Identification of diagnostic biomarkers for infection in premature neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

Portuguese version of the Tilburg Frailty Indicator: Transcultural adaptation and psychometric validation

Artigo científico disponível actualmente em Early View (Online Version of Record published before inclusion in an issue)

Role of surgery in the management of brain arteriovenous malformations: prospective cohort study.

BACKGROUND AND PURPOSE: Management of brain arteriovenous malformation (bAVM) is controversial. We have analyzed the largest surgical bAVM cohort for outcome. METHODS: Both operated and nonoperated cases were included for analysis. A total of 779 patients with bAVMs were consecutively enrolled between 1989 and 2014. Initial management recommendations were recorded before commencement of treatment. Surgical outcome was prospectively recorded and outcomes assigned at the last follow-up visit using modified Rankin Scale. First, a sensitivity analyses was performed to select a subset of the entire cohort for which the results of surgery could be generalized. Second, from this subset, variables were analyzed for risk of deficit or near miss (intraoperative hemorrhage requiring blood transfusion of ≥2.5 L, hemorrhage in resection bed requiring reoperation, and hemorrhage associated with either digital subtraction angiography or embolization). RESULTS: A total of 7.7% of patients with Spetzler-Ponce classes A and B bAVM had an adverse outcome from surgery leading to a modified Rankin Scale >1. Sensitivity analyses that demonstrated outcome results were not subject to selection bias for Spetzler-Ponce classes A and B bAVMs. Risk factors for adverse outcomes from surgery for these bAVMs include size, presence of deep venous drainage, and eloquent location. Preoperative embolization did not affect the risk of perioperative hemorrhage. CONCLUSIONS: Most of the ruptured and unruptured low and middle-grade bAVMs (Spetzler-Ponce A and B) can be surgically treated with a low risk of permanent morbidity and a high likelihood of preventing future hemorrhage. Our results do not apply to Spetzler-Ponce C bAVMs.

Frailty, an Emerging Research and Clinical Paradigm: Issues and Controversies

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Statistiques appliquées en chirurgie cardiaque adulte : analyses de survie et applications du “propensity score”

L'objectif principal de ce travail est d’étudier en profondeur certaines techniques biostatistiques avancées en recherche évaluative en chirurgie cardiaque adulte. Les études ont été conçues pour intégrer les concepts d'analyse de survie, analyse de régression avec “propensity score”, et analyse de coûts. Le premier manuscrit évalue la survie après la réparation chirurgicale de la dissection aigüe de l’aorte ascendante. Les analyses statistiques utilisées comprennent : analyses de survie avec régression paramétrique des phases de risque et d'autres méthodes paramétriques (exponentielle, Weibull), semi-paramétriques (Cox) ou non-paramétriques (Kaplan-Meier) ; survie comparée à une cohorte appariée pour l’âge, le sexe et la race utilisant des tables de statistiques de survie gouvernementales ; modèles de régression avec “bootstrapping” et “multinomial logit model”. L'étude a démontrée que la survie s'est améliorée sur 25 ans en lien avec des changements dans les techniques chirurgicales et d’imagerie diagnostique. Le second manuscrit est axé sur les résultats des pontages coronariens isolés chez des patients ayant des antécédents d'intervention coronarienne percutanée. Les analyses statistiques utilisées comprennent : modèles de régression avec “propensity score” ; algorithme complexe d'appariement (1:3) ; analyses statistiques appropriées pour les groupes appariés (différences standardisées, “generalized estimating equations”, modèle de Cox stratifié). L'étude a démontrée que l’intervention coronarienne percutanée subie 14 jours ou plus avant la chirurgie de pontages coronariens n'est pas associée à des résultats négatifs à court ou long terme. Le troisième manuscrit évalue les conséquences financières et les changements démographiques survenant pour un centre hospitalier universitaire suite à la mise en place d'un programme de chirurgie cardiaque satellite. Les analyses statistiques utilisées comprennent : modèles de régression multivariée “two-way” ANOVA (logistique, linéaire ou ordinale) ; “propensity score” ; analyses de coûts avec modèles paramétriques Log-Normal. Des modèles d’analyse de « survie » ont également été explorés, utilisant les «coûts» au lieu du « temps » comme variable dépendante, et ont menés à des conclusions similaires. L'étude a démontrée que, après la mise en place du programme satellite, moins de patients de faible complexité étaient référés de la région du programme satellite au centre hospitalier universitaire, avec une augmentation de la charge de travail infirmier et des coûts.

La qualité des soins obstétricaux en milieu rural malien : une étude exploratoire

Afin d’améliorer la santé maternelle, il est essentiel de mettre en œuvre des interventions qui agissent sur la période intrapartum, interventions qui consistent essentiellement en l’amélioration de l’accès aux soins obstétricaux et néonataux d’urgence (SONU). Néanmoins, plusieurs pays qui se sont tournés vers ce type d’interventions rencontrent d’importants défis au niveau de leur implantation et les taux élevés de mortalité maternelle persistent. Cette étude vise à identifier des caractéristiques de structure et de processus dans les centres de santé communautaire (CSCOM) où des décès maternels ont eu lieu et de comparer ces caractéristiques avec celles de CSCOM où aucun décès maternel n’a eu lieu. Nous avons opté pour une démarche exploratoire comparative des groupes de CSCOM qui diffèrent de par les issues des parturientes qui y ont été traitées ainsi que par leur configuration en termes de ressources humaines. La population à l’étude correspond à des CSCOM de la région de Kayes dans lesquels ont été prises en charge des femmes qui ont fait face à des urgences obstétricales. Les ressources humaines, les ressources matérielles, les ressources en pharmacie et les connaissances des prestataires de soins de ces établissements constituent les principaux objets à l’étude. L’analyse de nos données montre qu’il existe de grandes disparités au niveau des ressources disponibles dans les CSCOM, ressources pourtant nécessaires à une prise en charge adéquate des urgences obstétricales. Bien qu’aucune caractéristique des CSCOM ne puisse être associée aux issues défavorables des femmes qui y ont été traitées, l’accumulation de déficits au niveau des ressources matérielles et humaines ainsi que le faible niveau de connaissances de certaines catégories de personnel laissent penser que la prise en charge des parturientes est déficiente au point de menacer leur survie.

Le remplacement valvulaire aortique chez le jeune adulte

Chez le jeune adulte, le substitut valvulaire aortique idéal demeure inconnu. La prothèse mécanique est durable. Cependant, elle requiert une anticoagulation à vie. De récentes études ont démontré un excès de mortalité à long terme chez les patients après un remplacement valvulaire aortique (RVA) mécanique. D’autres part, plusieurs patientes sont en âge de procréer lorsqu’une chirurgie est indiquée. La grossesse chez les patientes porteuses de RVA mécanique est à risque d’évènements thromboemboliques. Dans ce contexte, ces derniers sont mieux prévenus par la warfarine comparativement à l’héparine chez les patientes enceintes porteuses de prothèses mécaniques. Cependant, la warfarine est associée à des malformations fœtales. Les prothèses biologiques évitent l’anticoagulation. Par contre, la dégénérescence structurelle de la prothèse est plus rapide chez les patients jeunes, ce qui les expose à un haut risque de réintervention. L’objectif de ce mémoire est d’étudier les issues à long terme suivant un RVA chez le jeune adulte. Deux études ont été réalisées dans le cadre de ce travail. La première avait pour objectif de déterminer la survie et les complications à long terme dans une population de jeunes adultes ayant subi un RVA mécanique isolé. La survie de ce groupe de patient est inférieure à celle de la population générale québécoise appariée pour l’âge et le sexe. De plus, il existe un risque faible, mais constant à long terme de dysfonction de la prothèse et de réopération dans cette population. La deuxième étude a pour objectif de déterminer les complications cardiaques, maternelles et fœtales durant la grossesse chez des patientes porteuses de RVA mécanique ou biologique. Les résultats obtenus démontrent que la grossesse chez ces patientes est associée à un risque de complications maternelles et cardiaques significatives, et ce surtout chez les patientes porteuses d’une prothèse mécanique.

Resultado postnatal de fetos con malformación adenomatoide quística pulmonar en la unidad maternofetal Clínica Colombia

Introducción La Malformación Adenomatoide Quística Pulmonar es una patología que se desarrolla durante estadíos tempranos de desarrollo embriológico y su pronóstico depende del tamaño de la lesión pulmonar. Existen muy pocos estudios que caractericen esta patología, ninguno en nuestro país. Metodología Se realizó una serie de casos para describir el resultado postnatal de los casos registrados en la Clínica Colombia entre 2005 hasta 2013. Resultados: Se incluyeron un total de 20 casos. La malformación más frecuente fue MAQ III con 45% de los casos, de localización izquierda (75%), el 65% nacieron después de la semana 35 y con un peso mayor de 2500 g. Tan solo 30 % desarrollaron hidrops asociado. Hubo una mortalidad de 35% (7 casos). Discusion La MAQ es un patología infrecuente que genera una alta morbimortalidad en la vida perinatal. Se requieren estudios con muestras más amplias para determinar los factores pronósticos para la ocurrencia de los desenlaces adversos como la necesidad de cirugía de urgencia, deterioro respiratorio o mortalidad.

Comparación de cuatro escalas de riesgo en pacientes que consultaron por síncope al servicio de urgencias

Introducción: El síncope es un motivo frecuente de consulta en Urgencias, definir el estudio y el destino de estos pacientes es motivo de controversia. Se han diseñado varias escalas para estratificación del riesgo en pacientes con esta entidad. En este estudio se comparan las características operativas de 4 escalas para la decisión de hospitalizar pacientes con síncope que consultan a un servicio de urgencias de una institución de III y IV Nivel Métodos. Estudio analítico transversal, en el que se aplicaron las 4 escalas de riesgo a pacientes que consultaron por síncope al servicio de Urgencias durante un período de 6 meses y que fueron hospitalizados en la institución donde se realizó. Se evaluaron los resultados aplicando el programa Epidat 3.1 para sensibilidad y especificidad, índice de Youden. Resultados. Se incluyeron en total 91 pacientes. La sensibilidad de las escalas San Francisco, OESIL, EGSYS y la institucional para el requerimiento de hospitalización fue de 79%, 87%. 63% y 95% respectivamente y la especificidad fue de 52%, 40%, 64% y 14%. EL riesgo de mortalidad no fue adecuadamente detectado por la escala de San Francisco.. Conclusiones. Ninguna de las escalas aplicadas a los pacientes hospitalizados que consultaron por síncope a urgencias superó el juicio clínico para definir la hospitalización. Sin embargo, la escala OESIL y la institucional pueden ayudar a corroborar la decisión clínica de hospitalizar en esta población.

Factores asociados a tratamiento quirúrgico en pacientes con obstrucción intestinal por adherencias

El manejo de la obstrucción intestinal por adherencias es un reto para cualquier especialista en Cirugía debido a que existe controversia sobre el alcance del manejo médico y el momento adecuado para llevar el paciente a cirugía para la resolución del cuadro clínico. En el presente trabajo se pretende, identificar los factores asociados a tratamiento quirúrgico en pacientes con obstrucción intestinal por adherencias. Metodología: Se realizó un estudio de casos y controles en una relación de 1:1, con una recolección de muestra estadística de 48 pacientes en cada grupo, entre mayo 2012 y mayo 2014 en el Hospital Universitario Mayor Mederi y en Barrios Unidos. Se consideraron casos los pacientes intervenidos quirúrgicamente por obstrucción intestinal por bridas y controles los pacientes manejados con tratamiento médico. Se evaluaron factores como edad, antecedentes personales patológicos y quirúrgicos, tiempo de evolución del cuadro clínico, hallazgos en imágenes y laboratorio entre otros. Resultados: Se recolectaron un total de 158 pacientes, (78 casos, 80 controles). Ambas poblaciones fueron comparables (p=0.13). Los factores asociados a tratamiento quirúrgico estadísticamente significativos fueron género masculino, presencia de fiebre al ingreso, el hallazgo de engrosamiento de la pared intestinal y de obstrucción de asa cerrada en imágenes diagnósticas (p<0,05). Discusión: Los principales factores asociados para que un paciente con obstrucción intestinal por bridas requiera de manejo quirúrgico son consistentes con literatura. Se requiere la socialización de los resultados para disminuir la morbimortalidad de nuestros pacientes.

Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response

OBJECTIVE: The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. METHOD: Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. RESULTS: Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. CONCLUSIONS: These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.

Saúde física e emocional de cuidadores da cidade de Santa Cruz-RN: perfil epidemiológico e fatores associados

Taking care for an impaired elderly is a hard and costly task that could affect directly the caregiver health. The purpose of this study was to evaluate the physical and mental health of elderly caregivers from the city of Santa Cruz-RN and analyze the potential correlated factors through an observational analytic design of a crosssectional. A multidimensional questionnaire was used to evaluation of the social demographics characteristics and those related to the care activity, as well as the caregivers´ physical and mental health. It was realized a descriptive analyze using frequency distribution and measures of the central tendency and dispersion to description of the caregivers. To verify the magnitude of the association between the variables was used the bivariate analysis through the Pearson and Spearman correlations and qui-square test. To evaluation of the association of the correlated factors to the adverse outcome with the caregivers´ physical and mental health was made a multivariate analysis by logistic binary regression and multiple linear regression models. The final sample was constituted by 304 persons, mostly women with a mean age of 50.3 ±16.8 years. The principal factors related to the physical health were age, stress and life satisfaction. Be a male caregiver, caring for a little while the elderly with cognitive deficit and not been spouse were related to worse mental health. Have worse physical health, high stress, depressive symptomatology, burden and low levels of satisfaction were also related to the mental health. After adjust through multiple linear regression was observed R2 values of R2=0,21 for Stress, R2 =0,17 for Depressive Symptomatology, R2 =0,21 for Burden and R2 =0,16 for Satisfaction. The attainment of the factors associated with caregiver´s health can help in the elaboration of specifics politics witch the goal is the integral attention to the elderly and his caregiver. The inability of continuous taking care could result in adverse outcomes such as institutionalization, impairment and death

Velocidade da marcha como preditor de fragilidade em uma amostra populacional de idosos brasileiros

Gait speed has been described as a predictive indicator of important adverse outcomes in older populations. Among the criteria to evaluate frailty, gait speed has been identified as the most reliable predictor of fragility, practical and low cost. Objective: This study assesses the discriminating capability of gait speed in determining the presence of fragility in the elderly community in northeast of Brazil. Method: We performed an observational analytic study with a transversal character with a sample of 391 community-living elders, aged 65 years or older, of both sexes, in the city of Santa Cruz-RN. Participants were interviewed using a multidimensional questionnaire to obtain sociodemographic information, physical-related and mental health-related information. The unintentional weight loss, muscle weakness, self-reported exhaustion, slow gait and low-physical activity were considered to evaluate the frailty syndrome. Gait velocity was measured as the time taken to walk the middle 4,6 meters of 8,6 meters (excluding 2 meters to warm-up phase and 2 meters to deceleration phase).We calculate the sensitivity and specificity of gait speed test in different cutoff points for the test run time, from which ROC curve was constructed as a measure of test predictive value to identify frail elders. The prevalence of frailty in Santa Cruz-RN was 17.1%. The gait speed test accuracy was 71%when speed is below 0,91m/s. Among women, the gait speed test accuracy was 80%(gait speed below 0.77m/s) and among men, the test accuracy was 86% (gait spend below 0,82%) (p<0,0001).Conclusion: our findings have clinical relevance when we consider that the detection of frailty presence by the gait speed test can be observed in elderly men and women by a simple, cheap and efficient exam

Glargine vs. NPH insulin therapy in pregnancies complicated by diabetes: An observational cohort study

Aims: The effects of glargine insulin therapy in pregnancies are not well established. We compared maternal and neonatal outcomes of women with pregestational and gestational diabetes treated with glargine or NPH insulin.Methods: A prospective cohort study was conducted analyzing outcomes from 56 women with pregestational and 82 with gestational diabetes treated with either insulin regimen.Results: Comparisons were performed among 138 women: 56 with pregestational and 82 with gestational diabetes. In relation to maternal complications, worsening of retinopathy and nephropathy, preeclampsia, micro and macroalbuminuria, and all kinds of hypoglycemia were found higher in women with pregestational diabetes NPH-treated vs. glargine-treated. In women with gestational diabetes NPH-treated, it was observed increased incidence of prepregnancy and new-onset pregnancy hypertension, micro and macroalbuminuria, as well as mild and frequent hypoglycemia, compared to glargine-treated. Among the neonatal outcomes, 1-min Apgar score <7, necessity of intensive care unit and fetal death in pregestational, while jaundice and congenital malformations in gestational diabetes, respectively, were more frequently observed in infants born to NPH-treated, compared to glargine-treated.Conclusions: Glargine use during pregnancy from preconception through delivery, showed to be safe since it is associated with decreased maternal and neonatal adverse outcomes compared with NPH insulin-treated patients. (C) 2010 Elsevier B.V. All rights reserved.

Association between different levels of dysglycemia and metabolic syndrome in pregnancy

Background: In this study, we sought to evaluate the prevalence of metabolic syndrome (MS) in a cohort of pregnant women with a wide range of glucose tolerance, prepregnancy risk factors for MS during pregnancy, and the effects of MS in the outcomes in the mother and in the newborn.Methods: One hundred and thirty six women with positive screening for gestational diabetes mellitus (GDM) were classified by two diagnostic methods: glycemic profile and 100 g OGTT as normoglycemic, mild gestational hyperglycemic, GDM, and overt GDM. Markers of MS were measured between 2428(th) during the screening.Results: The prevalence of MS was: 0%; 20.0%; 23.5% and 36.4% in normoglycemic, mild hyperglycemic, GDM, and overt GDM groups, respectively. Previous history of GDM with or without insulin use, BMI >= 25, hypertension, family history of diabetes in first degree relatives, non-Caucasian ethnicity, history of prematurity and polihydramnios were statistically significant prepregnancy predictors for MS in the index pregnancy, that by its turn increased the adverse outcomes in the mother and in the newborn.Conclusion: The prevalence of MS increases with the worsening of glucose tolerance; impaired glycemic profile identifies pregnancies with important metabolic abnormalities even in the presence of a normal OGTT, in patients that are not classified as having GDM.