CSV-ARG, Estudio multi-céntrico de validación de una escala de detección temprana de deterioro en pacientes internados / CSV-ARG, multicenter study of validation of an early detection scale of deterioration in hospitalized patients

Introducción: La detección precoz de un paciente con riesgo de deterioro, y la intervención temprana por un equipo de salud competente en el manejo de la vía aérea ha demostrado reducir la mortalidad intrahospitalaria. El NEWS (National Early Warning Score, Reino Unido) clasifica a los pacientes según su probabilidad de deterioro dentro de las siguientes doce horas; en baja (0-1), moderada (2-4) y alta posibilidad de deterioro (5-13), a partir de cuatro signos vitales: frecuencias cardíaca y respiratoria, temperatura y presión arterial sistólica sumados a la saturación de oxígeno y el estado de conciencia. Fue generada a partir de una gran base de datos de signos vitales obtenidos de manera electrónica en pacientes internados en Inglaterra. En las instituciones de nuestro país, los signos vitales son tomados manualmente y hay una percepción generalizada de que estos o "están mal tomados" o no se los ubica dentro del centro de la toma de decisiones. Objetivos: El objetivo de este estudio fue, a partir de signos vitales tal como se toman en nuestro medio, realizar una validación de la capacidad de discriminación de la escala NEWS de eventos severos durante la internación. Diseño, materiales y métodos: Ocho instituciones de la ciudad de Buenos Aires y del área metropolitana participaron recolectando de manera consecutiva los seis parámetros vitales que componen la escala NEWS en los pacientes internados, tal como se toman en las salas de internación, además de datos demográficos, presencia de comorbilidades, eventos de gravedad durante la internación como sepsis, trombo embolismo de pulmón, shock hipovolémico, distrés respiratorio, insuficiencia respiratoria, trastorno de la conciencia y muerte sin evento previo. Los datos se ingresaron a una base de datos virtual calculándose el puntaje de la escala NEWS. Se analiza en este primer trabajo las características de la población con medidas de tendencia central y de dispersión estándares según la distribución de los valores. Mediante regresión logística se analizó la capacidad del primer NEWS al ingreso de predecir un evento independientemente de la edad, el sexo y la presencia de comorbilidades. Resultados: Entre el 1 de enero de 2015 hasta el 31 de julio ingresaron en el estudio 1705 pacientes de nueve Instituciones del área metropolitana, 869 eran mujeres (51%), rango de edad 18 a 100. Un 10% de los pacientes presentó algún evento grave, y la mortalidad global fue de 3,5%. El 90% de los pacientes fue clasificado al ingreso como NEWS de bajo grado de deterioro (0-4), el 5% riesgo moderado (5-6) y el 5% de riesgo alto (mayor a 7). El valor de NEWS, al ingreso de la internación y tal como se toman los signos vitales en nuestro medio, predice el riesgo de presentar un evento severo durante la internación, independientemente de la edad, sexo y la presencia de comorbilidades. Discusión: En este estudio pudimos demostrar que los signos vitales, tomados de manera manual calculando la escala NEWS, es un excelente predictor de la ocurrencia de eventos durante la internación. En próximos análisis evaluaremos la capacidad de discriminación y la capacidad de predecir eventos entre 12 y 24 horas posteriores a la toma. (AU)

Background: Early warning scores at hospital settings have shown to reduce hospital mortality. The NEWS (National Early Warning Score, UK), classifies patients as per their risk to deteriorate in three categories, low risk (0-2), moderate risk (3-4) and high risk (5-13). The scale uses four vital signs, heart rate, respiratory rate, temperature and systolic arterial pressure, plus oxygen saturation and conscious state. It was developed and validated using a large database of electronic captured vital signs in England. In Argentina, most of the vital signs are taken manually. (AU)

The role of Toll-like receptor 4 polymorphisms in vaccine immune response.

Toll-like receptors (TLRs) are a class of pattern recognition receptors that are deputed to recognise a range of molecular structures in pathogens. One of the most studied members of this family is the TLR4, which is essential for the signalling of lipopolysaccharide. The gene encoding for TLR4 is highly polymorphic and this genetic variability may explain in part the interindividual variability observed in several clinical setting, including the response to vaccination. Herein, we review and systematise the available scientific evidence about the effect of TLR4 polymorphisms on vaccine response, including approved prophylactic, new therapeutic cancer vaccines and recently approved vaccine adjuvants. Data reviewed in this analysis indicate that TLR4 polymorphisms significantly affect vaccine response. If these results are confirmed by further analyses, the use of these genetic biomarkers may become a useful tool to tailor vaccination in specific subsets of patients.

A de novo 11p13 Microduplication in a Patient with Some Features Invoking Silver-Russell Syndrome.

Patients with Silver-Russell syndrome (SRS) show an intrauterine and postnatal growth restriction associated with a variable spectrum of additional features. Genetic or epigenetic alterations on chromosomes 7 and 11 can be detected in several SRS patients; however, a large fraction of cases remains with unknown genetic etiology. Here, we describe the clinical and molecular findings of a patient with a phenotype invoking SRS showing intrauterine and postnatal growth retardation, psychomotor retardation, relative macrocephaly, slightly triangular face with pointed chin, clinodactyly, and a slight body asymmetry, in whom single-nucleotide polymorphism oligonucleotide array analysis led to the identification of a de novo 11p13 duplication containing many genes that could be functionally related with the observed clinical features. Many deletions of chromosome 11p13, resulting in WAGR (Wilms tumor, aniridia, genital anomalies, mental retardation) syndrome, have been described, while only few duplications spanning the same region have been reported so far. To our knowledge, this is the first reported case presenting a SRS carrier of an 11p13 duplication. We propose candidate genes for the observed traits, and in particular, we discuss the possible role of the involvement of 2 noncoding RNAs in the etiology of the phenotype.

Acid sphingomyelinase determines melanoma progression and metastatic behaviour via the microphtalmia-associated transcription factor signalling pathway.

Melanoma is a rapidly growing and highly metastatic cancer with high mortality rates, for which a resolutive treatment is lacking. Identification of novel therapeutic strategies and biomarkers of tumour stage is thus of particular relevance. We report here on a novel biomarker and possible candidate therapeutic target, the sphingolipid metabolising enzyme acid sphingomyelinase (A-SMase). A-SMase expression correlates inversely with tumour stage in human melanoma biopsies. Studies in a mouse model of melanoma and on cell lines derived from mouse and human melanomas demonstrated that A-SMase levels of expression actually determine the malignant phenotype of melanoma cells in terms of pigmentation, tumour progression, invasiveness and metastatic ability. The action of A-SMase is mediated by the activation of the extracellular signal-regulated kinase, the subsequent proteasomal degradation of the Microphtalmia-associated transcription factor (Mitf) and inhibition of cyclin-dependent kinase 2, Bcl-2 and c-Met, downstream targets of Mitf involved in tumour cell proliferation, survival and metastatisation.

Oestrogens for preventing recurrent urinary tract infection in postmenopausal women.

BACKGROUND: Recurrent urinary tract infection (RUTI) is defined as three episodes of urinary tract infection (UTI) in the previous 12 months or two episodes in the last six months. The main factors associated with RUTI in postmenopausal women are vesical prolapse, cystocoele, post-voidal residue and urinary incontinence, all associated with a decrease in oestrogen. The use of oestrogens to prevent RUTI has been proposed. OBJECTIVES: To estimate the efficacy and safety of oral or vaginal oestrogens for preventing RUTI in postmenopausal women. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1950), EMBASE (from 1980), reference lists of articles without language restriction. Date of last search: February 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which postmenopausal women (more than 12 months since last menstrual period) diagnosed with RUTI received any type of oestrogen (oral , vaginal) versus placebo or any other intervention were included. DATA COLLECTION AND ANALYSIS: Authors extracted data and assessed quality. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Nine studies (3345 women) were included. Oral oestrogens did not reduce UTI compared to placebo (4 studies, 2798 women: RR 1.08, 95% CI 0.88 to 1.33). Vaginal oestrogens versus placebo reduced the number of women with UTIs in two small studies using different application methods. The RR for one was 0.25 (95% CI 0.13 to 0.50) and 0.64 (95% CI 0.47 to 0.86) in the second. Two studies compared oral antibiotics versus vaginal oestrogens (cream (1), pessaries (1)). There was very significant heterogeneity and the results could not be pooled. Vaginal cream reduced the proportion of UTIs compared to antibiotics in one study and in the second study antibiotics were superior to vaginal pessaries. Adverse events for vaginal oestrogens were breast tenderness, vaginal bleeding or spotting, nonphysiologic discharge, vaginal irritation, burning and itching. AUTHORS' CONCLUSIONS: Based on only two studies comparing vaginal oestrogens to placebo, vaginal oestrogens reduced the number of UTIs in postmenopausal women with RUTI, however this varied according to the type of oestrogen used and the treatment duration.

Duplications in addition to terminal deletions are present in a proportion of ring chromosomes: clues to the mechanisms of formation.

BACKGROUND AND METHODS: Ring chromosomes are often associated with abnormal phenotypes because of loss of genomic material at one or both ends. In some cases no deletion has been detected and the abnormal phenotype has been attributed to mitotic ring instability. We investigated 33 different ring chromosomes in patients with phenotypic abnormalities by array based comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH). RESULTS: In seven cases we found not only the expected terminal deletion but also a contiguous duplication. FISH analysis in some of these cases demonstrated that the duplication was inverted. Thus these ring chromosomes derived through a classical inv dup del rearrangement consisting of a deletion and an inverted duplication. DISCUSSION: Inv dup del rearrangements have been reported for several chromosomes, but hardly ever in ring chromosomes. Our findings highlight a new mechanism for the formation of some ring chromosomes and show that inv dup del rearrangements may be stabilised not only through telomere healing and telomere capture but also through circularisation. This type of mechanism must be kept in mind when evaluating possible genotype-phenotype correlations in ring chromosomes since in these cases: (1) the deletion may be larger or smaller than first estimated based on the size of the ring, with a different impact on the phenotype; and (2) the associated duplication will in general cause further phenotypic anomalies and might confuse the genotype-phenotype correlation. Moreover, these findings explain some phenotypic peculiarities which previously were attributed to a wide phenotypic variation or hidden mosaicism related to the instability of the ring.

Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy.

BACKGROUND: Knee arthroscopy is a frequent surgical procedure. Arthroscopy procedures are considered minimally invasive. However, some patients will need extended surgical time, suffer injury and immobilization thus increasing the risk for thromboembolic events. Incidence of deep venous thrombosis (DVT) in patients undergoing knee arthroscopy is reported to be from 0.6% to 17.9% depending on the diagnostic method used. Different approaches are available for thromboprophylaxis (mechanical or pharmacological). OBJECTIVES: To assess the effectiveness and safety of thromboprophylaxis to reduce the incidence of DVT in patients undergoing knee arthroscopy. SEARCH STRATEGY: We searched the Cochrane Peripheral Vascular Diseases Group Specialized Register (last searched October 2006) the CENTRAL (last searched Issue 4, 2006), MEDLINE (1966 to 2006), EMBASE (1980 to 2006), and Lilacs (1988 to 2006). We contacted specialists known to be involved in phlebology and interested in post thrombotic syndrome for details of unpublished and ongoing trials. SELECTION CRITERIA: Randomized clinical trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not (i.e. double blinded, single blinded or unblinded) of all type of interventions, whether mechanical or pharmacological, single or in combination, used to prevent DVT in males and females over 18 years old undergoing knee arthroscopy. There was no restriction on language. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Four trials involving 527 predominantly male participants were included. The main weakness of the studies was the lack of correct stratification of the arthroscopic intervention. The relative risk (RR) of thrombotic events was 0.20 (95% confidence interval (CI); 0.07 to 0.57) comparing any type of low molecular weight heparin (LMWH) versus placebo. All thrombotic events but one (pulmonary embolism in the LMWH group) were distal venous thrombosis. Adverse events were most common in the intervention group than in the control group, RR 2.11 (95% CI 1.26 to 3.55). There were 66 episodes of adverse events. The number needed to harm was 20 for any adverse events. AUTHORS' CONCLUSIONS: This meta-analysis suggests that LMWH reduces the incidence of distal DVT diagnosed by sonogram. The clinical benefit of this is uncertain. No strong evidence was found to conclude thromboprophylaxis is effective to prevent thromboembolic events and safe, in people with unknown risk factors for thrombosis, undergoing knee arthroscopy.

Cyclic GMP-dependent inhibition of acid sphingomyelinase by nitric oxide: an early step in protection against apoptosis.

Activation of acid and neutral sphingomyelinases, and the ensuing generation of ceramide, contributes to the biological effects of tumour necrosis factor-alpha (TNF-alpha), one of which is apoptosis. While the mechanisms of activation of sphingomyelinases by the cytokine are being unravelled, less is known about regulation of their activity. Nitric oxide has previously been shown to exert a cyclic GMP-dependent inhibition of early apoptotic events triggered by TNF-alpha in the U937 monocytic cell line. We therefore investigated whether inhibition of sphingomyelinases by nitric oxide plays a role in regulating such early events. We found that activation of both acid and neutral sphingomyelinases, triggered in the first minutes after U937 cell stimulation with TNF-alpha, is regulated in an inhibitory fashion by nitric oxide, working through generation of cyclic GMP and activation of protein kinase G. Using a range of inhibitors selective for either sphingomyelinase we found that the acid sphingomyelinase contributes to activation of the initiator caspase-8 and early DNA fragmentation and that inhibition of the acid enzyme by nitric oxide accounts for cyclic GMP-dependent early protection from apoptosis. We also found that the protective effect by both cGMP and acid sphingomyelinase inhibitors progressively disappeared at later stages of the apoptotic process. Inhibition of sphingomyelinases represents a novel action of nitric oxide, which might be of physiological relevance in regulating initial phases of apoptosis as well as other biological actions of ceramide.

Secreted heat shock proteins in sunflower suspension cell cultures.

Sunflower suspension cell cultures were subjected to different heat treatments and the electrophoretic patterns of heat-induced endocellular and secreted proteins were analyzed. In response to heat shock (3 h at 40°C), sunflower cells synthesized new polypeptides and secreted them into the medium, while the synthesis of other polypeptides was suppressed. Two major polypeptides of about 50 and 32 kDa were strongly induced. The two-dimensional electrophoretic analysis showed that the 32-kDa band is composed of at least four different polypeptides. Western blotting hybridizations of secreted proteins with various lectins were performed. The 32-kDa band gave a positive signal with concanavalin A.

Identification, characterization, and analysis of cDNA and genomic sequences encoding two different small heat shock proteins in Hordeum vulgare.

In vitro translation of mRNAs prepared from barley (Hordeum vulgare) seedlings (cv. Onice) exposed at 40 degrees C directed the synthesis of major heat shock proteins (HSPs) with molecular masses of 80-90, 70, 42 and 16-22 kDa. A cDNA library prepared from the 40 degrees C mRNAs and screened by differential hybridization led to the isolation of heat shock specific sequences. One of these (Hv hsp18) was confirmed by hybrid-arrested and hybrid-released translation as encoding for an 18-kDa HSP. The barley hsp18 sequence has an open reading frame encoding a 160 amino acid residue 18-kDa protein that is 63% identical to wheat 16.9-kDa HSP (clone C5-8), 54% identical to soybean (Glycine max) 17.5-kDa HSP, and 49% identical to Arabidopsis thaliana 17.6-kDa HSP. Lower similarities were found with class II plant small HSPs such as soybean 17.9-kDa HSP (27%), Pisum sativum 17.7-kDa HSP (30%), wheat (Triticum aestivum) 17.3-kDa HSP (clone Ta hsp 17.3) (30%), and with animal small HSPs and alpha-crystallins. The Hv hsp18 sequence was used to pick up Hv hsp17 genomic sequence encoding for another class I 17-kDa HSP. By computer analysis of the nucleotide sequence the TATA box, two heat shock promoter elements, a metal-ion response element, and the polyadenylation signals were identified. Barley HSP18 has an additional cysteine-rich region when compared with HSP17 mapping at the carboxy terminal end.

c-myc oncogene alterations in human thyroid carcinomas.

A possible role of the c-myc oncogene in the neoplastic transformation of the human thyroid has been investigated. The structure, the methylation status, and the copy number of this oncogene have been analyzed in normal and in tumor thyroid DNAs by Southern blotting technique and dot blot hybridization. Among six carcinomas, four presented abnormal c-myc DNA structure: Three cases showed a mutation in the 5' flanking region of the gene, originating a new EcoRI site; the other case showed a deletion of 5 kb involving the first exon of the gene. This deletion was also observed in the white blood cells of the same individual. In addition, in three carcinomas a double dose of the oncogene has been demonstrated. In all the carcinomas examined, undermethylation of the c-myc oncogene has been observed. These findings suggest that c-myc oncogene alterations might be involved in the malignant transformation of the human thyroids and can be considered as tumor markers.

[Globin synthesis in erythroid cultures from normal and thalassemic subjects]. / Studi globino-sintetici in colture eritroidi di cellule normali e talassemiche.

Relative alpha and beta chain synthesis in erythroid bursts derived from human bone marrow and peripheral blood are presented. The biosynthetic ratios obtained are compared with those of the reticulocytes. The data obtained cell culture are similar to the "in vivo" ones, showing and alpha/beta ratio of 1 in normal individuals and higher than 1 in beta thalassemic heterozygous. The use of erythroid cell culture as an experimental model for the study of differentiation at molecular level is therefore possible.