Modelo de riesgo de mortalidad a largo plazo en pacientes con infección atendidos por servicios de emergencias prehospitalarios / Long-term risk of death in patients with infection attended by prehospital emergency services

Objetivo: Diseñar y validar un modelo de riesgo con variables determinadas a nivel prehospitalario para predecir el riesgo de mortalidad a largo plazo (1 año) en pacientes con infección. Métodos: Estudio multicéntrico, observacional prospectivo, sin intervención, en pacientes adultos con sospecha infección atendidos por unidades de soporte vital avanzado y trasladados a 4 hospitales españoles entre el 1 de junio de 2020 y el 30 de junio de 2022. Se recogieron variables demográficas, fisiológicas, clínicas y analíticas. Se construyó y validó un modelo de riesgo para la mortalidad a un año usando una regresión de Cox.Resultados: Se incluyeron 410 pacientes, con una tasa de mortalidad acumulada al año del 49%. La tasa de diagnóstico de sepsis (infección e incremento sobre el SOFA basal $ 2 puntos) fue del 29,2% en supervivientes frente a un 56,7% en no supervivientes. El modelo predictivo obtuvo un área bajo la curva de la característica operativa del receptor para la mortalidad a un año fue de 0,89, e incluyó: edad, institucionalización, índice de comorbilidad de Charlson ajustado por edad, presión parcial de dióxido de carbono, potasio, lactato, nitrógeno ureico en sangre, creatinina, saturación en relación con fracción inspirada de oxígeno y diagnóstico de sepsis.Conclusiones: El modelo desarrollado con variables epidemiológicas, analíticas y clínicas mostró una excelente capacidad predictiva, y permitió identificar desde el primer contacto del paciente con el sistema sanitario, a modo de evento centinela, casos de alto riesgo.(AU)

Objectives: To develop and validate a risk model for 1-year mortality based on variables available from earlyprehospital emergency attendance of patients with infection. Methods: Prospective, observational, noninterventional multicenter study in adults with suspected infection transferred to 4 Spanish hospitals by advanced life-support ambulances from June 1, 2020, through June 30, 2022. We collected demographic, physiological, clinical, and analytical data. Cox regression analysis was used to develop and validate a risk model for 1-year mortality. Results: Four hundred ten patients were enrolled (development cohort, 287; validation cohort, 123). Cumulative mortality was 49% overall. Sepsis (infection plus a Sepsis-related Organ Failure Assessment score of 2 or higher) was diagnosed in 29.2% of survivors vs 56.7% of nonsurvivors. The risk model achieved an area under the receiver operating characteristic curve of 0.89 for 1-year mortality. The following predictors were included in the model: age; institutionalization; age-adjusted Charlson comorbidity index; PaCO2; potassium, lactate, urea nitrogen, and creatinine levels; fraction of inspired oxygen; and diagnosed sepsis. Conclusions: The model showed excellent ability to predict 1-year mortality based on epidemiological, analytical, andclinical variables, identifying patients at high risk of death soon after their first contact with the health care system.(AU)

Value of serum iron and urine neutrophil gelatinase-associated lipocalin in predicting the mortality of critically ill patients with sepsis.

INTRODUCTION: We aimed to investigate the association of iron metabolism-related parameters with 60-day mortality in critically ill patients with sepsis. METHODS: Serum or urine concentrations of iron metabolism-related parameters on intensive care unit admission were measured in a prospective cohort of 133 eligible patients with sepsis according to the Sepsis-3 criteria, and these values were compared between survivors and nonsurvivors, categorized according to their 60-day survival status. Cox regression analyses were performed to examine the association between iron parameters and 60-day mortality. Kaplan-Meier methods were used to illustrate the differences in survival between different iron parameters. RESULTS: Of the 133 patients included in the study, 61 (45.8%) had died by day 60. After adjusting for confounding variables, higher concentrations of serum iron (cut-off 9.5 µmol/mL) and higher concentrations of urine neutrophil gelatinase-associated lipocalin (uNGAL; cut-off 169.3 ng/mL) were associated with a significantly greater risk of death in the Cox regression analysis. These two biomarkers combined with Sequential Organ Failure Assessment (SOFA) scores increased the area under the receiver operating characteristic (AUROC) curve to 0.85. DISCUSSION: These findings suggest that higher concentrations of serum iron and uNGAL are each associated with higher 60-day mortality, and they add significant accuracy to this prediction in combination with SOFA. Abbreviations: uNGAL: urine neutrophil gelatinase-associated lipocalin; ICU: intensive care unit; SOFA: Sequential Organ Failure Assessment; APACHE II: the Acute Physiology and Chronic Health Evaluation II; ELISA: enzyme-linked immunosorbent assay; HR: hazard ratio; CIs: confidence intervals; WBC: white blood cell; TBIL: total bilirubin.

Raise the Flag II: sepsis mortality before and after the introduction of a whole-of-system quality improvement programme at a tertiary hospital in New Zealand.

AIMS: To study in-patient mortality before and after the introduction of a whole-of-system sepsis quality improvement programme at a tertiary hospital in New Zealand. METHODS: The "Raise the Flag" sepsis quality improvement programme was launched in 2018. Discharge coding data were used to identify sepsis cases between May 2015 and July 2021. RESULTS: Of 4,268 cases of sepsis identified, 81% were over 55 years old, 34% were of Maori or Pacific Island ethnicity, 61% had significant co-morbid illness and over two thirds (68%) lived in the two highest quintiles of socio-economic deprivation. The adjusted odds of in-patient mortality were lower in the post-launch period (adjusted odds ratio [aOR] 0.83, 95% confidence interval [CI] 0.7-0.98, p<0.05), and were higher in association with age (aOR 1.04 for every additional year of age, 95% CI 1.03-1.05, p<0.01), socio-economic status (aOR 1.47 comparing the highest quintile of socio-economic deprivation with the lowest, 95% CI 1.06-2.04, p=0.02) and comorbidity (aOR 2.42 comparing a comorbidity score of 1 with a score of 0, 95% CI 2.1-3.52, p<0.01). CONCLUSION: In patients with a sepsis diagnosis, the odds of in-patient death were lower following the launch of the Raise the Flag sepsis quality improvement programme.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Echocardiography Does not Reduce Mortality in Sepsis: A Re-Evaluation Using the Medical Information Mart for Intensive Care IV Dataset.

OBJECTIVES: Echocardiography is commonly used for hemodynamic assessment in sepsis, but data regarding its association with outcome are conflicting. The aim of this study was to evaluate the association between echocardiography and outcomes in patients with septic shock using the Medical Information Mart for Intensive Care IV database. DESIGN: Retrospective cohort study comparing patients who did or did not undergo transthoracic echocardiography within the first 5 days of admission for the primary outcome of 28-day mortality. SETTING: Admissions to the Beth Israel Deaconess Medical Center intensive care from 2008 to 2019. PATIENTS: Adults 16 years old or older with septic shock requiring vasopressor support within 48 hours of admission. Readmissions and patients admitted to the coronary care unit or cardiovascular intensive care were excluded, as well as patients with ST-elevation myocardial infarction or cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Echocardiography was performed in 1,515 (27%) of 5,697 eligible admissions. The primary outcome was analyzed using a marginal structural model and rolling entry matching to adjust for baseline and time-varying confounders. Patients who underwent echocardiography showed no significant difference in 28-day mortality (adjusted hazard ratio 1.09; 95% CI, 0.95-1.25; p = 0.24). This was consistent across multiple sensitivity analyses. Secondary outcomes were changes in management instituted within 4 hours of imaging. Treatment changes occurred in 493 patients (33%) compared with 431 matched controls (29%), with the most common intervention being the administration of a fluid bolus. CONCLUSIONS: Echocardiography in sepsis was not associated with a reduction in 28-day mortality based on observational data. These findings do not negate the utility of echo in cases of diagnostic uncertainty or inadequate response to initial treatment.

Parthanatos type programmed cell death and septic patient mortality / Muerte celular programada tipo Parthanatos y mortalidad de los pacientes sépticos

Objective: Parthanatos is a form of programmed cell death mediated by apoptosis-inducing factor (AIF). However, there are not data on parthanatos in septic patients. The objective of the current study was to explore whether parthanatos is associated with mortality of septic patients. Design: Observational and prospective study. Setting: Three Spanish Intensive Care Units during 2017. Patients: Patients with sepsis according to Sepsis-3 Consensus criteria. Interventions: Serum AIF concentrations were determined at moment of sepsis diagnosis. Main variable of interest: Mortality at 30 days. Results: There were included 195 septic patients, and non-surviving (n=72) had serum AIF levels (p<0.001), lactic acid (p<0.001) and APACHE-II (p<0.001) that surviving (n=123). Multiple logistic regression analysis showed that patients with serum AIF levels>55.6ng/mL had higher mortality risk (OR=3.290; 95% CI=1.551−6.979; p=0.002) controlling for age, SOFA and lactic acid. Conclusions: Parthanatos is associated with mortality of septic patients. (AU)

Objetivo: Parthanatos es un tipo de muerte celular programada mediada por el factor inductor de apoptosis (AIF). Sin embargo, no hay datos sobre Parthanatos en pacientes sépticos. Por ello, el objetivo de este estudio fue explorar si Parthanatos está asociado con la morlaidad de los pacientes sépticos. Diseño: Estudio observacional y prospective. Ámbito: Tres Unidades de Cuidados Intensivos españolas durante 2017. Pacientes: Pacientes con sepsis en base a los criterios del Consenso Sepsis-3. Intervenciones: Se determinaron las concentraciones séricas de AIF en el momento del diagnóstico de la sepsis. Variable de interés principal: Mortalidad a los 30 días. Resultados: Se incluyeron 195 pacientes sépticos, y los que fallecieron (n=72) presentaron mayores concentraciones séricas de AIF (p<0.001) y de ácido láctico (p<0.001), y mayor puntuación APACHE-II (p<0.001) que los pacientes supervivientes (n=123). El análisis de regresión logística múltiple mostró que los pacientes con concentraciones séricas de AIF>55.6ng/mL tuvieron mayor riesgo de fallecer (OR=3.290; 95% CI=1.551−6.979; p=0.002) controlando por edad, SOFA y ácido láctico. Conclusiones: Parthanatos está asociado con la mortalidad de pacientes sépticos. (AU)

Clinical evaluation of peripheral tissue perfusion as a predictor of mortality in sepsis and septic shock in the intensive care unit: Systematic review and meta-analysis / Evaluación clínica de la perfusión tisular periférica como predictor de mortalidad en sepsis y choque séptico en la unidad de terapia intensiva: Revisión sistemática y metaanálisis

Objective: To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality. Design: Systematic review and meta-analysis. Setting: Intensive care unit. Patients and participants: Patients with sepsis and septic shock. Intervention: Studies of patients with sepsis and/or septic shock that associated clinical monitoring of tissue perfusion with mortality were included. A systematic review was performed by searching the PubMed/MEDLINE, Cochrane Library, SCOPUS, and OVID databases. Main variables of interest: The risk of bias was assessed with the QUADAS-2 tool. Sensitivity and specificity were calculated to evaluate the predictive accuracy for mortality. Review Manager software version 5.4 was used to draw the forest plot graphs, and Stata version 15.1 was used to build the hierarchical summary receiver operating characteristic model. Results: Thirteen studies were included, with a total of 1667 patients and 17 analyses. Two articles evaluated the temperature gradient, four evaluated the capillary refill time, and seven evaluated the mottling in the skin. In most studies, the outcome was mortality at 14 or 28 days. The pooled sensitivity of the included studies was 70%, specificity 75.9% (95% CI, 61.6%–86.2%), diagnostic odds ratio 7.41 (95% CI, 3.91–14.04), and positive and negative likelihood ratios 2.91 (95% CI, 1.80–4.72) and 0.39 (95% CI, 0.30–0.51), respectively. Conclusions: Clinical evaluation of tissue perfusion at the bedside is a useful tool, with moderate sensitivity and specificity, to identify patients with a higher risk of death among those with sepsis and septic shock. (AU)

Objetivo: Determinar el rendimiento diagnóstico de la evaluación clínica de la perfusión tisular periférica en la predicción de mortalidad. Diseño: Revisión sistemática y metaanálisis. Ámbito: Unidad de cuidados intensivos. Pacientes y participantes: Pacientes con sepsis y shock séptico. Intervenciones: Se incluyeron estudios de pacientes con sepsis y/o shock séptico que asociaron la monitorización clínica de la perfusión tisular con la mortalidad. Se realizó una revisión sistemática buscando en las bases de datos PubMed/MEDLINE, Cochrane Library, SCOPUS y OVID. Variables de interés principales: El riesgo de sesgo se evaluó con la herramienta QUADAS-2. Se calcularon la sensibilidad y la especificidad para evaluar la precisión predictiva de la mortalidad. Resultados: Se incluyeron trece estudios, con un total de 1667 pacientes y 17 análisis. Dos artículos evaluaron gradiente de temperatura, cuatro evaluaron tiempo de llenado capilar y siete evaluaron moteado en la piel. La mayoría de los estudios midieron mortalidad a 14 o 28 días. La sensibilidad agrupada de los estudios incluidos fue 70% y especificidad 75,9% (IC del 95%, 61,6%–86,2%), la razón de probabilidad diagnóstica 7,41 (IC del 95%, 3,91–14,04) y la razón de probabilidad positiva y negativa 2,91 (IC del 95%, IC, 1,80–4,72) y 0,39 (IC 95%, 0,30–0,51), respectivamente. Conclusiones: La evaluación clínica de la perfusión tisular es una herramienta útil, con sensibilidad y especificidad moderadas, para identificar pacientes con sepsis y shock séptico con mayor riesgo de muerte. (AU)

Altered Ex Vivo NLRP3 Inflammasome Activation Is Associated with 28-Day Mortality in Septic Patients.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated response to infection. In this context, the aberrant activation of the NLRP3 inflammasome has been documented mostly through the measurement of increased plasmatic concentrations of IL-1ß and IL-18. At the cellular level, contradictory results have been published. However, no study has comprehensively monitored NLRP3 inflammasome activation at the basal level and after ex vivo reactivation of whole blood monocytes and neutrophils focusing on ICU patients with bacterial and viral sepsis, including a longitudinal analysis. Thus, we conducted a prospective longitudinal study, examining NLRP3 inflammasome functionality in COVID-19 ICU patients (n = 15) and bacterial septic shock patients (n = 17) during the first week of ICU hospitalization, compared with healthy donors. Using two whole-blood flow cytometry assays, we detected ASC speck-positive monocytes (i.e., monocytes presenting the polymerization of ASC proteins) and activated caspase-1 in polymorphonuclear cells as read-outs, both at baseline and following nigericin stimulation, a drug that forms pores and activates the NLRP3 inflammasome. Our findings showed that, at baseline and regardless of the type of infection, patients exhibited reduced ASC speck-positive monocytes and decreased activated caspase-1 in PMN compared to healthy volunteers. This decrease was prominent at day 0. Following nigericin stimulation, this reduction was also observed and persisted throughout the first week of hospitalization, irrespective of the cellular population or parameter being considered. Notably, at day 0, this diminished activation and response to stimulation of NLRP3 was associated with a higher 28-day mortality rate. Consequently, our observations highlighted a concurrent decline in both basal expression and ex vivo activation of the NLRP3 inflammasome in circulating myeloid cells from patients with bacterial and viral sepsis in association with increased mortality.

[Analysis of Pathogenic Bacterial Spectrum, Drug Resistance and Risk Factors for Mortality of Bloodstream Infection in Patients with Hematologic Diseases].

OBJECTIVE: To analyze the pathogenic bacterial spectrum, drug resistance, and risk factors associated with multidrug-resistant bacterial infection and mortality in patients with hematologic diseases complicated by bloodstream infections, so as to provide reference for rational drug use and improving prognosis. METHODS: Positive blood culture specimens of patients with hematologic diseases in two Class A tertiary hospitals of Shanxi province from January 2019 to December 2021 were retrospectively analyzed. Pathogen distribution, drug resistance and outcomes of patients with bloodstream infection were investigated, then the multivariate logistic analysis was performed to analyze the risk factors of multidrug-resistant bacterial infection and factors affecting prognosis. RESULTS: 203 strains of pathogens were identified, mainly Gram-negative bacteria (GNB) (69.46%, 141/203), of which Escherichia coli (E.coli) had the highest incidence (41.13%, 58/141), followed by Klebsiella pneumoniae (20.57%, 29/141) and Pseudomonas aeruginosa (12.77%, 18/141). Extended-spectrum beta-lactamase (ESBL)-producing E.coli and Klebsiella pneumoniae were 46.55% (27/58) and 37.93% (11/29), respectively. Carbapenem-resistant Gram-negative bacteria accounted for 10.64% (15/141). And Gram-positive bacteria accounted for 27.59% (56/203), Staphylococcus epidermidis, Streptococcus pneumoniae, and Staphylococcus aureus were the most frequently isolated pathogen among Gram-positive bacteria (14.29%, 12.50% and 10.71%, respectively), of which methicillin-resistant Staphylococcus aureus accounted for 33.33% (2/6), coagulase-negative staphylococci accounted for 87.50% (7/8), without vancomycin- or linezolid-resistant strain. Additionally, fungi accounted for 2.95% (6/203), all of which were Candida. Multidrug-resistant Gram-negative bacteria (MDR-GNB) accounted for 53.90% (76/141). Duration of neutropenia >14 days was a risk factor for developing MDR-GNB infection. The 30-day all-cause mortality was 10.84%. Multivariate logistic regression analysis showed that the significant independent risk factors for mortality were age≥60 years (P <0.01, OR =5.85, 95% CI: 1.80-19.07) and use of vasopressor drugs (P <0.01, OR =5.89, 95% CI: 1.83-18.94). CONCLUSION: The pathogenic bacteria of bloodstream infection in patients with hematological diseases are widely distributed, and the detection rate of multidrug-resistant bacteria is high. The clinicians should choose suitable antibiotics according to the results of bacterial culture and antibiotic susceptibility test.

Atrial fibrillation is not an independent determinant of 28-day mortality among critically III sepsis patients.

This study was conducted to investigate the relationship between atrial fibrillation and the clinical prognosis of patients with sepsis in intensive care unit. A total of 21,538 sepsis patients were enrolled in the study based on the Medical Information Mart for Intensive Care IV database, of whom 6,759 had AF. Propensity score matching was used to compare the clinical characteristics and outcomes of patients with and without AF. Besides, the inverse probability of treatment weighting, univariate and multivariate Cox regression analyzes were performed. Of the 21,538 patients, 31.4% had AF. The prevalence of AF increased in a step-by-step manner with growing age. Patients with AF were older than those without AF. After PSM, 11,180 patients remained, comprising 5,790 matched pairs in both groups. In IPTW, AF was not associated with 28-day mortality [hazard ratio (HR), 1.07; 95% confidence interval (CI), 0.99-1.15]. In Kaplan-Meier analysis, it was not observed difference of 28-day mortality between patients with and without AF. AF could be associated with increased ICU LOS, hospital LOS and need for mechanical ventilation; however, it does not remain an independent short-term predictor of 28-day mortality among patients with sepsis after PSM with IPTW and multivariate analysis.

Herramientas para el diagnóstico de la sepsis / Tools for Diagnosis in Sepsis

La sepsis representa en la actualidad un problema emergente en salud. Los consensos alcanzados sobre las definiciones de sepsis y sus complicaciones asociadas han permitido establecer con mayor precisión la magnitud del problema. A pesar de la instauración de protocolos uniformes de actuación, la sepsis continúa siendo la primera causa de muerte en la Unidad de Cuidados Intensivos Pediátricos (UCIP) y la cuarta causa de defunción en los hospitalizados no coronarios.1 La sepsis severa fue definida en The Third International Consensus Definitions for Sepsis an Septic Shock como el síndrome de respuesta inflamatoria sistémica asociada a infección que cursa con disfunción aguda de un órgano, hipoperfusión o hipotensión, considerada como un proceso continuo.2 Se han realizado diversos estudios donde la mortalidad anual atribuible a sepsis grave es de 135 000 casos en Europa, y es superior en Estados Unidos con 200 000 casos, superada discretamente por las muertes por infarto agudo de miocardio. Estados Unidos ocupa el lugar número 11 como causa aislada de fallecimiento, se estima que más de 500 pacientes mueren diariamente a consecuencia de esta enfermedad, hecho que se transforma en un significativo desafío para la salud pública.3 Por lo que significa lo anteriormente expuesto, en reuniones de consensos, los laboratorios se han visto retados y han facilitado el diagnóstico con herramientas útiles. Marcadores biológicos de infección El retraso en la instauración de un tratamiento adecuado de las infecciones y de la sepsis se asocia a una mayor mortalidad, por lo que es crucial establecer un diagnóstico precoz en este contexto. Los análisis microbiológicos que confirman o no la presencia de infección suelen tardar, en ese sentido se han buscado marcadores biológicos que puedan servir como indicadores fiables de la infección grave y la sepsis. Dada la complejidad creciente de la fisiopatología de la sepsis a medida que avanza en su conocimiento, es probable que el éxito llegue, no a través de un único marcador, sino a través de la combinación de varios de ellos que tengan en cuenta distintos aspectos de la respuesta del huésped. La combinación de varios marcadores puede ayudar a vencer las limitaciones en sensibilidad y especificidad de un solo biomarcador. Características de un marcador ideal Precisión Sensibilidad alta: pacientes que presentan respuesta inflamatoria mínima o ausente. Especificidad: lograr discriminar la infección de otros padecimientos que causan el síndrome de respuesta inflamatoria sistémica (SRIS). Valor predictivo positivo (VPP) y valor predictivo negativo (VPN). Diagnóstico certero con reactantes de fase aguda La proteína C reactiva (PCR) de alta sensibilidad es un marcador precoz de infección e inflamación con una vida media plasmática de 19 h. Su concentración plasmática en adulto sano es de 0,08 mg/dL. Su biocinética se hace útil como marcador de respuesta terapéutica y diagnóstica de infecciones intercurrentes. Las determinaciones seriadas de estas es un buen indicador de la actividad inflamatoria. Sus grandes elevaciones se deben a infecciones bacterianas. Las determinaciones seriadas diarias de PCR pueden ser útiles para el diagnóstico precoz en las infecciones nosocomiales es de ≥ 5 mg/dL o ≥ 25 % del valor previo. La procalcitonina es una hormona producida por células parenquimatosas, proteína de la familia CAPA precursora de la calcitonina. En condiciones normales las concentraciones en sangre son muy bajas, menor de 0,09 ng/mL. Tienen una vida media de 22-35 h. No se conocen valores umbrales, diagnósticos y pronósticos, pero los valores mayores de 2 ng/mL suelen indicar la presencia de sepsis. Los valores mayores de 10 ng/mL suelen asociarse a sepsis grave y shock séptico. Los niveles de procalcitonina (PCT) son superiores a la PCR en el diagnóstico de sepsis por lo que debería ser incluida en las guías diagnósticas de sepsis. Podemos decir además, que la interleucina 6 (IL-6), fue descrita inicialmente como interferón beta-2, como factor de crecimiento de plasmocitoma o factor estimulante de hepatocitos.4 Es generada por un único gen que codifica un producto de 212 aminoácidos y es la citoquina que más consistentemente se ha asociado con la mortalidad por sepsis, por su acción proinflamatoria es uno de los principales inductores de la síntesis de la PCR en el hígado, por lo que muestra picos séricos más precoces que esta.5 Las determinaciones secuenciales de estas en el suero plasma en pacientes internados en la unidad de cuidados intensivos han demostrado ser útiles para evaluar la severidad del síndrome de respuesta inflamatoria(AU)

Capacidad del qSOFA1-lactato para predecir mortalidad a 30 días en los pacientes atendidos por infección en urgencias / Ability of qSOFA1-lactate to predict 30-day mortality in patients seen for infection in the Emergency Department

Objetivo. Evaluar y comparar la capacidad del lactato y del quick Sepsis-related Organ Failure Assessment (qSOFA) para predecir mortalidad a 30 días en los pacientes que acuden al servicio de urgencias (SU) por un episodio de sospecha de infección.Método. Estudio observacional de cohortes, multicéntrico, prospectivo. Se incluyó por oportunidad a pacientes ≥18 años atendidos por sospecha de infección en 71 SU españoles del 01/10/2019 al 31/03/2020. Se analizó la capacidad predictiva con el área bajo la curva (ABC) de la característica operativa del receptor (COR) y los valores de sensibilidad (Se), especificidad (Es), valor predictivo positivo (VPP) y negativo (VPN). Resultados. Se incluyeron 4.439 pacientes con edad media de 67 (DE:18) años, 2.648 (59,7%) fueron hombres y fallecieron a los 30 días 459 (10,3%). Para la mortalidad a 30 días el ABC-COR obtenida con el modelo qSOFA=1 más lactato 2 mmol/l fue de 0,66 (IC 95%: 0,63-0,69) con una Se:68%, Es:70% y VPN:92%, mientras que qSOFA=1 obtuvo ABC-COR de 0,52 (IC 9%: 0,49-0,55) con una Se:42%, Es:64% y VPN:90%.Conclusiones. Para predecir mortalidad a los 30 días en los pacientes que acuden al SU por un episodio de infección, el modelo qSOFA=1 + lactato≥2 mmol/L mejora significativamente el poder predictivo conseguido de forma individual por qSOFA1 y llega a ser muy similiar al de qSOFA≥2 (AU)

Objectives. To evaluate lactate and the Quick Sepsis-Related Organ Failure Assessment (qSOFA) and compare their ability to predict 30-day mortality in patients treated for infection in emergency departments (ED). Methods. Prospective multicenter observational cohort study. We enrolled a convenience sample of patients aged 18 years or older attended in 71 Spanish ED from October 1, 2019, to March 31, 2020. Each model’s predictive power was analyzed with the area under the receiver operating characteristic curve (AUC), and its values of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative (NPV). Results. A total of 4439 patients with a mean (SD) age of 18 years were studied; 2648 (59.7%) were men and 459 (10.3%) died within 30 days. For 30-day mortality, the AUC-COR obtained with the qSOFA = 1 model plus 2 mmol/l lactate was 0.66 (95% CI, 0.63-0.69) with Se: 68%, Es: 70% and NPV:92%, while qSOFA = 1 obtained AUC-COR of 0.52 (95% CI, 0.49-0.55) with a Se:42%, Es:64% and NPV:90%. Conclusions. To predict 30-day mortality in patients presenting to the ED due to an episode of infection, the qSOFA =1 + lactate≥2 mmol/L model significantly improves the predictive power achieved individually by qSOFA1 and becomes very similar to qSOFA≥2 (AU)

PATHWAYS ASSOCIATED WITH POSITIVE SEPSIS SURVIVAL OUTCOMES IN AFRICAN AMERICAN/BLACK AND NON-HISPANIC WHITE PATIENTS WITH URINARY TRACT INFECTION.

ABSTRACT: Urinary tract infections (UTIs) are a common cause of sepsis worldwide. Annually, more than 60,000 US deaths can be attributed to sepsis secondary to UTIs, and African American/Black adults have higher incidence and case-fatality rates than non-Hispanic White adults. Molecular-level factors that may help partially explain differences in sepsis survival outcomes between African American/Black and Non-Hispanic White adults are not clear. In this study, patient samples (N = 166) from the Protocolized Care for Early Septic Shock cohort were analyzed using discovery-based plasma proteomics. Patients had sepsis secondary to UTIs and were stratified according to self-identified racial background and sepsis survival outcomes. Proteomics results suggest patient heterogeneity across mechanisms driving survival from sepsis secondary to UTIs. Differentially expressed proteins (n = 122, false discovery rate-adjusted P < 0.05) in Non-Hispanic White sepsis survivors were primarily in immune system pathways, while differentially expressed proteins (n = 47, false discovery rate-adjusted P < 0.05) in African American/Black patients were mostly in metabolic pathways. However, in all patients, regardless of racial background, there were 16 differentially expressed proteins in sepsis survivors involved in translation initiation and shutdown pathways. These pathways are potential targets for prognostic intervention. Overall, this study provides information about molecular factors that may help explain disparities in sepsis survival outcomes among African American/Black and Non-Hispanic White patients with primary UTIs.

Mortality and Cumulative Kidney Score are Associated with Transient and Persistent Acute Kidney Injury in Septic Patients: A Retrospective Study Based on MIMIC-IV

Background: Acute kidney injury (AKI) is frequently caused by sepsis. Recently, the Acute Disease Quality Initiative (ADQI) workgroup further classified AKI as transient or persistent. Oliguria and increased serum creatinine represent two different kinds of renal impairment. The aim of the study was to assess mortality and cumulative AKI score associated with transient and persistent AKI in septic patients. Methods: Septic patients were stratified according to the presence and AKI development (considered persistent when remaining >48 h) were included. An adjusted logistic regression model was used to determine hospital mortality. In addition, we calculated an AKI score by combining both Kidney Disease: Improving Global Outcomes (KDIGO) criteria of urine output and creatinine AKI stages. The relationship between the cumulative AKI score and persistent AKI was further examined using the logistic regression model and receiver operating characteristic (ROC) curve analysis. Results: 12928 septic patients were enrolled in the study. AKI occurred in 73.7% of septic patients, in 39.5% was transient and in 60.5% was persistent. Patients with persistent AKI had higher severity scores and more severe renal dysfunction upon admission. Persistent AKI, but not transient AKI, was associated with increased intensive care units (ICUs) and hospital mortality. Then we found that the cumulative AKI score was associated with an increased risk of persistent AKI. This association was consistent across three original KDIGO severity stages and subgroup analyses. Conclusions: It was found that persistent AKI was independently associated with mortality in septic patients. Furthermore, serum creatinine and urine output criteria had cumulative effects on KDIGO AKI staging and provided more information about the relationship between AKI and outcomes (AU)

Machine-learning models for prediction of sepsis patients mortality / Modelos de aprendizaje automático para la predicción de la mortalidad de pacientes con sepsis

Objectives Sepsis is an infection-caused syndrome, that leads to life-threatening organ damage. We aim to develop machine learning models with large-scale data to predict sepsis patients’ mortality. Design we extracted sepsis patients from two databases, Medical Information Mart for Intensive Care IV (MIMIC-IV) as a train set and Philips eICU Collaborative Research Database as a test set. Setting ICUs in multicenter hospitals in the USA during 2012–2019. Patients or participants A total of 21,680 sepsis-3 patients are included in the study, in which, 3771 patients were dead and 17,909 survived during hospitalization, respectively.Interventions No interventions. Main variables of interest Basic information, examination items during hospitalization and some medication and treatment information are incorporated into analyzed. Seven different models were built with a Support vector machine, Decision Tree Classifier, Random Forest, Gradients Boosting, Multiple Layer Perception, Xgboost, light Gradients Boosting to predict dead or live during hospitalization. Results Algorithms with an AUC value in the test set of the top three: light GBM, GBM, Xgboost. Considering the performance of the training set and the test set, the light GBM model performs best, and then the parameters of the model were adjusted, after that the AUC value was 0.99 in the train set, 0.96 in the test set, respectively. Conclusions Models built with light GBM algorithm from real-world sepsis patients from electronic health records accurately predict whether sepsis patients are dead and can be incorporated into clinical decision tools to enhance the prognosis of the patient and prevent adverse outcomes (AU)

Objetivos Desarrollar modelos de aprendizaje automático con datos a gran escala para predecir la mortalidad de los pacientes con sepsis. Diseño Extrajimos pacientes con sepsis de 2 bases de datos: MIMIC-IV como conjunto de entrenamiento y eICU-CRD como conjunto de prueba. Ámbito Una UCI de un hospital multicéntrico de EE. UU. durante 2012-2019. Pacientes o participantes Se incluyó en el estudio a un total de 21.680 pacientes con sepsis-3, de los cuales 3.771 fallecieron y 17.909 sobrevivieron durante la hospitalización. Intervenciones Sin intervenciones. Principales variables de interés Se analizaron informaciones básicas, ítems de examen durante la hospitalización y algunos datos de medicación y tratamiento. Se utilizaron 7 modelos diferentes, por ejemplo, la GBM impulsado, para predecir la mortalidad o superviviencia durante la hospitalización. Resultados Los 3 primeros valores de AUC en el conjunto de pruebas fueron: GBM, GBM, Xgboost. Considerando el rendimiento del conjunto de entrenamiento y el conjunto de prueba, el modelo máquina de gradiente ligero impulsado funciona mejor; una vez se ajustaron los parámetros del modelo, el valor de AUC fue 0,99 en el conjunto de entrenamiento y 0,96 en el conjunto de prueba. Conclusiones os modelos de pacientes con sepsis del mundo real construidos con el algoritmo de la GBM impulsado a partir de registros de salud electrónicos predicen con precisión si los pacientes con sepsis morirán. También se pueden incorporar a las herramientas de decisión clínica para prevenir resultados adversos (AU)

Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.