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Código de sepsis; Gestión de la sepsis; Indicadores de calidad Codi de sèpsia; Gestió de la sèpsia; Indicadors de qualitat Sepsis Code; Sepsis management; Quality indicators Introduction. This study aimed to identify the common barriers leading to delayed initial management, microbiological diagnosis, and appropriate empirical antimicrobial treatment in sepsis. Patients and methods. A cross-sectional study was performed by the application of a population-based survey. Four different surveys were designed, targeting the healthcare personnel located in main hospital areas [emergency department (SEMES); infectious diseases and clinical microbiology-microbiological diagnosis (SEIMC-M); intensive care and infectious diseases, (SEMICYUC-GTEIS); and infectious diseases and clinical microbiology-clinical diagnosis, (SEIMC-C)]. Results. A total of 700 valid surveys were collected from June to November 2019: 380 (54.3%) of SEMES, 127 (18.1%) of SEIMC-M, 97 (13.9%) de SEMICYUC-GTEIS and 96 (13.7%) of SEIMC-C, in 270 hospitals of all levels of care. The qSOFA score was used as a screening tool. The most used biomarker was procalcitonin (n=92, 39.8%). The sepsis code was implemented in 157 of 235 participating centers (66.2%), particularly in tertiary level hospitals. The mean frequency of contaminated blood cultures was 8.9% (8.7). In 85 (78.7%) centers, positive results of blood cultures were available within the first 72 hours and were communicated to the treating physician effectively by phone or e-mail in 76 (81.7%) cases. The main reason for escalating treatment was clinical deterioration, and the reason for de-escalating antimicrobials was significantly different between the specialties. Quality indicators were not frequently monitored among the different participating centers. Conclusion. There are significant barriers that hinder adequate management processes in sepsis in Spanish hospitals. Introducción. Este estudio tuvo como objetivo identificar las barreras comunes que conducen al retraso en el manejo inicial, el diagnóstico microbiológico y el tratamiento antimicrobiano empírico adecuado en la sepsis. Pacientes y métodos. Se realizó un estudio transversal mediante la aplicación de una encuesta de base poblacional. Se diseñaron cuatro encuestas diferentes, dirigidas al personal de salud ubicado en las principales áreas hospitalarias [urgencias (SEMES); enfermedades infecciosas y microbiología clínica-diagnóstico microbiológico (SEIMC-M); cuidados intensivos y enfermedades infecciosas (SEMICYUC-GTEIS); y enfermedades infecciosas y microbiología clínica-diagnóstico clínico, (SEIMC-C)]. Resultados. Se recogieron un total de 700 encuestas válidas de junio a noviembre de 2019: 380 (54,3%) de SEMES, 127 (18,1%) de SEIMC-M, 97 (13,9%) de SEMICYUC-GTEIS y 96 (13,7%) de la SEIMC-C, en 270 hospitales de todos los niveles de atención. El qSOFA se utilizó principalmente como herramienta de detección. El biomarcador más utilizado fue la procalcitonina (n=92, 39,8%). El código sepsis estaba implementado en 157 de 235 centros participantes (66,2%), particularmente en hospitales de tercer nivel. La frecuencia media de hemocultivos contaminados fue del 8,9% (8,7). En 85 (78,7%) de los centros, los resultados de los hemocultivos positivos estuvieron disponibles en las primeras 72 horas y se comunicaron al médico responsable del paciente por teléfono o correo electrónico en 76 casos (81,7%). El motivo principal de la escalada del tratamiento fue el deterioro clínico y el motivo de la desescalada de los antimicrobianos fue significativamente diferente entre las especialidades. Los indicadores de calidad no se monitorizaban con frecuencia en los diferentes centros. Conclusión. Existen importantes barreras que dificultan los procesos de manejo adecuado de la sepsis en los hospitales españoles. This research has received an unrestricted grant Beckton, Dickinson and Company (BD), S.A.

Proteomic profile; Organ dysfunction; Septic shock Perfil proteòmic; Disfunció orgànica; Xoc sèptic Perfil proteómico; Disfunción orgánica; Choque séptico Introduction The search for new biomarkers that allow an early diagnosis in sepsis and predict its evolution has become a necessity in medicine. The objective of this study is to identify, through omics techniques, potential protein biomarkers that are expressed in patients with sepsis and their relationship with organ dysfunction and mortality. Methods Prospective, observational and single-center study that included adult patients (≥ 18 years) who were admitted to a tertiary hospital and who met the criteria for sepsis. A mass spectrometry-based approach was used to analyze the plasma proteins in the enrolled subjects. Subsequently, using recursive feature elimination classification and cross-validation with a vector classifier, an association of these proteins with mortality and organ dysfunction was established. The protein-protein interaction network was analyzed with String software. Results 141 patients were enrolled in this study. Mass spectrometry identified 177 proteins. Of all of them, and by recursive feature elimination, nine proteins (GPX3, APOB, ORM1, SERPINF1, LYZ, C8A, CD14, APOC3 and C1QC) were associated with organ dysfunction (SOFA > 6) with an accuracy of 0.82 ± 0.06, precision of 0.85 ± 0.093, sensitivity 0.81 ± 0.10, specificity 0.84 ± 0.10 and AUC 0.82 ± 0.06. Twenty-two proteins (CLU, LUM, APOL1, SAA1, CLEBC3B, C8A, ITIH4, KNG1, AGT, C7, SAA2, APOH, HRG, AFM, APOE, APOC1, C1S, SERPINC1, IGFALS, KLKB1, CFB and BTD) were associated with mortality with an accuracy of 0.86 ± 0.05, a precision of 0.91 ± 0.05, a sensitivity of 0.91 ± 0.05, a specificity of 0.72 ± 0.17, and an area under the curve (AUC) of 0.81 ± 0.08 with a confidence interval of 95%. Conclusion In sepsis there are proteomic patterns associated with organ dysfunction and mortality. To Toni del Pino, Rosa Ras and Pol Herrero from the Proteomics and Metabolomics Area of the Center for Omic Sciences (COS), a Joint between Rovira I Virgili University and Eurecat (Reus, Spain), for their contribution to the proteomics analysis. Samples and data from patients included in this study were provided by the Vall d’Hebron University Hospital Biobank (PT20/00107), integrated in the Spanish National Biobanks Network, and they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committees. The authors kindly appreciate the generous donation of samples and clinical data of the donors of the Sepsis Bank of HUVH Biobank.

Endotype; Organ dysfunction; Sepsis Endotipo; Disfunción de órganos; Sepsis Endotip; Disfunció d'òrgans; Sèpsia Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support. However, specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms. Herein, we will review the framework for identifying subpopulations of patients with sepsis, septic shock, and multiorgan dysfunction who may benefit from specific therapies. Some of these approaches are still in the early stages of research, while others are already in routine use in clinical practice, but together will help in the effective generation and safe implementation of precision medicine in sepsis.

Background The incidence of sepsis can be estimated between 250 and 500 cases/100.000 people per year and is responsible for up to 6% of total hospital admissions. Identified as one of the most relevant global health problems, sepsis is the condition that generates the highest costs in the healthcare system. Important changes in the management of septic patients have been included in recent years; however, there is no information about how changes in the management of sepsis-associated organ failure have contributed to reduce mortality. Methods A retrospective analysis was conducted from hospital discharge records from the Minimum Basic Data Set Acute-Care Hospitals (CMBD-HA in Catalan language) for the Catalan Health System (CatSalut). CMBD-HA is a mandatory population-based register of admissions to all public and private acute-care hospitals in Catalonia. Sepsis was defined by the presence of infection and at least one organ dysfunction. Patients hospitalized with sepsis were detected, according ICD-9-CM (since 2005 to 2017) and ICD-10-CM (2018 and 2019) codes used to identify acute organ dysfunction and infectious processes. Results Of 11.916.974 discharges from all acute-care hospitals during the study period (2005–2019), 296.554 had sepsis (2.49%). The mean annual sepsis incidence in the population was 264.1 per 100.000 inhabitants/year, and it increased every year, going from 144.5 in 2005 to 410.1 in 2019. Multiorgan failure was present in 21.9% and bacteremia in 26.3% of cases. Renal was the most frequent organ failure (56.8%), followed by cardiovascular (24.2%). Hospital mortality during the study period was 19.5%, but decreases continuously from 25.7% in 2005 to 17.9% in 2019 (p p p Conclusions The incidence of sepsis has been increasing in recent years in our country. However, hospital mortality has been significantly reduced. In septic patients, all organ failures except liver have shown a statistically significant reduction on associated mortality, with cardiovascular failure as the most relevant.

Metilación del ADN; Tolerancia a la endotoxina; Monocitos DNA methylation; Endotoxin tolerance; Monocytes Metilació de l'ADN; Tolerància a l'endotoxina; Monòcits Microbial challenges, such as widespread bacterial infection in sepsis, induce endotoxin tolerance, a state of hyporesponsiveness to subsequent infections. The participation of DNA methylation in this process is poorly known. In this study, we perform integrated analysis of DNA methylation and transcriptional changes following in vitro exposure to gram-negative bacterial lipopolysaccharide, together with analysis of ex vivo monocytes from septic patients. We identify TET2-mediated demethylation and transcriptional activation of inflammation-related genes that is specific to toll-like receptor stimulation. Changes also involve phosphorylation of STAT1, STAT3 and STAT5, elements of the JAK2 pathway. JAK2 pathway inhibition impairs the activation of tolerized genes on the first encounter with lipopolysaccharide. We then confirm the implication of the JAK2-STAT pathway in the aberrant DNA methylome of patients with sepsis caused by gram-negative bacteria. Finally, JAK2 inhibition in monocytes partially recapitulates the expression changes produced in the immunosuppressive cellular state acquired by monocytes from gram-negative sepsis, as described by single cell-RNA-sequencing. Our study evidences both the crucial role the JAK2-STAT pathway in epigenetic regulation and initial response of the tolerized genes to gram-negative bacterial endotoxins and provides a pharmacological target to prevent exacerbated responses. EB was funded by the Spanish Ministry of Science, Innovation and Universities (grant numbers SAF2017-88086-R & PID2020-117212RB-I00), and was cofunded by FEDER funds/European Regional Development Fund (ERDF) - a way to build Europe. OM-P holds an i-PFIS PhD fellowship (grant number IFI17/00034) from Acción Estratégica en Salud 2013-2016 ISCIII, cofinanced by the Fondo Social Europeo.

Background: Pre-evaluation of endogenous immunoglobulin levels is a potential strategy to improve the results of intravenous immunoglobulins in sepsis, but more work has to be done to identify those patients who could benefit the most from this treatment. The objective of this study was to evaluate the impact of endogenous immunoglobulins on the mortality risk in sepsis depending on disease severity. Methods: This was a retrospective observational study including 278 patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed into two groups depending on their Sequential Organ Failure Assessment score at ICU admission (SOFA < 8, n = 122 and SOFA >= 8, n = 156), and the association between immunoglobulin levels at ICU admission with mortality was studied in each group by Kaplan-Meier and multivariate logistic regression analysis. Results: ICU/hospital mortality in the SOFA < 8 group was 14.8/23.0%, compared to 30.1/35.3% in the SOFA >= 8 group. In the group with SOFA < 8, the simultaneous presence of total IgG < 407 mg/dl, IgM < 43 mg/dl and IgA < 219 mg/dl was associated with a reduction in the survival mean time of 6.6 days in the first 28 days and was a robust predictor of mortality risk either during the acute or during the post-acute phase of the disease (OR for ICU mortality: 13.79; OR for hospital mortality: 7.98). This predictive ability remained in the absence of prior immunosuppression (OR for ICU mortality: 17.53; OR for hospital mortality: 5.63). Total IgG < 407 mg/dl or IgG1 < 332 mg/dl was also an independent predictor of ICU mortality in this group. In contrast, in the SOFA >= 8 group, we found no immunoglobulin thresholds associated with neither ICU nor hospital mortality. Conclusions: Endogenous immunoglobulin levels may have a different impact on the mortality risk of sepsis patients based on their severity. In patients with moderate organ failure, the simultaneous presence of low levels of IgG, IgA and IgM was a consistent predictor of both acute and post-acute mortalities., The GRECIA study was supported by Proyectos de Investigacion en Biomedicina, Consejeria de Sanidad, JCYL (Grant Code BOCYL-D-26072010). The authors thank also Instituto de Salud Carlos III for their financial support (Grant Code EMER 07/050, ISCIII-FIS-PI12-01815). The funding agencies were not involved neither in the design of the study and collection, nor in the analysis, interpretation of data or manuscript writing.

Sèpsia; Serveis sanitaris; Malalties infeccioses Sepsis; Health services; Infectious diseases Sepsis; Servicios sanitarios; Enfermedades infecciosas Des de l’any 2015 existeix, a tot Catalunya, el Codi sèpsia. Aquest model integral d’atenció busca reduir el temps de resposta del sistema sanitari, afavorir la detecció i coordinar tots els recursos, per tal que el pacient afectat rebi les mesures diagnòstiques i terapèutiques apropiades, en els diferents punts de la xarxa assistencial. Since the year 2015, the Sepsis Code has existed throughout Catalonia. This comprehensive care model seeks to reduce the response time of the healthcare system, favor the detection and coordination of all resources, so that the affected patient receives the appropriate diagnostic and therapeutic measures, in the different points of the healthcare network Desde el año 2015 existe, en toda Cataluña, el Código sepsis. Este modelo integral de atención busca reducir el tiempo de respuesta del sistema sanitario, favorecer la detección y coordinar todos los recursos, para que el paciente afectado reciba las medidas diagnósticas y terapéuticas apropiadas, en los diferentes puntos de la red asistencial

Codi sèpsia greu; Planificació sanitària; Catalunya Severe sepsis code; Health planning; Catalonia Código septicemia grave; Planificación sanitaria; Cataluña Aquesta Instrucció té com a objecte la definició i ordenació del model d'atenció inicial i de la coordinació entre els diferents nivells i dispositius per a l'atenció a pacients adults o pediàtrics amb sèpsia greu (Codi sèpsia greu)

Epidemiologia; Mortalitat; Shock sèptic Epidemiología; Mortalidad; Shock séptico Epidemiology; Mortality; Septic shock Background Up-to-date identification of local trends in sepsis incidence and outcomes is of considerable public health importance. The aim of our study was to estimate annual incidence rates and in-hospital mortality trends for hospitalized patients with sepsis in a European setting, while avoiding selection bias in relation to different complexity hospitals. Methods A large retrospective analysis of a 5-year period (2008–2012) was conducted of hospital discharge records obtained from the Catalan Health System (CatSalut) Minimum Basic Data Set for Acute-Care Hospitals (a mandatory population-based register of admissions to all public and private acute-care hospitals in Catalonia). Patients hospitalized with sepsis were detected on the basis of ICD-9-CM codes used to identify acute organ dysfunction and infectious processes. Results Of 4,761,726 discharges from all acute-care hospitals in Catalonia, 82,300 cases (1.72%) had sepsis diagnoses. Annual incidence was 212.7 per 100,000 inhabitants/year, rising from 167.2 in 2008 to 261.8 in 2012. Length of hospital stay fell from 18.4 to 15.3 days (p < .00001), representing a relative reduction of 17%. Hospital mortality fell from 23.7 to 19.7% (p < .0001), representing a relative reduction of 16.9%. These differences were confirmed in the multivariate analysis (adjusted for age group, sex, comorbidities, ICU admission, emergency admission, organ dysfunction, number of organ failures, sepsis source and bacteraemia). Conclusions Sepsis incidence has risen in recent years, whereas mortality has fallen. Our findings confirm reports for other parts of the world, in the context of scarce administrative data on sepsis in Europe. The study was partially funded by the Mataró Sepsis Challenge (www.sepsischallenge.cat) through the Fundació Salut del Consorci Sanitari del Maresme.