Powder diet exacerbates oropharyngeal candidiasis in a mouse model.

This study reports on the influence of a powder diet in a mouse model of oropharyngeal candidiasis (OPC), a significant health concern caused primarily by Candida albicans. Despite identical nutritional composition, we found that a powdered diet significantly increased Candida burdens and oral lesions, and aggravated weight loss compared to a standard pelleted diet. High fungal burdens and severe oral lesions were accomplished within 48 hours after infection with only one dose of cortisone. Moreover, mice on a powder diet recovered a week after infection. Using a powder diet, we thus modified the cortisone OPC murine model in a way that simplifies the infection process, enhances reproducibility, and facilitates studies investigating both pathogenesis and recovery processes. Our findings also underscore the pivotal role of the physical form of the diet in the progression and severity of oral Candida infection in this model. Future research should investigate this relationship further to broaden our understanding of the underlying mechanisms, potentially leading to novel prevention strategies and improved disease management.IMPORTANCEOropharyngeal candidiasis (OPC) is a multifactorial disease and a significant health concern. We found that the physical form of the diet plays a critical role in the severity and progression of OPC. We developed a modified cortisone OPC murine model that facilitates studies investigating pathogenesis and recovery processes.

Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.

Composite 2D Material-Based Pervaporation Membranes for Liquid Separation: A Review.

Today, chemistry and nanotechnology cover molecular separations in liquid and gas states by aiding in the design of new nano-sized materials. In this regard, the synthesis and application of two-dimensional (2D) nanomaterials are current fields of research in which structurally defined 2D materials are being used in membrane separation either in self-standing membranes or composites with polymer phases. For instance, pervaporation (PV), as a highly selective technology for liquid separation, benefits from using 2D materials to selectively transport water or other solvent molecules. Therefore, this review paper offers an interesting update in revising the ongoing progress of PV membranes using 2D materials in several applications, including solvent purification (the removal of water from organic systems), organics removal (the removal of organic molecules diluted in water systems), and desalination (selective water transport from seawater). In general, recent reports from the past 3 years have been discussed and analyzed. Attention has been devoted to the proposed strategies and fabrication of membranes for the inclusion of 2D materials into polymer phases. Finally, the future trends and current research gaps are declared for the scientists in the field.

Impact of high-pressure processing on the bioactive compounds of milk - A comprehensive review.

High-pressure processing (HPP) is a promising alternative to thermal pasteurization. Recent studies highlighted the effectivity of HPP (400-600 MPa and exposure times of 1-5 min) in reducing pathogenic microflora for up to 5 logs. Analysis of modern scientific sources has shown that pressure affects the main components of milk including fat globules, lactose, casein micelles. The behavior of whey proteins under HPP is very important for milk and dairy products. HPP can cause significant changes in the quaternary (> 150 MPa) and tertiary (> 200 MPa) protein structures. At pressures > 400 MPa, they dissolve in the following order: αs2-casein, αs1-casein, k-casein, and ß-casein. A similar trend is observed in the processing of whey proteins. HPP can affect the rate of milk fat adhering as cream with increased results at 100-250 MPa with time dependency while decreasing up to 70% at 400-600 MPa. Some studies indicated the lactose influencing casein on HP, with 10% lactose addition in case in suspension before exposing it to 400 MPa for 40 min prevents the formation of large casein micelles. Number of researches has shown that moderate pressures (up to 400 MPa) and mild heating can activate or stabilize milk enzymes. Pressures of 350-400 MPa for 100 min can boost the activity of milk enzymes by up to 140%. This comprehensive and critical review will benefit scientific researchers and industrial experts in the field of HPP treatment of milk and its effect on milk components.

Membrane distillation assisting food production processes of thermally sensitive food liquid items: a review.

Physical separation technologies have become important tool for processing in the current food manufacturing industries, especially for the products containing bioactive compounds thanks to their health benefits in costumers. As for the processing of bioactive food ingredients implies the implementation of integrated systems oriented to their separation, fractionation, and recovery. In this field, membrane distillation (MD), which is a thermally driven membrane process, has been proposed as an alternative for the separation and concentration of liquid food items. In principle, MD can separate water and volatile compounds from aqueous feed solutions through a permeate that passes across microporous hydrophobic membranes. The separation via MD is thanks to the vapor pressure difference on both membrane sides. In this review, we analyzed the ongoing experimental efforts aimed to recover and purify food bioactive compounds from the concentration of fruit juices and extracts using MD. Also, the processing of dairy products, concentration of food by-products, and ethanol production and its removal from beverages using MD have been reviewed. Additionally, a feedback on the distinct membrane module configurations and membrane requirements for successful operation is addressed.

Implementing fermentation technology for comprehensive valorisation of seafood processing by-products: A critical review on recovering valuable nutrients and enhancing utilisation.

Fermentation technology is a biorefining tool that has been used in various industrial processes to recover valuable nutrients from different side streams. One promising application of this technique is in the reclamation of nutritional components from seafood side streams. Seafood processing generates significant amounts of waste, including heads, shells, and other side streams. These side streams contain high quantities of valued nutritional components that can be extracted using fermentation technology. The fermentation technology engages the application of microorganisms to convert the side stream into valuable products like biofuels, enzymes, and animal feed. Natural polymers such as chitin and chitosan have various purposes in the food, medicinal, and agricultural industry. Another example is the fish protein hydrolysates (FPH) from seafood side streams. FPHs are protein-rich powders which could be used in animal nutrition and nutraceutical industry. The resulting hydrolysate is further filtered and dried resulting in a FPH powder. Fermentation technology holds great possibility in the recovery of valuable nutrients from seafood side streams. The process can help reduce waste and generate new value-added products from what would otherwise be considered a waste product. With further research and development, fermentation technology can become a key tool in the biorefining industry.

Deep eutectic solvents for the food industry: extraction, processing, analysis, and packaging applications - a review.

Food factories seek the application of natural products, green feedstock and eco-friendly processes, which minimally affect the properties of the food item and products. Today, water and conventional polar solvents are used in many areas of food science and technology. As modern chemistry evolves, new green items for building eco-friendly processes are being developed. This is the case of deep eutectic solvents (DESs), named the next generation of green solvents, which can be involved in many food industries. In this review, we timely analyzed the progress on applying DES toward the development of formulations, extraction of target biomolecules, food processing, extraction of undesired molecules, analysis and determination of specific analytes in food samples (heavy metals, pesticides), food microbiology, and synthesis of new packaging materials, among many other applications. For this, the latest developments (over the last 2-3 years) have been discussed emphasizing innovative ideas and outcomes. Relevantly, we discuss the hypothesis and the key features of using DES in the mentioned applications. To some extent, the advantages and limitations of implementing DES in the food industry are also elucidated. Finally, based on the findings of this review, the perspectives, research gaps and potentialities of DESs are stated.

Current evidence in high throughput ultrafiltration toward the purification of monoclonal antibodies (mAbs) and biotechnological protein-type molecules.

Pressure-driven membrane-based technologies, such as microfiltration (MF), ultrafiltration (UF), and nanofiltration (NF), have been successfully implemented in recovering different types of biomolecules and high-value-added compounds from various streams. Especially, UF membranes meet the requirements for separating specific bioproducts in downstream processes, e.g. monoclonal antibodies (mAbs), which are recognized as proteins produced mainly by plasma cells. According to the importance and functionality of the mAbs, their recovery is a current challenge with these bioseparations. Nevertheless, mAbs recovery using UF-assisted processes has been smartly performed over the last decade. To the best of our knowledge, there are no reviews of the reported developments using UF technology toward mAbs separation. Therefore, the goal of this paper is to collect and elucidate ongoing research studies implemented for the featured separation of mAbs and other biotechnological protein-type molecules (e.g. adenovirus serotype, extracellular vesicles, red fluorescent protein, cyanovirin-N, among others) via ultrafiltration-aided systems. The literature evidence (e.g. research papers, patents, etc.) has been analyzed and discussed according to the purpose of the study. Importantly, the relevant findings and novel approaches are discussed in detail. To finalize this document, the advantages, drawbacks, and guidelines in applying membrane-based techniques for such a recovery are presented.

A Review on Current Strategies for Extraction and Purification of Hyaluronic Acid.

Since it is known that hyaluronic acid contributes to soft tissue growth, elasticity, and scar reduction, different strategies of producing HA have been explored in order to satisfy the current demand of HA in pharmaceutical products and formulations. The current interest deals with production via bacterial and yeast fermentation and extraction from animal sources; however, the main challenge is the right extraction technique and strategy since the original sources (e.g., fermentation broth) represent a complex system containing a number of components and solutes, which complicates the achievement of high extraction rates and purity. This review sheds light on the main pathways for the production of HA, advantages, and disadvantages, along with the current efforts in extracting and purifying this high-added-value molecule from different sources. Particular emphasis has been placed on specific case studies attempting production and successful recovery. For such works, full details are given together with their relevant outcomes.

Ultrasound-Assisted Dispersive Liquid-Liquid Microextraction Using Deep Eutectic Solvents (DESs) for Neutral Red Dye Spectrophotometric Determination.

Deep eutectic solvents (DES), which have low toxicity and are low cost, biodegradable, and easily synthesized, were used for the extraction of neutral red (NR) dye before its spectrophotometric analysis. DES, containing choline chloride as a hydrogen bond acceptor and phenol as a hydrogen bond donor with a molar ratio of 1:2, was used for the extraction of NR dye from aqueous media. The possible interaction of different DESs with NR was studied using density functional theory (DFT) calculations. Experimentally, a UV-visible spectrophotometer was used for the quantitative analysis. The most important parameters affecting method performance, such as pH, extraction temperature, DES type, its volume, THF volume, sonication time, and centrifugation time, were optimized. The developed method provides exceptional sensitivity in terms of LOD and LOQ, which were 2.2 and 7.3 µg/L respectively. The relative standard deviation was 1.35−1.5% (n = 10), and the pre-concentration factor was 40. The method was found to be linear in the range of 2−300 µg/L (R2 = 0.9967). The method was successfully used for the determination of NR in wastewater samples. Finally, the DES-based method presents operational simplicity, high sensitivity, and rapid determination (<5 min) compared with other analytical procedures.

A comprehensive review on current and emerging technologies toward the valorization of bio-based wastes and by products from foods.

Industries in the agro-food sector are the largest generators of waste in the world. Agro-food wastes and by products originate from the natural process of senescence, pretreatment, handling, and manufacturing processes of food and beverage products. Notably, most of the wastes are produced with the transformation of raw materials (such as fruits, vegetables, plants, tubers, cereals, and dairy products) into different processed foods (e.g., jams, sauces, and canned fruits/vegetables), dairy derivatives (e.g., cheese and yogurt), and alcoholic (e.g., wine and beer) and nonalcoholic beverages (e.g., juices and soft drinks). Current research is committed not only to the usage of agro-food wastes and by products as a potential source of high-value bioactive compounds (e.g., phenolic compounds, anthocyanins, and organic acids) but also to the implementation of emerging and innovative technologies that can compete with conventional extraction methods for the efficient extraction of such biomolecules from the residues. Herein, specific valorization technologies, such as membrane-based processes, microwave, ultrasound, pulsed electric-assisted extraction, supercritical/subcritical fluids, and pressurized liquids, have emerged as advanced techniques in extracting various added-value biomolecules, showing multiple advantages (improved extraction yields, reduced process time, and protection to the bioactive properties of the compounds). Hence, this comprehensive review aims to analyze the ongoing research on applying such techniques in valorization protocols. A last-five-year review, together with a featured analysis of the relevant findings in the field, is provided.

Entropy-Based Diversification Approach for Bio-Computing Methods.

Nature-inspired computing is a promising field of artificial intelligence. This area is mainly devoted to designing computational models based on natural phenomena to address complex problems. Nature provides a rich source of inspiration for designing smart procedures capable of becoming powerful algorithms. Many of these procedures have been successfully developed to treat optimization problems, with impressive results. Nonetheless, for these algorithms to reach their maximum performance, a proper balance between the intensification and the diversification phases is required. The intensification generates a local solution around the best solution by exploiting a promising region. Diversification is responsible for finding new solutions when the main procedure is trapped in a local region. This procedure is usually carryout by non-deterministic fundamentals that do not necessarily provide the expected results. Here, we encounter the stagnation problem, which describes a scenario where the search for the optimum solution stalls before discovering a globally optimal solution. In this work, we propose an efficient technique for detecting and leaving local optimum regions based on Shannon entropy. This component can measure the uncertainty level of the observations taken from random variables. We employ this principle on three well-known population-based bio-inspired optimization algorithms: particle swarm optimization, bat optimization, and black hole algorithm. The proposal's performance is evidenced by solving twenty of the most challenging instances of the multidimensional knapsack problem. Computational results show that the proposed exploration approach is a legitimate alternative to manage the diversification of solutions since the improved techniques can generate a better distribution of the optimal values found. The best results are with the bat method, where in all instances, the enhanced solver with the Shannon exploration strategy works better than its native version. For the other two bio-inspired algorithms, the proposal operates significantly better in over 70% of instances.

Association of calprotectin with other inflammatory parameters in the prediction of mortality for ischemic stroke.

BACKGROUND: Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi. METHODS: Among the 748 patients treated at a comprehensive stroke center between 2015 and 2017, 413 patients with confirmed acute ischemic injury were prospectively evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24 h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3 months (defined as modified Rankin Scale < 3) and hemorrhagic transformation (HT) after ischemic stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n = 44). RESULTS: Higher calprotectin levels were associated with 3-month mortality, HT, and lower 3-month FI. After adjusting for potential confounders, plasma calprotectin remained associated with 3-month mortality [OR (95% CI) 2.31 (1.13-4.73)]. Patients with calprotectin ≥ 2.26 µg/mL were 4 times more likely to die [OR 4.34 (1.95-9.67)]. Addition of calprotectin to clinical variables led to significant improvement in the discrimination capacity of the model [0.91 (0.87-0.95) vs 0.89 (0.85-0.93); p < 0.05]. A multimarker approach demonstrated that patients with increased calprotectin, CRP, and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p = 0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p < 0.002), leukocytes (0.45, p < 0.01), and neutrophil elastase (0.70, p < 0.001) thrombus content. CONCLUSIONS: Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. The presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation, and further studies are needed to determine its influence in resistance to reperfusion.

Emerging techniques assisting nixtamalization products and by-products processing: an overview.

The production of worldwide nixtamalized products has increased in Latin American countries over the last years. For a better maize handling and exploitation of its nutritional elements, maize is subjected to a nixtamalization pretreatment protocol, which produces meaningful chemical, nutritional and quality changes in maize and its derived products, but large amounts of its primary by-product, well-known as 'nejayote', are also produced. Importantly, nejayote is usually discarded into the urbanized sewage with minimal treatment. Today, according to the recent research reports, new emerging techniques and protocols have been implemented to improve the nixtamalization products and by-products processing. New valorization approaches and biotechnological developments (including biotransformations) toward the reuse of nejayote have been developed according to its considerable content of biomolecules. Therefore, the goal of this paper is to provide a comprehensive review of the main development works at assisting nixtamalization products and by-products processing. Herein, particular attention is paid to experimental insights dealing with the valorization of nejayote.

Membrane separation processes for the extraction and purification of steviol glycosides: an overview.

Steviol glycosides (SGs), as natural sweeteners from Stevia rebaudiana, are currently employed for replacing sugar and its derivatives in several food products and formulations. Such compounds play an essential role in human health. Their usage provides a positive effect on preventing diseases related to sugar consumption, including diabetes mellitus, cancer, and lipid metabolism disorders. The traditional extraction of SGs is performed by means of solvent extraction, which limits their application since the removal of residual solvents is a challenging task requiring further downstream purification steps. In addition, the presence of residual solvents negatively affects the quality of such compounds. Today, food technicians are looking for innovative and improved techniques for the extraction, recovery and purification of SGs. Membrane-based technologies, including microfiltration, ultrafiltration, and nanofiltration, have long been proven to be a valid alternative for efficient extraction and purification of several high added-value molecules from natural sources. Such processes and their possible coupling in integrated membrane systems have been successfully involved in recovery protocols of several compounds, such as metabolites, polyphenols, anthocyanins, natural pigments, proteins, from different sources (e.g., agro-food wastes, plant extracts, fruits, fermentation broths, among others). Herein, we aim to review the current progresses and developments about the extraction of SGs with membrane operations. Our attention has been paid to the latest insights in the field. Furthermore, key process parameters influencing the extraction and purification of SGs are also discussed in detail.

A Learning Analytics Framework to Analyze Corporal Postures in Students Presentations.

Communicating in social and public environments are considered professional skills that can strongly influence career development. Therefore, it is important to proper train and evaluate students in this kind of abilities so that they can better interact in their professional relationships, during the resolution of problems, negotiations and conflict management. This is a complex problem as it involves corporal analysis and the assessment of aspects that until recently were almost impossible to quantitatively measure. Nowadays, a number of new technologies and sensors have being developed for the capture of different kinds of contextual and personal information, but these technologies were not yet fully integrated inside learning settings. In this context, this paper presents a framework to facilitate the analysis and detection of patterns of students in oral presentations. Four steps are proposed for the given framework: Data collection, Statistical Analysis, Clustering, and Sequential Pattern Mining. Data Collection step is responsible for the collection of students interactions during presentations and the arrangement of data for further analysis. Statistical Analysis provides a general understanding of the data collected by showing the differences and similarities of the presentations along the semester. The Clustering stage segments students into groups according to well-defined attributes helping to observe different corporal patterns of the students. Finally, Sequential Pattern Mining step complements the previous stages allowing the identification of sequential patterns of postures in the different groups. The framework was tested in a case study with data collected from 222 freshman students of Computer Engineering (CE) course at three different times during two different years. The analysis made it possible to segment the presenters into three distinct groups according to their corporal postures. The statistical analysis helped to assess how the postures of the students evolved throughout each year. The sequential pattern mining provided a complementary perspective for data evaluation and helped to observe the most frequent postural sequences of the students. Results show the framework could be used as a guidance to provide students automated feedback throughout their presentations and can serve as background information for future comparisons of students presentations from different undergraduate courses.

Pervaporation Zeolite-Based Composite Membranes for Solvent Separations.

Thanks to their well-defined molecular sieving and stability, zeolites have been proposed in selective membrane separations, such as gas separation and pervaporation. For instance, the incorporation of zeolites into polymer phases to generate composite (or mixed matrix) membranes revealed important advances in pervaporation. Therefore, the goal of this review is to compile and elucidate the latest advances (over the last 2-3 years) of zeolite applications in pervaporation membranes either combining zeolites or polymers. Here, particular emphasis has been focused on relevant insights and findings in using zeolites in pervaporative azeotropic separations and specific aided applications, together with novel concepts of membranes. A brief background of the pervaporation process is also given. According to the findings of this review, we provide future perspectives and recommendations for new researchers in the field.

Latest Insights on Novel Deep Eutectic Solvents (DES) for Sustainable Extraction of Phenolic Compounds from Natural Sources.

Phenolic compounds have long been of great importance in the pharmaceutical, food, and cosmetic industries. Unfortunately, conventional extraction procedures have a high cost and are time consuming, and the solvents used can represent a safety risk for operators, consumers, and the environment. Deep eutectic solvents (DESs) are green alternatives for extraction processes, given their low or non-toxicity, biodegradability, and reusability. This review discusses the latest research (in the last two years) employing DESs for phenolic extraction, solvent components, extraction yields, extraction method characteristics, and reviewing the phenolic sources (natural products, by-products, wastes, etc.). This work also analyzes and discusses the most relevant DES-based studies for phenolic extraction from natural sources, their extraction strategies using DESs, their molecular mechanisms, and potential applications.

Inter-observer variability with five computed tomography severity scales for COVID-19 pneumonia assessment.

INTRODUCTION: By the end 2019 there was an outbreak of pneumonia caused by a new coronavirus, a disease that was called coronavirus disease 2019 (COVID-19). Computed tomography (CT) has played an important role in the diagnosis of COVID-19 patients. OBJECTIVE: To demonstrate inter-observer variability with five scales proposed for measuring the extent of COVID-19 pneumonia on tomography. METHODS: Thirty five initial chest CT scans of patients who attended respiratory triage for suspected COVID-19 pneumonia were analyzed. Three radiologists classified the tomographic images according to the severity scales proposed by Yang (1), Yuan (2), Chun (3), Wang (4) and Instituto Nacional de Enfermedades Respiratorias-Chung-Pan (5). The percentage of agreement between the evaluators for each scale was calculated using the intra-class correlation index. RESULTS: In most patients were five pulmonary lobes compromised (77.1% of the patients). Scales 1, 2, 4 and 5 showed an intra-class correlation > 0.91 (p < 0.0001), with agreement thus being almost perfect. CONCLUSIONS: Scale 4 (proposed by Wang) showed the best inter-observer agreement, with a coefficient of 0.964 (p = 0.001).

INTRODUCCIÓN: A finales de 2019 se presentó un brote de neumonía causada por un nuevo coronavirus, enfermedad a la que se denominó COVID-19. La tomografía computarizada ha desempeñado un papel importante en el diagnóstico de los pacientes con COVID-19. OBJETIVO: Demostrar la variabilidad interobservador con cinco escalas propuestas para la medición de la extensión de la neumonía ocasionada por COVID-19 mediante tomografía. MÉTODOS: Se analizaron 35 tomografías de tórax iniciales de pacientes que asistieron al triaje respiratorio por sospecha de neumonía por COVID-19. Tres radiólogos realizaron la clasificación de las imágenes tomográficas de acuerdo con las escalas de severidad propuestas por Yang (1), Yuan (2), Chun (3), Wang (4) e INER-Chung-Pan (5). Se calculó el porcentaje de concordancia entre los evaluadores para cada escala con el índice de correlación intraclase. RESULTADOS: La mayoría de los pacientes presentó afección de cinco lóbulos pulmonares (77.1 % de los pacientes). Las escalas 1, 2, 4 y 5 mostraron una correlación intraclase > 0.91, con p < 0.0001, por lo que la concordancia fue casi perfecta. CONCLUSIONES: La escala 4 (de Wang) mostró la mejor concordancia interobservador, con un coeficiente de 0.964 (p = 0.001).

Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study.

BACKGROUND: Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. METHODS: This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. RESULTS: The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with 18F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant. CONCLUSIONS: Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.