The Interleukin-11/IL-11 Receptor Promotes Glioblastoma Survival and Invasion under Glucose-Starved Conditions through Enhanced Glutaminolysis.

Glioblastoma cells adapt to changes in glucose availability through metabolic plasticity allowing for cell survival and continued progression in low-glucose concentrations. However, the regulatory cytokine networks that govern the ability to survive in glucose-starved conditions are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma survival, proliferation and invasion when cells are starved of glucose. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients. Glioblastoma cell lines over-expressing IL-11Rα displayed greater survival, proliferation, migration and invasion in glucose-free conditions compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα reversed these pro-tumorigenic characteristics. In addition, these IL-11Rα-over-expressing cells displayed enhanced glutamine oxidation and glutamate production compared to their low-IL-11Rα-expressing counterparts, while knockdown of IL-11Rα or the pharmacological inhibition of several members of the glutaminolysis pathway resulted in reduced survival (enhanced apoptosis) and reduced migration and invasion. Furthermore, IL-11Rα expression in glioblastoma patient samples correlated with enhanced gene expression of the glutaminolysis pathway genes GLUD1, GSS and c-Myc. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell survival and enhances cell migration and invasion in environments of glucose starvation via glutaminolysis.

Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes.

Precise control of activating H3K4me3 and repressive H3K27me3 histone modifications at bivalent promoters is essential for normal development and frequently corrupted in cancer. By coupling a cell surface readout of bivalent MHC class I gene expression with whole-genome CRISPR-Cas9 screens, we identify specific roles for MTF2-PRC2.1, PCGF1-PRC1.1 and Menin-KMT2A/B complexes in maintaining bivalency. Genetic loss or pharmacological inhibition of Menin unexpectedly phenocopies the effects of polycomb disruption, resulting in derepression of bivalent genes in both cancer cells and pluripotent stem cells. While Menin and KMT2A/B contribute to H3K4me3 at active genes, a separate Menin-independent function of KMT2A/B maintains H3K4me3 and opposes polycomb-mediated repression at bivalent genes. Release of KMT2A from active genes following Menin targeting alters the balance of polycomb and KMT2A at bivalent genes, facilitating gene activation. This functional partitioning of Menin-KMT2A/B complex components reveals therapeutic opportunities that can be leveraged through inhibition of Menin.

Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses.

There is increasing recognition of the prognostic significance of tumor cell major histocompatibility complex (MHC) class II expression in anti-cancer immunity. Relapse of acute myeloid leukemia (AML) following allogeneic stem cell transplantation (alloSCT) has recently been linked to MHC class II silencing in leukemic blasts; however, the regulation of MHC class II expression remains incompletely understood. Utilizing unbiased CRISPR-Cas9 screens, we identify that the C-terminal binding protein (CtBP) complex transcriptionally represses MHC class II pathway genes, while the E3 ubiquitin ligase complex component FBXO11 mediates degradation of CIITA, the principal transcription factor regulating MHC class II expression. Targeting these repressive mechanisms selectively induces MHC class II upregulation across a range of AML cell lines. Functionally, MHC class II+ leukemic blasts stimulate antigen-dependent CD4+ T cell activation and potent anti-tumor immune responses, providing fundamental insights into the graft-versus-leukemia effect. These findings establish the rationale for therapeutic strategies aimed at restoring tumor-specific MHC class II expression to salvage AML relapse post-alloSCT and also potentially to enhance immunotherapy outcomes in non-myeloid malignancies.

Tumor de colon como hallazgo incidental en un paciente con endocarditis por Streptococcus gallolyticus: experiencia desde la práctica clínica / Colon tumor as an incidental finding in a patient with endocarditis due to Streptococcus gallolyticus: experience from clinical practice

El Streptococcus gallolyticus del colon. La fisiopatología que explica este fenómeno implica el aumento local de niveles de lactato puede presentarse como el germen causal de la endocarditis infecciosa en pacientes con lesiones premalignas y malignas, colágeno, fibrinógeno y fibronectina secundario a la hiperactividad metabólica tumoral que genera un ambiente adecuado para el crecimiento y adhesión bacteriana a la pared intestinal y posterior translocación al torrente sanguíneo. Simultáneamente, se establece la presencia de infecciones secundarias por la formación de biofilms, tanto a nivel colorrectal como en válvulas cardíacas. El objetivo del manuscrito es un mapeo en la literatura médica disponible sobre la correlación entre la endocarditis por Streptococcus gallolyticus y las lesiones premalignas y malignas de colon. Simultáneamente, exponer la experiencia clínica de un hombre de 82 años con diagnóstico de endocarditis por Streptococcus gallolyticus y el hallazgo incidental de pólipos adenomatosos del colon(AU)

Streptococcus gallolyticus can present as the causative germ of infective endocarditis in patients with premalignant and malignant lesions of the colon. The pathophysiology that explains this phenomenon involves the local increase in lactate that can be presented as the causal germ of infective endocarditis in patients with premalignant and malignant lesions, collagen, fibrinogen, and fibronectin levels secondary to tumor metabolic hyperactivity, which generates a suitable environment for bacterial growth and adhesion to the intestinal wall and subsequent translocation to the bloodstream. Simultaneously, the presence of secondary infections is established due to the formation of biofilms, both at the colorectal level and in the heart valves. The objective of the manuscript is a mapping in the available medical literature on the correlation between Streptococcus gallolyticus endocarditis and premalignant and malignant colonic lesions. Simultaneously, to present the clinical experience of an 82-year-old man diagnosed with Streptococcus gallolyticus endocarditis and the incidental finding of adenomatous polyps of the colon(AU)

Carfilzomib Promotes the Unfolded Protein Response and Apoptosis in Cetuximab-Resistant Colorectal Cancer.

Cetuximab is a common treatment option for patients with wild-type K-Ras colorectal carcinoma. However, patients often display intrinsic resistance or acquire resistance to cetuximab following treatment. Here we generate two human CRC cells with acquired resistance to cetuximab that are derived from cetuximab-sensitive parental cell lines. These cetuximab-resistant cells display greater in vitro proliferation, colony formation and migration, and in vivo tumour growth compared with their parental counterparts. To evaluate potential alternative therapeutics to cetuximab-acquired-resistant cells, we tested the efficacy of 38 current FDA-approved agents against our cetuximab-acquired-resistant clones. We identified carfilzomib, a selective proteosome inhibitor to be most effective against our cell lines. Carfilzomib displayed potent antiproliferative effects, induced the unfolded protein response as determined by enhanced CHOP expression and ATF6 activity, and enhanced apoptosis as determined by enhanced caspase-3/7 activity. Overall, our results indicate a potentially novel indication for carfilzomib: that of a potential alternative agent to treat cetuximab-resistant colorectal cancer.

EGFRvIII Promotes Cell Survival during Endoplasmic Reticulum Stress through a Reticulocalbin 1-Dependent Mechanism.

Reticulocalbin 1 (RCN1) is an endoplasmic reticulum (ER)-residing protein, involved in promoting cell survival during pathophysiological conditions that lead to ER stress. However, the key upstream receptor tyrosine kinase that regulates RCN1 expression and its potential role in cell survival in the glioblastoma setting have not been determined. Here, we demonstrate that RCN1 expression significantly correlates with poor glioblastoma patient survival. We also demonstrate that glioblastoma cells with expression of EGFRvIII receptor also have high RCN1 expression. Over-expression of wildtype EGFR also correlated with high RCN1 expression, suggesting that EGFR and EGFRvIII regulate RCN1 expression. Importantly, cells that expressed EGFRvIII and subsequently showed high RCN1 expression displayed greater cell viability under ER stress compared to EGFRvIII negative glioblastoma cells. Consistently, we also demonstrated that RCN1 knockdown reduced cell viability and exogenous introduction of RCN1 enhanced cell viability following induction of ER stress. Mechanistically, we demonstrate that the EGFRvIII-RCN1-driven increase in cell survival is due to the inactivation of the ER stress markers ATF4 and ATF6, maintained expression of the anti-apoptotic protein Bcl-2 and reduced activity of caspase 3/7. Our current findings identify that EGFRvIII regulates RCN1 expression and that this novel association promotes cell survival in glioblastoma cells during ER stress.

Serial Perioperative Assessment of Free Flap Perfusion With Laser Angiography.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Reconstruction with microvascular free flaps is quite predictable but excessive fluids intraoperatively and excessive use of vasopressors have been implicated in postoperative complications. However, vasopressors assist in limiting fluid administration and counteract vasodilatory effects of general anesthetics, while maintaining proper intravascular volume. This is of paramount importance during surgery to ensure adequate tissue and organ perfusion. The purpose of this study is to quantify perfusion changes in free flaps at specific time points during peri- and postoperative periods, incorporating SPY technology. METHODS: A prospective study of patients who underwent free flap reconstruction was conducted (n = 9), using SPY laser angiography with indocyanine green to assess effects of general anesthetics and vasopressors on flap perfusion. Free flaps were evaluated prior to pedicle division, after inset and anastomosis, and in the immediate postoperative setting. Mean perfusion, mean arterial pressure, total operative time, fluid shifts, and vasopressor use were recorded. Data were analyzed with univariate and multivariable analyses. RESULTS: Those with major complications in this cohort, on average received less vasopressors, had shorter operation times and less blood loss, however, they received more fluids intraoperatively. CONCLUSION: Changes in mean perfusion to the free flap during the intraoperative and immediate postoperative period are nominal.

Chemical Characterization and Antiradical Properties of Pyroligneous Acid from a Preserved Bamboo, Guadua angustifolia Kunth

Abstract Pyroligneous acid (PA) was obtained by condensation of the vapors produced in the thermal decomposition of culms residues from Guadua angustifolia Kunth (G. angustifolia) cultivated in Colombia, with and without previous preservation treatment with borax salts. Chemical characterization by GC-MS showed that PA extracts has high content of phenolic compounds. Mequinol, isocreosol, 4-ethylphenol, 4-ethyl-2-methoxyphenol, 3,5-dimethoxy-4-hydroxytoluene and 2,6-dimethoxyphenol were the most abundant substances, identified. The total phenolic content (TPC) and DPPH free radical scavenging activity, were investigated. TPC showed a concentration of 1.959 mg GA g-1±0.010 and 3.844 mg GA g-1±0.027 to PAC and PAS samples. These samples also exhibited high DPPH activity of 70.975%±0.921 and, 16.667%±0.298, respectively. The chemical composition, TPC and DPPH results indicate that the PA extracts obtained from G. angustifolia may be used as a raw material in the food industry as natural preservative, in medicine as alternative to antibiotics and in agriculture as insect repellent and foliar fertilizer.

Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma.

Despite aggressive treatment with temozolomide and radiotherapy and extensive research into alternative therapies there has been little improvement in Glioblastoma patient survival. Median survival time remains between 12 and 15 months mainly due to treatment resistance and tumor recurrence. In this study, we aimed to explore the underlying mechanisms behind treatment resistance and the lack of success with anti-EGFR therapy in the clinic. After generating a number of treatment resistant Glioblastoma cell lines we observed that resistant cell lines lacked EGFR activation and expression. Furthermore, cell viability assays showed resistant cells were significantly less sensitive to the anti-EGFR agents when compared to parental cell lines. To further characterise the resistance mechanism in our cells microRNA prediction software identified miR-221 as a negative regulator of EGFR expression. miR-221 was up-regulated in our resistant cell lines, and this up-regulation led to a significant reduction in EGFR expression in both our cultured cell lines and a large cohort of glioblastoma patient tumor tissue.

Estudio retrospectivo observacional de los cambios del metabolismo mineral óseo post cirugía bariátrica / Observational retrospective study of changes in bone mineral metabolism after bariatric surgery

Introducción. Se ha descripto previamente que la cirugía bariátrica (CB) podría producir pérdida de la masa ósea dadas por alteraciones en el metabolismo mineral óseo. Se realizó este estudio con el objetivo de describir el impacto de la CB en el metabolismo óseo de pacientes en nuestro centro. Materiales y métodos. Estudio retrospectivo en el período 6/2007-3/2016. Se analizaron pacientes con datos de metabolismo óseo que requirieron CB. Se analizaron parámetros de laboratorio previos a la cirugía y a los 18 meses posteriores. Resultados. Se incluyeron 56 pacientes, con una mediana de edad de 47 años en un rango entre 26 y 70. Del total de los pacientes, 50 fueron intervenidos por gastrectomía vertical en manga y 6 por bypass gástrico. A pesar de no haber resultado estadísticamente significativos, se observó un incremento de los valores de vitamina D previos a la cirugía en comparación con este valor 18 meses posteriores (22 ng/ml vs 37 ng/ml respectivamente; p=0.194). Discusión. Se constató deficiencia de vitamina D prequirúrgica que revirtió en el pos operatorio, probablemente debido a la pérdida de peso, con la consiguiente liberación de la vitamina D secuestrada en el tejido adiposo, y a menor esteatosis y por consiguiente mayor metabolización hepática. Consideramos que es necesaria la realización de un estudio prospectivo con evaluación de la densidad mineral ósea en esta población de pacientes.(AU)

Movilidad temprana: un reto para el contexto colombiano / Early mobility: a challenge for the Colombian context

El 15 % de la población mundial tiene algún tipo de discapacidad y necesita de productos de apoyo. En el caso de los niños, estos son fundamentales ya que permiten la exploración del entorno y potencian sus capacidades. En países como Colombia, donde el acceso a los productos de apoyo está parcialmente reglamentado pero no todas las personas acceden estos, un programa como Go baby Go se hace relevante; este es un programa que modifica y entrega carritos de batería para favorecer el juego y la participación de niños con discapacidad.

15% of the world's population has some kind of disability and needs assistive products. In the case of children, these are essential as they allow them to explore their environment and enhance their capabilities. In countries like Colombia, where access to assistive products is partially regulated but not all people have access to them, a program like Go baby Go becomes relevant; this is a program that modifies and delivers battery carts to encourage play and participation of children with disabilities.

Hipoglucemia post cirugía bariátrica. Presentación de un caso con buena respuesta a octreótide / HYPOGLYCEMIA COMPLICATING BARIATRIC SURGERY. CASE REPORT WITH SUCCESSFUL RESPONSE TO OCTROTIDE

El Bypass Gástrico (BPG) representa la herramienta terapéutica más efectiva para el manejo de la obesidad. Sin embargo, la hipoglucemia con neuroglucopenia post BPG es una complicación que se describe cada vez con mayor frecuencia. Se presenta el caso de una paciente con hipoglucemia hiperinsulinémica (HH) post BPG y los distintos esquemas terapéuticos utilizados, pudiendo controlar finalmente los valores de glucemia con octreótide y evitando así, la realización de una pancreatectomía para el tratamiento de las hipoglucemias

Gastric Bypass (GBP) is the most effective treatment for patients with severe obesity. Hyperinsulinemic hypoglycemia with neuroglycopenia is an increasingly late complication of GBP. A case of a post GBP hyperinsulinemic hypoglycemia is reported, and the different drugs used for its treatment, being able to control the glycemia with octreotide and avoiding a pancreatectomy surgery as hypoglycemia treatment

Bloqueo del plano transverso del abdomen en herniorrafia inguinal. Ensayo clínico controlado / Lactate serial measurements and predictive validity of early mortality in trauma patients admitted to the intensive care unit

Abstract Introduction: Patients who have experienced trauma usually develop hypovolemic shock, which determines different levels of tissue hypoperfusion. The determination of lactate levels has been used as a reliable biomarker in the assessment of the magnitude of hypo-perfusion. Additionally, it has been established that lactic clearance in the first 6 h has value as a prognostic measurement for the mortality rate of these patients. However, beyond 6 h its utility is controversial. Objective: To evaluate the predictive capacity of serial lactic acid as well as clearance (at the time admitted, 12 and 24 h) in mortality cases for trauma patients admitted to the ICU. Materials and methods: During the period between 2010 and 2014, an observational longitudinal cohort study was conducted with trauma patients admitted to the Intensive Care Unit (ICU) at the Clínica Universidad de la Sabana. The clinical and demographic data was registered in a data base using Microsoft Excel and analyzed in STATA 12® statistical software. In order to determine the association between each measurement with mortality after seven days, serial measurements of lactic acid were taken at admission time, 12-24 h as well as the clearance of lactic acid at 12 and 24 h. Results: 233 patients participated during the time of the study. The average age was 38 years. 78% of the patients were male, with 21% of the mortality at seven days in the ICU. Among the severity indexes, an average of 14 in APACHE II, 9 in SOFA and 25 in ISS was found. The average of length of stay for survive patients was nine days in contrast to five days of mortality patients. In brief, the lactic acid average was associated with mortality at seven days in the three time measurements. On the other hand, the values of the receptor curve operating showed the best performance of the discrimination at 24 h with a 2.35 cut-off point and OR 1.65 (CI 95% 1.27-2.13). Conclusions: Our findings determined a similar performance of the lactic acid as compared to other studies, especially in the lactic acid level at 24h with relevant discrimination over 2.35 mEq/L at 24. Nonetheless, reverse causality can eventually occur.

Resumen Introducción: La herniorrafia inguinal es una de las cirugías más realizadas en el mundo, y está asociada con dolor postoperatorio de moderado a severo. El bloqueo del plano transverso del abdomen (transversus abdominus plane [TAP]) parece ser una técnica útil para disminuir la morbilidad asociada con el dolor en herniorrafia inguinal. Objetivo: Evaluar el efecto analgésico del bloqueo TAP a la hora y a las 24 h postoperatorias en herniorrafia inguinal. Materiales y métodos: Se realizó un estudio doble ciego donde se aleatorizaron 45 pacientes para recibir bloqueo TAP vs placebo, se analizaron variables clínicas, quirúrgicas y anestésicas, y se evaluó como resultado primario la intensidad de dolor agudo postoperatorio (pop) una hora después de la cirugía y, como resultados secundarios, el dolor a las 24 h, el consumo de opiáceos y la presencia de reacciones adversas. Resultados: El dolor agudo postoperatorio a la primera hora en el grupo control fue de 6, con valores máximos de 9 en el 22% de los pacientes, mientras que el dolor en la primera hora en el grupo intervención fue de 2 (DE: 1) (p = 0,03). De igual forma, el dolor a las 24h pop y el consumo de opiáceos fue menor en el grupo intervención que en el grupo control. Conclusiones: El bloqueo TAP es útil en la reducción del dolor agudo pop y del consumo de opiáceos en herniorrafia inguinal.

Diagnóstico de muerte cerebral: uso de la angiografía por tomografía axial computarizada como herramienta diagnóstica no invasiva al alcance de todos / Diagnosis of Brain Death: Use of Computed Tomography Angiography as a Non-invasive Diagnostic Tool Available to Everyone

Introducción: La muerte cerebral (MC) se define como la pérdida irreversible de la función cerebral y la ausencia de reflejos del tallo cerebral y de movimientos respiratorios. Objetivo: Describir los hallazgos en la angioTAC cerebral en pacientes con signos clínicos de MC, para evaluar su aplicabilidad como método diagnóstico. Métodos: Se realizó un estudio retrospectivo, entre septiembre de 2013 y abril de 2015; se incluyeron pacientes entre 21 y 60 años, a quienes se les practicó angioTAC para verificar MC. El diagnóstico clínico de MC se realizó mediante el examen neurológico y el test de apnea. Adicionalmente se realizó una angioTAC con tomógrafo multicorte de cuatro detectores, con tres adquisiciones, mediante cortes axiales de 2 mm desde el cuerpo vertebral de C6 hasta 5 cm arriba. El diagnóstico escanográfico de MC se hizo basado en criterios de ausencia completa de circulación intracraneal con una escala de 6 puntos. Resultados: Se identificaron 12 pacientes que cumplían con los criterios de inclusión (5 hombres y 7 mujeres), con edad media 46,6 años (21-60). Los diagnósticos de base fueron: neurovascular (n=8), trauma craneoencefálico (n=2), meningioma (n=1) y paro cardiorespiratorio (n=1). Solo un paciente no cumplió con los 6 puntos de los criterios propuestos para la evaluación con angioTAC. Conclusiones: La angioTAC puede suministrar información suficiente para realizar el diagnóstico confirmatorio imaginológico de MC en los pacientes con duda diagnostica clínica; sin embargo, es necesario compararlo en el futuro con la angiografía por catéter.

Introduction: Brain death (BD) is defined as an irreversible loss of brain function, and the absence of reflexes of the brain stem and of respiratory movements. Objective:To describe the brain CT angiography findings in patients with clinical signs of brain death (BD) and to evaluate its applicability as a diagnostic method of BD as well. Methods: A retrospective study was performed between September 2013 and April 2015, which included patients between the ages of 21 and 60, who underwent CT angiography with BD protocol. The clinical diagnosis of BD was made by neurological examination and with an apnea test. Additionally, a multi-slice CT angiography was performed with a 4-detectors tomograph, with three acquisitions, with 2mm axial slices from the vertebral body of C6 to 5 cm above. The BDscan diagnostic criteria was performed based on criteria of complete absence of intra-cranial circulation with a 6 point scale. Results: 12 patients that met the inclusion criteria (5 males and 7 females), with a mean age of 46.6 years (21-60) were identified. The initial diagnosis of the patients were neurovascular (n = 8), head trauma (n = 2), meningioma (n = 1) and cardiopulmonary arrest (n = 1). Only one patient did not meet the 6 points of the proposed criteria for the evaluation with CT angiography. Conclusions: CT angiography could provide enough information to perform confirmatory diagnostic imaging of BD in patients with clinical doubts of diagnosis of BD, however it is necessary in the future to compare it with catheter angiography.

Caracterización clínica, bioquímica e imagenológica en una cohorte de pacientes diagnosticados con hiperglicinemia no cetósica clásica: estudio ambispectivo 2000-2014, Medellín, Colombia / Clinical, biochemical and imaging characterization in a cohort of patients diagnosed with classical nonketotic hyperglycinemia: ambispective study 2000-2014, Medellin-Colombia

Introducción: La hiperglicinemia no cetósica (HGNC) es un error innato del metabolismo del grupo de las aminoacidopatías, de carácter autosómico recesivo, causado por un defecto en el sistema de clivaje de la glicina. Es una entidad rara y no se conoce su incidencia en Colombia. Objetivo: Describir características clínicas, bioquímica e imagenológicas en una cohorte de pacientes diagnosticados con hiperglicinemia no cetósica clásica Materiales y métodos: Estudio de tipo descriptivo, ambispectivo, en el periodo enero 2000-2014, en varios centros de Medellín. Resultados: Se incluyeron 20 pacientes que cumplían criterios de inclusión, de los 35 pacientes que cumplían con el criterio de búsqueda, en su mayoría de sexo femenino y con un Apgar adecuado al nacer. El promedio de inicio de los síntomas fue de 2,6 días; somnolencia, hipoactividad, apnea, convulsiones y singulto fueron los principales síntomas, y las convulsiones de tipo focal las más frecuentes. La relación glicina LCR/plasma en promedio fue 0,42. El patrón estallido-supresión en el electroencefalograma y la ausencia o retraso en la mielinización de la sustancia blanca supratentorial en la resonancia magnética fueron hallazgos comunes. Conclusión: La HGNC es frecuente en nuestro medio, por lo cual es necesario que se disponga de pruebas bioquímicas y moleculares necesarias para diagnóstico oportuno, manejo integral y asesoría genética.

Introduction: Nonketotic Hyperglycinemia is an inborn error of metabolism in a group of aminoacidopathies, autosomal recessive, caused by a defect in the system of the glycine cleavage. It is rare, and the incidence is unknown in Colombia. Objective:To describe clinical, biochemical and imaging characteristics in a cohort of patients diagnosed with classical nonketotic hyperglycinemia. Materials and methods: This is a descriptive-ambispective study during the period January 2000 - 2014 in some centers of Medellin. Results: There were 35 patients who met the search criteria and finally 20 patients who met inclusion criteria. We found in this cohort more girls than boys, and most of them with a good APGAR. The average onset of symptoms was 2.6 days, with drowsiness, hypoactivity, apnea, seizures and singultus the main symptoms. The focal seizures were the most frequent type. The average value of CSF glycine to plasma glycine ratio was 0.42. The burst suppression pattern in the EEG and the absence or delayed myelination in the supratentorial white matter on MRI were common findings. All patients received dextromethorphan as part of their treatment and the vast majority of sodium benzoate. Conclusion: HGNC is common in our environment. It´s necessary to have available biochemical and molecular evidence for timely diagnosis, comprehensive management and genetic counseling.

Isolated central nervous system relapse in chronic myeloid leukemia.

Chronic myeloid leukemia is a myeloproliferative disorder that has three distinguished phases: chronic, accelerated, and blastic. In extremely rare cases, the blast phase can affect the central nervous system without concomitant bone marrow involvement. We report the case of a patient with chronic myeloid leukemia who, despite having achieved complete cytogenetic remission in the bone marrow for several years, experienced a blast crisis of the central nervous system following an episode of infectious meningoencephalitis.

Indicadores de la poligrafía respiratoria y su relación con los parámetros antropométricos en obesos evaluados para cirugía bariátrica / Indicators of Respiratory Polygraphy and their Relation with Anthropometric Parameters in Obesity Patients Evaluated for Bariatric Surgery

Objetivo: Correlacionar indicadores antropométricos; índice de cintura-cadera (ICC) y diámetro sagital (DS) con IAH en candidatos a cirugía bariátrica (CB). Materiales y métodos: Se registraron el IMC, ICC y DS. Se evaluó IAH relevante (> 15 eventos/hora) mediante poligrafía respiratoria (PR) y se correlacionó con sexo, edad > de 50 años, escala de Berlín, HTA, DS ≥ 30 e ICC ≥ 1. Resultados: Fueron analizados 81 pacientes (mujeres 50/61.73%). Las medias fueron; edad: 46.32, SD: 11.53, IMC: 45.98 SD: 8.41 (rango: 35-77 kg/m²) y Epworth (ESS): 8.87, SD: 4.86. El 100% presentó alto riesgo por Berlín, ESS >10: 33.86% e HTA: 39.51%. Los indicadores poligráficos (medias) fueron; tiempo de registro: 407 minutos (SD: 110) e IAH: 20.66 (SD: 24.02). La prevalencia de IAH > 5/hora fue del 77.77%, IAH > 15/hora; 34.56% y el 21% obtuvo > 30/hora. La media del DS fue de 30.9 (SD: 4.60) y del ICC de 0.97 (SD: 0.09). Modelos de regresión para DS ≥ 30 cm (OR: 1.97 y p = 0.239) + ICC ≥ 1 (OR: 1.394 y p = 0.636) no alcanzaron significación cuando se adicionó sexo masculino (OR: 5.29 y p = 0.003). En regresión logística las variables no alcanzaron significación; DS ≥ 30 cm: OR de 1.25 (CI95%: 0.33-4.66) p = 0.739, ICC ≥ 1; OR 0.93 (SD: 0.19-4.62) p = 0.939 y muestran predictor exclusivamente al sexo masculino (OR: 4.20. CI95%: 1.21-14.5) p = 0.023. Conclusiones: La obesidad central según ICC ≥ 1 y DS ≥ 30 cm no tuvo correlación con IAH > 15/hora. Continúan siendo necesarios métodos objetivos (PR o polisomnografía) para evaluar la severidad del trastorno.

Objective: To assess correlation between anthropometric indexes; waist to hip ratio (WHI), sagital diameter (SD) and AHI obtained from home respiratory polygraphy (RP) in bariatric surgery candidates (BS). Methods: BMI, WHI and SD were recorded for BS candidates. Sleep apnea was defined as significant if AHI >15 events/hour. Variables included in the model were; sex, age greater than 50 years, Berlin questionnaire, history of hypertension (HBP), SD ≥ 30 and WHI ≥ 1. Results: Data from 81 patients were analyzed (50 women, 61.73%), age 46.32, SD 11.53, BMI 45.98 SD: 8.41 (range: 35-77 kg/m²) and ESS: 8.87 (SD: 4.86). 100% had high risk by Berlin questionnaire, 33.86% had ESS >10, and 39.51% HBP. Respiratory polygraphy data were: recording time: 407 minutes (SD: 110) and AHI: 20.66 (SD: 24.02). Prevalence of AHI > 5/hour (pathological) was 77.77%; significant AHI (> 15/hour) 34.56%, and 21% had > 30/hour. The SD was 30.9 (SD: 4.60) and WHI of 0.97 (SD: 0.09). 48.15% had a WHI ≥ 1. Logistic regression showed: DS ≥ 30 cm (OR: 1.97, p = 0.239) + WHI ≥ 1 (OR 1.394, p = 0.636) and it did not reach significance when male sex is added. Both variables included in the model did not reach statistical significance; SD ≥ 30 cm: OR of 1.25 (95% CI: 0.33-4.66) p = 0.739, ICC ≥ 1, OR 0.93 (SD: 0.19-4.62) p = 0.939. In the model, male sex was the only predictor (OR: 4.20, CI 95%: 1.21. -14.5) p = 0.023. Conclusions: Central obesity measured by WHI ≥ 1 and SD ≥ 30 cm had no significant correlation with AHI > 15/h. Objective methods (RP or polysomnography) are needed to assess the severity of the disorder before prescribing bariatric surgery.

Alteraciones electrocardiográficas en anorexia nervosa: revisión crítica de la literatura / Electrocardiographic abnormalities in anorexia nervosa: a critical review of the literature

Introducción: La anorexia nervosa (AN) es un trastorno de la conducta alimentaria y, entre sus causas de mortalidad, las arritmias cardiacas y la muerte súbita son frecuentes, por lo que es indispensable la monitorización electrocardiográfica. Se han descrito muchos hallazgos con resultados contradictorios, por lo que es necesaria una revisión crítica de la literatura científica. Metodología: Revisión de los estudios relevantes sobre cambios electrocardiográficos en AN, consultados en PubMed desde 1974 hasta febrero de 2014, utilizando los términos MeSH: Eating disorders, nervosa anorexia, sinusal bradycardia, QT prolongation, QT dispersion, electrocardiography, EKG, electrocardiogram. Resultados y discusión: Las dos alteraciones más comunes reportadas incluyen la bradicardia sinusal y los cambios en la repolarización evidenciados en prolongación del QT e incremento de su dispersión. Los trastornos electrolíticos parecen ser la causa de estas alteraciones en algunos pacientes, pero otras razones se discuten en detalle, como la desviación del eje del QRS a la derecha, la alteración en variabilidad de la frecuencia cardiaca, R en derivación V6 de bajo voltaje, disminución de la amplitud del QRS y onda T y alargamiento del QRS. La mayoría de los autores hablan de reversibilidad de los cambios después del tratamiento. Conclusiones: Estos resultados siguen apoyando la necesidad de valorar a los pacientes con AN con electrocardiogramas inicial y de seguimiento, para el diagnóstico temprano y tratamiento de alteraciones cardiovasculares relacionadas con alta morbimortalidad. También apoyan la necesidad del uso racional de psicofármacos para no aumentar el riesgo de arritmias cardiacas y muerte súbita.

Background: Anorexia nervosa is an eating disorder in which cardiac arrhythmias and sudden death are frequent causes of mortality, which makes electrocardiographic monitoring indispensable in these patients. There are many suggestive findings but results are contradictory, making a critical review of the scientific literature is necessary. Methods: The most relevant studies on electrocardiographic (EKG) changes in patients with AN, found in PubMed from 1974 to February 2014, were reviewed using the MeSH terms: eating disorders, nervosa anorexia, sinus bradycardia, QT prolongation, QT dispersion, electrocardio graphy, EKG, and electrocardiogram. Findings and discussion: The two most common EKG findings reported in the literature are sinus bradycardia and changes in depolarization, as shown by prolongation and increased dispersion of the QT interval. Electrolyte disturbances seem to be the cause of these disturbances in some patients, but other reasons are also discussed in detail, such as QRS right axis deviation, disturbances of heart rate variability, low R wave voltage in V6, amplitude decrease of the QRS and T wave, and QRS prolongation. The majority of authors report that these changes are reversible after treatment of AN. Conclusions: These findings support the need for initial and follow-up EKGs in patients with AN and for early diagnosis and treatment of cardiovascular disturbances that are associated with morbidity and mortality. They also support the need for the rational use of psychop harmacology, and that does not increase the risk of arrhythmias and sudden death in these patients.

Caracterización morfológica, biológica y genética de un aislamiento Colombiano de granulovirus de Erinnyis ello (L.) (Lepidoptera: Sphingidae) / Characterization of a Colombian isolate of Erinnyis ello granulovirus (L.) (Lepidoptera: Sphingidae)

El gusano cachón Erinnyis ello (L.) es una plaga polífaga que puede causar graves pérdidas en cultivos de caucho. El uso de granulovirus representa una alternativa interesante para el control biológico de este insecto. Tres aislamientos colombianos del granulovirus de E. ello (EeGV) recuperados en larvas de campo, fueron caracterizados morfológica y molecularmente. Los cuerpos de inclusión de los tres aislamientos presentaron forma ovoide con una única nucleocápside, con tamaño promedio de 302,9 ± 22 x 181,5 ± 16 nm. El análisis de los perfiles de restricción con diferentes endonucleasas no mostró diferencias entre los tres aislamientos, lo cual sugiere que son muestras de la misma cepa viral, denominada VG010, cuyo tamaño del genoma se estimó en 88,7 Kb. El análisis de las relaciones filogenéticas basado en las secuencias de lef-8, lef-9 y gran mostró con alta consistencia la estrecha relación entre VG010 y un aislamiento de EeGV (M34-4) previamente descrito, lo cual sugiere que son variantes genotípicas de la misma especie viral. La eficacia del aislamiento VG010 en condiciones de laboratorio sobre larvas de segundo y cuarto estadio fue de 100 % y 64 % respectivamente, mientras que la concentración letal media (CL50) fue 4,3 x 103 CI/mL. La productividad viral, osciló entre 2,1 x 109 y 3,8 x 109 CI/gramo de larva. Estos resultados representan la base para el desarrollo de un nuevo bioinsecticida para el control de la plaga en campo.

Erinnyis ello (L.) is a polyphagous lepidopteran pest that may cause serious annual losses in the rubber industry. The use of granulovirus represents an interesting alternative as a biological control agent for this insect. Three Colombian isolates of granulovirus for E. ello (EeGV) were obtained from field larvae and characterized at morphological, biological and molecular level. Occlusion bodies (OB) of the three isolates showed an oval morphology with a unique nucleocapsid, with a size of 302.9 ± 22 x 181.5 ± 16 nm. Analysis of DNA endonuclease restriction profiles did not showed differences among the three viral isolates, which means that they correspond to samples of the same viral strain, denominated VG010. The VG010 viral genome size was estimated to be approximately 88.7 kb. The analysis of the phylogenetic relationships based on selected gene sequences lef-8, lef-9 and gran showed a close relationship between VG010 and the previously described isolate EeGV (M34-4). These sequence similarities suggest that the three isolates are genotypic variants of the same viral species. The in vitro efficacy of the VG010 isolate against second and fourth instar larvae was 100 and 64%, respectively, while the mean lethal concentration (LC50) was 4,3 x 103 OB/mL. The viral productivity ranged between 2.1 x 109 and 3.8 x 109 OB/g of larvae. These results represent the basis to develop a new biopesticide control agent for the pest in the field.