Objective: Although ventilator-associated pneumonia (VAP) is a major cause of nosocomial infection, its role in the prognosis of patients remains undefined. The objective of this study was to evaluate the impact of VAP on the clinical evolution of patients. Methods: This was a prospective cohort study involving 233 patients on mechanical ventilation (VAP group, n = 64; control group, n = 169). Primary outcomes were time on mechanical ventilation (TMV), time in ICU (TICU), overall length of hospital stay (LHS) and in-ICU mortality. Secondary outcomes were in-hospital mortality, microbiological profile, prior use of antibiotics and risk factors for VAP acquisition. Results: Control and VAP group outcomes were, respectively, as follows: median TMV (days), 9 (interquartile range [IQR]: 5-15) and 23 (IQR: 15-37; p < 0.0001); median TICU (days), 12 (IQR: 8-21) and 27 (IQR: 17-42; p < 0.0001); median LHS (days), 33 (IQR: 18-64) and 46 (IQR: 25-90; p = 0.05); and in-ICU mortality, 38% (95% CI: 31-45) and 55% (95% CI: 42-67; p = 0.02). VAP was a predictor of in-ICU mortality (OR = 3.40; 95% CI: 1.54-7.48). TMV (OR = 2.27; 95% CI: 1.05-4.87) and prior use of antibiotics (OR = 1.07; 95% CI: 1.04-1.10) were risk factors for VAP. VAP did not affect in-hospital mortality. Acinetobacter spp. was the most common isolate (28%). Inappropriate empirical antibiotic therapy was administered in 48% of cases. Conclusions: In this study, there was a high incidence of infection with resistant bacteria and inappropriate initial antibiotic therapy. Long TMV and prior use of antibiotics are risk factors for VAP.Keywords: Pneumonia, ventilator-associated; Cross infection; Intensive care units; Hospital mortality; Risk factors. ResumoObjetivo: Apesar de representar uma das principais causas de infecção nosocomial, o papel da pneumonia associada à ventilação mecânica (PAVM) no prognóstico ainda permanece indefinido. O objetivo deste estudo foi avaliar o impacto dessa doença na evolução clínica dos pacientes. Métodos: Estabeleceu-se uma coorte prospectiva de 233 pacientes sob ventilação mecânica (grupo PAV, n = 64; grupo controle, n = 169). Os desfechos primários foram tempo de ventilação mecânica (TVM), tempo de permanência na UTI (TUTI), tempo de permanência hospitalar (TH) e mortalidade na UTI. Os desfechos secundários foram mortalidade hospitalar, perfil microbiológico, uso prévio de antibióticos e fatores de risco para PAVM. Resultados: Os desfechos dos grupos controle e PAVM foram, respectivamente, os seguintes: mediana do TVM (dias), 9 (intervalo interquartílico [II]: 5-15) e 23 (II: 15-37; p < 0,0001); mediana do TUTI (dias), 12 (II: 8-21) e 27 (II: 17-42; p < 0,0001); mediana do TH (dias), 33 (II: 18-64) e 46 (II: 25-90; p = 0,02); e mortalidade na UTI, 38% (IC95%: 31-45) e 55% (IC95%: 42-67; p = 0,02). A PAVM foi um preditor de mortalidade na UTI (OR = 3,40; IC95%: 1,78). O TVM (OR = 2,27; IC95%: 1,05-4,87) e o uso prévio de antibióticos (OR = 1,07; IC95%: 1,04-1,10) foram fatores de risco para PAVM. A PAVM não afetou a morta...

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Sepsis results from a dyshomeostatic response to infection, which may lead to hyper or hypoimmune states. Monocytes are central regulators of the inflammatory response, but our understanding of their role in the genesis and resolution of sepsis is still limited. Here, we report a comprehensive exploration of monocyte molecular responses in a cohort of patients with septic shock via proteomic profiling. The acute stage of septic shock was associated with an impaired inflammatory phenotype, indicated by the down-regulation of MHC class II molecules and proinflammatory cytokine pathways. Simultaneously, there was an up-regulation of glycolysis enzymes and a decrease in proteins related to the citric acid cycle and oxidative phosphorylation. On the other hand, the restoration of immunocompetence was the hallmark of recovering patients, in which an upregulation of interferon signaling pathways was a notable feature. Our results provide insights into the immunopathology of sepsis and propose that, pending future studies, immunometabolism pathway components could serve as therapeutic targets in septic patients.

Background Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. MethodsIn this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middleincome countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42•4% vs 44•2%; absolute difference -1•69 [-9•58 to 6•11] p=0•67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H 2 O; p=0•0011). ICU mortality was higher in MICs than in HICs (30•5% vs 19•9%; p=0•0004; adjusted effect 16•41% [95% CI 9•52-23•52]; p<0•0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0•80 [95% CI 0•75-0•86]; p<0•0001).Interpretation Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status.