RESUMO
OBJECTIVES: Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis. DESIGN: Cohort study. SETTING: The medical and surgical ICUs at an academic medical center. SUBJECTS: We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy. INTERVENTIONS: We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve. MEASUREMENTS AND MAIN RESULTS: Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ≤ 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve > 0.76 for 14-d and 0.74 for total mortality). CONCLUSIONS: Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.
Assuntos
Estado Terminal/mortalidade , Sepse/mortalidade , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Coortes , Ferritinas/sangue , Fibrinogênio/análise , Haptoglobinas/análise , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pró-Calcitonina/sangue , Sepse/sangue , Sepse/diagnóstico , Proteína Amiloide A Sérica/análise , Componente Amiloide P Sérico/análise , Ativador de Plasminogênio Tecidual/sangue , alfa-Macroglobulinas/análiseRESUMO
Research use only (RUO) assays do not undergo a validation process similar to test kits used for clinical purposes. Several studies have suggested that RUO assays need to be validated prior to use in any research studies. We evaluated a research use only Luminex platform based assay for measuring serum procalcitonin levels (Bio-Plex ProTM Human Acute Phase Multiplex Assay, Bio-Rad Laboratories, Hercules, CA) for comparability with an FDA cleared assay for procalcitonin (VIDAS B.R.A.H.M.S. PCT Assay, bioMérieux, Durham, NC). We tested 1,072 serum samples collected from patients with suspected sepsis in an intensive care unit setting for the comparison. There was poor correlation of the luminex based assay (r=0.081) with the VIDAS PCT Assay in the clinically relevant measurement range (<10 ng/mL). Additionally the Bio-Plex assay showed poor precision. Mass-spectrometry analysis of material eluted from PCT beads did not reveal any identifiable procalcitonin. The results show that research use only assays need to be validated to determine their suitability for research studies.
RESUMO
BACKGROUND: We evaluated the importance of measuring early vaginal levels of eight bacterial vaginosis (BV)-associated bacteria, at two points in pregnancy, and the risk of spontaneous preterm delivery (SPTD) among pregnant women and the subgroup of pregnant women with a history of preterm delivery (PTD). METHODS: This prospective cohort study enrolled women at five urban obstetric practices at Temple University Hospital in Philadelphia PA. Women with singleton pregnancies less than 16 weeks gestation self-collected vaginal swabs at two points in pregnancy, prior to 16 weeks gestation and between 20-24 weeks gestation, to measure the presence and level of eight BV-associated bacteria. Women were followed-up for gestational age at delivery via medical records. RESULTS: Among women reporting a prior PTD, women with higher levels of Leptotrichia/Sneathia species, BVAB1 and Mobiluncus spp., prior to 16 weeks gestation, were significantly more likely to experience a SPTD. In addition, pregnant women with a prior PTD and increasing levels of Leptotrichia/Sneathia species (aOR: 9.1, 95% CI 1.9, 42.9), BVAB1 (aOR: 16.4, 95% CI 4.3, 62.7) or Megasphaera phylotype 1 (aOR: 6.2, 95% CI 1.9, 20.6), through 24 weeks gestation, were significantly more likely to experience an SPTD. Among the overall group of pregnant women, the levels of BV-associated bacteria were not related to SPTD. CONCLUSION: Among the group of women reporting a prior PTD, increasing levels of BVAB1, Leptotrichia/Sneathia species, and Megasphaera phylotype 1, through mid-pregnancy were related to an increased risk of SPTD.