RESUMEN
This data descriptor presents a curated dataset for pathogen detection and identification (Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) directly from whole-blood samples. The dataset was created using differential cell lysis combined with rapid extraction, digestion, and mass spectrometry-based proteomics. Our method offers a rapid diagnostic alternative to traditional culture, enabling timely disease management, such as sepsis. Highlighting our dataset's uniqueness, it features a three-tier structure: Spectral Libraries of Pathogens for identifying peptide peaks for putative biomarkers; Spiked pathogen in blood MS data for biomarker panel optimization through varied concentration samples; and Parallel Reaction Monitoring (PRM) data from sepsis patients for validating our biomarker panel, achieving 83.3% sensitivity within seven hours without microbial enrichment culture. This dataset serves as a comprehensive reference for bioinformatic tool development and biomarker panel proposals, advancing microbial detection, antimicrobial resistance, and epidemiological studies.
Asunto(s)
Biomarcadores , Candida albicans , Proteómica , Pseudomonas aeruginosa , Sepsis , Staphylococcus aureus , Humanos , Proteómica/métodos , Biomarcadores/sangre , Sepsis/sangre , Sepsis/diagnóstico , Sepsis/microbiología , Espectrometría de MasasRESUMEN
A lactate/albumin ratio (LAR) greater than 0.5 measured early in the course of pediatric critical illness is associated with greater mortality. Whether the elevated LAR can be explained by microcirculation disorders in children with sepsis is not known. In this longitudinal retrospective study (January 2021-January 2024), serum albumin and lactate were measured on admission to the pediatric intensive care unit (PICU), with sublingual video microscopy performed simultaneously to measure microcirculation. A total of 178 children were included, 37% of whom had septic shock measured with the Phoenix Sepsis Score. Patients with remote sepsis had greater odds of an elevated LAR (aOR 6.87: 95% CI 1.98-23.73; p < 0.01). Children with an elevated LAR had more microvascular blood flow abnormalities (aOR 1.31 95% CI 1.08-1.58; p < 0.01), lower 4-6-micron capillary density (aOR 1.03 95% CI 1.01-1.05; p < 0.01) and greater odds of dying (aOR 3.55 95% CI 1.21-10.38; p = 0.02) compared to those with a low LAR. We found no association between LAR and endothelial glycocalyx degradation. A normal LAR is associated with less risk of microcirculatory injury (aOR 0.77 95% CI 0.65-0.93; p < 0.01). In children with sepsis, an elevated LAR is associated with microcirculation abnormalities (microvascular density and flow). The lactate/albumin ratio is a potentially useful biomarker for microcirculatory injury in sepsis.
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Ácido Láctico , Microcirculación , Sepsis , Humanos , Masculino , Femenino , Preescolar , Sepsis/sangre , Niño , Estudios Retrospectivos , Ácido Láctico/sangre , Lactante , Unidades de Cuidado Intensivo Pediátrico , Estudios Longitudinales , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Biomarcadores/sangre , Choque Séptico/sangreRESUMEN
Aim: To evaluate the urinary biomarkers related to sepsis in preterm newborns (NBs) and to investigate the predictive capacity of these biomarkers for a longer hospital stay.Methods: Serum and urine were collected from 27 healthy NBs, 24 NBs with neonatal infection without sepsis and 11 NBs with sepsis for the measurement of sindecan-1, lipocalin associated with urinary neutrophil gelatinase (uNGAL), urinary cystatin-C (uCysC) and urinary kidney injury molecule-1.Results: Levels of uNGAL and urinary cystatin-C were elevated in NBs with sepsis and neonatal infection, and uNGAL was significant predictor of hospital stay longer than 30 days (odds ratio: 1.052; 95% CI: 1.012-1.093; p = 0.01).Conclusion: uNGAL was associated with sepsis in preterm NBs and was useful to predict extended hospital stay.
[Box: see text].
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Biomarcadores , Cistatina C , Recien Nacido Prematuro , Tiempo de Internación , Lipocalina 2 , Sepsis , Humanos , Recién Nacido , Cistatina C/sangre , Cistatina C/orina , Lipocalina 2/orina , Lipocalina 2/sangre , Biomarcadores/orina , Biomarcadores/sangre , Sepsis/orina , Sepsis/diagnóstico , Sepsis/sangre , Masculino , Femenino , Recien Nacido Prematuro/orina , Proteínas de Fase Aguda/orina , Proteínas Proto-Oncogénicas/orina , Proteínas Proto-Oncogénicas/sangreRESUMEN
Ischemic stroke occurs due a blockage in the blood flow to the brain, leading to damage to the nervous system. The prevalent morbidities resulting from stroke include post-stroke infection, as sepsis. Additionally, oxidative stress is recognized for inducing functional deficits in peripheral organs during sepsis. Therefore, sex differences in stroke exist and we aimed to investigate the peripheral oxidative stress caused by sepsis after stroke in male and female rats. Wistar rats (male and female) were divided into sham+sham, middle cerebral artery occlusion (MCAO) + sham, sham+ cecal ligation and perforation (CLP) and MCAO+CLP groups to males and female rats. Animals were subjected to MCAO or sham and after 7 days, were subjected to sepsis by CLP or sham. After 24 h, serum, total brain, lung, liver, heart, and spleen were collected. Brain edema, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, oxidative damage to lipids and proteins, and catalase activity were evaluated. Brain edema was observed only in male rats in MCAO+CLP group compared to MCAO+sham. Regarding MPO activity, an increase was verified in male in different organs and serum in MCAO+CLP group. For N/N levels, the increase was more pronounced in females submitted to MCAO+CLP. In general, to oxidative stress, an increase was only observed in animals exposed to MCAO+CLP, or with a greater increase in this group compared to the others. The findings provided the first indication that animals exposed to MCAO exhibit a heightened vulnerability to the harmful impacts of sepsis, as evidenced by brain edema and peripheral oxidative stress, and this susceptibility is dependent of sex.
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Edema Encefálico , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media , Estrés Oxidativo , Peroxidasa , Ratas Wistar , Sepsis , Animales , Femenino , Masculino , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Infarto de la Arteria Cerebral Media/sangre , Sepsis/metabolismo , Sepsis/fisiopatología , Sepsis/complicaciones , Sepsis/sangre , Factores Sexuales , Peroxidasa/metabolismo , Edema Encefálico/metabolismo , Edema Encefálico/patología , Edema Encefálico/fisiopatología , Nitratos/sangre , Nitratos/metabolismo , Nitritos/sangre , Nitritos/metabolismo , Ratas , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/irrigación sanguínea , Catalasa/metabolismoRESUMEN
Bloodstream infection (BSI) is associated with increased morbidity and mortality in the pediatric intensive care unit (PICU) and high healthcare costs. Early detection and appropriate treatment of BSI may improve patient's outcome. Data on machine-learning models to predict BSI in pediatric patients are limited and neither study included time series data. We aimed to develop a machine learning model to predict an early diagnosis of BSI in patients admitted to the PICU. This was a retrospective cohort study of patients who had at least one positive blood culture result during stay at a PICU of a tertiary-care university hospital, from January 1st to December 31st 2019. Patients with positive blood culture results with growth of contaminants and those with incomplete data were excluded. Models were developed using demographic, clinical and laboratory data collected from the electronic medical record. Laboratory data (complete blood cell counts with differential and C-reactive protein) and vital signs (heart rate, respiratory rate, blood pressure, temperature, oxygen saturation) were obtained 72 hours before and on the day of blood culture collection. A total of 8816 data from 76 patients were processed by the models. The machine committee was the best-performing model, showing accuracy of 99.33%, precision of 98.89%, sensitivity of 100% and specificity of 98.46%. Hence, we developed a model using demographic, clinical and laboratory data collected on a routine basis that was able to detect BSI with excellent accuracy and precision, and high sensitivity and specificity. The inclusion of vital signs and laboratory data variation over time allowed the model to identify temporal changes that could be suggestive of the diagnosis of BSI. Our model might help the medical team in clinical-decision making by creating an alert in the electronic medical record, which may allow early antimicrobial initiation and better outcomes.
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Diagnóstico Precoz , Unidades de Cuidado Intensivo Pediátrico , Aprendizaje Automático , Humanos , Masculino , Femenino , Lactante , Estudios Retrospectivos , Preescolar , Niño , Sepsis/diagnóstico , Sepsis/sangre , Bacteriemia/diagnóstico , Recién Nacido , AdolescenteRESUMEN
CONTEXT: Candida-related infections are nowadays a serious Public Health Problem emerging multidrug-resistant strains. Candida biofilm also leads bloodstream infections to invasive systemic infections. OBJECTIVE: The present meta-analysis aimed to analyze Candida biofilm rate, type, and antifungal resistance among hospitalized patients between 1995 and 2020. DATA SOURCES: Web of Science, Scopus, PubMed, and Google Scholar databases were searched for English papers using the following medical subject heading terms (MESH): "invasive candidiasis"; "bloodstream infections"; "biofilm formation"; "biofilm-related infections"; "mortality"; and "prevalence". STUDY SELECTION: The major inclusion criteria included reporting the rate of biofilm formation and the prevalence of biofilm-related to Candida species, including observational studies (more exactly, cohort, retrospective, and case-control studies). Furthermore, data regarding the mortality rate, the geographical location of the study set, and the use of anti-fungal agents in clinical isolates were also extracted from the studies. DATA EXTRACTION: Independent extraction of articles by 2 authors using predefined data fields, including study quality indicators. DATA SYNTHESIS: A total of 31 studies from publicly available databases met our inclusion criteria. The biofilm formation in the data set varied greatly from 16 to 100% in blood samples. Most of the studies belonged to Europe (17/31) and Asia (9/31). Forest plot showed a pooled rate of biofilm formation of 80.0% (CI: 67-90), with high heterogeneity (Q = 2567.45, I2 = 98.83, τ2 = 0.150) in random effects model (p < 0.001). The funnel plot and Egger's linear regression test failed to find publication bias (p = 0.896). The mortality rate in Candida-related bloodstream infections was 37.9% of which 70.0% were from biofilm-associated infections. Furthermore, Candida isolates were also characterized in low, intermediate, or high biofilm formers through their level of biofilm mass (crystal violet staining or XTT assays) after a 24h growth. When comparing between countries, statistical differences were obtained (p = 0.0074), showing the lower and higher biofilm prevalence values in Italy and Spain, respectively. The prevalence of low, intermediate, and high biofilms were 36.2, 18.9, and 35.0% (p < 0.0001), respectively. C. tropicalis was the prevalent species in high biofilm formation (67.5%) showing statistically significant differences when compared to other Candida species, except for C. krusei and C. glabrata. Finally, the rates of antifungal resistance to fluconazole, voriconazole, and caspofungin related to biofilm were 70.5, 67.9 and 72.8% (p < 0.001), respectively. CONCLUSIONS: Early detection of biofilms and a better characterization of Candida spp. bloodstream infections should be considered, which eventually will help preserve public health resources and ultimately diminish mortality among patients.
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Biopelículas , Candida , Candidemia/sangre , Candidiasis/sangre , Sepsis/sangre , Candidemia/microbiología , Candidiasis/microbiología , Caspofungina/farmacología , Farmacorresistencia Fúngica , Fluconazol/farmacología , Hospitalización , Humanos , Prevalencia , Sepsis/microbiología , Voriconazol/farmacologíaRESUMEN
Sepsis remains one of the main causes of death in intensive care unit (ICU) worldwide, despite all technological and scientific advances. Microvesicles (MV) have become promising biomarkers for quick and accurate monitoring of several illnesses. The aim of this pilot study was to characterize and evaluate the performance of MV as biomarker of clinical outcome in septic and trauma patients. For this purpose, 39 subjects, both genders, aging from 18 to 85 years were included in three groups referred as Sepsis, Trauma and Healthy Control. Kinetic analysis of MV was carried out at four consecutive time points: admission (baseline)/T1, 24 h/T2, 72 h/T3 and outcome/T4 of discharge or death. At admission, an overall increase in total MV (Annexin V+) was observed in Sepsis.MV CD14+ (monocytes) was a putative biomarker to identify trauma patients, while MV CD3+ (T-cells) and CD41+ (platelets) were qualified to discriminated Trauma from Sepsis. Sepsis (Death) presented an increase in MV Annexin V+, CD45+, CD16+, CD14+, and CD41+ in comparison to Sepsis (Discharge). Moreover, Trauma (Death) presented an increase of MV CD3+ and CD235+ as compared to Trauma (Discharge). Analysing the ROC curve of specific MV evaluated according to performance, an accuracy of 100% was found to segregate the outcome in sepsis, and 95% in trauma. Our findings suggest that MV might be useful as a potential role in discriminating outcome in patients with sepsis/septic shock and trauma with high accuracy. However, further studies with a larger number of participants will be necessary to validate our findings.
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Biomarcadores , Micropartículas Derivadas de Células , Sepsis/sangre , Heridas y Lesiones/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/inmunología , Enfermedad Crítica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Pronóstico , Estudios Retrospectivos , Sepsis/inmunología , Heridas y Lesiones/inmunología , Adulto JovenRESUMEN
Correct processing of blood cultures may impact individual patient management, antibiotic stewardship, and scaling up of antimicrobial resistance surveillance. To assess the quality of blood culture processing, we conducted four assessments at 16 public hospitals across different regions of Peru. We assessed the following standardized quality indicators: 1) positivity and contamination rates, 2) compliance with recommended number of bottles/sets and volume of blood sampled, 3) blood culture utilization, and 4) possible barriers for compliance with recommendations. Suboptimal performance was found, with a median contamination rate of 4.2% (range 0-15.1%), with only one third of the participating hospitals meeting the target value of < 3%; and a median positivity rate of 4.9% (range 1-8.1%), with only 6 out of the 15 surveilled hospitals meeting the target of 6-12%. None of the assessed hospitals met both targets. The median frequency of solitary blood cultures was 71.9% and only 8.9% (N = 59) of the surveyed adult bottles met the target blood volume of 8 - 12 mL, whereas 90.5% (N = 602) were underfilled. A high frequency of missed opportunities for ordering blood cultures was found (69.9%, 221/316) among patients with clinical indications for blood culture sampling. This multicenter study demonstrates important shortcomings in the quality of blood culture processing in public hospitals of Peru. It provides a national benchmark of blood culture utilization and quality indicators that can be used to monitor future quality improvement studies and diagnostic stewardship policies.
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Cultivo de Sangre/normas , Hospitales Públicos/normas , Sepsis/diagnóstico , Manejo de Especímenes/normas , Cultivo de Sangre/estadística & datos numéricos , Humanos , Perú , Control de Calidad , Sepsis/sangre , Manejo de Especímenes/estadística & datos numéricos , Encuestas y Cuestionarios/normasRESUMEN
OBJECTIVES: Circulating nucleosomes and their component histones have been implicated as pathogenic in sepsis and acute respiratory distress syndrome in adults. However, their role in pediatric acute respiratory distress syndrome is unknown. DESIGN: We performed a prospective cohort study in children with acute respiratory distress syndrome, with plasma collection within 24 hours of acute respiratory distress syndrome onset. We associated nucleosome levels with severity of acute respiratory distress syndrome and with nonpulmonary organ failures and tested for association of nucleosomes with PICU mortality and ventilator-free days at 28 days in univariate and multivariable analyses. We also performed proteomics of DNA-bound plasma proteins in a matched case-control study of septic children with and without acute respiratory distress syndrome in order to identify specific histone proteins elevated in acute respiratory distress syndrome. SETTING: Large academic tertiary-care PICU. PATIENTS: Intubated children meeting Berlin criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled 333 children with acute respiratory distress syndrome, with 69 nonsurvivors (21%). Plasma nucleosomes were correlated with acute respiratory distress syndrome severity and with the number of nonpulmonary organ failures at acute respiratory distress syndrome onset. Nucleosomes were higher (p < 0.001) in nonsurvivors (0.40 [interquartile range, 0.20-0.71] arbitrary units) relative to survivors (0.10 [interquartile range, 0.04-0.25] arbitrary units). Nucleosomes were associated with PICU mortality in multivariable analysis (adjusted odds ratio 1.84 per 1 sd increase; 95% CI, 1.38-2.45; p < 0.001). Nucleosomes were also associated with a lower probability of being extubated alive by day 28 after multivariable adjustment (adjusted subdistribution hazard ratio, 0.74; 95% CI, 0.63-0.88; p = 0.001). Proteomic analysis demonstrated higher levels of the core nucleosome histones H2A, H2B, H3, and H4 in septic children with acute respiratory distress syndrome, relative to septic children without acute respiratory distress syndrome. CONCLUSIONS: Plasma nucleosomes are associated with acute respiratory distress syndrome severity, nonpulmonary organ failures, and worse outcomes in pediatric acute respiratory distress syndrome.
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Histonas/sangre , Nucleosomas/metabolismo , Síndrome de Dificultad Respiratoria/sangre , Síndrome de Dificultad Respiratoria/mortalidad , Adolescente , Extubación Traqueal , Estudios de Casos y Controles , Niño , Preescolar , ADN/sangre , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidado Intensivo Pediátrico , Masculino , Insuficiencia Multiorgánica/mortalidad , Pronóstico , Estudios Prospectivos , Proteómica , Respiración Artificial , Síndrome de Dificultad Respiratoria/complicaciones , Sepsis/sangre , Sepsis/complicaciones , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaRESUMEN
Las enfermedades infecciosas son un problema de salud que a pesar de los avances médicos siguen cobrando vi-das en todo el mundo; como las septicemias. La presente investigación tuvo por objetivo diseñar, estandarizar e implementar un protocolo inexistente en Guatemala, para el diagnóstico rutinario de hemocultivos positivos dentro de las instalaciones del Laboratorio Clínico del Hospital General San Juan de Dios, lugar en donde se encuentra el único espectrómetro de masas de tipo Maldi-tof (Matrix Assisted Laser Desorption Ionization-Time of flight-mass spectrometry).Se utilizaron 240 muestras de pacientes de los diferentes servicios. El diagnóstico se realizó compa-rando las identificaciones obtenidas a partir de cultivos microbiológicos puros con muestras directas de botellas con caldo BHI(Brain Heart Infusion).Los resultados de las dos metodologías fueron evaluados con el diseño estadístico "apareado o emparejado en grupo". La comparación no evidenció discordancia en las identificaciones; pero sí en los tiempos de respuesta. La reducción de tiempo fue de 42.9 h para bacterias Gram positivo, 45.0 h para bacterias Gram negativo y 126.2 h para levaduras, todos a favor de identificaciones a partir de muestras directas. Con esta investigación se pretende ofrecer una nueva alternativa que permitirá brindar un diagnóstico rápido, confiable y certero a la población guatemalteca. También permitirá reducir la morbimortalidad de los pacientes con septicemias, promover el ahorro de insumos hospitalarios, disminuir el tiempo de estancia hospitalaria, ahorrar el consumo de antibióticos innecesarios y contribuir indirectamente a combatir la resistencia antimicrobiana; un problema actual de gran importancia a nivel mundial.
Infectious diseases are a health problem that despite medical advances in terms of diagnosis continue to take lives worldwide, such is the case of sepsis. The purpose of this research was to design, standardize and implement a non-existent protocol in Guatemala, for the routine diagnosis of positive blood cultures, within the facilities of the clinical laboratory of the San Juan de Dios General Hospital; where the only Maldi-tof (Matrix Assisted Laser Desorp-tion Ionization-Time of flight-mass spectrometry) type mass spectrometer is located. For this, 240 samples of positive blood cultures were used, coming from patients of the different services. The microbiological diagnosis was made by comparing the identification data obtained from pure microbiological cultures and direct samples of BHI broth (Brain Heart Infusion) bottles. The results of the two methodologies were evaluated based on "paired or matched in groups" statistical design. The Maldi-tof technique did not show disagreement regarding identification between the two types of samples; but it did in the response time. The time reduction was 42.9 h for Gram positive bacteria, 45.0 h for Gram negative and 126.2 h for yeasts, supporting identification from direct samples. This research aims to provide a new diagnostic alternative that will allow access to fast, reliable, and accurate results for the Guatemalan population. It will also help to reduce e morbidity and mortality rates of patients with sepsis, to promote hospital supplies savings, decrease the patient length of stay, save unnecessary antibiotics and indirectly contribute to combating antimicrobial resistance; a critical problem faced by the world today.
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Humanos , Sepsis/diagnóstico , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/instrumentación , Cultivo de Sangre/métodos , Bacterias Grampositivas/aislamiento & purificación , Factores de Tiempo , Sepsis/microbiología , Sepsis/sangre , Farmacorresistencia Bacteriana , Bacterias Gramnegativas/aislamiento & purificaciónRESUMEN
Microcirculatory disorders have been consistently linked to the pathophysiology of sepsis. One of the major organs affected is the kidneys, resulting in sepsis-associated acute kidney injury (SA-AKI) that correlates considerably with mortality. However, the potential role of clinical assessment of peripheral perfusion as a possible tool for SA-AKI management has not been established. To address this gap, the purpose of this study was to investigate the prevalence of peripheral hypoperfusion in SA-AKI, its association with mortality, and fluid balance. This observational cohort study enrolled consecutive septic patients in the Intensive Care Unit. After fluid resuscitation, peripheral perfusion was evaluated using the capillary filling time (CRT) and peripheral perfusion index (PI) techniques. The AKI was defined based on both serum creatinine and urine output criteria. One hundred and forty-one patients were included, 28 (19%) in the non-SA-AKI group, and 113 (81%) in the SA-AKI group. The study revealed higher peripheral hypoperfusion rates in the SA-AKI group using the CRT (OR 3.6; 95% CI 1.35-9.55; p < 0.05). However, this result lost significance after multivariate adjustment. Perfusion abnormalities in the SA-AKI group diagnosed by both CRT (RR 1.96; 95% CI 1.25-3.08) and PI (RR 1.98; 95% CI 1.37-2.86) methods were associated to higher rates of 28-day mortality (p < 0.01). The PI's temporal analysis showed a high predictive value for death over the first 72 h (p < 0.01). A weak correlation between PI values and the fluid balance was found over the first 24 h (r = - 0.20; p < 0.05). In conclusion, peripheral perfusion was not different intrinsically between patients with or without SA-AKI. The presence of peripheral hypoperfusion in the SA-AKI group has appeared to be a prognostic marker for mortality. This evaluation maintained its predictive value over the first 72 hours. The fluid balance possibly negatively influences peripheral perfusion in the SA-AKI.
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Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/fisiopatología , Microcirculación/fisiología , Sepsis/fisiopatología , Lesión Renal Aguda/sangre , Estudios de Cohortes , Creatinina/sangre , Femenino , Fluidoterapia/métodos , Humanos , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Perfusión/métodos , Pronóstico , Sepsis/sangre , Sepsis/mortalidad , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
OBJECTIVE: To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness. METHODS: A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection. RESULTS: Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p < 0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m. CONCLUSION: Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.
OBJETIVO: Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica. MÉTODOS: Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção. RESULTADOS: Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p < 0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção. CONCLUSÃO: A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse.
Asunto(s)
Glicocálix/metabolismo , Hiperemia/etiología , Sepsis/diagnóstico , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Enfermedad Crítica , Selectina E/metabolismo , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hiperemia/diagnóstico , Unidades de Cuidados Intensivos , Masculino , Manometría , Persona de Mediana Edad , Estudios Prospectivos , Sepsis/sangre , Índice de Severidad de la Enfermedad , Sindecano-1/metabolismoRESUMEN
RESUMO Objetivo: Investigar se a hiperemia reativa correlaciona-se com marcadores de disfunção endotelial e pode ser utilizada para identificar sepse na doença crítica. Métodos: Trata-se de estudo prospectivo em uma coorte de pacientes críticos. A disfunção endotelial foi avaliada quando da admissão, por meio da quantificação de hiperemia por tonometria arterial periférica e níveis plasmáticos de endotelina 1, E-selectina solúvel, endocana e sindecano 1. Os pacientes sépticos foram comparados com pacientes sem evidência de infecção. Resultados: Cinquenta e oito pacientes sépticos foram comparados com 28 controle. O logaritmo natural da tonometria arterial periférica teve correlação negativa com comorbidades cardiovasculares, severidade da doença e níveis plasmáticos de E-selectina solúvel (p = 0,024) e sindecano 1 (p < 0,001). O logaritmo natural da tonometria arterial periférica foi mais baixo nos pacientes sépticos quando comparado com os de pacientes controle (0,53 ± 0,48 versus 0,69 ± 0,42, respectivamente) e, quando ajustado à idade, o modelo multivariado predisse que cada 0,1 de diminuição em unidades de logaritmo natural da tonometria arterial periférica levou a aumento de 14,6% na probabilidade de infecção. Conclusão: A hiperemia reativa avaliada por tonometria arterial periférica tem estreita relação com E-selectina solúvel e sindecano 1, o que sugere associação entre ativação endotelial, degradação de glicocálix e reatividade vascular. A hiperemia reativa por tonometria arterial periférica parece estar comprometida em pacientes críticos, especialmente os com sepse.
Abstract Objective: To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness. Methods: A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection. Results: Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p < 0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m. Conclusion: Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Sepsis/diagnóstico , Glicocálix/metabolismo , Hiperemia/etiología , Índice de Severidad de la Enfermedad , Endotelio Vascular/fisiopatología , Biomarcadores/sangre , Estudios Prospectivos , Estudios de Cohortes , Enfermedad Crítica , Sepsis/sangre , Selectina E/metabolismo , Sindecano-1/metabolismo , Unidades de Cuidados Intensivos , ManometríaRESUMEN
BACKGROUND: A level < 35 g/L of albumin (hypoalbuminemia) has been determined as a parameter to predict mortality and morbidity. METHOD: Prospective observational study, in a period of 12 months, to patients diagnosed with sepsis of abdominal origin, they are divided into two groups based on albumin levels (cut: 3.5 g/dL) to assess mortality between both groups. RESULTS: We studied 23 patients admitted to the intensive care unit. The mean albumin was 2.77 g/dL (± 0.71). When calculating the odds ratio (OR) that was a 23-fold greater risk of dying when hypoalbuminemia presented compared to the normal albumin group (OR = 23.3; 95% CI: 1,948 to 279.42). The mean albumin for patients who died was 2.04 g/dL (± 0.31) vs. 3.03 g/dL (± 0.35) (p = 0.02; 95% CI: -1.551 to -0.416). We do not assess morbidity, however, we identify a certain tendency to a longer stay in the ICU which is accompanied by a higher risk of complications and in the end a higher risk of mortality. CONCLUSION: We conclude that hypoalbuminemia represents a predictor of mortality in patients with abdominal sepsis.
ANTECEDENTES: Un valor de albúmina < 35 g/l (hipoalbuminemia) ha demostrado ser un parámetro para predecir mortalidad y morbilidad. MÉTODO: Estudio observacional, prospectivo, en un periodo de 12 meses, en pacientes con diagnóstico de sepsis de origen abdominal a quienes se dividió en dos grupos según las cifras de albúmina (corte: 3.5 g/dl) para valorar la mortalidad en ambos grupos. RESULTADOS: Estudiamos 23 pacientes ingresados a la unidad de terapia intensiva. La media de albúmina fue de 2.77 g/dl (± 0.71). Al calcular la odds ratio (OR) identificamos un riesgo 23 veces mayor de fallecer al presentar hipoalbuminemia en comparación con el grupo con albúmina normal (OR = 23.3; intervalo de confianza del 95% [IC 95%]: 1.948 a 279.42). La media de los valores de albúmina para los pacientes que fallecieron fue de 2.04 g/dl (± 0.31) vs. a 3.03 g/dl (± 0.35) para el otro grupo (IC 95%: −1.551 a −0.416; p = 0.02)]. Aunque no valoramos la morbilidad, identificamos cierta tendencia a un mayor tiempo de estancia en la unidad de terapia intensiva, lo que se acompaña de mayor riesgo de complicaciones y de un mayor riesgo de muerte. CONCLUSIÓN: La hipoalbuminemia representa un predictor de mortalidad en los pacientes con sepsis abdominal.
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Hipoalbuminemia/mortalidad , Infecciones Intraabdominales/mortalidad , Sepsis/mortalidad , APACHE , Intervalos de Confianza , Femenino , Humanos , Unidades de Cuidados Intensivos , Infecciones Intraabdominales/sangre , Tiempo de Internación , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Puntuaciones en la Disfunción de Órganos , Estudios Prospectivos , Sepsis/sangre , Albúmina Sérica/análisisRESUMEN
Sepsis is a severe disease with a high mortality rate. Identification and treatment in the initial hours of the disease improve outcomes. Some biomarkers like procalcitonin and C-reactive protein are used for diagnosis and to access sepsis prognosis and they can help in clinical decision-making, but none has sufficient specificity or sensitivity to be routinely employed in clinical practice. This review seeks to evaluate lipid metabolism alterations in patients with sepsis and the possibility of using the respective metabolites as biomarkers of the disease. A search of the main electronic biomedical databases was conducted for the 20-year period ending in February 2020, focused on primary research articles on biomarkers in sepsis. The keywords included sepsis, septic shock, biomarker, metabolomic, lipidomic and lysophosphatidylcoline.. It concludes that altered lipid profiles, along with the progress of the disease should provide new insights, enabling a better understanding of the pathogenic mechanisms and making it possible to design new early diagnosis and therapeutic procedures for sepsis.
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Biomarcadores/sangre , Lipidómica , Sepsis/sangre , Atención a la Salud , Humanos , Inflamación/sangre , Inflamación/patología , Redes y Vías MetabólicasRESUMEN
INTRODUCTION: Sepsis is an important cause of mortality and morbidity, and inflammatory response and oxidative stress play major roles underlying its pathophysiology. Here, we evaluated the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats. METHODS: Twenty-eight adult Sprague Dawley rats were classified into Control (Group 1), Sepsis (Group 2), Sepsis+Cefazolin (Group 3), and Sepsis+Cefazolin+Etanercept (Group 4) groups. Kidney tissue and serum samples were obtained for biochemical and histopathological investigations and examined for the C reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), triggering receptor expressed on myeloid cells (TREM), and malondialdehyde (MDA) levels. RESULTS: The levels of TNF-α, TREM, and MDA in serum and kidney samples were significantly higher in rats from sepsis group than in rats from control group (p < 0.05). Group 3 showed a significant reduction in serum levels of TNF-α, CRP, and TREM as compared with Group 2 (p < 0.05). Serum TNF-α, CRP, TREM, and MDA levels and kidney TNF-α and TREM levels were significantly lower in Group 4 than in Group 2 (p < 0.05). Serum TNF-α and TREM levels in Group 4 were significantly lower than those in Group 3, and histopathological scores were significantly lower in Group 3 and Group 4 than in Group 2 (p < 0.05). Histopathological scores of Group 4 were significantly lower than those of Group 3 (p < 0.05). CONCLUSIONS: Etanercept, a TNF-α inhibitor, may ameliorate sepsis-induced oxidative stress, inflammation, and histopathological damage.
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Antiinflamatorios no Esteroideos/administración & dosificación , Etanercept/administración & dosificación , Inflamación/prevención & control , Riñón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sepsis/patología , Factor de Necrosis Tumoral alfa/sangre , Animales , Antiinflamatorios no Esteroideos/farmacología , Modelos Animales de Enfermedad , Etanercept/farmacología , Inflamación/patología , Inyecciones Intraperitoneales , Ratas , Ratas Sprague-Dawley , Sepsis/sangreRESUMEN
BACKGROUND: Biomarker combinations can improve timely diagnosis and survival. OBJECTIVE: To determine the usefulness of serum procalcitonin concentration (PCT), C-reactive protein (PCR) and the PCR / PCT index as predictors of mortality. METHOD: Retrospective study of patients diagnosed with abdominal sepsis during the period from April 2017 to February 2018. RESULTS: We included 182 cases. In the survivors, the mean PCR was 170 and procalcitonin (PCT) 10.5. In the deceased, the mean of C-reactive protein (CRP) was 328 and that of PCT was 17.6. When applying the student's t-test for independent samples, it was found that these differences were significant for PCR (p = 0.001); however, for PCT it was not significant (p = 0.460). Afterwards, the PCR/PCT index was studied, as a predictor of mortality, in the deceased cases a PCR/PCT score of 7534 (standard deviation [SD]: 19,303) and for survivors of 538 (SD:805) (p = 0.001) was obtained. CONCLUSION: CRP is associated with mortality, serum PCT does not correlate with mortality. The PCR/PCT index seems to be a better indicator to predict mortality in patients with abdominal sepsis due to secondary peritonitis.
ANTECEDENTES: Las combinaciones de biomarcadores pueden mejorar el diagnóstico oportuno y la supervivencia. OBJETIVO: Determinar la utilidad de la concentración sérica de procalcitonina (PCT), la proteína C reactiva (PCR) y el índice PCR/PCT como predictores de mortalidad. MÉTODO: Estudio retrospectivo de pacientes con diagnóstico de sepsis abdominal durante el periodo de abril de 2017 a febrero de 2018. RESULTADOS: Se incluyeron 182 casos. En los sobrevivientes, la media de los valores de PCR fue de 170 y la de PCT fue de 10.5. En los fallecidos, la media de los valores de PCR fue de 328 y la de PCT fue de 17.6. Al aplicar el estadístico t de Student para muestras independientes se obtuvo que estas diferencias resultaron significativas para la PCR (p = 0.001), pero no para la PCT (p = 0.460). Posteriormente se estudió el índice PCR/PCT como predictor de mortalidad: en los fallecidos se obtuvo un valor de 7534 (desviación estándar [DE]:± 19,303) y en los sobrevivientes de 538 (DE± 805) (p = 0.001). CONCLUSIÓN: La PCR se asocia con la mortalidad, mientras que la PCT no guarda relación con la mortalidad. El índice PCR/PCT parece ser un mejor indicador para predecir la mortalidad en los pacientes con sepsis abdominal por peritonitis secundaria.
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Proteína C-Reactiva/análisis , Polipéptido alfa Relacionado con Calcitonina/sangre , Sepsis/sangre , Sepsis/mortalidad , Abdomen , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
OBJECTIVES: Systemic endothelial activation may contribute to sepsis-associated organ injury, including acute respiratory distress syndrome. We hypothesized that children with extrapulmonary sepsis with versus without acute respiratory distress syndrome would have plasma biomarkers indicative of increased endothelial activation and that persistent biomarker changes would be associated with poor outcome. DESIGN: Observational cohort. SETTING: Academic PICU. PATIENTS: Patients less than 18 years old with sepsis from extrapulmonary infection with (n = 46) or without (n = 54) acute respiratory distress syndrome and noninfected controls (n = 19). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Endothelial (angiopoietin-1, angiopoietin-2, tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2, vascular endothelial growth factor, soluble fms-like tyrosine kinase, von Willebrand factor, E-selectin, intercellular adhesion molecule, vascular cell adhesion molecule, thrombomodulin) and inflammatory biomarkers (C-reactive protein, interleukin-6, and interleukin-8) were measured from peripheral plasma collected within 3 days (time 1) of sepsis recognition and at 3-6 days (time 2) and 7-14 days (time 3). Time 1 biomarkers and longitudinal measurements were compared for sepsis patients with versus without acute respiratory distress syndrome and in relation to complicated course, defined as greater than or equal to two organ dysfunctions at day 7 or death by day 28. Angiopoietin-2, angiopoietin-2/angiopoietin-1 ratio, tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2, vascular endothelial growth factor, von Willebrand factor, E-selectin, intercellular adhesion molecule, vascular cell adhesion molecule, thrombomodulin, endocan, C-reactive protein, interleukin-6, and interleukin-8 were different between sepsis and noninfected control patients at time 1. Among patients with sepsis, those with acute respiratory distress syndrome had higher angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor, vascular cell adhesion molecule, thrombomodulin, endocan, interleukin-6, and interleukin-8 than those without acute respiratory distress syndrome (all p < 0.003). Angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratio remained higher in sepsis with versus without acute respiratory distress syndrome after multivariable analyses. Time 1 measures of angiopoietin-2, angiopoietin-2/-1 ratio, von Willebrand factor, and endocan were indicative of complicated course in all sepsis patients (all area under the receiver operating curve ≥ 0.80). In sepsis without acute respiratory distress syndrome, soluble fms-like tyrosine kinase decreased more quickly and von Willebrand factor and thrombomodulin decreased more slowly in those with complicated course. CONCLUSIONS: Children with extrapulmonary sepsis with acute respiratory distress syndrome had plasma biomarkers indicative of greater systemic endothelial activation than those without acute respiratory distress syndrome. Several endothelial biomarkers measured near sepsis recognition were associated with complicated course, whereas longitudinal biomarker changes yielded prognostic information only in those without sepsis-associated acute respiratory distress syndrome.
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Endotelio/fisiopatología , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Síndrome de Dificultad Respiratoria/epidemiología , Sepsis/epidemiología , Sepsis/fisiopatología , Adolescente , Biomarcadores , Proteínas Sanguíneas/metabolismo , Moléculas de Adhesión Celular/metabolismo , Niño , Preescolar , Femenino , Mortalidad Hospitalaria , Humanos , Lactante , Mediadores de Inflamación , Estudios Longitudinales , Masculino , Puntuaciones en la Disfunción de Órganos , Pronóstico , Síndrome de Dificultad Respiratoria/sangre , Sepsis/sangre , Factores de TiempoRESUMEN
Background: Alterations in the lipid profile are part of the acute phase response, this corresponds to the so-called lipemia of sepsis. Objective: To determine if the serum level of high density lipoprotein (HDL) is related to severity and mortality. Method: Retrospective, descriptive, cross-sectional study of patients diagnosed with abdominal sepsis. During the period from April 2016 to February 2017. The severity was determined by APACHE II, SOFA, Mannheim, CONUT, the presence of organic faults and mortality. Results: We included 154 cases, 59 female and 95 male; The main organ causing abdominal sepsis was the appendix 41.6%. The overall mortality was 14.3%. The presence of organic faults was 35.1%. The mean HDL level was 37.64 mg/dl (SD ± 16.16). The findings, subjected to statistical verification by Student's t-test, showed significance among the cases with SOFA > 4 (p = 0.01) and Mannheim > 26 (p = 0.001), CONUT > 6 (p = 0.001), presence of organic failures (p = 0.001), and mortality (p = 0.003). Conclusions: HDL levels are related to severity, with the development of organic failures and mortality in sepsis.
Antecedentes: Las alteraciones en el perfil de lípidos son parte de la respuesta de fase aguda, lo que corresponde a la denominada lipemia de la sepsis. Objetivo: Determinar si la concentración sérica de lipoproteínas de alta densidad (HDL) se relaciona con la gravedad y la mortalidad. Método: Estudio retrospectivo, descriptivo, transversal, de pacientes con diagnóstico de sepsis abdominal, durante el periodo de abril de 2016 a febrero de 2017. Se determinó la gravedad mediante APACHE II, SOFA, Mannheim, CONUT, la presencia de fallas orgánicas y la mortalidad. Resultados: Se incluyeron 154 casos, 59 mujeres y 95 hombres. El principal órgano causante de sepsis abdominal fue el apéndice (41.6%). La mortalidad global fue del 14.3%. La presencia de fallas orgánicas fue del 35.1%. El valor medio de HDL se situó en 37.64 mg/dl (desviación estándar: ± 16.16). Los hallazgos, sometidos a verificación estadística mediante la prueba t de Student, mostraron significancia entre los casos con SOFA > 4 (p = 0.01) y Mannheim > 26 (p = 0.001), CONUT > 6 (p = 0.001), presencia de fallas orgánicas (p = 0.001) y mortalidad (p = 0.003). Conclusión: Los valores de HDL se relacionan con la gravedad, con el desarrollo de fallas orgánicas y con la mortalidad en la sepsis.