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Objective: there exists controversy about the pathophysiology and lung mechanics of COVID-19 associated ARDS, because some report severe hypoxemia with preserved respiratory system mechanics, contrasting with “classic” ARDS. We performed a detailed hourly analysis of the characteristics and time course of lung mechanics and biochemical analysis of patients requiring invasive mechanical ventilation for COVID-19-associated ARDS, comparing survivors and non-survivors.Methods and measurements: retrospective analysis of the data stored in the ICU information system of patients admitted in our hospital ICU that required invasive mechanical ventilation due to confirmed SARS-CoV-2 pneumonia between March 5th and April 30th, 2020. We compare respiratory system mechanics and gas exchange during the first ten days of IMV, discriminating volume and pressure controlled modes, between ICU survivors and non-survivors.Results: 140 patients were analyzed, analyzing 11,138 respiratory mechanics recordings. Global mortality was 38.6%. Multivariate analysis showed that age (OR 1,092, 95% (CI 1,014-1,176)), previous use of ACEI/ARBs (OR 4,612, (95% CI 1,19-17,84)) and need of renal replacement therapies (OR 10,15, (95% CI 1,58-65,11)) were associated with higher mortality. Respiratory variables start to diverge significantly between survivors and non-survivors after the 96 to 120 hours from mechanical ventilation initiation, particularly respiratory system compliance. In non survivors, mechanical power at 24 and 96 hs was higher regardless ventilatory mode. Conclusions: in patients admitted for SARS-CoV-2 pneumonia and requiring mechanical ventilation, non survivors have different respiratory system mechanics than survivors in the first 10 days of ICU admission. We propose a checkpoint at 96-120 hs to assess patients` improvement or worsening in order to consider escalating to extracorporeal therapies.“TAKE HOME MESSAGE”: assessing respiratory mechanics in the first 96-120 hs from ICU admission could predict the outcome of Covid-19 patients under mechanical ventilation.

Summary Background Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation. Methods We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland. Eligible patients were in the ICU, aged ≥18 years, were intubated and on mechanical ventilation, were positive for S aureus colonisation of the lower respiratory tract, as assessed by quantitative PCR (qPCR) analysis of endotracheal aspirate, and had not been diagnosed with new-onset pneumonia. Patients were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received antibiotics for S aureus infection for more than 48 h within 72 h of randomisation; had a Clinical Pulmonary Infection Score of 6 or higher; had an acute physiology and chronic health evaluation II score of 25 or higher with a Glasgow coma scale (GCS) score of more than 5, or an acute physiology and chronic health evaluation II score of at least 30 with a GCS score of 5 or less; had a Sequential Organ Failure Assessment score of 9 or higher; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Colonised patients were randomly assigned (1:1:1), by use of an interactive voice or web response system, to receive either a single intravenous infusion of suvratoxumab 2000 mg, suvratoxumab 5000 mg, or placebo. Randomisation was done in blocks of size four, stratified by country and by whether patients had received systemic antibiotics for S aureus infection. Patients, investigators, and study staff involved in the treatment or clinical evaluation of patients were masked to patient assignment. The primary efficacy endpoint was the incidence of S aureus pneumonia at 30 days, as determined by a masked independent endpoint adjudication committee, in all patients who received their assigned treatment (modified intention-to-treat [ITT] population). Primary safety endpoints were the incidence of treatment-emergent adverse events at 30 days, 90 days, and 190 days after treatment, and the incidence of treatment-emergent serious adverse events, adverse events of special interest, and new-onset chronic disease at 190 days after treatment. All primary safety endpoints were assessed in the modified ITT population. This trial is registered with ClinicalTrials.gov ( NCT02296320 ) and the EudraCT database (2014-001097-34). Findings Between Oct 10, 2014, and April 1, 2018, 767 patients were screened, of whom 213 patients with confirmed S aureus colonisation of the lower respiratory tract were randomly assigned to the suvratoxumab 2000 mg group (n=15), the suvratoxumab 5000 mg group (n=96), or the placebo group (n=102). Two patients in the placebo group did not receive treatment after randomisation because their clinical conditions changed and they no longer met the eligibility criteria for dosing. As adjudicated by the data monitoring committee at an interim analysis, the suvratoxumab 2000 mg group was discontinued on the basis of predefined pharmacokinetic criteria. At 30 days after treatment, 17 (18%) of 96 patients in the suvratoxumab 5000 mg group and 26 (26%) of 100 patients in the placebo group had developed S aureus pneumonia (relative risk reduction 31·9% [90% CI −7·5 to 56·8], p=0·17). The incidence of treatment-emergent adverse events at 30 days were similar between the suvratoxumab 5000 mg group (87 [91%]) and the placebo group (90 [90%]). The incidence of treatment-emergent serious adverse events at 30 days were also similar between the suvratoxumab 5000 mg group (36 [38%]) and the placebo group (32 [32%]). No significant difference in the incidence of treatment-emergent adverse events between the two groups at 90 days (89 [93%] in the suvratoxumab 5000 mg group vs 92 [92%] in the placebo group) and at 190 days (93 [94%] vs 93 [93%]) was observed. 40 (40%) patients in the placebo group and 50 (52%) in the suvratoxumab 5000 mg group had a serious adverse event at 190 days. In the suvratoxumab 5000 mg group, one (1%) patient reported at least one treatment-emergent serious adverse event related to treatment, two (2%) patients reported an adverse event of special interest, and two (2%) reported a new-onset chronic disease. Interpretation In patients in the ICU receiving mechanical ventilation with qPCR-confirmed S aureus colonisation of the lower respiratory tract, the incidence of S aureus pneumonia at 30 days was not significantly lower following treatment with 5000 mg suvratoxumab than with placebo. Despite these negative results, monoclonal antibodies still represent one promising therapeutic option to reduce antibiotic consumption that require further exploration and studies. Funding AstraZeneca, with support from the Innovative Medicines Initiative Joint Undertaking.

Expongo una experiencia de aula vinculada a la asignatura Educación Literaria y Estética en la enseñanza primaria (cuarto curso del Grado de Educación Primaria). Esta se ha desarrollado con alumnado de la mención de Educación Física. He conjugado la animación lectora con actividades relacionadas con el cuerpo y las emociones propiciando un enfoque competencial. El objetivo es integrar dos disciplinas aparentemente lejanas (Literatura y Educación Física) con propuestas que favorezcan la creación de actividades imaginativas, evitando la ‘parcelación’ de los futuros docentes en compartimentos estancos. No se pretende dar a conocer libros de literatura relacionados con el deporte, sino propiciar dinámicas de aula que trabajen tanto el goce lector y estético como el desarrollo emocional, físico y creativo. Los resultados son positivos, pues se ha favorecido tanto una visión interdisciplinar y creativa de los futuros docentes como el trabajo en equipo. Todo ello redunda en un aprendizaje más abierto y participativo. Lehen Hezkuntzan Literatura eta Estetika Hezkuntza gaiari lotutako ikasgelako esperientzia aurkezten dut (Lehen Hezkuntzako Graduko laugarren maila). Gorputz Hezkuntzako aipameneko ikasleekin garatu da hori. Irakurketa animazioa gorputzarekin eta emozioekin lotutako jarduerekin konbinatu dut, gaitasun ikuspegiaren alde eginez. Helburua itxuraz urrun dauden bi diziplina (Literatura eta Gorputz Hezkuntza) irudimenezko jarduerak sortzea bultzatzen duten proposamenekin integratzea da, etorkizuneko irakasleen ‘banaketa’ konpartimentu estankotan saihestuz. Ez da kirolarekin lotutako literatura liburuak ezagutzera eman nahi, irakurketaren eta gozamen estetikoaren eta garapen emozionala, fisikoa eta sortzailea lantzen duten ikasgelako dinamikak sustatzeko baizik. Emaitzak positiboak dira, etorkizuneko irakasleen eta talde-lanaren diziplina arteko eta sormenezko ikuspegia sustatu baitu. Hori guztia ikaskuntza irekiagoa eta parte-hartzaileagoa bilakatzen da. I present a classroom experience linked to the subject Literary and Aesthetic Education in primary education (fourth year of the Primary Education Degree). This has been developed with students of the mention of Physical Education. I have combined reading animation with activities related to the body and emotions, promoting a competence approach. The objective is to integrate two seemingly distant disciplines (Literature and Physical Education) with proposals that favor the creation of imaginative activities, avoiding the ‘division’ of future teachers in watertight compartments. It is not intended to publicize literature books related to sports, but rather to promote classroom dynamics that work both on reading and aesthetic enjoyment as well as on emotional, physical and creative development. The results are positive because both an interdisciplinary and creative vision of future teachers and teamwork have been favored. All this results in a more open and participatory learning.

Muchas actividades son esenciales para la vida en sociedad, como la justicia, la educación, la salud, entre otras. Con ocasión de este escrito, podemos identificar cómo las dinámicas urbanísticas y específicamente la construcción permiten la satisfacción de múltiples necesidades, pero también crean un riesgo, el cual ha llevado a que incluso su ejercicio se considere como una actividad peligrosa, generando unas teorías muy puntuales en cuanto a la responsabilidad, tanto en el sector privado como en el público.

[EN] In this article we expose the characteristics and possibilities related to the reading revitalization that literary routes offer. This strategy allows, through visiting places that are part of literary works, to link the reader more with the text. For this, we focus on the experience carried out by Bilenio Publicaciones, a publisher based in Las Palmas de Gran Canaria and which since 2010 has been developing this proposal as a complement to the publication of some of its books set on the island of Gran Canaria with very successful results. The students (the experience is carried out mainly with ESO students) show great satisfaction, since the reading of the works is reinforced with an experience that contextualizes the vital space of the works read., [ES] En este artículo exponemos las características y posibilidades relacionadas con la dinamización lectora que ofrecen las rutas literarias. Esta estrategia permite, a través de la visita a lugares que forman parte de obras literarias, vincular más al lector con el texto. Para ello nos centramos en la experiencia realizada por Bilenio Publicaciones, una editorial radicada en Las Palmas de Gran Canaria y que desde año 2010 viene desarrollando esta propuesta como complemento a la publicación de algunos de sus libros ambientados en la isla de Gran Canaria con resultados muy positivos. El alumnado (la experiencia se realiza fundamentalmente con alumnado de ESO) muestra una gran satisfacción, pues la lectura de las obras se ve reforzada con una experiencia que contextualiza el espacio vital de las obras leídas.

Objetivo Conocer la epidemiología y evolución al alta de los pacientes oncológicos que precisan ingreso en UCI. Diseño Estudio descriptivo observacional de datos del registro ENVIN-HELICS combinado con variables registradas específicamente. Se comparan pacientes con y sin neoplasia. Se identifican grupos de pacientes neoplásicos con peor evolución. Ámbito UCI participantes en ENVIN-HELICS del año 2018 con participación voluntaria en el registro oncológico. Pacientes Ingresados más de 24 horas. Entre estos aquellos diagnosticados de neoplasia en los últimos 5 años. Variables principales Las generales epidemiológicas del registro ENVIN-HELICS y variables relacionadas con la neoplasia. Resultados En las 92 UCI con datos completos se seleccionaron 11.796 pacientes, de los que 1.786 (15,1%) son pacientes con neoplasia. La proporción de pacientes con cáncer por unidad fue muy variable (rango: 1-48%). La mortalidad en UCI de los pacientes oncológicos fue superior a los no oncológicos (12,3% versus 8,9%; p < 0,001). En pacientes oncológicos predominaron los ingresados en el postoperatorio programado (46,7%) o urgente (15,3%). Los pacientes con proceso patológico médico fueron más graves, con mayor estancia y mortalidad (27, 5%). Aquellos ingresados en UCI por enfermedad no quirúrgica relacionada con el cáncer tuvieron la mortalidad más alta (31,4%). Conclusión Existe una gran variabilidad en el porcentaje de pacientes oncológicos en las diferentes UCI. El 46,7% de los pacientes ingresa tras someterse a cirugía programada. La mayor mortalidad corresponde a pacientes con enfermedad médica (27,5%) y a los ingresados por complicaciones relacionadas con el cáncer (31,4%). Objective To assess the epidemiology and outcome at discharge of cancer patients requiring admission to the Intensive Care Unit (ICU). Design A descriptive observational study was made of data from the ENVIN-HELICS registry, combined with specifically compiled variables. Comparisons were made between patients with and without neoplastic disease, and groups of cancer patients with a poorer outcome were identified. Setting Intensive Care Units participating in ENVIN-HELICS 2018, with voluntary participation in the oncological registry. Patients Subjects admitted during over 24 hours and diagnosed with cancer in the last 5 years. Primary endpoints The general epidemiological endpoints of the ENVIN-HELICS registry and cancer-related variables. Results Of the 92 ICUs with full data, a total of 11,796 patients were selected, of which 1786 (15.1%) were cancer patients. The proportion of cancer patients per Unit proved highly variable (1-48%). In-ICU mortality was higher among the cancer patients than in the non-oncological subjects (12.3% versus 8.9%; P < .001). Elective postoperative (46.7%) or emergency admission (15.3%) predominated in the cancer patients. Patients with medical disease were in more serious condition, with longer stay and greater mortality (27.5%). The patients admitted in ICU due to nonsurgical disease related to cancer exhibited the highest mortality rate (31.4%). Conclusions Great variability was recorded in the percentage of cancer patients in the different ICUs. A total of 46.7% of the patients were admitted after undergoing scheduled surgery. The highest mortality rate corresponded to patients with medical disease (27.5%), and to those admitted due to cancer-related complications (31.4%).

Purpose: The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). Methods: In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). Results: Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58–78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. Conclusions: No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation. Trial registration: NCT01420744., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Background Community-acquired bacterial pneumonia (CABP) can lead to sepsis and is associated with high mortality rates in patients presenting with shock and/or respiratory failure and who require mechanical ventilation and admission to intensive care units, thus reflecting the limited effectiveness of current therapy. Preclinical studies support the efficacy of expanded allogeneic adipose-derived mesenchymal stem cells (eASCs) in the treatment of sepsis. In this study, we aim to test the safety, tolerability and efficacy of eASCs as adjunctive therapy in patients with severe CABP (sCABP). Methods In addition to standard of care according to local guidelines, we will administer eASCs (Cx611) or placebo intravenously as adjunctive therapy to patients with sCABP. Enrolment is planned for approximately 180 patients who will be randomised to treatment groups in a 1:1 ratio according to a pre-defined randomization list. An equal number of patients is planned for allocation to each group. Cx611 will be administered on Day 1 and on Day 3 at a dose of 160 million cells (2 million cells / mL, total volume 80 mL) through a 20–30 min (240 mL/hr) intravenous (IV) central line infusion after dilution with Ringer Lactate solution. Placebo (Ringer Lactate) will also be administered through a 20–30 min (240 mL/hr) IV central line infusion at the same quantity (total volume of 80 mL) and following the same schedule as the active treatment. The study was initiated in January 2017 and approved by competent authorities and ethics committees in Belgium, Spain, Lithuania, Italy, Norway and France; monitoring will be performed at regular intervals. Funding is from the European Union’s Horizon 2020 Research and Innovation Program. Discussion SEPCELL is the first trial to assess the effects of eASCs in sCABP. The data generated will advance understanding of the mode of action of Cx611 and will provide evidence on the safety, tolerability and efficacy of Cx611 in patients with sCABP. These data will be critical for the design of future confirmatory clinical investigations and will assist in defining endpoints, key biomarkers of interest and sample size determination. Trial registration NCT03158727, retrospectively registered on 9 May 2017.

Aim Exploratory analyses evaluated patient characteristics and outcomes among patients with complicated skin and soft tissue infection (cSSTI) in the phase 3 COVERS study who were admitted to an intensive care unit (ICU). Methods Adults with cSSTI (surface area ≥ 75 cm2) and evidence of systemic inflammation and/or underlying comorbidities were randomized 2:1 to intravenous ceftaroline fosamil (600 mg every 8 h [q8h]) or vancomycin (15 mg/kg every 12 h) plus aztreonam (1 g q8h) for 5–14 days. Clinical response and ICU length of stay (LOS) within first hospitalization were evaluated in the modified intent-to-treat (MITT) and clinically evaluable (CE) populations; a Cox proportional hazards model identified factors associated with increased hospital LOS. Results Overall, 42 of 761 randomized patients were admitted to the ICU (ceftaroline fosamil, n = 32; vancomycin plus aztreonam, n = 10) prior to, or at start of, study treatment. Baseline differences between the ICU and non-ICU populations were indicative of more severe disease in ICU patients; within this subset, there were also some notable imbalances between treatment groups. Clinical cure rates at test-of-cure (ceftaroline fosamil vs. vancomycin plus aztreonam) were generally similar in the non-ICU and ICU subsets (MITT population 79% vs. 79% and 69% vs. 90.0%, respectively; CE population 87% vs. 85% and 80% vs. 89%, respectively). Median ICU LOS was 8 vs. 13 days, respectively. ICU admission was a risk factor predicting increased hospital LOS (P

To assess the epidemiology and outcome at discharge of cancer patients requiring admission to the Intensive Care Unit (ICU).A descriptive observational study was made of data from the ENVIN-HELICS registry, combined with specifically compiled variables. Comparisons were made between patients with and without neoplastic disease, and groups of cancer patients with a poorer outcome were identified.Intensive Care Units participating in ENVIN-HELICS 2018, with voluntary participation in the oncological registry.Subjects admitted during over 24 h and diagnosed with cancer in the last 5 years.The general epidemiological endpoints of the ENVIN-HELICS registry and cancer-related variables.Of the 92 ICUs with full data, a total of 11,796 patients were selected, of which 1786 (15.1%) were cancer patients. The proportion of cancer patients per Unit proved highly variable (1%-48%). In-ICU mortality was higher among the cancer patients than in the non-oncological subjects (12.3% versus 8.9%; p .001). Elective postoperative (46.7%) or emergency admission (15.3%) predominated in the cancer patients. Patients with medical disease were in more serious condition, with longer stay and greater mortality (27.5%). The patients admitted to the ICU due to nonsurgical disease related to cancer exhibited the highest mortality rate (31.4%).Great variability was recorded in the percentage of cancer patients in the different ICUs. A total of 46.7% of the patients were admitted after undergoing scheduled surgery. The highest mortality rate corresponded to patients with medical disease (27.5%), and to those admitted due to cancer-related complications (31.4%).

Objectives The aim of this study was to define the relationship between age and response to tigecycline among patients treated for complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs). Methods Pooled data derived from five European observational studies on the use of tigecycline (July 2006–October 2011), either as monotherapy or in combination with other antibiotics, for the treatment of cSSTI or cIAI were used in the analysis. Results The total population (N = 1782 patients) was divided into three age categories: 80 years (139 patients) (data unknown/missing for 3 patients). The overall mean Acute Physiology and Chronic Health Evaluation (APACHE) II score for patients with cSSTI and cIAI was 15.0 ± 7.9 and 16.9 ± 7.6, respectively, and the overall mean Sequential Organ Failure Assessment (SOFA) score was 5.8 ± 3.9 and 7.0 ± 4.2, respectively. Overall, patients with cSSTI and cIAI in the three age groups showed a good response to tigecycline treatment (76.2–80.0% and 69.2–81.1%, respectively) with patients aged ≤80 years showing higher response rates. Patients with cIAI appeared to be at greater risk for all types of adverse events compared with those with cSSTI, particularly in the older age groups. Conclusion In these real-life studies, tigecycline, either alone or in combination, achieved favourable clinical response rates in all age categories of patients with cSSTIs and cIAIs with a high severity of illness.

Background Suvratoxumab (suvra), an extended half-life (~80 days), Staphylococcus aureus (SA) alpha toxin-neutralizing IgG monoclonal antibody, is under investigation for prevention of SA pneumonia in patients on mechanical ventilation (MV). We characterized the serum PK of suvra using population pharmacokinetics (popPK) in both healthy volunteers and MV patients and quantified the proportion of patients reaching the serum target of 211 μg/mL at 30 days post-dose. Methods The popPK analysis included 1,368 serum samples from two early phase studies (NCT02296320; EudraCT 2014-001097-34): (1) Phase 1 study in 26 healthy adults receiving single IV suvra doses ranging from 0.225g to 5g, with PK sampled up to 360 days; and (2) Phase 2 study in MV patients with PCR-confirmed SA colonization of lower respiratory tract receiving one suvra IV dose of 2g (n = 15) or 5g (n = 96), with PK sampled up to 100 days. Results A two-compartment linear model with weight-based scaling of the PK parameters adequately described the serum PK data (Figure 1). MV status, number of days on MV, and age impacted the PK of suvra. A moderate between-subject variability ( Conclusion MV status, post-dose duration on MV, body weight, and age were identified as statistically significant covariates influencing the PK of suvra. Serum PK and popPK analyses support the 5g dose for future studies with suvra in MV patients. Disclosures All authors: No reported disclosures.

Objective To describe the utility of determining plasma cystatin C concentrations in the diagnosis of acute incident kidney injury in septic shock. Patients and methods Prospective series of 50 patients with septic shock and plasma creatinine levels Results Twenty patients (40%) developed acute kidney injury: 8 (16%) were categorized as RIFLE-R, 5 (10%) as RIFLE-I and 7 (14%) as RIFLE-F. All patients categorized as RIFLE-F required extracorporeal renal clearance. Eighteen (36%) patients died, 8 (20%) of whom had developed acute kidney injury in their evolution. There was poor correlation between plasma creatinine and cystatin C levels (r = .501; p = .001), which disappeared upon reaching any degree of renal impairment on the RIFLE scale. Cystatin C levels increased earlier on and were better able to identify patients who would develop serious renal function impairment (RIFLE-F) than creatinine and urea levels. The initial cystatin C levels were related to mortality at 30 days (OR = 1.16; 95% CI: 03–.85). Conclusions For patients who developed acute septic kidney injury, the plasma cystatin C levels increased before the classical markers of renal function. Cystatin C also constitutes a severity biomarker that correlates with progression to RIFLE-F, the need for extrarenal clearance and, ultimately, mortality. This precocity could be useful for starting measures that prevent the progression of renal dysfunction.

Resumen Objetivo Describir la utilidad de la determinacion de la concentracion plasmatica de cistatina C en el diagnostico precoz de la lesion renal aguda en el shock septico. Pacientes y metodos Serie prospectiva de 50 pacientes ingresados en una unidad de cuidados intensivos con shock septico y creatinina plasmatica Resultados Veinte pacientes (40%) desarrollaron lesion renal aguda: 8 (16%) RIFLE «R», 5 (10%) RIFLE «I» y 7 (14%) RIFLE «F». Todos los RIFLE «F» precisaron depuracion renal extracorporea. Fallecieron 18 pacientes (36%); de ellos 8 (20%) habian desarrollado lesion renal aguda en su evolucion. Hubo una correlacion pobre entre creatinina y cistatina C plasmaticas (r = 0,501; p = 0,001), que desaparecia cuando se alcanzaba cualquier grado de deterioro renal en la escala RIFLE. La cistatina C se elevaba antes e identificaba mejor que la creatinina y la urea a aquellos pacientes que iban a desarrollar un deterioro severo de su funcion renal (RIFLE «F») y sus valores iniciales se relacionaban con la mortalidad a los 30 dias (OR = 1,16; IC 95%: 0,03-0,85). Conclusiones En los pacientes que desarrollan lesion renal aguda septica la cistatina C plasmatica se incrementa antes que los marcadores clasicos de funcion renal. Ademas constituye un biomarcador de severidad que se correlaciona con la evolucion a RIFLE «F», la necesidad depuracion extrarrenal y la mortalidad. Esta precocidad puede ser util para instaurar medidas que eviten la progresion de la disfuncion renal.

Background Catheter suctioning of respiratory secretions in intubated subjects is limited to the proximal airway and associated with traumatic lesions to the mucosa and poor tolerance. “Mechanical insufflation-exsufflation” exerts positive pressure, followed by an abrupt drop to negative pressure. Potential advantages of this technique are aspiration of distal airway secretions, avoiding trauma, and improving tolerance. Methods We applied insufflation of 50 cmH2O for 3 s and exsufflation of − 45 cmH2O for 4 s in patients with an endotracheal tube or tracheostomy cannula requiring secretion suctioning. Cycles of 10 to 12 insufflations-exsufflations were performed and repeated if secretions were aspirated and visible in the proximal artificial airway. Clinical and laboratory parameters were collected before and 5 and 60 min after the procedure. Subjects were followed during their ICU stay until discharge or death. Results Mechanical insufflation-exsufflation was applied 26 times to 7 male and 6 female subjects requiring suctioning. Mean age was 62.6 ± 20 years and mean Apache II score 23.3 ± 7.4 points. At each session, a median of 2 (IQR 1; 2) cycles on median day of intubation 11.5 (IQR 6.25; 25.75) were performed. Mean insufflation tidal volume was 1043.6 ± 649.9 ml. No statistically significant differences were identified between baseline and post-procedure time points. Barotrauma, desaturation, atelectasis, hemoptysis, or other airway complication and hemodynamic complications were not detected. All, except one, of the mechanical insufflation-exsufflation sessions were productive, showing secretions in the proximal artificial airway, and were well tolerated. Conclusions Our preliminary data suggest that mechanical insufflation-exsufflation may be safe and effective in patients with artificial airway. Safety and efficacy need to be confirmed in larger studies with different patient populations. Trial registration EudraCT 2017-005201-13 (EU Clinical Trials Register).

Background Patients with lower airway Staphylococcus aureus (SA) colonization are at great risk (> 20%) of early-onset ventilator-associated pneumonia (VAP). Thus, a rapid test is required to identify patients at risk. Suvratoxumab (formerly MEDI4893) is a human monoclonal antibody that neutralizes SA alpha toxin. SAATELLITE, a phase 2 study of safety and efficacy of suvratoxumab for reducing the incidence of SA pneumonia (NCT02296320) was conducted and recently completed within the consortium for Combatting Bacterial Resistance in Europe. We investigated the performance of a rapid PCR test (Xpert MRSA/SA SSTI™, Cepheid) as a screening tool during the study and the association between SA load and suvratoxumab efficacy. Methods The PCR assay was used to detect SA and methicillin-resistant SA (MRSA) in lower respiratory tract (LRT) samples. Culture was performed on PCR SA+ LRT samples according to local procedures. PCR SA+ subjects were randomized 1:1 to either a single intravenous infusion of 5000 mg suvratoxumab (n = 96) or placebo (n = 100) and followed for 190 days post dose. Efficacy of suvratoxumab was defined as relative risk reduction (RRR) in incidence of SA pneumonia within 30 days post-dose compared with placebo. Results 299 (41.5%) out of 720 screened subjects were SA+ by PCR. Of 209 subjects with culture data, there were 162 (77.5%) SA+, 47 (22.5%) SA- and 9 (5.6%) MRSA by culture. Culture results could have been affected by antibiotic use and site variability in limits of detection ranging from 3.3 to 100,000 colony-forming units per mL (CFU/mL). No discordance was noted between PCR and culture for MRSA detection. An inverse linear correlation was observed between the PCR cycle threshold (Ct) values for SA protein A gene (spa) and SA CFU/mL counts from quantitative culture. In subjects with low SA load (Ct ≥ 29; n = 72), suvratoxumab provided 66.7% RRR [90% confidence interval (CI): 21.3%, 86.2%] compared with 31.9% RRR [90% CI: -7.5%, 56.8%] in total study population. Conclusion Cepheid Xpert PCR assay was easy to perform, sensitive and standardized, and provided better sensitivity than conventional culture for detection of SA. Additionally, quantitative PCR Ct output was associated with the efficacy of suvratoxumab in reducing SA pneumonia incidence. Disclosures All authors: No reported disclosures.

Background Staphylococcus aureus (SA) pneumonia imposes significant morbidity and mortality in mechanically ventilated, intensive care unit (MV ICU) patients despite best clinical care. We assessed efficacy, PK, AT-neutralizing antibodies (AT NAbs), and safety of suvratoxumab (suvra) in MV ICU subjects in the placebo-controlled, randomized Phase 2 SAATELLITE study (NCT02296320; EudraCT 2014-001097-34). Methods Subjects with PCR-confirmed SA colonization of the lower respiratory tract were randomized to either a single intravenous infusion of 5,000 mg suvra (n = 96) or placebo (n = 100) and followed for 190 days post dose. Efficacy endpoints were Endpoint Adjudication Committee-determined relative risk reduction (RRR) of SA pneumonia incidence in suvra vs. placebo recipients within 30 days post dose (primary endpoint, tested at 2-sided α = 0.1), incidence of all-cause pneumonia, and all-cause pneumonia or death. Serum suvra PK and levels of AT NAbs were measured through 90 days post dose and analyzed for statistical correlation. Treatment-emergent adverse events (TEAEs) and serious AEs (SAEs) were assessed through 190 days post dose. Results Baseline characteristics were similar between groups. Suvra provided 31.9% RRR in incidence of SA pneumonia vs. placebo (17.7% vs. 26%; P = 0.166), 30% RRR (P = 0.146) in incidence of all-cause pneumonia, and 23% RRR (P = 0.164) in incidence of all-cause pneumonia or death. Suvra reduced mean hospital stay and ICU duration by 3.0 and 2.4 days, resp. vs. placebo. Mean serum ± SD suvra level was 296 ± 131 µg/mL at 30 days post dose. Serum AT Nab ± SD levels reached 156.03 ± 72.48 IU/mL at 2 days post dose, declining slowly to 33.74 ± 16.04 IU/mL by 90 days post dose. AT NAbs correlated with PK (r2 = 0.7), thereby confirming functional activity of suvra over time. Proportion of subjects with TEAEs or SAEs was similar between groups: ≥1 TEAE (93.8% suvra; 93.0% placebo); ≥1 serious; and/or ≥grade 3 severity SAE (66.7% suvra; 58.0% placebo). Conclusion A single intravenous dose of suvra produced a trend toward reduced incidence of SA pneumonia, health resource savings, sustained functional exposure in serum, and an acceptable safety profile. These results support continued development of suvra in MV ICU patients. Disclosures All Authors: No reported Disclosures.

This article discusses a narratological study of the literary work The secret of the blue egg, by the writer Catalina Gonzalez Vilar, that won El Barco de Vapor prize in 2012. It examines the different constitutive elements of the text (topic approach, prominent figures, syntactic structure, narrative technique…) and his contribution to the development of the story with the purpose of discovering the aesthetic and literary values that contribute to the fable. It aims at demonstrating the proper use of them all as they shape a text rich in nuances, striking, suggestive. All these qualities of great importance both in creations aimed at adults as well as at children and young people because they enrich the final value of the work, and by extension, the cultural background of their readers.Este trabajo aborda el estudio narratológico de la obra El secreto del huevo azul, de la escritora Catalina González Vilar, que obtuvo el Premio El Barco de Vapor en el año 2012. Examina los diferentes elementos constitutivos del texto (el enfoque del tema, la caracterización de los personajes, la estructura sintáctica, el tratamiento del lenguaje, la técnica narrativa utilizada…) y su aporte al desarrollo de la historia con la finalidad de descubrir los valores estéticos y literarios que aporta a la fábula. Pretende demostrar el adecuado uso de todos ellos dado que favorecen un texto rico en matices, llamativo, sugerente. Cualidades, todas ellas, de gran importancia tanto en creaciones destinadas al público adulto como al infantil y juvenil pues enriquece el valor final de la obra, y por extensión, el bagaje cultural de sus lectores.

Tigecycline is an approved treatment for complicated skin and soft-tissue infections (cSSTIs). The efficacy of tigecycline as monotherapy or in combination with other antibacterials in the treatment of cSSTI in routine practice is described.Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011).A total of 254 cSSTI patients who received tigecycline were included (mean age 63.2 ± 14.9 years). Of these, 34.4% were in intensive care units, 54.5% acquired their infection in hospital and 90.9% had at least one comorbidity. Infection most commonly affected the limbs (62.4%) and 43.8% of infections were classified as necrotizing. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at the beginning of treatment were 15.0 ± 7.9 (n = 205) and 5.8 ± 3.9 (n = 32), respectively, indicating high disease severity. Staphylococcus aureus (52.7%), Escherichia coli (18.0%) and Enterococcus faecium (12.0%) were the most frequently isolated pathogens; 32.9% of infections were polymicrobial and 30.5% were due to resistant pathogens. Overall, 71.8% received tigecycline as monotherapy and 28.2% as combination therapy for a mean duration of 12 days. Clinical response rates at the end of treatment were 79.6% for all patients who received the standard dosage (183/230), 86.7% for patients who received tigecycline as monotherapy (143/165), 75.0% for patients with a nosocomial infection (96/128), 75.3% for patients with an APACHE II score15 (61/81) and 58.3% for patients with a SOFA score ≥ 7 (7/12).In these real-life studies, tigecycline, alone and in combination, achieved favourable clinical response rates in patients with cSSTI with a high severity of illness.

Tigecycline is approved for the treatment of complicated skin and soft-tissue infections (cSSTIs) and complicated intra-abdominal infections (cIAIs) in adults. In this analysis the safety and tolerability profile of tigecycline (used alone or in combination) for the treatment of patients with approved indications of cSSTI and cIAI were examined under real-life clinical conditions.Individual patient-level data were pooled from five European observational studies (July 2006 to October 2011). A total of 254 cSSTI and 785 cIAI patients were included. The mean age was 63 years; 34.4% and 56.6% were in intensive care units, 90.9% and 88.1% had at least one comorbidity and mean Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the beginning of treatment were 15.0 ± 7.9 and 16.9 ± 7.6, respectively.Data on adverse events (AEs) were available for 198 cSSTI and 590 cIAI patients in three studies. Nausea and vomiting were reported in ≤ 2% of patients. The most common serious AEs were multi-organ failure (4.0% and 10.0% in cSSTI and cIAI patients, respectively) and sepsis (4.0% and 6.1%, respectively). Death was recorded for 24/254 (9.4%) cSSTI and 147/785 (18.7%) cIAI patients. Mortality rates were higher in the group with a baseline APACHE II score of15 compared with those with a score of ≤ 15 (18.7% versus 3.5% for cSSTI patients and 23.8% versus 16.0% for cIAI patients). A similar trend was seen when cIAI patients were stratified by Sequential Organ Failure Assessment (SOFA) score.The safety and tolerability of tigecycline, alone and in combination, are consistent with the level of critical illness among patients in these real-life studies.

BACKGROUND: Low-tidal-volume ventilation may be associated with repetitive opening and closing of terminal airways. The use of PEEP is intended to keep the alveoli open. No method of adjusting the optimal PEEP has shown to be superior or to improve clinical outcomes. We conducted a pilot study to evaluate the effect of setting an individualized level of PEEP at the highest compliance on oxygenation, multiple-organ-dysfunction, and survival in subjects with ARDS. METHODS: Subjects with ARDS ventilated with low tidal volumes and limitation of airway pressure to 30 cm H2O were randomized to either a compliance-guided PEEP group or an FIO2-guided group. RESULTS: Of the 159 patients with ARDS admitted during the study period, 70 met the inclusion criteria. Subjects in the compliance-guided group showed nonsignificant improvements in PaO2/FIO2 during the first 14 days, and in 28-day mortality (20.6% vs. 38.9%, P = .12). Multiple-organ-dysfunction-free days (median 6 vs 20.5 d, P = .02), respiratory-failure-free days (median 7.5 vs 14.5 d, P = .03), and hemodynamic-failure-free days (median 16 vs 22 d, P = .04) at 28 days were significantly lower in subjects with compliance-guided setting of PEEP. CONCLUSIONS: In ARDS subjects, protective mechanical ventilation with PEEP application according to the highest compliance was associated with less organ dysfunction and a strong nonsignificant trend toward lower mortality. ClinicalTrials.gov Number [NCT01119872][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01119872&atom=%2Frespcare%2F58%2F9%2F1416.atom

Ceftazidime-avibactam (CAZ-AVI) is a recently approved β-lactam–β-lactamase inhibitor combination with the potential to treat serious infections caused by carbapenem-resistant organisms. Few patients with such infections were included in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a case series of patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had prescribed CAZ-AVI completed a case report form. We used descriptive statistics to summarize patient characteristics and treatment outcomes. We used the Wilcoxon rank sum test and Fisher's exact test to compare patients by treatment outcome. The sample included 36 patients infected with CRE and two with CRPa. The most common infections were intra-abdominal. Physicians categorized 60.5% of patients as having life-threatening infections. All but two patients received other antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ-AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received other antibiotics to which their pathogen was nonresistant in vitro . Twenty-eight patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced clinical and/or microbiological cure. Five patients (20.8%) with documented microbiological cure died, whereas 10 patients (71.4%) with no documented microbiological cure died ( P = 0.01). In three-quarters of cases, CAZ-AVI (alone or combined with other antibiotics) cured infections caused by carbapenem-resistant organisms, 95% of which had failed previous therapy. Microbiological cure was associated with improved survival. CAZ-AVI shows promising clinical results for infections for which treatment options are limited.

The present article is an update of the literature on endocarditis. A multidisciplinary group of Spanish physicians with an interest in cardiac infections selected the most important papers produced lately in the field. Two of the members of the group discussed the content of each of the selected papers, with a critical review by others members of the panel. After a review of the state of the art papers from the fields of epidemiology, new causative microorganisms (bacterial and fungal), clinical findings including those in special patients, laboratory diagnosis, prognostic factors, nosocomial endocarditis, prophylaxis, new drugs and guidelines for antibiotic treatment were discussed by the group.

Motion estimation has many applications in fluid analysis, and a lot of work has been carried out using Particle Image Velocimetry (PIV) to capture and measure the flow motion from sequences of 2D images. Recent technological advances allow capturing 3D PIV sequences of moving particles. In the context of 3D flow motion, the assumption of incompressibility is an important physical property that is satisfied by a large class of problems and experiments. Standard motion estimation techniques in computer vision do not take into account the physical constraints of the flow, which is a very interesting and challenging problem. In this paper, we propose a new variational motion estimation technique which includes the incompressibility of the flow as a constraint to the minimization problem. We analyze, from a theoretical point of view, the influence of this constraint and we design a new numerical algorithm for motion estimation which enforces it. The performance of the proposed technique is evaluated from numerical experiments on synthetic and real data.

We present in this paper a variational approach to accurately estimate simultaneously the velocity field and its derivatives directly from PIV image sequences. Our method differs from other techniques that have been presented in the literature in the fact that the energy minimization used to estimate the particles motion depends on a second order Taylor development of the flow. In this way, we are not only able to compute the motion vector field, but we also obtain an accurate estimation of their derivatives. Hence, we avoid the use of numerical schemes to compute the derivatives from the estimated flow that usually yield to numerical amplification of the inherent uncertainty on the estimated flow. The performance of our approach is illustrated with the estimation of the motion vector field and the vorticity on both synthetic and real PIV datasets.

Invasive Candida spp. infections in non-neutropenic critically ill patients admitted to intensive care units can be classified as focal and systemic. Both types of infection usually occur after episodes of candidemia, although some focal infections may be of exogenous development, like those occurring after trauma or be device-related.The clinical spectrum of invasive Candida spp. infections includes focal urinary tract, abdominal, ocular, respiratory tract, renal and hepato-biliary infections, as well as systemic infections like candidemia and acute systemic candidiasis with multiorgan involvement after hematogenous seeding. Candida spp. isolates in "significant" samples, like synovial fluid, cerebrospinal fluid and blood cultures, represent true infection. However, the diagnosis of invasive infection based on "non-significant" samples, like surgical drains and digestive tract exudates, requires additional criteria. The total number of isolates from different sites, the presence of risk factors, the clinical host response, as well as severity of illness need to be taken into account for the diagnosis of invasive candidiasis. The clinical signs of systemic infection due to Candida spp. are completely non-specific and cannot be differentiated from bacterial peritonitis, urinary tract infection or bacteremia. These infections may be associated with signs of sepsis,severe sepsis, septic shock or multiorgan dysfunction. In the future clinical multicentre observational and interventional studies are necessary to reach agreement on clinical definitions and classification of invasive Candida spp. infections in critically ill non-immunocompromised patients.

RATIONALE: Iseganan, an antimicrobial peptide, is active against aerobic and anaerobic gram-positive and gram-negative bacteria as well as fungi and yeasts. The drug has shown little resistance in vitro and to be safe and well tolerated in 800 patients with cancer treated for up to 6 wk. OBJECTIVES: To determine the efficacy of iseganan for the prevention of ventilator-associated pneumonia (VAP). METHODS: Mechanically ventilated patients in the United States and Europe were randomized to oral topical iseganan or placebo (1:1) and treated six times per day while intubated for up to 14 d. Patients were eligible if randomized within 24 h of intubation and estimated to survive and remain mechanically ventilated for 48 h or more. The primary efficacy endpoint of the study was VAP measured among survivors at Day 14. MEASUREMENTS AND MAIN RESULTS: A total of 709 patients were randomized and received at least one dose of study drug. The two groups were comparable at baseline except iseganan-treated patients were, on average, 3 yr older. The rate of VAP among survivors at Day 14 was 16% (45/282) in patients treated with iseganan and 20% (57/284) in those treated with placebo (p = 0.145). Mortality at Day 14 was 22.1% (80/362) in the iseganan group compared with 18.2% (63/347) in the placebo group (p = 0.206). No pattern of excess adverse events in the iseganan group compared with placebo was observed. CONCLUSIONS: Iseganan is not effective in improving outcome in patients on prolonged mechanical ventilation.

El estado de Oaxaca representa un importante acervo de maíz en México. Estudios previos han indicado la presencia de muchas variedades locales y razas agronómicas en la Sierra Norte y Valles Centrales. La Sierra Sur ha sido poco estudiada a pesar de la presencia de comunidades indígenas zapotecas, las cuales cultivan maíz, entre otras especies, y han preservado las variedades locales. El presente estudio responde a las siguientes preguntas: ¿cuál es la diversidad de maíz en términos de variedades tradicionales y razas agronómicas en la región zapoteca de Los Loxicha?, ¿la diversidad de maíz sigue un patrón de distribución a lo largo de un gradiente altitudinal?, ¿cuáles prácticas promueven y mantienen esta diversidad? Para contestar estas preguntas se realizó un estudio en cinco municipios de la Sierra Sur de Oaxaca. Durante 2007 se aplicaron entrevistas estructuradas a 930 agricultores para describir el proceso de manejo de semilla. La caracterización morfológica de las razas agronómicas se basó en muestras de mazorcas obtenidas en 375 milpas, con 20 plantas por milpa. Se encontraron altos niveles de diversidad local de maíz, con 36 variedades tradicionales correspondientes a 10 razas agronómicas. Las razas exhibieron diferencias en términos de variación fenotípica, distribución altitudinal y algunas muestran adaptación local. Los agricultores practican algunas formas de manejo ancestral para la selección de mazorcas y semillas, manteniendo, así, ciertos niveles de diferenciación entre las variedades y las razas agronómicas. Sin embargo, al sembrar diferentes variedades dentro de la misma parcela, se promueve el flujo génico y la introgresión entre ellas, manteniendo y promoviendo la diversidad fenotípica y genética.

The data accumulated so far from experimental animals, clinical observations, and clinical trials of gut-oriented interventions are considered by many acceptably good evidence for the role of the gut in septic states. In fact, the hypothesis that the systemic inflammatory response syndrome (SIRS) and associated organ dysfunctions are initiated, perpetuated, and/or exacerbated by microbiological and immunological phenomena that occur at the gut level has attracted the effort of many investigators over the last two decades. The changes of the gut microbial flora, bacterial translocation, and the functional and morphological abnormalities of the intestinal mucosa and the gut-associated lymphatic tissue (GALT) that occur in experimental as well as human septic states have been made responsible for the clinical syndromes of SIRS and multiple organ dysfunction syndrome (MODS). The potential pathways of an inflammatory signal from the gut to the systemic circulation and distant organ systems are the portal vein and the lymphatic drainage of the gut via the mesenteric lymph nodes and the thoracic duct. The present article reviews the current state of our knowledge of the lymphatic drainage of the gut that may provide the route of access to the systemic circulation for a gut-associated inflammatory signal.