Search

Background: Uncontrolled proteolysis contributes to cell injury and organ dysfunction in animal models of circulatory shock. We investigated in humans the relationship between septic shock, proteolysis, and outcome. Methods: Intensive care patients with septic shock (n=29) or sepsis (n=6) and non-hospitalised subjects (n=9) were recruited as part of the prospective observational trial ‘ShockOmics’ (ClinicalTrials.gov Identifier NCT02141607). A mass spectrometry-based approach was used to analyse the plasma peptidomes and the origin of circulating peptides from proteolysis in the enrolled subjects. Results: Evidence of systemic proteolysis was indicated by a larger number of circulating peptides in septic shock patients, compared with septic patients and non-hospitalised healthy subjects. The peptide count and abundance in the septic shock patients were greater in patients who died (n=6) than in survivors (n=23), suggesting an association between magnitude of proteolysis and outcome. In silico analysis of the peptide sequences and of the sites of cleavage on the proteins of origin indicated a predominant role for serine proteases, such as chymotrypsin, and matrix metalloproteases in causing the observed proteolytic degradation. Conclusions: Systemic proteolysis is a novel fundamental pathological mechanism in septic shock. Plasma peptidomics is proposed as a new tool to monitor clinical trajectory in septic shock patients. Clinical trial registration: NCT02141607., SCOPUS: ar.j, info:eu-repo/semantics/published

subterráneo. Para ello, es necesario dotar a los acuartelamientos de instalaciones que permitan reproducir escenarios similares a la realidad con el objetivo de alcanzar el mayor nivel de instrucción posible. Atendiendo a las necesidades del Ejército de Tierra este proyecto plantea la utilización del Fuerte “Alfonso XII” como polígono de combate en zonas urbanizadas y subsuelo. Dicho Fuerte se localiza en el norte de la ciudad de Pamplona, en el monte San Cristóbal-Ezkaba, y ofrece un gran número de posibilidades para la instrucción de las unidades en este tipo de ambiente. Para llevar a cabo este proyecto se han analizado las diferentes infraestructuras del Fuerte, así como manuales nacionales y extranjeros, relativos al combate en este tipo de ambiente. Además, se han llevado a cabo un gran número de entrevistas con personal experto en la materia con el objetivo de conseguir una selección de ejercicios de instrucción y adiestramiento que permitan optimizar el tiempo de instrucción de las unidades usuarias del Fuerte. Asimismo, con la finalidad de convertir esta instalación en un centro de instrucción y adiestramiento pionero y único en España se plantea crear una sala de entrenamiento la cual prepare a los usuarios a enfrentarse a situaciones altamente estresantes, como es el combate. Esto permitirá aumentar el rendimiento de los combatientes durante el conflicto.Durante el desarrollo del proyecto se han realizado encuestas al personal de la unidad, con el objetivo de conocer situación actual no solo del uso de las instalaciones del Fuerte, sino también para conocer el nivel de instrucción de las unidades en este ámbito. Permitiendo conocer la viabilidad social del proyecto. Asimismo, se ha elaborado un análisis de aquellas personas que tendrían una mayor capacidad de decisión para que el proyecto se materializase. En esta memoria se ha querido incluir una estimación del coste económico del proyecto. Además, se ha comparado la instalación que se plantea con diferentes polígonos de combate en zonas urbanizadas y subsuelo tanto dentro del territorio nacional como en bases extranjeras. El resultado muestra la innovación y versatilidad que tiene el proyecto planteado.Palabras clave: Combate en zonas urbanizadas, Combate en subsuelo, Estrés, Rendimiento, Polígonos de entrenamiento

Objective To analyze the evolution of sepsis-related mortality in Spanish Intensive Care Units (ICUs) following introduction of the Surviving Sepsis Campaign (SSC) guidelines and the relationship with sepsis process-of-care. Design A prospective cohort study was carried out, with the inclusion of all consecutive patients presenting severe sepsis or septic shock admitted to 41 Spanish ICUs during two time periods: 2005 (Edusepsis study pre-intervention group) and 2011 (ABISS-Edusepsis study pre-intervention group). Scope Patients with severe sepsis or septic shock admitted to Spanish ICUs. Patients All ICU admissions from the emergency department or wards and all ICU patients with a diagnosis of severe sepsis or septic shock. A total of 1348 patients were included: 630 in the 2005 group and 718 in the 2011 group. Intervention None. Primary endpoints ICU mortality, 28-day mortality and Hospital mortality, hospital length of stay, ICU length of stay and compliance with the resuscitation bundle. Results Compliance with the resuscitation bundle was significantly greater in the 2011 group (5.7% vs. 9.9%; p = 0.005), and was associated to lower mortality (OR 0.602 [0.365–0.994]; p = 0.048). The 2011 group had lower absolute in-hospital mortality (44.0% vs. 32.6%; p = 0.01), 28-day mortality (36.5% vs. 23.0%; p = 0.01), and adjusted mortality (OR 0.64 [0.49–0.83], p = 0.001). Conclusions Mortality related to severe sepsis or septic shock in Spain decreased between two patient cohorts in 2005 and 2011, and was attributable to earliness and improvement in sepsis care.

Background We aimed to analyze compliance with 2010 European guidelines' quality criteria for external chest compressions (ECC) during 2 minutes of uninterrupted cardiopulmonary resuscitation. Methods Seventy-two healthy nurses and physicians trained in advanced cardiopulmonary resuscitation performed 2 uninterrupted minutes of ECC on a training manikin (Resusci Anne Advanced SkillTrainer; Laerdal Medical AS, Stavanger, Norway) that enabled us to measure the depth and rate of ECC. When professionals agreed to participate in the study, we recorded their age, body mass index (BMI), smoking habit, and their own subjective estimation of their physical fitness. To measure fatigue, we analyzed participants' heart rates, percentage of maximum tolerated heart rate (MHR), and subjective perception of their fatigue on a visual analog scale. Results Nearly half (48.6%) the rescuers failed to achieve a minimum average ECC depth of 50 mm. Only 48.1% of ECCs fulfilled the 2010 guidelines' quality criteria; quality deteriorated mainly after the first minute. Poor ECC quality and deteriorating quality after the first minute were associated with BMI 2 . Rescuers with BMI ≥ 23 kg/m 2 fulfilled the quality criteria throughout the 2 minutes, whereas those with BMI 2 fulfilled them for 80% of ECCs during the first minute, but for only 30% at the end of the 2 minutes. Conclusions Compliance with the 2010 guidelines' quality criteria is often poor, mainly due to lack of proper depth. The greater depth recommended in the 2010 guidelines with respect to previous guidelines requires greater force, so BMI 2 could hinder compliance. Limiting each rescuer's uninterrupted time doing ECC to 1 minute could help ensure compliance.

Objective To describe the alterations of the cortical microcirculation of the brain (blood flow and vessel density) in TBI patients who and compare them with a control group. Methods Prospective and observational study in a third-level university hospital. Cortical microcirculation in the brain was directly observed using sidestream dark-field (SDF) imaging in 14 patients who underwent surgery: 5 subdural hematomas (SDH) and 9 parenchymal lesions (contusions/hematomas). In this last set of patients, images were recorded in the “pericontusional” areas and in the “surrounding” brain (areas that were as far from the lesion as the craniotomy allowed). These patients were compared to five patients who underwent craniotomy for a disease that did not affect the cortex. Results There were fewer “pericontusional” images that could be analyzed due to the presence of subarachnoid hemorrhage. The proportion or perfused vessels was similar in all groups: control 99.5% ± 1.3%; SDH 98.6% ± 2.4%; “pericontusional” area 98.2% ± 2.4%; “surrounding” area 98.4% ± 2.5% (p = 0.145). The perfused vessel density index was smaller in the “pericontusional” area: control 6.5 ± 1.6 l/mm; SDH 6.5 ± 2.5 l/mm; “pericontusional” area 5.4 ± 2.6 l/mm; “surrounding” 6.6 ± 2.1 l/mm (p = 0.07). Conclusions Although the analysis of pericontusional zone was difficult, there were fewer vessels than in the controls and there was no change in the flow. In the surrounding zone and in patients with SDH, we did not document alterations in the microcirculation. Direct imaging of cerebral microcirculation in TBI patients showed that despite serious brain injury the cerebral microcirculation was remarkably well preserved.

Sepsis is the response of the host to an infection that produces lesions in its own organs and tissues. Despite the great advances in modern medicine, including vaccines, antibiotics and intensive care, it is still the primary cause of death due to infection. Sepsis may result in shock, multi-organic failure and death unless there is a rapid identification of the infection and timely administration of treatment. Its mortality rates can reach up to 45.7% for septic shock, its most acute manifestation. In this paper we also present these conditional independence maps in the context of algebraic statistics. The results of this analysis over a small cohort of nine patients at three different times (ICU admission, 48h and ICU discharge) showed that there is a significant interaction between C3- DC / C4-OH (Hydroxybutyrylcarnitine) and C5 (Valerylcarnitin) for the three time snapshots. We also found a significant interaction between C3-DC / C4-OH (Hydroxybutyrylcarnitine) and C5 (Valerylcarnitine) and Isoleucine (Ile) at 48h and ICU discharge.

Background: The ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock. Methods and Design: Ninety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hôpital Erasme, Université Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hôpitaux Universitaires de Genève, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1 < 16 h from T0; ii) T2 = 48 h after T0; iii) T3 = day 7 or before discharge or before discontinuation of therapy in case of fatal outcome; iv) T4 = day 100. The inclusion criteria are: shock, Sequential Organ Failure Assessment (SOFA) score > 5 and lactate levels ≥ 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre-existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses. Discussion:ShockOmics will provide new insights into the pathophysiological mechanisms underlying shock as well as new biomarkers for the timely diagnosis of cardiac dysfunction in shock and quantitative indices for assisting the therapeutic management of shock patients., SCOPUS: ar.j, info:eu-repo/semantics/published

In recent years, technological improvements have reduced the complexity of extracorporeal membrane oxygenation devices. This have enabled the development of specific devices for the extracorporeal removal of CO2. These devices have a simpler configuration than extracorporeal membrane oxygenation devices and uses lower blood flows which could reduce the potential complications. Experimental studies have demonstrated the feasibility, efficacy and safety of extracorporeal removal of CO2 and some of its effects in humans. This technique was initially conceived as an adjunct therapy in patients with severe acute respiratory distress syndrome, as a tool to optimize protective ventilation. More recently, the use of this technique has allowed the emergence of a relatively new concept called "tra-protective ventilation"whose effects are still to be determined. In addition, the extracorporeal removal of CO2 has been used in patients with exacerbated hypercapnic respiratory failure with promising results. In this review we will describe the physiological and technical fundamentals of this therapy and its variants as well as an overview of the available clinical evidence, focused on its current potential.

The relentless increase in healthcare costs and the global economic crisis require us to rethink the way research is done. The heterogeneity of patients is a major challenge in designing and coordinating high-quality studies about sepsis. Studies on new treatments and devices, such as polymyxin B hemoperfusion, must be optimized not only for potential benefits for a specific population (i.e. efficacy), but also for their eventual implementation in real-world situations (i.e. effectiveness) and for economic costs (i.e. efficiency). In this regard, theragnosis and newer statistical tools could help us obtain useful information from real-life observational data. In this review, we discuss the basic components required for sustainable research in polymyxin B hemoperfusion.

An increasing body of evidence exists emphasizing that microcirculatory alterations are associated with morbidity and mortality in a wide array of clinical scenarios. Despite efforts to optimize the balance between micro- and macrohemodynamics, high mortality rates still persist in the critically ill – especially with septic patients. The severity and persistence of microcirculatory abnormalities are believed to be directly associated with a poor prognosis in critically ill patients. In the present chapter, we review some of the techniques that have been used to monitor the microcirculation in critically ill patients. Handheld optical spectroscopic-based imaging instruments have been used extensively to clinically monitor and quantify perfusion abnormalities associated with profound microvascular perfusion heterogeneities. However, using these techniques to diagnose and guide resuscitation remains a challenge. Technological advances in microcirculatory image acquisition and analysis should provide a platform enabling microcirculation-targeted resuscitation by providing rapid clinical feedback on the efficacy of applied therapeutic strategies aimed at normalizing the microcirculation in critically ill patients. It is anticipated that more complete and personalized treatments based on resuscitation of the microcirculation will ultimately improve patient outcome in the near future as technology related to bedside microcirculatory monitoring progresses.