Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Más filtros











Base de datos
Intervalo de año de publicación
2.
Chest ; 158(1): 183-194, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32247714

RESUMEN

BACKGROUND: Acute skeletal muscle wasting in critical illness is associated with excess morbidity and mortality. Continuous feeding may suppress muscle protein synthesis as a result of the muscle-full effect, unlike intermittent feeding, which may ameliorate it. RESEARCH QUESTION: Does intermittent enteral feed decrease muscle wasting compared with continuous feed in critically ill patients? STUDY DESIGN AND METHODS: In a phase 2 interventional single-blinded randomized controlled trial, 121 mechanically ventilated adult patients with multiorgan failure were recruited following prospective informed consultee assent. They were randomized to the intervention group (intermittent enteral feeding from six 4-hourly feeds per 24 h, n = 62) or control group (standard continuous enteral feeding, n = 59). The primary outcome was 10-day loss of rectus femoris muscle cross-sectional area determined by ultrasound. Secondary outcomes included nutritional target achievements, plasma amino acid concentrations, glycemic control, and physical function milestones. RESULTS: Muscle loss was similar between arms (-1.1% [95% CI, -6.1% to -4.0%]; P = .676). More intermittently fed patients received 80% or more of target protein (OR, 1.52 [1.16-1.99]; P < .001) and energy (OR, 1.59 [1.21-2.08]; P = .001). Plasma branched-chain amino acid concentrations before and after feeds were similar between arms on trial day 1 (71 µM [44-98 µM]; P = .547) and trial day 10 (239 µM [33-444 µM]; P = .178). During the 10-day intervention period the coefficient of variation for glucose concentrations was higher with intermittent feed (17.84 [18.6-20.4]) vs continuous feed (12.98 [14.0-15.7]; P < .001). However, days with reported hypoglycemia and insulin usage were similar in both groups. Safety profiles, gastric intolerance, physical function milestones, and discharge destinations did not differ between groups. INTERPRETATION: Intermittent feeding in early critical illness is not shown to preserve muscle mass in this trial despite resulting in a greater achievement of nutritional targets than continuous feeding. However, it is feasible and safe. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02358512; URL: www.clinicaltrials.gov.


Asunto(s)
Nutrición Enteral/métodos , Insuficiencia Multiorgánica/terapia , Síndrome Debilitante/prevención & control , Cuidados Críticos , Enfermedad Crítica , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/complicaciones , Respiración Artificial , Método Simple Ciego
4.
N Engl J Med ; 371(18): 1695-703, 2014 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-25268516

RESUMEN

BACKGROUND: Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS. METHODS: In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety. RESULTS: The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug. CONCLUSIONS: Simvastatin therapy, although safe and associated with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the U.K. National Institute for Health Research Efficacy and Mechanism Evaluation Programme and others; HARP-2 Current Controlled Trials number, ISRCTN88244364.).


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Simvastatina/uso terapéutico , Adulto , Anciano , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Unidades de Cuidados Intensivos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Respiración Artificial , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/terapia , Simvastatina/efectos adversos , Volumen de Ventilación Pulmonar , Insuficiencia del Tratamiento
5.
Crit Care Med ; 36(4): 1267-76, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18379254

RESUMEN

OBJECTIVE: Examination of the interaction between gram-positive bacterial superantigens and toll-like receptor 2 (TLR2) in health and critical illness. DESIGN: Laboratory ex vivo model and prospective clinical, cohort study. SETTING: Two research laboratories in university hospitals and two intensive care units. SUBJECTS/PATIENTS: Laboratory study was performed in transfected HeLa cells and primary human monocytes from healthy volunteers. Clinical study used cells from 20 healthy controls and 45 critically ill patients with circulatory shock. INTERVENTIONS: HeLa cells and purified monocytes were exposed to purified superantigens or isogenic bacterial supernatants and readout obtained by cytokine enzyme-linked immunosorbent assay, flow cytometry, and quantitative real-time polymerase chain reaction. Peripheral blood mononuclear cells from patients with circulatory shock were compared with controls using flow cytometry and measurement of cytokines after ligand exposure. MEASUREMENTS AND MAIN RESULTS: Superantigens were unable to signal through ligation by TLR2. However, TLR2 was up-regulated on the surface of primary human monocytes, without detectable TLR2 messenger RNA neosynthesis, by a range of superantigens and superantigen-containing Streptococcus pyogenes supernatants, although not by isogenic superantigen-negative strains. Superantigen mutant constructs with disrupted major histocompatibility complex class II-binding sites did not support TLR2 up-regulation. TLR2 up-regulation was associated with an increase in the proinflammatory response to TLR2 ligands only at high ligand concentrations. TLR2 was up-regulated in a small subset of patients with severe S. pyogenes sepsis but not in patients with any other category of septic or circulatory shock; responses to TLR2 ligands were reduced in all categories of critically ill patient, however. CONCLUSIONS: Superantigens up-regulate monocyte surface TLR2 expression through major histocompatibility complex class II signaling. Enhanced surface TLR2 expression may be a specific feature of patients with S. pyogenes-induced shock. Importantly, intensity of TLR2 signaling is not necessarily coupled to TLR2 expression when ligand concentrations are low or after onset of critical illness.


Asunto(s)
Fascitis Necrotizante/microbiología , Monocitos/microbiología , Sepsis/microbiología , Staphylococcus aureus/inmunología , Streptococcus pyogenes/inmunología , Superantígenos/farmacología , Receptor Toll-Like 2/efectos de los fármacos , Fascitis Necrotizante/inmunología , Femenino , Citometría de Flujo , Células HeLa , Humanos , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Sepsis/inmunología , Sepsis/mortalidad , Superantígenos/inmunología , Transfección , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/inmunología
6.
Blood ; 105(9): 3655-62, 2005 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-15644417

RESUMEN

The devastating systemic effects of bacterial superantigens may be explained by powerful proinflammatory synergy with lipopolysaccharide (LPS). However, the mechanism underlying this phenomenon remains unclear and has never been investigated in humans. Specifically, there is no known link between superantigen-induced immune effects and the pattern recognition of LPS at toll-like receptor 4 (TLR4). Here we show that bacterial superantigens induce rapid transcription and increased membrane expression of TLR4 in primary human monocytes by ligation of major histocompatibility complex (MHC) class II. We also demonstrate that superantigens are solely responsible for monocyte TLR4 up-regulation induced by products from Gram-positive bacteria. In parallel with enhanced TLR4 expression, priming of purified monocytes or mixed peripheral blood mononuclear cells with superantigens significantly enhanced the induction of proinflammatory cytokines by known TLR4 ligands. Staphylococcal enterotoxin A constructs containing targeted mutations were used to demonstrate a requirement for MHC class II ligation in both TLR4 up-regulation and enhanced responses to endotoxin. In contrast to results from animal models, superantigen-endotoxin interaction was not dependent on T-cell receptor ligation by superantigen or interferon gamma production. Pattern recognition of bacterial superantigens by MHC class II receptors may exacerbate the proinflammatory response of monocytes to Gram-negative infection or endotoxin by up-regulation of TLR4.


Asunto(s)
Citocinas/biosíntesis , Antígenos de Histocompatibilidad Clase II/inmunología , Glicoproteínas de Membrana/genética , Monocitos/inmunología , Receptores de Superficie Celular/genética , Superantígenos/inmunología , Regulación hacia Arriba/inmunología , Citocinas/inmunología , Bacterias Gramnegativas/inmunología , Bacterias Grampositivas/inmunología , Humanos , Inflamación/inmunología , Ligandos , Lipopolisacáridos/farmacología , Glicoproteínas de Membrana/inmunología , Monocitos/metabolismo , Receptores de Superficie Celular/inmunología , Receptor Toll-Like 4 , Receptores Toll-Like , Transcripción Genética/inmunología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA