Anti-TIGIT therapies for solid tumors: a systematic review.

Programmed death-ligand 1[PD-(L)1], cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) inhibitors are recent breakthroughs in cancer treatment, however not all patients benefit from it. Thus new therapies are under investigation, such as anti-TIGIT [anti-T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif domains] antibodies. TIGIT is an immune checkpoint inhibiting lymphocyte T cells by several mechanisms. In vitro models showed its inhibition could restore antitumor response. Furthermore, its association with anti-PD-(L)1 therapies could synergistically improve survival. We carried out a review of the clinical trial about TIGIT referenced in the PubMed database, finding three published clinical trials on anti-TIGIT therapies. Vibostolimab was evaluated in a phase I alone or in combination with pembrolizumab. The combination had an objective response rate of 26% in patients with a non-small-cell lung cancer (NSCLC) naïve of anti-programmed cell death protein 1 (anti-PD-1). Etigilimab was tested in a phase I alone or in combination with nivolumab, but the study was stopped due to business reasons. In the phase II CITYSCAPE trial, tiragolumab demonstrated higher objective response rate and progression-free survival in combination with atezolizumab than atezolizumab alone in advanced PD-L1-high NSCLC. The ClinicalTrials.gov database references 70 trials of anti-TIGIT in patients with cancer, 47 of them with ongoing recruitment. Only seven were phase III, including five about patients with NSCLC, mostly with combination therapy. Data from phase I-II trials highlighted that targeting TIGIT represents a safe therapeutic approach, with an acceptable toxicity profile maintained when adding anti-PD-(L)1 antibodies. Frequent adverse events were pruritus, rash, and fatigue. Grade 3-4 adverse events were reported in nearly one in three patients. Anti-TIGIT antibodies are under development as a novel immunotherapy approach. A promising research area includes the combination with anti-PD-1 therapies in advanced NSCLCs.

Comparison of the prognostic value of AJCC cancer staging system 7th and 8th editions for differentiated thyroid cancer.

BACKGROUND: In the last American Joint Committee on Cancer/Tumor, Node, Metastasis (AJCC/TNM) 8th edition (TNM8), several changes were introduced to this risk stratification system to improve the prognosis of differentiated thyroid cancer (DTC). AIM: To validate the impact of TNM8 vs. TNM 7th edition (TNM7) in DTC in terms of predictive value in two hospitals from Buenos Aires, Argentina. METHODS: Retrospective study of DTC patients from two institutions. Reclassification from TNM7 to TNM8, disease-specific survival (DSS), and final clinical outcomes at the end of follow-up (recurrent/persistent structural disease) (median 5 years) were analyzed. The proportion of variation explained (PVE) was used to compare the predictive capability of DSS of both classification systems. RESULTS: Reclassification of 245 patients, aged (mean ± SD) 55 ± 15.36 years, 91% women, to TNM8 from TNM7 showed: 82% vs 57% stage I (SI), 10% vs 8.5% SII, 5% vs 22% SIII, 3% vs 12% SIV (p < 0.01). Forty percent of the population was downstaged with TNM8. Ten-year DSS rates for SI, SII, SIII and SIV in TNM7 were 100, 100, 100 and 74%, respectively and in TNM8: 97.6, 100, 100 and 37.5%, respectively. Out of 4 disease-specific deaths in SIV TNM7, one was subclassified to SI TNM8, corresponding to a 53-year-old patient with structural persistence. PVE for TNM8 (29%) was more than twice that of TNM7 (13%). CONCLUSION: In this Argentinian DTC patients sample, it was confirmed that the new TNM8 classification is more accurate in predicting survival attributable to cancer than its previous version.

Angioedema hereditario, ponderación de evidencias. parte 2 - tratamiento / Hereditary angioedema, weighting of evidence. Part 2 - Treatment

Desde las observaciones de Quincke y Osler, que refirieron pacientes con una "tumefacción" diferente de las que provocaban habitualmente los mecanismos alérgicos hasta el descubrimiento de un nuevo mediador responsable de esos edemas dolorosos y deformantes, se han sucedido los aportes de los investigadores en el esclarecimiento de la patogenia y el tratamiento del AEH hasta la actualidad, en que el arsenal terapéutico se ve notablemente enriquecido por medicamentos altamente eficaces y específicos. Intentaremos describirlos. (AU)

From the observations of Quincke and Osler, who referred patients with a "swelling" different from those that usually provoked the allergic mechanisms until the discovery of a new mediator responsible for these painful and deforming edemas, have been the contributions of researchers in the Clarification of the pathogenesis and treatment of HAE to date, where the therapeutic arsenal is remarkably enriched by highly effective and specific drugs. We will try to describe them.(AU)

Development and validation of a multiplex methylation specific PCR-coupled liquid bead array for liquid biopsy analysis.

BACKGROUND: Liquid biopsy is based on minimally invasive blood tests and has the potential to characterize the evolution of a solid tumor in real time, by extracting molecular information from circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Epigenetic silencing of tumor and metastasis suppressor genes plays a key role in survival and metastatic potential of cancer cells. Our group was the first to show the presence of epigenetic alterations in CTCs. METHODS: We present the development and analytical validation of a highly specific and sensitive Multiplex Methylation Specific PCR-coupled liquid bead array (MMSPA) for the simultaneous detection of the methylation status of three tumor and metastasis suppressor genes (CST6, SOX17 and BRMS1) in liquid biopsy material (CTCs, corresponding ctDNA) and paired primary breast tumors. RESULTS: In the EpCAM-positive CTCs fraction we observed methylation of: a) CST6, in 11/30(37%) and 11/30(37%), b) BRMS1 in 8/30(27%) and 11/30(37%) c) SOX17 in 8/30(27%) and 13/30(43%) early breast cancer patients and patients with verified metastasis respectively. In ctDNA we observed methylation of: a) CST6, in 5/30(17%) and 10/31(32%), b) BRMS1 in 8/30 (27%) and 8/31 (26%) c) SOX17 in 5/30(17%) and 13/31(42%) early breast cancer patients and patients with verified metastasis respectively. CONCLUSIONS: Our results indicate a high cancerous load at the epigenetic level in EpCAM-positive CTCs fractions and corresponding ctDNA in breast cancer. The main principle of the developed methodology has the potential to be extended in a large number of gene-targets and be applied in many types of cancer.

MicroRNA-125b regulates microglia activation and motor neuron death in ALS.

Understanding the means by which microglia self-regulate the neuroinflammatory response helps modulating their reaction during neurodegeneration. In amyotrophic lateral sclerosis (ALS), classical NF-κB pathway is related to persistent microglia activation and motor neuron injury; however, mechanisms of negative control of NF-κB activity remain unexplored. One of the major players in the termination of classical NF-κB pathway is the ubiquitin-editing enzyme A20, which has recognized anti-inflammatory functions. Lately, microRNAs are emerging as potent fine-tuners of neuroinflammation and reported to be regulated in ALS, for instance, by purinergic P2X7 receptor activation. In this work, we uncover an interplay between miR-125b and A20 protein in the modulation of classical NF-κB signaling in microglia. In particular, we establish the existence of a pathological circuit in which termination of A20 function by miR-125b strengthens and prolongs the noxious P2X7 receptor-dependent activation of NF-κB in microglia, with deleterious consequences on motor neurons. We prove that, by restoring A20 levels, miR-125b inhibition then sustains motor neuron survival. These results introduce miR-125b as a key mediator of microglia dynamics in ALS.

EPIDEMIOLOGÍA DE LA URTICARIA AGUDA EN UN SISTEMA DE SALUD PREPAGO DE LA CIUDAD DE BUENOS AIRES, ARGENTINA / Epidemiology of acute urticaria in a health maintenance organization of Buenos Aires, Argentina

Antecedentes. A pesar de la frecuencia de la urticaria aguda (UA), no existen estudios epidemiológicos sobre su prevalencia y distribución en Argentina. Objetivo. Determinar la prevalencia y otras características epidemiológicas de la UA en los miembros de una organización privada de salud de Buenos Aires, la mayor área poblada de Argentina. Marco de referencia: Hospital Italiano (HIBA) de la Ciudad de Buenos Aires, Argentina. Diseño: Cohorte retrospectivo. Población. Pacientes con diagnóstico de UA miembros del HIBA, y con al menos 12 meses de seguimiento. Métodos. Se analizaron todos los registros médicos para calcular las tasas de prevalencia de UA por 100.000 habitantes con intervalo de confianza del 95% (IC95%) para el período comprendido entre el 1 de enero de 2013 y el 31 de diciembre de 2014. La tasa de prevalencia se calculó para toda la población y luego se discrimino para pacientes adultos y pediátricos (menores de 18 años en el momento del diagnóstico). Resultados. Se analizaron 158.926 miembros de la prepaga. Se identificó un total de 2100 casos de UA en el período analizado (1151 en pediatría, 949 en adultos), con una tasa de prevalencia de 1,32% (IC95%: 1,11-1,55%). La prevalencia de UA en la población adulta fue de 0,83% (IC95%: 0,64-0,97%), mientras que en la población pediátrica fue del 2,5% (IC95%: 1,9-2,8%). Conclusiones: este es el primer estudio que describe la prevalencia de UA en una población cerrada de Argentina y de la región.(AU)

Background. In spite of the frequency of acute urticaria (AU), there are no epidemiological studies on its prevalence and distribution in Argentina. Objetive. Was to estimate the prevalence and other epidemiological characteristics of AU in the members of a health maintenance organization of Buenos Aires, the largest populated area in Argentina. Setting: Italian Hospital, Buenos Aires, Argentina. Design. Retrospective cohort. Population. All patients with diagnosis of AU who are members of the IHMCP, and with at least 12 months of follow up were included in the study. Methods. All medical records were analyzed to calculate the prevalence rates for AU per 100,000 population with 95% CI for the period of January 1, 2013 and December 31, 2014. Prevalence rate was calculated for the entire population and then discriminated for adults and pediatric members (less than 18 years old at diagnosis). Results. 158,926 members were analyzed. A total of 2100 cases of AU were identified on prevalence period (1151 in pediatrics, 949 in adults), yielding a prevalence rate of 1.32% (CI 95% 1.11-1.55%). The prevalence of AU in adult population observed was 0.83 % (95% CI 0.64-0.97%), while in pediatrics it was 2.5 % (95% CI 1.9-2.8%). Conclusions. This is the first study to describe the prevalence of AU in a closed population of Argentina and the region(AU)

ANGIOEDEMA HEREDITARIO, PONDERACIÓN DE EVIDENCIAS. PARTE 1 / Hereditary angioedema, weighting of evidence. Part 1

A pesar de que el angioedema hereditario es un padecimiento raro, tiene una amplia bibliografía que ratifica que la fisiopatología de esta enfermedad es compleja. La constante investigación de la industria farmacéutica no solo ha aportado nuevos recursos terapéuticos sino que ha logrado despertar un inusitado interés en la comunidad médica, permitiendo que tengamos una mayor comprensión sobre los mecanismos que presiden la aparición de las crisis. El Comité de Angioedema Hereditario de la AAAeIC ha desarrollado una puesta al día sobre esta entidad, que, por las características de sus síntomas, es abordada principalmente por los especialistas en alergia e inmunología clínica(AU)

Although hereditary angioedema is a rare condition, it has a large number of references that confirm that the pathophysiology of this disease is complex. The constant research of the pharmaceutical industry has not only brought new therapeutic resources, but also aroused an unusual interest in the medical community, allowing us to have a better understanding of the mechanisms that perform the onset of crises. The AAA e IC Hereditary Angioedema Committee has developed an update on this entity, which, due to the characteristics of its symptoms, is mainly addressed by specialists in allergy and clinical immunology.(AU)

ALERGIA A LA PROTEíNA DE LA LECHE DE VACA. EVALUACIóN DE SU RESOLUCIóN ESPONTáNEA POR MEDIO DE DESAFíOS DOBLE CIEGO PLACEBO CONTROLADOS / cows milk allergy. an assesment of its spontaneous resolution through double blind placebo controlled challenges.

Introducción. la alergia a la leche de vaca (aplv) es un problema sanitario global. Su diagnóstico adecuado y su seguimiento son esenciales ya que la leche de vaca es un alimento importante en la dieta de muchos lactantes. los desafíos orales doble ciego controlados por placebo (ddcpc) son la herramienta ideal para el diagnóstico y seguimiento de las alergias alimentarias. este estudio describe las características evolutivas de pacientes con aplv y las posibles variables que la pudieran modificar. material y métodos. Se estudiaron pacientes con diagnóstico de aplv previo con desafíos abiertos. Se catalogaron las reacciones de acuerdo a la normativa dracma. positivas fueron las pruebas en las que se presentaron alteraciones clínicas o variaciones hemodinámicas. negativas fueron aquellas en las que el paciente toleró la leche. Se consideraron edades de inicio y de realización del ddcpc, sexo y patología de aplv. resultados. Se estudiaron 106 pacientes (50 masculinos, 56 femeninos), promedio edad de inicio de síntomas 5,31 m (rango: 1-48 meses) y al procedimiento 23,14 m (5 meses - 5 años), y 13 pruebas positivas. un conjunto se refirió al mecanismo fisiopatológico y se dividió en ige mediadas (n=55) con 8 pruebas positivas y mixtas/celulares (n=51) con 5 pruebas positivas. otro conjunto fueron no gastrointestinales (n=61) con 7 pruebas positivas y gastrointestinales (n=45) con 6 pruebas positivas. todos los grupos fueron similares en cuanto a las variables demográficas. el sexo masculino y el diagnóstico de anafilaxia fueron factores de riesgo para no resolver su aplv (p=0,0125 y p=0,002 respectivamente). conclusiones. el momento de resolución de la aplv es independiente del mecanismo fisiopatológico subyacente o la edad de inicio de los síntomas. en general resuelven el problema de manera espontánea hacia los dos años de vida en más de un 87% de los casos. el sexo masculino (en ige mediadas) y el antecedente de anafilaxia podrían ser factores de riesgo para tener menos probabilidades de resolver la APLV. (AU)

Introduction: cow´s milk allergy (cma) is a global health issue. a proper diagnosis and follow up become essential. double blind placebo controlled challenges (dbpcc) is the gold standard for this purpose. this paper describes clinical evolution and characteristics of cma, as well as variables that may modify the affection course. methods & material: a group of patients, with a previous diagnosis of cma by open challenges, has been studied and its results cataloged according to dracma guidelines. tests with hemodynamic changes or clinical symptoms were considered as positives, while those with no clinical reaction were considered as negatives. variables involved were: age of symptoms starting, age of dbpcc performing, gender and cma clinical manifestations. results: 106 patients has been studied (50 male, 56 female), with a median age of 5,31 mo (range 5 ­ 48 mo) at the starting symptoms, and a median age of 23,14 mo (range 5 mo ­ 5 y) at the performing of dbpcc. 13 tests were negative. as regards to the different immune mechanisms, 55 were ige dependent (8 negative), and 51 were mediated by mixed/cellular (5 negative). patients were divided into two groups: with gastrointestinal symptoms (n=45) and with no gastrointestinal symptoms (n=61). they showed 6 and 7 negative results, respectively. all groups were similar. male gender, and anaphylaxis diagnosis turned out to be risk factors not to resolve cma (p=0,0125 and p=0,002 respectively). conclusions: cma resolution is independent of the immune mechanisms involved or the age of its symptoms starting. cma is solved spontaneously towards the age of two in 87% of the cases. male gender, and anaphylaxis may become risk factors not to resolve cma.(AU)

EPIDEMIOLOGÍA DE ANAFILAXIA EN UN SISTEMA DE SALUD PREPAGO DE LA CIUDAD DE BUENOS AIRES, ARGENTINA / Epidemiology of anaphylaxis in a medical care program in Buenos Aires, Argentina

Fundamentos. Anafilaxia es una reacción alérgica seria y que puede causar la muerte. Existen pocos datos sobre la incidencia y las características de anafilaxia en Argentina. Objetivos. Estimar la incidencia de anafilaxia en un sistema de salud prepago de la Ciudad de Buenos Aires. Describir el conocimiento de los pacientes con diagnóstico de anafilaxia sobre medidas de prevención y tratamiento. Marco de referencia. Hospital Italiano de la Ciudad de Buenos Aires, Argentina. Diseño. Cohorte retrospectiva Población. Padrón del Hospital Italiano de Buenos Aires con diagnóstico de anafilaxia desde enero de 2006 a abril de 2014. Método. Se revisaron las historias clínicas electrónicas de 211 pacientes. La evaluación comprendió tanto el ámbito ambulatorio como internación y central de emergencias. Se realizó una encuesta telefónica para conocer el comportamiento y conocimiento de los pacientes que presentaron un episodio de anafilaxia. Se utilizó el software estadístico SPSS 19.0. Resultados. La densidad de incidencia calculada por cada 100.000 personasaño fue de 9,03 (IC95%: 7,53-10,84) para todas las causas de anafilaxia. Las causas más comunes reportadas fueron medicamentos 49,5% y alimentos 19,79%. El 63,4% no recibió prescripción de adrenalina autoinyectable, sólo el 30,9% tienen un plan de acción ante un nuevo evento. Conclusión. La anafilaxia es un problema de salud importante y común. Este estudio demuestra posibles deficiencias en la atención de los episodios de anafilaxia, no sólo en el tratamiento de episodios pasados, sino también por la falta de preparación adecuada para futuros episodios. (AU)

Background. Anaphylaxis is a serious allergic reaction that can cause death. There are few data of the incidence and characteristics of anaphylaxis in the population of Argentina. Objectives. estimate the incidence of anaphylaxis in medical care program of Buenos Aires city. Describe the knowledge of patients with diagnosis of anaphylaxis about prevention and treatment. Setting. Italian Hospital of Buenos Aires, Argentina. Design. Retrospective cohort. Population. Census of the Italian Hospital of Buenos Aires with a diagnosis of anaphylaxis in electronic health records from January 2006 to April 2014. Method. Electronic medical records of 211 patients were reviewed, the evaluation included both inpatient and outpatient setting and emergency center. A telephone survey was conducted to understand the behavior and knowledge of the patients who had an episode of anaphylaxis. SPSS 19.0 statistical software was used. Results. The density of incidence calculated per 100,000 person-years was 9.03 (95% CI: 7.53-10.84) for all causes of anaphylaxis. The most commonly reported causes were drugs 49.5% and food 19.79%. The 63.4% of patients had never received the prescription of self-injectable epinephrine; only 30.9% have a plan of action before a new event. Conclusion. Anaphylaxis is an important and common health problem. This study demonstrates the potential gaps in care episodes of anaphylaxis, not only in the treatment of past episodes, also by the lack of adequate preparation for future episodes(AU)

Dysregulated microRNAs in amyotrophic lateral sclerosis microglia modulate genes linked to neuroinflammation.

MicroRNAs (miRNAs) regulate gene expression at post-transcriptional level and are key modulators of immune system, whose dysfunction contributes to the progression of neuroinflammatory diseaseas such as amyotrophic lateral sclerosis (ALS), the most widespread motor neuron disorder. ALS is a non-cell-autonomous disease targeting motor neurons and neighboring glia, with microgliosis directly contributing to neurodegeneration. As limited information exists on miRNAs dysregulations in ALS, we examined this topic in primary microglia from superoxide dismutase 1-G93A mouse model. We compared miRNAs transcriptional profiling of non-transgenic and ALS microglia in resting conditions and after inflammatory activation by P2X7 receptor agonist. We identified upregulation of selected immune-enriched miRNAs, recognizing miR-22, miR-155, miR-125b and miR-146b among the most highly modulated. We proved that miR-365 and miR-125b interfere, respectively, with the interleukin-6 and STAT3 pathway determining increased tumor necrosis factor alpha (TNFα) transcription. As TNFα directly upregulated miR-125b, and inhibitors of miR-365/miR-125b reduced TNFα transcription, we recognized the induction of miR-365 and miR-125b as a vicious gateway culminating in abnormal TNFα release. These results strengthen the impact of miRNAs in modulating inflammatory genes linked to ALS and identify specific miRNAs as pathogenetic mechanisms in the disease.

Purinergic signalling: what is missing and needed next? The use of transgenic mice, crystallographic analysis and MicroRNA.

While ATP is recognized as an intracellular energy source for many biochemical reactions, it is now recognised it is also an important extracellular signalling molecule. ATP is involved in both physiological and pathological events in most cell types, and receptor subtypes have been cloned and characterised. An important goal of purinergic research today is to annotate the human genome with functional information regarding the role of genes for purinergic receptors, ectonucleotidases and transporters, in brain physiology and pathology. Insights into these roles have been gained also from studies of the various purinergic knockouts, and here we report on the generation of these purinergic receptor/ectonucleotidase-null mice. Recent X-ray structures of purinergic ligand-activated receptors provide promising templates to understand the molecular mechanism of receptor actions at the atomic level, and to deploy X-ray structures to be used for structure-based drug design. In the present work we also summarize recent findings about X-ray structures of ionotropic and metabotropic purinergic receptors and ectonucleotidases. A novel and prominent role as modulators of signal propagation in animal cells is played by microRNAs. By acting as genetic switches, they might become stringent regulators of the variety of cellular responses triggered by the dynamic interactions between purinergic receptors, nucleotides/nucleosides, transporters and ectonucleotidases. In this review we highlight data on the regulation of purinergic mechanisms by microRNAs. Finally, we would like to illustrate what information is still missing or needed for the acquisition of a more complete knowledge of purinergic signalling.

Development of a multiplexed PCR-coupled liquid bead array assay for vascular endothelial growth factor (VEGF) splice variants.

OBJECTIVES: To develop a multiplex PCR-coupled liquid bead array assay for the expression of VEGF splice variants. DESIGN AND METHODS: The assay was based on the combination of multiplex PCR with liquid bead array technology, and optimized and evaluated in terms of analytical sensitivity, specificity, and reproducibility using the MCF-7 cell line. Clinical performance was evaluated in 16 pairs of fresh frozen cancerous and corresponding noncancerous adjacent tissues from NSCLC patients. RESULTS: The assay is highly sensitive, reproducible and can detect specifically VEGF splice variants in clinical samples. When applied in 32 clinical samples it gave comparable results to RT-qPCR (concordance of 81%, 75%, 88% and 81% for PBGD, VEGF(121), VEGF(165), and VEGF(189) respectively). CONCLUSIONS: The developed assay can simultaneously detect three VEGF splice variants with high specificity and sensitivity and can be further used to evaluate the role of each individual VEGF splice variant in molecular therapies targeted against VEGF.

Alergia al huevo en Pediatría. Documento del Comité de Pediatría de la Asociación Argentina de Alergia e Inmunología Clínica / Egg allergy in pediatrics. Pediatric Committee document of the Argentina Association of Allergy and Clinical Immunology

El huevo de gallina es una fuente de proteínas de alto valor biológico de bajo costo y de vitaminas del complejo B, importantes para la alimentación del niño. Culturalmente es uno de los alimentos básicos de nuestra dieta y, debido a esto, la alergia a sus proteínas es una de las más frecuentes en la infancia y tiene su mayor impacto en niños en edad preescolar. Estos niños representan una población vulnerable debido a que se encuentran en una etapa importante de su crecimiento y desarrollo, y el tratamiento de esta patología genera la adopción de dietas restrictivas que pueden impactar en forma negativa en su salud y calidad de vida. Este impacto está dado en parte por la ubicuidad de sus proteínas, que limita ampliamente la dieta y genera riesgos de reacciones alérgicas que se incrementan a medida que el niño crece y alcanza una mayor independencia. Teniendo en cuenta la importancia de esta patología, el Comité de Pediatría realizó una revisión actualizada con el fin de proveer herramientas útiles para el manejo adecuado de la misma. (AU)

Eggs are a source of low cost high biological value protein and complex B vitamins important for the child's nutrition. Culturally it is one of the staples of our diet and because of this, egg allergy is one of the most common food allergies in childhood and has its greatest impact on preschool children. These children represent a vulnerable population because they are at an important stage in their growth and development and the treatment of this condition generates the adoption of restrictive diets that may impact negatively on their health and quality of life. This impact is given in part by the ubiquity of their proteins that largely restrict the diet and generates risks of allergic reactions that increase as the child grows and earns greater independence. Given the importance of this issue the Pediatrics Committee conducted an updated review to provide useful tools to manage this condition.(AU)

Estudio multicéntrico de evaluación del conocimiento de los pediatras acerca de reacciones alérgicas a vacunas para enfermedades infecciosas / A multicenter study assessing pediatrician's knowledge about allergic reactions to infectious disease vaccines

Resumen. Las reacciones alérgicas a las vacunas contra agentes infecciosos han generado preocupación entre los pediatras. Sin embargo, se desconoce el grado de información que tienen estos especialistas de nuestro país sobre este tema. Objetivo. Contar con datos estadísticos acerca de este problema. Población. Trescientos veinte pediatras encuestados. Método. Estudio multicéntrico descriptivo prospectivo de corte transversal realizado con encuestas estandarizadas Resultados. El 12,5% de los encuestados reconoció la presencia de síntomas de aparición rápida como reacción de hipersensibilidad inmediata. (61,6%) consideró a estas reacciones como infrecuentes. El 72,6% reconoció a la neomicina como causa de alergia, el 51,6 % al timerosal, el 73% a los conservantes, un 30,4% a la gelatina y la mitad de los encuestados al componente activo. El 62,3% reconoció a la proteína del huevo como componente de la vacuna MMR. Ante antecedentes de alergia al huevo, el 35% de los médicos contestó que contraindica siempre las vacunas que contienen proteína del huevo, el 14% no las contraindica nunca y el 9% no sabe. Los médicos de menos de 5 años de recibidos reconocieron con mayor frecuencia la presencia de una reacción alérgica a vacunas (p = 0,004). Los médicos de más de 10 años de recibidos solicitan más frecuentemente interconsulta con el especialista ante casos de vacunación de pacientes con alergia a la proteína del huevo (p = 0,01). Conclusiones. Existe un grado importante de desconocimiento acerca de las reacciones alérgicas a vacunas, los componentes de las vacunas involucrados en dichas reacciones y las conductas a tomar frente a pacientes con alergia al huevo.(AU)

Background: Allergic reactions to infectious disease vaccines have generated concern among pediatricians. It is unknown the level of pediatrician's knowledge about this issue. The aim of this study is to obtain statistical data about this issue in our country. Population: 320 pediatricians. Methods: A transversal prospective descriptive multicenter study by means of a survey. Results: 12.5% of participants were capable to identify symptoms of immediate hypersensitivity reactions and 61.6% considered that these reactions are not frequent. The pediatricians pointed out as the most commonly allergen components the following ones: Neomicine (72.6%), thymerosal (51.6 %), preservatives (73%), gelatin (30.4%) and active component (nearly 50%). 62.3% knew that eggs proteins are part of MMR vaccine. In the case of patient with history of egg allergy, 35% answered that they always contraindicate vaccination with egg protein vaccines while14% do not contraindicate and 9% do not know what to do. Physicians less than 5 years of graduation recognized more frequently the presence of allergic reactions (p: 0.004). Physicians with 10 or more years of graduation asked for specialist opinion more frequently in the case of patients with egg allergy (p: 0.01). Conclusions: It was found an important lack of information about allergic vaccine reactions, the involved vaccine constituents and the correct management of situations related to egg allergy.(AU)

Home rehabilitation for brain tumor patients.

UNLABELLED: To determine whether a program of post-discharge rehabilitation at home for patients operated for brain tumor was associated with functional gain and improvement in Quality of Life (QoL). One hundred and twenty-one patients affected by malignant brain tumor were enrolled in a program of post-discharge home care including neurorehabilitation. Functional outcome was evaluated with Barthel Index (BI) and Karnofsky Performance Status (KPS) measured before and after rehabilitation. The impact of rehabilitation on quality of life was evaluated with a quality of life questionnaire (EORTC QLQ-C30-BM 20). RESULTS: Barthel Index improved in 47 (39%) patients, was stable in 20 (16%) and worsened in 54 (44%). Only 54 patients completed the QoL questionnaire before and after treatment. After three months of rehabilitation, 72% of patients were found to have an improvement in at least one domain score compared with their baseline QoL scores. Rehabilitation at home in brain tumor patients was associated with significant functional gain measured both with BI and KPS. The benefit of rehabilitation may influence patient's perception of quality of life.

Combined cardiohepatic transplantation due to severe heterozygous familiar hypercholesteremia type II: first case in Argentina--a case report.

Heterozygous familial hypercholesteremia type II is a recessive autonomic disease with a population incidence

Impact of leukapheresis cell composition on immunomagnetic cell selection with the Baxter Isolex 300i device: a statistical analysis.

Immunomagnetic cell selection (ICS) of CD34(+) cells is increasingly adopted in allogeneic and autologous transplant settings. Because many variables can affect the final results of ICS, we focused our study toward the influence exerted by the leukapheresis (LKF) cell composition on recovery, purity, and log of T and B depletion of the immunoselected cells. A total of 39 consecutive CD34(+) ICS were performed with the Isolex 300i (Baxter) device on 39 LKF from 9 HLA haploidentical donors and 20 patients. Flow cytometric analysis was performed both on the leukapheresis content and on the immunoselected cells. The statistical analysis was performed utilizing the Pearson's correlation test and the Mann-Whitney U test. The median purity and recovery of the immunoselected CD34(+) cells were 95.3% (IR: 93.0-99.0) and 55.1% (IR: 41.8-68.2), respectively. The median log of T and B depletion were 3.87 (IR: 3.5-4.3) and 2.9 (IR: 2.5-3.5), respectively. Our data indicate that not only the CD34(+) cell load but also the ratio among the cells belonging to the starting fraction can influence the results of ICS. LKF collection protocols have to be addressed to collect an high number of CD34(+) cells (>500 x 10(6)) without taking care of the contaminating cells when the Baxter Isolex 300i device is employed.

Topical anesthesia for hysteroscopy in postmenopausal women.

STUDY OBJECTIVE: To evaluate the efficacy and safety of topical anesthesia in reducing pain and the frequency of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: A university hospital. PATIENTS: Forty-two postmenopausal women undergoing diagnostic hysteroscopy and endometrial biopsy. INTERVENTIONS: Two milliliters of 2% mepivacaine or saline solution was injected transcervically into the uterine cavity before performing the procedures. MEASUREMENTS AND MAIN RESULTS: Pain was evaluated on a visual analog scale, and heart rate and blood pressure were monitored continuously. Anesthesia reduced the pain experienced at hysteroscopy and endometrial biopsy, but not significantly. The frequency of vasovagal reactions was significantly lower in the anesthetized group. CONCLUSIONS: Topical anesthesia effectively prevents the occurrence of vasovagal reactions in postmenopausal women undergoing hysteroscopy and endometrial biopsy.