Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

In silico analysis of antidiabetic potential of phenolic compounds from blue corn (Zea mays L.) and black bean (Phaseolus vulgaris L.).

The growing interest in bioactive compounds, especially in polyphenols, is due to their abundance in the human diet and potentially positive effects on health. The consumption of polyphenols has been shown to possess anti-diabetic properties by preventing insulin resistance or insulin secretion through different signaling pathways, this effect is associated with their capacity to exert genomic modulations. Several studies have suggested that polyphenols could also bind to cellular proteins and modulate their activity, however, the mechanisms of action underlying their beneficial effects are complex and are not fully understood. The aim of this work was to characterize phenolic compounds present in blue corn and black bean extracts as well as identify their potential interactions with target proteins involved in diabetes pathogenesis using in silico approach. Total polyphenols content of both blue corn and black beans was identified using UPLC-ESI/qTOF/MS and quantified by colorimetric assays. In this work we identified twenty-eight phenolic compounds in the extracts, mainly anthocyanins, flavonols, hydroxycinamic acids, dihydroxybenzoic acids, flavones, isoflavones, and flavanols. Interactome of these compounds with thirteen target proteins involved in type 2 diabetes mellitus was performed in-silico. In total, 312 bioactive compounds/protein interaction analyses were acquired. Molecular docking results highlighted that nine of the top ten interactions correspond to anthocyanins, cyanidin 3-glucoside with 11ß-HS, GFAT, PPARG; delphinidin 3-glucoside with 11ß-HS, GFAT, PTP and RTKs; and petunidin 3-glucoside with 11ß-HS and PTP. These proteins are involved in mechanisms regulating functions such as inflammation, insulin resistance, oxidative stress, glucose and lipid metabolism. In conclusion, this work provides a prediction of the potential molecular mechanism of black bean and blue corn polyphenols, specifically anthocyanins and could constitute new pathways by which compounds exert their antidiabetic benefits.

Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

Breve Descripción de la Biología Sintética y la Importancia de su Relación con otras Disciplinas / Brief description of Synthetic Biology and the importance of its relationship with other disciplines

Resumen La biología sintética (SynBio) es una disciplina de reciente aparición que sirve para diseñar o re-diseñar sistemas biológicos y otorgarles cualidades mejoradas o nuevas cualidades. En la SynBio el diseño de nuevos sistemas biológicos requiere de herramientas moleculares muy precisas, tales como: a) la bioinformática, b) la secuenciación NGS (Next Generation Sequencing), el ensamble y/o síntesis de ADN c) y la edición de genomas a través de CRISPR-Cas9. En la SynBio encontramos además otras disciplinas con un perfil más hacia el ámbito social, las cuales tocan aspectos éticos, legales, filosóficos y económicos, considerándose así una multidisciplina. La SynBio está propiciando el desarrollo de nuevas tecnologías (emergentes) partiendo de una óptica ingenieril. En la SynBio, al ADN se le entiende de forma práctica y abstracta como una serie de partes que se pueden ensamblar en cierto orden para obtener los productos deseados una vez que se conoce la funcionalidad de cada parte. La SynBio ha dado pie a una nueva concepción de la economía a nivel mundial y por consecuencia se ha tomado muy seriamente el termino Bioeconomía como una nueva disciplina que transformará a las sociedades.

Abstract Synthetic biology (SynBio) it is considered a very recent discipline. View as a tool serves to design or re-design biological systems, giving them improved qualities or new qualities. In the SynBio, the design of new biological systems requires very precise molecular tools, such as: a) bioinformatics, b) sequencing NGS (Next Generation Sequencing), assembly and synthesis of DNA c) and CRISPR- Cas9 genome editing. Within the SynBio there are other social profile disciplines which concerned to ethical, legal, philosophical, and economic, and for that reason it is considered a multidiscipline. The SynBio is promoting the development of new (emerging) technologies based on an engineering perspective. In SynBio, DNA is understood in a practical and abstract way as a series of parts that can be assembled in a certain order to obtain the desired products once the functionality of each part is known. The SynBio has given rise to a new conception of the economy worldwide and consequently the term Bioeconomy is already taken very seriously as a new discipline that will transform societies.

Arsenic accumulation in lettuce (Lactuca sativa L.) and broad bean (Vicia faba L.) crops and its potential risk for human consumption.

Exposure to arsenic (As) is considered one of the primary health risks humans face worldwide. This study was conducted to determine As absorption by broad beans and lettuce crops grown in soil with As contents and irrigated with water contaminated with this toxic element, in Pastos Chicos, Jujuy (Argentina). Total dry biomass (TDB) and total As were determined in soils, roots, leaves, pods and seeds. These data were used to determine several parameters, such as translocation (TF) and bioconcentration (BCF) factors, target hazard quotient (THQ), and carcinogenic risk (CR). Broad bean plants had the lowest biomass production when exposed to As in irrigation water and soil. Lettuce plants presented TDB reductions of 33.3 and 42.8% when grown in soil polluted with As, and in control soil under irrigation with contaminated water, respectively. The presence of this toxicant in broad bean seeds and lettuce leaves (edible parts) exceeded the limits established by Código Alimentario Argentino, i.e. 0.10 and 0.30 mg/kg, respectively. THQ values for lettuce leaves were higher than 1, the same as those for broad bean seeds when grown in soil with As contents and irrigated with arsenic-contaminated water, thus suggesting that consumers would run significant risks when consuming these vegetables. Furthermore, this type of exposure to As implied a CR that exceeded the acceptable 1 × 10-4 risk level. Hence, we may conclude that consuming lettuce and broad beans grown at the evaluated site brings about considerable health risks for local residents.

Absorption of arsenic from soil and water by two chard (Beta vulgaris L.) varieties: A potential risk to human health.

The accumulation of arsenic (As) in vegetables poses a risk of contamination to humans via the food chain. Two chard (var. cicla and var. d'ampuis) crops were grown for 60 days in greenhouses on Aridisol soil, and irrigated with water from Pastos Chicos, Jujuy (Argentina). The soil and water used in the trial presented 49 and 1.44 mg/L As concentration levels, respectively. Total dry biomass (TDB) and total As were determined in soils, roots and leaves. The latter was quantified by atomic absorption spectrometry with hydride generation, and bioconcentration and translocation factors were determined. TDB in var. cicla showed statistically significant differences when the plant was cultivated in control soil and watered with the toxicant (2.04 g), as compared with the treatment without exposure (2.8 g). TDB in var. d'ampuis presented statistically significant differences with respect to that of the control when the plants were grown in soils with As and watered with the toxicant (3.3 g). This variety increased its biomass in the presence of As. In the two Swiss chard varieties evaluated, the largest As accumulation in root and leaves was found when they were cultivated in contaminated soil and watered with distilled water. The presence of the toxicant in the leaves exceeded the limits established by Código Alimentario Argentino, i.e. 0.30 mg/kg. Total target hazard quotient (THQ) values for As were higher than 1, suggesting that consumers would run significant risks when consuming these chard varieties. Furthermore, it was determined that the carcinogenic risk (CR) posed by this type of exposure to As exceeded the acceptable risk level of 1 × 10-6. Based on this evidence, we may conclude that consuming chard cultivated on the evaluated site brings about considerable risks to local residents' health.

Biomonitoring of persistent organic pollutants (POPs) in child populations living near contaminated sites in Mexico.

The aim of this study was to conduct a POP biomonitoring programme for children in high-risk areas. We evaluated 247 serum samples from children between the ages of 6 and 12years old from two zones in Mexico: (1) indigenous zones, which included Cuatlamayan (CUA), Tocoy (TOC), and Santa Maria Picula (SAM); and (2) industrial zones, which included Tercera Chica (TC), Industrial San Luis (IND) and Rincon de San Jose (SJR); Mundo Nuevo (MN); and Alpuyeca (ALP). Our results showed that α-endosulfan was similar to CUA, TOC, SAM, TC and MN (178.6-306.9ng/g lipid). ß-Endosulfan levels were higher in ALP (901.5ng/g lipid), followed by CUA (139.9ng/g lipid) and TOC, SAM, TC and MN, which had similar levels (55.4-64.5ng/g lipid). For endosulfan sulfate, the ALP community had the highest concentration levels (1096.4ng/g lipid), whereas CUA and TOC (212.3 and 289ng/g lipid, respectively) had concentrations similar to those found in SAM and TC (99.5 and 119.1ng/g lipid, respectively). DDE levels were found in malaria-endemic areas of SAM, CUA and TOC (1782.2, 1358.3 and 57.0ng/g lipid), followed by MN (35.1ng/g lipid). HCB concentration levels were found to be higher in MN and SJR (691.8 and 575.4ng/g lipid, respectively), followed by CUA and TC (363.9 and 269.1ng/g lipid, respectively), with levels similar to those found in TOC and SAM (191.8 and 181.9ng/g lipid, respectively). Finally, PCB 101 concentration levels were found to be the highest in ALP (1032.7ng/g lipid), followed by similar levels of SJR and IND (567.5 and 327.3ng/g lipid, respectively) and TC and MN, with 109.1 and 144.5ng/g lipid, respectively. The evidence provided by this exploratory study indicates that the evaluation of the health risks posed to children living in contaminated areas is a high priority health issue.

Bipartición embrionaria temprana: descripción de una serie de 9 casos / Early embryo bisection: Nine cases description

Resumen ANTECEDENTES: La tasa de bipartición temprana en concepciones naturales es de 0.4% de los nacimientos. Se ha descrito un aumento de estos casos en tratamientos de reproducción asistida, especialmente durante la transferencia en estadio de blastocisto. CASO CLÍNICO: se describen nueve casos retrospectivos (2014-2016) de pacientes a quienes se transfirió un embrión y se visualizaron dos sacos, o en las que se transfirieron 2 embriones y se visualizaron 3 sacos. En el periodo de estudio se transfirieron 3737 embriones: 1470 en fresco y 827 desvitrificados. Los 9 casos suponen una tasa de bipartición temprana embrionaria de 0.39% del total de las transferencias y 0.86% del total de los embarazos. CONCLUSIONES: no existe relación entre el riesgo de división embrionaria y la eclosión (hatching) asistida, ni entre la edad avanzada ovocitaria y la edad paterna. La transferencia de embrión único es la mejor opción en pacientes que reciben ovocitos de donantes jóvenes o participan en protocolos de FIV-ICSI.

Abstratc BACKGROUND: The cases in which the embryo divides in two identic embryos is causing real concerns in the treatments of assisted reproduction. The percentage of early bisection in natural conception is about 0.4% on life birth. There is noticed an increase of this cases in treatments of the assisted reproduction, especially when transferring in blastocyst stage. CASE REPORT: We have collected series of 9 cases in a retrospective way, between 2014-2016 in which we have transferred 1 embryo and we have visualized 2 sacs, and the cases in which we have transferred 2 embryos and we have visualized 3 sacs. This year we have transferred a total of 3737 embryos, 1470 fresh embryo transfers and 827 frozen embryo transfers. These 9 cases mean the 0.39% of early embryo division and the 0.86% of total of pregnancies. CONCLUSION: We didn't observe a relationship in the risk of embryo division with the hatching. Neither with advanced age of the eggs, non the father's age. The rate of division of the embryos in cycles of the assisted reproduction in our clinic using ICSI increase in comparison with the spontaneous gestations, howbeit it would be necessary to do more studies in order to prove this statement. We consider single embryo transfer the best practice in IVF in young women or donor eggs.

Experience with anidulafungin in patients with allogeneic hematopoietic stem cell transplantation and graft-versus-host disease.

BACKGROUND: It is well known that both acute and chronic graft-versus-host disease (GVHD) are associated with invasive fungal disease (IFD). Because the galactomannan antigen diagnostic test has low specificity and sensitivity outside of the neutropenic period, many institutions use posaconazole or voriconazole for IFD prophylaxis during GVHD treatment. Moreover, several factors, mainly hepatic impairment, can limit the use of extended spectrum azoles, both in prophylaxis or treatment. METHODS: We retrospectively analyzed 25 patients with allogeneic hematopoietic stem cell transplantation (HSCT) and GVHD - grade III-IV acute GHVD (n = 15), progressive chronic GVHD (n = 7), and "overlap" GVHD (n = 3) - who received intravenous anidulafungin (200 mg on day 1, followed by 100 mg once daily). If necessary, anidulafungin treatment was followed by oral administration of 200 mg voriconazole twice a day or 200 mg posaconazole 3 times daily until patients were considered not at risk for IFD. RESULTS: Twenty-one patients (85%) received anidulafungin as prophylaxis and 5 patients (15%) received it as treatment. Median duration of intravenous anidulafungin administration was 8 days (range 6-17). Seven patients (28%) presented mild adverse effects, with no significant interactions with calcineurin inhibitors. Sequentially, 4 patients received voriconazole and 6 posaconazole. Two patients (8%) developed IFD after anidulafungin withdrawal: 1 with Candida albicans and the other with Mucor, 8 and 5 days after withdrawal, respectively. CONCLUSIONS: Our results are of interest owing to the absence of data in the literature on anidulafungin use in HSCT patients with GVHD, and suggest that anidulafungin, because of its spectrum, pharmacological profile, low toxicity, and absence of interactions with immunosuppressants, could be a drug of choice in this setting.

Anatomía radiológica del seno esfenoidal: análisis en 120 pacientes intervenidos / Radiologic anatomy of sphenoidal sinus, analysis of 120 surgically intervened patients

Introducción: La patología tumoral hipofisiaria es una consulta frecuente en Neurocirugía. La vía de abordaje a elegir preferentemente es transesfenoidal. Por esto, es de suma importancia conocer la anatomía de los senos paranasales cuando se planifica este abordaje. Materiales y Métodos: Se describe la anatomía radiológica de estudios por Tomografía Computada (TC) y Resonancia Magnética (RM) de 120 pacientes con diagnóstico de adenoma hipofisiario, que se sometieron a cirugía transesfenoidal de hipófisis, prestando especial interés en la morfología de las cavidades paranasales esfenoidales. Resultados: Tipo de neumatización: preselar 25 por ciento y postselar 75 por ciento; Septos: simples 45 por ciento y múltiples 55 por ciento; diámetros promedio: antero-posterior 2,3 cm, transverso: 3,3 cm y vertical: 2,25 cm. Los Senos esfenoidales con neumatización postselar tienen un diámetro anteroposterior significativamente mayor (P < 0,005) que los preselares. Los senos esfenoidales con septo simple tienen un diámetro transverso significativamente mayor (P < 0,007) que los con múltiples septos. El 50 por ciento de los septos siguen una trayectoria paramediana, y el 50 por ciento se desvía hacia una de las arterias carótidas. Conclusión: se confirma la gran variación anatómica del seno esfenoidal siendo independiente del sexo del paciente, además hemos constatado que la relación establecida por los septos intraselares con elementos vasculares intracraneales es muy variable, siendo este hallazgo de suma importancia en la planificación preoperatoria. Los hallazgos realizados por Tomografía computada (TC), pueden ser homologables a lo descrito por otros autores en disecciones cadavéricas.

Introduction: The pituitary tumor pathology is a common query in Neurosurgery. The choice of approach is transsphenoidal preferably, so it is extremely important to know the anatomy of the sinuses when planning this approach. Materials and Methods: We describe the radiological anatomy studies Computerized tomography (CT) and Magnetic Resonance (MR) of 120 patients with pituitary adenoma who underwent transsphenoidal pituitary surgery, with special attention to the morphology of the sphenoid sinuses. Results: Neumatization type: pre-sellar 25 percent and 75 percent post-sellar; Septa: Single 45 percent, multiple 55 percent, mean diameters: 2.3 cm anteroposterior, transverse: 3.3 cm and vertical: 2.25 cm. The sphenoid sinuses with postsellar neumatization have anteroposterior diameter significantly higher (P < 0.005) than the pre-sellar. The sphenoid sinuses are single septum transverse diameter significantly higher (P < 0.007) than those with multiple septa. The 50 percent of the septa paramedian follow a path, and 50 percent is diverted to one of the carotid arteries. Conclusion: Results support the large sphenoid sinus anatomical variation is independent of patient sex, and we found that the relationship established by the intrasellar septa with intracranial vascular elements is very variable, this finding being paramount in preoperative planning. The findings by computed tomography (CT) may be comparable to that described by other authors in cadaveric dissections.

Analysis of post-transplant chimerism by using a single amplification reaction of 38 Indel polymorphic loci.

In order to detect chimerism after allogeneic hematopoietic SCT (HSCT), several methods have been developed. In this study we describe the use of a set of insertion/deletion (Indel) polymorphic loci to determine the level of donor cell engraftment. We analyzed 50 DNA samples from patients who had undergone HSCT, and also several artificial chimeric samples created by mixing different DNA specimens from non-transplanted donors in various proportions. A specific set of 38 autosomic Indel polymorphisms were analyzed. For comparison purposes, a set of 15 short tandem repeats (STRs) were analyzed using the Identifiler Plus Amplification Kit. Our results suggest that Indel-based and STR-based procedures behave similarly in most cases. However, Indel analysis may provide additional information in some cases with a small minor chimeric component or when the presence of stutter bands complicates chimerism estimation.

Chemometric analysis for the detection of biogenic amines in Chilean Cabernet Sauvignon wines: a comparative study between organic and nonorganic production.

UNLABELLED: In this work, the presence of biogenic amines (BAs) was correlated with the type of wine grape culture (traditional or organic) and their concentration in the different stages of winemaking (must, alcoholic fermentation [AF] and malolactic fermentation [MLF]). The formation of BA occurred mainly during MLF in which the percentages for putrescine, cadaverine, phenylethylamine, histamine, and tyramine were 100%, 70%, 13%, 61%, and 44% for the wines produced with traditional grapes and 100%, 94%, 25%, 88%, and 13% for the wines produced with organic grapes, respectively. In general, these latter wines exhibited a lower concentration of total amines. The principal component analysis and partial least-square discriminate analysis indicated that the generation of BA has a certain behavioral pattern in the wines analyzed, which is associated with the different stages of wine production and with the type of culture (traditional or organic) used in the wine grapes. PRACTICAL APPLICATION: Chemometrics tools can be useful as a method of characterization and classification in a global overview of the process variables involved in the development of toxic chemicals in foods, such as the production of BA in wine.

Assessment of exposure to lead in humans and turtles living in an industrial site in Coatzacoalcos Veracruz, Mexico.

The intake of lead from the environment may occur thru various receptors. In order to measure lead levels absorbed, samples were taken from Children who live in three localities surrounding an industrial complex in Coatzacoalcos, Veracruz. Samples were also taken from turtles. Samples were analyzed and results were compared against the general population. In children tested, over 75% of all values were determined to be above CDC's safety levels of (10 µg/dL). The geometric mean lead concentration was 11.4 µg/dL, which is clearly higher around the industrial complex than in the general population. In turtles, lead blood levels in the exposed population were 2-fold above (24.2 µg/dL) those of turtles in the reference population (10.1 µg/dL). Lead levels observed represent a risk for both human and fauna health.

Assessment of dioxin-like soil contamination in Mexico by enzyme-linked immunosorbent assay.

In this work, we describe the results of a preliminary soil assessment program for the detection of dioxins at different sites in Mexico performed by immunoassay. We studied five different sectors considered relevant sources of dioxins: Anaversa and Tekchem industrial areas where organochlorine pesticides were manufactured and released by accidental explosions, secondary smelters, brick kilns, and rural dwellings. In the context of the Agency for Toxic Substances and Disease Registry (ATSDR) guidelines, only the brick kilns sites can be considered as low-risk areas. The dioxin concentrations detected in the vicinity of the Anaversa and Tekchem chemical plants and secondary smelters exceed the screening level of 0.05 ppb set by the ATSDR, and therefore further site-specific studies are needed. The dioxin levels found in all soot samples from indigenous dwellings where wood is used for indoor cooking were above the evaluation level. Considering that the studied areas are representative examples of dioxin sources in less developed countries, our work demonstrates the useful application of dioxin immunoassays as a tool for dioxin screening for environmental assessment programs in developing countries.

Intervención del profesional de enfermería durante la contingencia de influenza A H1N1, en el Instituto Nacional de Enfermedades Respiratorias / Intervention of the professional nursing during the contingency of influenza AH1N1 in the National Institute of respiratory diseases

El INER es una institución normativa en las afecciones respiratorias, quien a lo largo de su historia ha enfrentado desafíos ante situaciones emergentes de salud, como lo son la tuberculosis y el VIH. Actualmente afronta un nuevo reto de salud respiratoria, la epidemia de influenza A H1N1, la cual se presentó de forma inesperada en México en la primavera del 2009, provocando la implementación de medidas sanitarias urgentes, al rebasarse la capacidad de atención médica en el Instituto. Por ello, fue necesario organizar todos sus recursos humanos, físicos y materiales. Instaurar el Comité de Influenza Institucional y en apoyo y coordinación con el Comité de Control de Infecciones, tomar decisiones urgentes enfocadas a la prevención, manejo y control de la enfermedad. Se implementó el Triage en los servicios de concentración para la atención integral del paciente con sospecha y/o confirmación de influenza (Consulta Urgencias, Urgencias Observación, Unidades de Terapia Intensiva e Intermedia y clínico 5). Con todo ello y gracias a la intervención y el trabajo en equipo que realizó el profesional de enfermería del Instituto, se logró controlar la propagación de la epidemia y una vez más lograr conciencia en el personal de salud (médicos y enfermeras), para afrontar manera exitosa, nuevos retos en la salud respiratoria.

INER is a respiratory-illness treating institution which has faced diverse health challenges including tuberculosis and VIH; yet, at present, it is facing a new one: the unexpected 2009 A H1N1 influenza outbreak in Mexico. This massive incident provoked the implementation of urgent sanitary measurements including: the organization of human, physical and material resources; the establishment of-Infection Committee coordinated measurement towards illness prevention, control and management; and the establishment of the TRIAGE on concentration services towards patients with confirmed or dubious influenza (Urgencies, Consult, Urgencies Observation, Intensive Therapy Unit, Intermediate Therapy Unit and Clinical 5). Thanks to these measurements and the INER's nursing personnel team work, we were able to control the outbreak propagation, but also to create consciousness among doctors and nurses to successfully face the new respiratory-illnesses challenges.

Refractory anemia with ringed sideroblasts associated with thrombocytosis: comparative analysis of marked with non-marked thrombocytosis, and relationship with JAK2 V617F mutational status.

The World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (2001) defined a provisional entity named refractory anemia with ringed sideroblasts associated to marked thrombocytosis (RARS-MT). Diagnosis of RARS-MT requires more than 15% of ringed sideroblasts in bone marrow aspirate and the existence of a thrombocytosis in blood, with a platelet count above 600 x 10(9)/L. Nevertheless, controversy exists regarding this platelet count "cut-off" value and, when RARS-MT was defined, the JAK2 mutation and its importance in the study of myeloproliferative disorders was unknown. We present the results of a Spanish retrospective multicentric study, which includes 76 cases of RARS with associated thrombocytosis (platelet count above 400 x 10(9)/L) at diagnosis (RARS-T), 36 of them with a platelet count above 600 x 10(9)/L. Our aim was to analyze their clinical, analytical and morphological characteristics, and to establish correlations with the JAK2 mutational status.

Molecular heterogeneity in chronic lymphocytic leukemia is dependent on BCR signaling: clinical correlation.

Chronic lymphocytic leukemia (CLL), the most frequent form of adult leukemia in Western countries, is characterized by a highly variable clinical course. Expression profiling of a series of 160 CLL patients allowed interrogating the genes presumably playing a role in pathogenesis, relating the expression of functionally relevant signatures with the time to treatment. First, we identified genes relevant to the biology and prognosis of CLL to build a CLL disease-specific oligonucleotide microarray. Second, we hybridized a training series on the CLL-specific chip, generating a biology-based predictive model. Finally, this model was validated in a new CLL series. Clinical variability in CLL is related with the expression of two gene clusters, associated with B-cell receptor (BCR) signaling and mitogen-activated protein kinase (MAPK) activation, including nuclear factor-kappaB1 (NF-kappaB1). The expression of these clusters identifies three risk-score groups with treatment-free survival probabilities at 5 years of 83, 50 and 17%. This molecular predictor can be applied to early clinical stages of CLL. This signature is related to immunoglobulin variable region somatic hypermutation and surrogate markers. There is a molecular heterogeneity in CLL, dependent on the expression of genes defining BCR and MAPK/NF-kappaB clusters, which can be used to predict time to treatment in early clinical stages.

Tendencia de la mortalidad por tumores cerebrales malignos en Chile: Análisis de tasas / Analysis of Chilean trends in mortality from malignant brain tumors

Objective: To analyse the Chilean trends in mortality from brain malignancies between 1985 and 1999. Methods: We calculated mortality rates from malignant brain tumors using data obtained from death certificates available at the National Statistics Office. The following International Classification of Diseases categories were selected: 191.0 to 191.9 (ICD-9), and C71.0 to C71.9 (ICD-10). The rates were adjusted using direct standardization. Prais-Winsten methodology was used for time correlation analysis. Results: Sex-specific rates varied from 0.9 to 1.75 per 100.000 in men and from 0.7 to 1.22 in women. The trend was toward a statistically significant increase in mortality from malignant brain tumors in both groups. The analysis by age group showed no statistically significant variation in those below 35 years old, and a statistically significant increase in those between 35 and 39 years old, and in those above 45 years old. Conclusions: The trend in mortality from malignant brain tumors, in Chile, shows a statistically significant increase in those between 35 and 39 years old, and in those above 45 years old.

Existe controversia en el aumento de la incidencia en las tasas de tumores primarios malignos de cerebro. Este incremento podría explicarse por el crecimiento exponencial en el número de Tomografías computarizadas. Objetivo: Evaluar la tendencia de la mortalidad por tumores cerebrales primarios malignos en Chile (TCM). Metodología: Estudio de tasas de mortalidad de datos obtenidos en índices demográficos (años 1985 a 1999). Se utilizó la población de Chile de los años estudiados y se ajustó a la población estimada de 1999. Se usó las categorías 191,0 a 191,9 y C 71-0 a C 71-9 de la Clasificación Internacional, correspondiendo al grupo de tumores malignos del SNC. Se estudiaron tasas específicas por edad y sexo. Se calculó la tendencia utilizando las tasas ajustada por edad y sexo. Se utilizó una prueba de regresión lineal (Prais-Winsten) para mediciones correlacionales en el tiempo (Stata 7). Resultados: Se obtuvo 2.304 TCM. Las tasas específicas por sexo varían entre 0,90 a 1,75 x 100.000 en hombres y de 0,7 a 1,22 en mujeres. La tendencia global de la mortalidad por tumores tiende al ascenso en ambos grupos y es significativamente más alta en hombres (0,47 95 % IC 0,18 a 0,42 p = < 0,005) El estudio por grupos etarios no muestra un aumento significativo en menores de 14 años, ni entre 15 y 34 años. En los grupos de 45 años y más es estadísticamente significativa. Conclusión: La tendencia a la mortalidad por TCM aparece en ascenso en los grupos etarios 35 a 39 años y 45 años y más.

[Atypical presentation of acute myeloblastic leukemia in two pediatric patients]. / Presentación inusual de leucemia mieloblástica aguda en dos pacientes pediátricos.

Acute myeloblastic leukemia (MLA) is an uncommon disease in childhood and its prognosis is worse than that of lymphoblastic leukemia. Severe hemorrhage, infections and perfusion disorders secondary to leukostasis are the main complications leading to its high mortality rate. Two pediatric patients with MLA (M5a and M2) are presented. Both patients were admitted to the pediatric intensive care unit with acute respiratory distress syndrome and intracranial hemorrhage respectively, secondary to leukostasis. The first patient showed favorable clinical course and underwent bone marrow transplantation four months later; in contrast, the second patient died a few hours after admission. The physiopathology of each case, the therapeutic approach and the use of leukopheresis as a therapeutic alternative in patients with hyperleukocytosis and leukostasis are discussed. A high degree of suspicion is required to make a diagnosis as early as possible in order to avoid the death of a large percentage of patients before cytostatic treatment begins.