Fiabilidad de los biomarcadores procalcitonina y proteína C reactiva para diferenciar el origen vírico o bacteriano de las infecciones pediátricas / Limits of biomarkers C-reactive protein and procalcitonin to differentiate between bacterial and viral infections in hospitalized children

INTRODUCCIÓN: La patología infecciosa es un motivo de consulta muy frecuente. Distinguir entre infecciones bacterianas y víricas es un reto que ocasiona tratamientos antibióticos inapropiados. Nuestro objetivo fue estudiar la fiabilidad de la PCT, la PCR y el recuento de leucocitos y neutrófilos totales para diferenciar infecciones en pacientes hospitalizados. MÉTODOS: Estudio retrospectivo unicéntrico en el que se revisaron las historias clínicas de los mayores de 3 meses ingresados con infección confirmada por cultivo o PCR viral, desde el 1 de enero hasta el 31 de diciembre de 2016 en el servicio de pediatría de un hospital de primer nivel. Se dividieron en función de si la etiología comprobada de su infección era bacteriana o vírica. RESULTADOS: Se identificaron 328 pacientes, con una media de edad de 2,3 años y DE= 3,5; el 40,2% presentó una infección bacteriana y el 59,8% una vírica. Los primeros presentaron cifras mayores de leucocitos, neutrófilos totales, PCR y PCT que los segundos, con diferencias estadísticamente significativas (p <0,05). En las curvas ROC del modelo predictivo, el ABC para leucocitos fue de 0,58, neutrófilos 0,55, PCR 0,6 y PCT 0,59. Con la regresión logística se obtuvieron unas fórmulas de predicción de infección bacteriana significativas combinando valores de PCR y leucocitos en sangre pero con una R cuadrado de 0,107 y un ABC de 0,665. Se evaluaron las pruebas diagnósticas para niveles de PCR superiores a 7 mg/dL con una sensibilidad del 49%, una especificidad del 77%, un VPP del 56% y un VPN del 69%. CONCLUSIONES: Los instrumentos analíticos de la práctica clínica habitual son poco fiables para distinguir entre infecciones bacterianas y víricas. Sería recomendable elaborar modelos predictivos que tengan en cuenta valores analíticos y clínicos. Será útil el empleo de técnicas diagnósticas como la PCR para virus respiratorios

INTRODUCTION: Infectious pathology is a common cause of paediatric consultations. The aim of this study was to analyse the usefulness of CRP, PCT levels, leukocytes and absolute neutrophils counts, to differentiate between bacterial and viral infections in hospitalized children, with the purpose of avoiding a high percentage of unnecessary antibiotic prescriptions. METHODS: A retrospective study was conducted on children older than 3 months, admitted to the hospital paediatric service, with confirmed infection by positive culture or viral CRP. We reviewed the data of the clinical histories from January 1 to December 31, 2016. Patients were divided into two groups depending on whether the proven aetiology of their infection was bacterial or viral. RESULTS: A total of 328 patients were included, with a mean age of 2.3 years, SD= 3,5, of which 40.2% had a confirmed bacterial infection and 59.8% had a viral infection. Patients with confirmed bacterial infection had higher levels of leukocytes, total neutrophils, CRP and PCT than patients with viral infections, there being statistically significant differences in these variables (p <0.05). Regarding the ROC curves performed in the predictive model, the AUC for leukocytes was 0.58, for neutrophils 0.55, for CRP 0.6 and for PCT 0.59. With the logistic regression, some prediction formulas for bacterial infection were obtained that were only significant combining the values of CRP and leukocytes in blood, but with a coefficient of determination (r2) of 0.107 and an AUC of 0.665. Diagnostic tests were also evaluated for CRP levels higher than 7 mg/dL with a sensitivity of 49%, a specificity of 77%, as well as a PPV of 56% and a NPV of 69%. CONCLUSIONS: The analitic techniques used in the routine clinical practice are unreliable to distinguish between bacterial and viral infections. Therefore, it would be advisable to develop predictive models of bacterial infection that take into account both analytical and clinical values. It would also be useful to use, in routine clinical practice, diagnostic techniques such as CRP for respiratory viruses

Involvement of corticotropin-releasing hormone and endogenous opioid peptides in prolactin-suppressed gonadotropin-releasing hormone release in vitro.

Corticotropin-releasing hormone (CRH) has been shown capable of inhibiting hypothalamic gonadotropin-releasing hormone (GnRH) release through activation of an endogenous opioid peptide (EOP)-dependent mechanism. Recently, we have shown that prolactin (PRL) stimulates CRH release and inhibits GnRH release by hypothalami explanted from male rats. Thus, the present study was undertaken to investigate whether the inhibitory effect of PRL on GnRH release in vitro is mediated by CRH and/or EOP. To this aim, the release of GnRH in response to PRL was evaluated in presence of CRH9-41 alpha-helical (CRH-9-41), a CRH receptor antagonist, and/or naloxone (NAL), a nonselective opioid receptor antagonist, using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated longitudinally halved hypothalamic. As previously shown, PRL at the concentration of 100 nmol/l inhibited basal iGnRH release by about 35%. CRH9-41 or NAL overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. The simultaneous co-incubation with both antagonists was not more effective than each single antagonist. CRH9-41 did not have any effect on basal iGnRH release whereas NAL, as previously reported, increased it. In addition, PRL at the concentration of 100 nmol/l stimulated basal hypothalamic beta-endorphin (beta-EP) release. In conclusion, these data show that antagonism to CRH receptors counteracts the suppressive effects of PRL upon GnRH release and that PRL is able to stimulate hypothalamic beta-EP release in vitro.

Effects of endothelin-1 and endothelin-3 on rat hypothalamic corticotrophin-releasing hormone and pituitary ACTH release in vitro.

Endothelins (ETs) are potent vasoconstrictor peptides that also participate in the regulation of endocrine function. Indeed, immunoreactive ET, ET mRNA and ET receptors have been found in the brain and the pituitary gland and ETs stimulate arginine vasopressin, LH, FSH, TSH and gonadotrophin-releasing hormone and inhibit prolactin release in vitro. The present study was undertaken to evaluate the effects of ET-1 and ET-3, two members of this family, on corticotrophin-releasing hormone (CRH) release by explanted male rat hypothalami in vitro and on ACTH release by primary pituitary cell culture. ET-3 decreased basal CRH release in a concentration-related manner. The lowest effective concentration tested was 3 nmol/l but a more pronounced inhibitory effect was obtained at a concentration of 10 nmol/l. On the other hand, ET-1 did not have any detectable effect on basal CRH release. Neither ET-1 nor ET-3 had any effect on the release of CRH stimulated by potassium chloride. ET-1 increased basal ACTH release, whereas ET-3 did not have any effect. Both ET-1 and ET-3 suppressed the release of ACTH stimulated by 1 nmol CRH/l. These data suggest that both ET-1 and ET-3 are able to modulate the hypothalamic-pituitary-adrenal axis function in vitro. However, they act at different levels and seem to have opposite effects. Indeed, while ET-1 stimulated pituitary ACTH release, ET-3, the peptide produced mainly in the brain, inhibited hypothalamic CRH release in vitro.

Luteinizing hormone-releasing hormone (LHRH) agonist restoration of age-associated decline of thymus weight, thymic LHRH receptors, and thymocyte proliferative capacity.

The presence of specific LHRH-binding sites within the rat thymus gland and the ability of LHRH and its agonistic and antagonistic analogs to directly modulate thymus function prompted us to study the possible changes in the number of thymic LHRH-binding sites during aging-induced physiological immunosenescence. Moreover, the effects of chronic treatment of aging rats with a potent LHRH agonist (LHRH-A) on thymic LHRH receptors, thymus weight and histology, as well as thymocyte proliferative capacity were assessed. For comparison, the effects of castration on the same parameters was also investigated. The process of aging is accompanied by a sharp reduction in LHRH-A-binding sites within the thymus gland of both female and male rats. Starting at 7 months of age, a 50% decrease in thymic LHRH-A binding was followed, at 11-13 months of age, by a nearly 65% inhibition of receptor numbers. In 16- to 19-month-old rats, LHRH-A binding was almost completely lost. Thymus weight was 30% reduced in 7-month-old animals, while a 50% reduction in thymic size was reached at 11 months of age in males and 13 months in female rats. A further decrease in thymic mass was observed at 16 and 19 months. Chronic (45-day) treatment of aging (15-16 months old) female and male rates with the potent LHRH-A, [D-Trp6,Des-Gly10]LHRH-N-ethylamide, reversed the age-related decreases in both thymus weight and thymic LHRH-binding sites. Similarly, surgical removal of testicular hormones by castration restored thymus weight and increased LHRH-A binding in the thymus of aged rats. While thymus histology in 3-month-old rats was characterized by a clear demarcation of cortical and medullary regions, only thymic remnants were present in 16- to 17-month-old animals. Castration of old rats resulted in a partial restoration of thymic structure, while chronic treatment of aging rats with the LHRH-A produced a homogeneous organization of both cortical and medullary compartments accompanied by a marked increase in the width of the cortical layer, densely packed with lymphocytes. While the process of aging was accompanied by an almost complete loss of the proliferative response of thymocytes to optimal concentrations of the mitogen Concanavalin-A, thymocyte cultures from old rats treated with LHRH-A or from castrated animals, displayed significantly greater proliferative responses. Furthermore, the combination of both manipulations resulted in a further significant increase in thymocyte proliferative capacity.(ABSTRACT TRUNCATED AT 400 WORDS)