RESUMO
BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most commonly encountered intensive care unit (ICU) acquired infections worldwide. The objective of the study was to identify the immune alteration occurring in patients suffering from VAP at the transcriptomic level and explore its potential use for clinical diagnoses of this disease. METHODS: We performed a prospective observational study in five medical ICUs. Immunological gene expression profiles in the blood of VAP patients were compared with those of controls by using whole transcriptome microarrays and droplet digital polymerase chain reaction (ddPCR) in the first 24 hours following diagnosis. RESULTS: VAP patients showed significantly lower expression levels of HLA-DOA, HLA-DMA, HLA-DMB, ICOS, ICOSLG, IL2RA, CD1, CD3, CD28 and CD40LG. The molecules coded by these genes participate of the immunological synapse. CD1C, CD40LG and ICOS showed the highest values of area under the receiver operating characteristic curve (AUROC) with a good balance between sensibility and specificity. CONCLUSIONS: Patients with VAP show a transcriptomic depression of genes participating of the immunological synapse. It takes a commonplace event, namely VAP, and highlights a quite significant underlying immune suppressive state. In effect this small study will change how we regard VAP, and proposes that we regard it as an infection in an immune compromised host, and that immunity has a central role for ICU acquired infections. This may in time change clinical practice, as it has profound implications for the role of protocolised care, or bundles, in the prevention of VAP. Quantifying the expression in blood of this genes using ddPCR could be a useful approach for the diagnosis of VAP.
RESUMO
Nephrotoxicity is a well-known side effect of platinum-based chemotherapy. We retrospectively assessed the incidence and prognostic impact of nephrotoxicity with ESHAP rescue chemotherapy in 74 lymphoma patients (61 aggressive lymphomas). A higher incidence of nephrotoxicity (estimated glomerular filtration rate <60mL/min) was found when ESHAP was administred on an outpatient vs. inpatient basis (14/39 vs. 4/35). Patients submitted to ASCT with renal failure had a lower overall survival (OS) than those with normal renal function (2-yr OS probability [95%CI]: 88% [77%-99%] vs. 50% [22%-78%]). Outpatient administration of ESHAP may not be optimal for all patients and the impact of ESHAP-induced renal failure on ASCT outcomes in lymphoma needs to be assessed in prospective studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Linfoma/tratamento farmacológico , Terapia de Salvação/efeitos adversos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Continuous aspiration of subglottic secretions is effective in preventing ventilator-associated pneumonia, but it involves a risk of mucosal damage. The main objective of our study was to determine the incidence of airway complications related to continuous aspiration of subglottic secretions. METHODS: In consecutive adult patients with continuous aspiration of subglottic secretions, we prospectively recorded clinical airway complications during the period after extubation. A multidetector computed tomography of the neck was performed during the period of 5 days following extubation to classify subglottic and tracheal lesions as mucosal thickening, cartilage thickening or deep ulceration. RESULTS: In the 86 patients included in the study, 6 (6.9%) had transient dyspnea, 7 (8.1%) had upper airway obstruction and 18 (20.9%) had dysphonia at extubation. Univariate analysis identified more attempts required for intubation (2.3 ± 1.1 vs. 1.2 ± 0.5; p = 0.001), difficult intubation (71.4 vs. 10.1%, p = 0.001) and Cormack score III-IV (71.4 vs. 8.8%; p < 0.001) as risk factors for having an upper airway obstruction at extubation. The incidence of failed extubation among patients after planned extubation was 18.9% and 11 patients (12.7%) required tracheostomy. A multidetector computed tomography was performed in 37 patients following extubation, and injuries were observed in 9 patients (24.3%) and classified as tracheal injuries in 2 patients (1 cartilage thickening and 1 mild stenosis with cartilage thickening) and as subglottic mucosal thickenings in 7 patients. CONCLUSIONS: The incidence of upper airway obstruction after extubation in patients with continuous aspiration of subglottic secretions was 8.1%, and the injuries observed by computed tomography were not severe and located mostly in subglottic space.