Diagnostic accuracy of HMGB-1, sTREM-1, and CD64 as markers of sepsis in patients recently admitted to the emergency department.

OBJECTIVES: The objectives were to evaluate the diagnostic accuracy for sepsis in an emergency department (ED) population of the cluster of differentiation-64 (CD64) glycoprotein expression on the surface of neutrophils (nCD64), serum levels of soluble triggering receptor expressed on myeloid cells-1 (s-TREM-1), and high-mobility group box-1 protein (HMGB-1). METHODS: Patients with any of the following as admission diagnosis were enrolled: 1) suspected infection, 2) fever, 3) delirium, or 4) acute hypotension of unexplained origin within 24 hours of ED presentation. Levels of nCD64, HMGB-1, and s-TREM-1 were measured within the first 24 hours of the first ED evaluation. Baseline clinical data, Sepsis-related Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE II) score, daily clinical and microbiologic information, and 28-day mortality rate were collected. Because there is not a definitive criterion standard for sepsis, the authors used expert consensus based on clinical, microbiologic, laboratory, and radiologic data collected for each patient during the first 7 days of hospitalization. This expert consensus defined the primary outcome of sepsis, and the primary data analysis was based in the comparison of sepsis versus nonsepsis patients. The cut points to define sensitivity and specificity values, as well as positive and negative likelihood ratios (LRs) for the markers related to sepsis diagnosis, were determined using receiver operative characteristics (ROC) curves. The patients in this study were a prespecified nested subsample population of a larger study. RESULTS: Of 631 patients included in the study, 66% (95% confidence interval [CI] = 62% to 67%, n = 416) had sepsis according with the expert consensus diagnosis. Among these sepsis patients, SOFA score defined 67% (95% CI = 62% to 71%, n = 277) in severe sepsis and 1% (95% CI = 0.3% to 3%, n = 6) in septic shock. The sensitivities for sepsis diagnosis were CD64, 65.8% (95% CI = 61.1% to 70.3%); HMGB-1, 57.5% (95% CI = 52.7% to 62.3%); and s-TREM-1, 60% (95% CI = 55.2% to 64.7%). The specificities were CD64, 64.6% (95% CI = 57.8% to 70.8%), HMGB-1, 57.8% (95% CI = 51.1% to 64.3%), and s-TREM-1, 59.2% (95% CI = 52.5% to 65.6%). The positive LR (LR+) for CD64 was 1.85 (95% CI = 1.52 to 2.26) and the negative LR (LR-) was 0.52 (95% CI = 0.44 to 0.62]; for HMGB-1 the LR+ was 1.36 (95% CI = 1.14 to 1.63) and LR- was 0.73 (95% CI = 0.62 to 0.86); and for s-TREM-1 the LR+ was 1.47 (95% CI = 1.22 to 1.76) and the LR- was 0.67 (95% CI = 0.57 to 0.79). CONCLUSIONS: In this cohort of patients suspected of having any infection in the ED, the accuracy of nCD64, s-TREM-1, and HMGB-1 was not significantly sensitive or specific for diagnosis of sepsis.

New promising Euphorbiaceae extracts with activity in human lymphocytes from primary cell cultures.

CONTEXT: Euphorbiaceae plants exhibit anti-inflammatory and immunomodulatory properties. METHODS: We evaluated the activity of 14 extracts from seven Euphorbiaceae plants on primary immune cell cultures from healthy individuals. Peripheral blood mononuclear cells (PBMC) were exposed to the extracts w/o phytohaemagglutinin A or cycloheximide as agents that induce proliferation or apoptosis in PBMC, respectively. RESULTS: We found that five up to 14 Euphorbiaceae's extracts had the ability to modulate at least one of the immune parameters evaluated in this study. However, only the latex extracts of Euphorbia cotinifolia and Euphorbia tirucalli strongly induced both proliferation and apoptosis in PBMC. These extracts were further subfractioned by silica gel column chromatography. Two subfractions with enhanced activity in comparison to the crude extracts were obtained. Although these subfractions induced proliferation on both CD3(+) and CD3(-) cells, the most prominent effects were observed in the former subpopulation. Interestingly, the subfraction from E. tirucalli induced lymphocyte proliferation without the need of accessory cells; this ability was not inhibited by the carbohydrates d-galactose and α-Methyl-D-Mannopyranoside. CONCLUSIONS: Altogether, these results reveal the presence of novel candidates within the Euphorbia plants to induce proliferation and apoptosis in human lymphocytes, mainly in CD3(+) T cells.

Presencia de un polimorfismo de la CSP-12 relacionado consusceptibilidad a sepsis grave en una muestra de trespoblaciones colombianas / Presence of a polymorphism of the csp-12 related with susceptibility to severe sepsis in colombian individuals from three different populations

La sepsis, un síndrome de respuesta sistémica a la infección, es un problema de salud pública asociado a alta morbilidad y mortalidad alrededor del mundo. Entre los múltiples genes asociados a esta enfermedad se encuentra el gen que codifica para la caspasa-12 (csp-12), en el cual se ha identificado un polimorfismo de un sólo nucleótido (125T>C) en el exón 4 que predice una forma larga (L) de la proteína, que a su vez se ha asociado con riesgo de sepsis grave y alta mortalidad. Además, se ha demostrado que la frecuencia del alelo L es mucho mayor en poblaciones afroamericanas. Este estudio evalúa la presencia ó el polimorfismo 125T®C de la csp-12 en 128 individuos: 81 pacientes de Medellín con diagnóstico de sepsis, 23 individuos sanos de una población afroamericana del Chocó y24 individuos sanos provenientes de Medellín. En las tres poblaciones se encontraron 121 individuos homocigotos S/S (csp-12 corta) y 7 heterocigotos S/L discriminados así: 3 pacientes con diagnóstico de sepsis, 3 individuos afroamericanos y 1 de la población sana de Medellín. Nuestros resultados muestran que, a pesar de ser una muestra pequeña, en nuestra población existe el alelo L, encontrándose en mayor frecuencia en individuos afroamericanos y en una menor proporción en los mestizos, tanto pacientes como en los individuos sanos. Esto indica que la población afroamericana de Colombia podría tener mayor susceptibilidad a sepsis grave que las poblaciones mestizas, las cuales, se ha demostrado, son producto de mezcla europea, amerindia y africana, ésta última en una baja proporción. Por lo tanto, se deben efectuar estudios más amplios para un mejor entendimiento de las bases genéticas de la respuesta inmune de pacientes con sepsis, con el fin de diseñar terapias más racionales y personalizadas para prevenir este síndrome.

Sepsis, a syndrome of systemic response to infection is a major public health problem, because it is associated with high morbidity and mortality. Among the genes shown to be associated with this syndrome, there is one which encodes for caspase-12 (csp-12). Within this gene, the single nucleotide polymorphism 125T>C located in exon4, which predicts a long form of the protein, has been associated with severe sepsis and increased related mortality. On the other hand, higher frequency of allele L has been reported in African American populations. The present study evaluated the csp-12 polymorphism125T>C in 128 individuals: 81 patients with sepsis, 23 healthy African Colombian subjects and 24 healthy individuals from Medellin-Colombia. We found 121 individuals homozygous S/S (csp-12 short) in these three populations and 7 heterozygotes S/L, discriminated as follows: 3 septic patients, 3 African Colombians and 1 healthy subject from Medellin. This preliminary data suggest that the csp-12L allele is present in the Colombian population, both in African Colombians and Mestizo individuals (either septic patients or healthy individuals). Therefore, more comprehensive studies should be performed to better understand the genetic basis of the immune response of patients with sepsis in order to design more rational and personalized therapies to prevent this syndrome.