with organoleptic properties of ripe fruit, FaMYB123 expression is ripening-related, receptacle-specific, and antagonistically regulated by ABA and auxin. Knockdown of FaMYB123 expression by RNAi in ripe strawberry fruit receptacles downregulated the expression of enzymes involved in the late steps of anthocyanin/flavonoid biosynthesis. Transgenic fruits showed a parallel decrease in the contents of total anthocyanin and flavonoid, especially malonyl derivatives of pelargonidin and cyanidins. The decrease was concomitant with accumulation of proanthocyanin, propelargonidins, and other condensed tannins associated mainly with green receptacles. Potential coregulation between FaMYB123 and FaMYB10, which may act on different sets of genes for the enzymes involved in anthocyanin production, was explored. FaMYB123 and FabHLH3 were found to interact and to be involved in the transcriptional activation of FaMT1, a gene responsible for the malonylation of anthocyanin components during ripening. Taken together, these results demonstrate that FaMYB123 regulates the late steps of the flavonoid pathway in a specific manner. In this study, a new function for an R2R3 MYB transcription factor, regulating the expression of a gene that encodes a malonyltransferase, has been elucidated.

Economic and Environmental Performance of an Integrated CO2 Refinery.

The consequences of global warming call for a shift to circular manufacturing practices. In this context, carbon capture and utilization (CCU) has become a promising alternative toward a low-emitting chemical sector. This study addresses for the first time the design of an integrated CO2 refinery and compares it against the business-as-usual (BAU) counterpart. The refinery, which utilizes atmospheric CO2, comprises three synthesis steps and coproduces liquefied petroleum gas, olefins, aromatics, and methanol using technologies that were so far studied decoupled from each other, hence omitting their potential synergies. Our integrated assessment also considers two residual gas utilization (RGU) designs to enhance the refinery's efficiency. Our analysis shows that a centralized cluster with an Allam cycle for RGU can drastically reduce the global warming impact relative to the BAU (by ≈135%) while simultaneously improving impacts on human health, ecosystems, and resources, thereby avoiding burden-shifting toward human health previously observed in some CCU routes. These benefits emerge from (i) recycling CO2 from the cycle, amounting to 11.2% of the total feedstock, thus requiring less capture capacity, and (ii) reducing the electricity use while increasing heating as a trade-off. The performance of the integrated refinery depends on the national grid, while its high cost relative to the BAU is due to the use of expensive electrolytic H2 and atmospheric CO2 feedstock. Overall, our work highlights the importance of integrating CCU technologies within chemical clusters to improve their economic and environmental performance further.

Risk Factors Involved in the High Incidence of Bladder Cancer in an Industrialized Area in North-Eastern Spain: A Case-Control Study.

Bladder cancer (BC) is the most common of the malignancies affecting the urinary tract. Smoking and exposure to occupational and environmental carcinogens are responsible for most cases. Vallès Occidental is a highly industrialized area in north-eastern Spain with one of the highest incidences of BC in men. We carried out a case-control study in order to identify the specific risk factors involved in this area. Three hundred and six participants were included (153 cases BC and 153 controls matched for age and sex): in each group, 89.5% (n = 137) were male and the mean age was 71 years (range 30-91; SD = 10.6). There were no differences between groups in family history, body mass index, or dietary habits. Independent risk factors for CV were smoking (OR 2.08; 95% CI 1.30-3.32; p = 0.002), the use of analgesics in nonsmokers (OR 10.00; 95% CI 1.28-78.12; p = 0.028), and profession (OR: 8.63; 95% CI 1.04-71.94; p = 0.046). The consumption of black and blond tobacco, the use of analgesics in nonsmokers, and occupational exposures are risk factors for the development of BC in this area, despite the reduction in smoking in the population and the extensive measures taken in the last few decades in major industries to prevent exposure to occupational carcinogens.

Textbook outcome en cirugía gástrica oncológica, ¿qué implicaciones tiene sobre la supervivencia? / Textbook outcome in gastric surgery, what implications does it have on survival?

Introducción: El textbook outcome (TO), o resultado de libro, es una medida multidimensional para evaluar la calidad de la práctica asistencial. Ésta viene reflejada como el resultado quirúrgico «ideal», atendiendo a una serie de indicadores o puntos de referencia establecidos que se adaptan en función de la patología quirúrgica que queramos analizar. Son pocas las referencias bibliográficas y las series publicadas al respecto, todas ellas muy recientes. Objetivo: Valorar el grado de cumplimiento del TO y su impacto sobre la supervivencia. Método: Estudio observacional retrospectivo de todas las neoplasias gástricas intervenidas en nuestro centro. Periodo: desde enero del 2015 hasta diciembre del 2020. Se determinaron los siguientes criterios TO: márgenes R0, > 15 ganglios linfáticos en el estudio histológico, sin complicaciones mayores (Clavien-Dindo > IIIa), estancia hospitalaria < 21 días, no presentar mortalidad en los 30 días posoperatorios ni readmisión durante esos 30 días. Se realizó un análisis comparativo entre el grupo de TO vs. grupo no TO. Resultados: Se intervinieron 93 pacientes. Alcanzamos el TO en un 34,1% de los pacientes. La variable > 15 ganglios linfáticos fue la que más afectó a conseguir un TO Al realizar el análisis de supervivencia, observamos que el grupo en que se obtuvo el TO presentó mayor supervivencia (p < 0,008). Conclusión: En nuestra serie, la obtención del TO tiene impacto sobre la supervivencia con un grado de cumplimiento del 34,1%. (AU)

Introduction: The textbook outcome (TO) is a multidimensional measure to assess the quality of healthcare practice. This is reflected as the “ideal” surgical result, attending to a series of indicators or established reference points that are adapted depending on the surgical disease that we want to analyze. There are few references and series published about TO, all of them very recent. Objective: We present a series of gastric surgery from the TO perspective and we analyze its impact on survival. Method: Retrospective observational study of all gastric neoplasms operated on in our center. Period: January 2015 - December 2020. The criteria for TO were: margins R0, > 15 lymph nodes in the histological study, no Clavien-Dindo complications > IIIa, hospital stay < 21 days, no mortality or readmission in the 30 postoperative days. A comparative analysis was performed between the TO group versus the non-TO group. Results: 91 patients were operated on. We reached the TO in 34.1% of the patients. The variable > 15 lymph nodes was the one that most affected to achieve a TO. When performing the survival analysis, we obtained that the group in which the TO was obtained had a greater survival (p < 0.008). Conclusion: In our series, obtaining the TO has an impact on survival which 34,1% of degree of compliance. (AU)