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Hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) is a rare, potentially fatal, bradykinin-mediated disease. Icatibant is a bradykinin B2 receptor antagonist originally approved in 2008 in the European Union and 2011 in the United States as an acute therapy option for HAE attacks in adults.

2 p. 22nd Congress of the European Hematology Association. Madrid, Spain, June 22 - 25, 2017, Endocannabinoid system is a set of ligands, receptors and endogenous enzymes which modulate a variety of physiological effects. There are two well-characterized cannabinoid receptors, CB1 (mainly expressed in Central Nervous System) and CB2 (mainly in hematopoietic cells). Here, we tested the effect of the cannabinoid WIN-55 212-2 in acute myeloid leukemia (AML) in vitro and in vivo and studied the molecular signaling pathways involved in this effect, specially the role of sphingolipids. Moreover, we synthesized a new family of twelve cannabinoids that are specific to CB2 receptor.

The Icatibant Outcome Survey (IOS) is an observational study monitoring safety and effectiveness of icatibant in the real-world setting. We analyzed safety data from 3025 icatibant-treated attacks in 557 patients (enrolled between July 2009 and February 2015). Icatibant was generally well tolerated. Excluding off-label use and pregnancy, 438 patients (78.6%) did not report adverse events (AEs). The remaining 119 (21.4%) patients reported 341 AEs, primarily gastrointestinal disorders (19.6%). Of these, 43 AEs in 17 patients (3.1%) were related to icatibant. Serious AEs (SAEs) occurred infrequently. A total of 143 SAEs occurred in 59 (10.6%) patients; only three events (drug inefficacy, gastritis, and reflux esophagitis) in two patients were considered related to icatibant. Notably, no SAEs related to icatibant occurred in patients with cardiovascular disease, nor in those using icatibant at a frequency above label guidelines. Additionally, no major differences were noted in AEs occurring in on-label vs off-label icatibant users.

BackgroundAlthough consensus guidelines have been proposed in 2010 for the diagnostic screening of paroxysmal nocturnal hemoglobinuria (PNH) by flow cytometry (FCM), so far no study has investigated the efficiency of such medical indications in multicentric vs. reference laboratory settings. MethodsHere we evaluate the efficiency of consensus medical indications for PNH testing in 3,938 peripheral blood samples submitted to FCM testing in 24 laboratories in Spain and one reference center in Brazil. ResultsOverall, diagnostic screening based on consensus medical indications was highly efficient (14% of PNH+ samples) both in the multicenter setting in Spain (10%) and the reference laboratory in Brazil (16%). The highest frequency of PNH+ cases was observed among patients screened because of bone marrow (BM) failure syndrome (33%), particularly among those with aplastic anemia (AA; 45%) and to a less extent also a myelodysplastic syndrome (MDS; 10%). Among the other individuals studied, the most efficient medical indications for PNH screening included: hemolytic anemia (19%), hemoglobinuria (48%) and unexplained cytopenias (9%). In contrast, only a minor fraction of the patients who had been submitted for PNH testing because of unexplained thrombosis in the absence of cytopenia, were positive (0.4%). ConclusionsIn summary, our results demonstrate that the current medical indications for PNH screening by FCM are highly efficient, although improved screening algorithms are needed for patients presenting with thrombosis and normal blood cell counts. (c) 2016 International Clinical Cytometry Society

Presentamos la descripción del diagnóstico y manejo de una secuencia anemia-policitemia (SAP) que se presenta como complicación de una terapia láser exitosa en un embarazo gemelar monocorial cursando una transfusión feto-fetal (TFF) severa. Describimos la manifestación de esta complicación tardía de la terapia láser de la TFF severa y realizamos una revisión de la literatura internacional al respecto. A pesar del éxito de la introducción de la terapia láser en cuanto a la sobrevida y secuelas neonatales, recientemente se han descrito una serie de complicaciones de presentación tempranas o tardías. Entre las tardías, destacan la muerte de uno o ambos gemelos, recidiva de la TFF, y aparición de una SAP. Varios autores han descrito que la SAP sería secundaria a la presencia, o persistencia, de comunicaciones vasculares extremadamente pequeñas de flujo lento, las cuales llevan a una discordancia en los niveles de hemoglobina entre ambos gemelos, sin diferencias en sus volúmenes sanguíneos.

BACKGROUND: The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE.METHODS: During an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), pediatric data were presented and discussed and a consensus was developed by voting.RESULTS: The symptoms of C1-INH-HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1-INH-HAE, but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1-INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1-INH-HAE family member should be screened for C1-INH deficiency. Pediatric patients should always carry a C1-INH-HAE information card and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma-derived C1-INH, recombinant C1-INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow up patients in an HAE comprehensive care center.CONCLUSIONS: The pediatric-focused international consensus for the diagnosis and management of C1-INH-HAE patients was created.

Cellular reprogramming to iPSCs has uncovered unsuspected links between tumor suppressors and pluripotency factors. Using this system, it was possible to identify tumor suppressor p27 as a repressor of Sox2 during differentiation. This led to the demonstration that defects in the repression of Sox2 can contribute to tumor development. The members of the retinoblastoma family of pocket proteins, pRb, p107 and p130, are negative regulators of the cell cycle with tumor suppressor activity and with roles in differentiation. In this work we studied the relative contribution of the retinoblastoma family members to the regulation of Sox2 expression. We found that deletion of Rb or p130 leads to impaired repression of Sox2, a deffect amplified by inactivation of p53. We also identified binding of pRb and p130 to an enhancer with crucial regulatory activity on Sox2 expression. Using cellular reprogramming we tested the impact of the defective repression of Sox2 and confirmed that Rb deficiency allows the generation of iPSCs in the absence of exogenous Sox2. Finally, partial depletion of Sox2 positive cells reduced the pituitary tumor development initiated by Rb loss in vivo. In summary, our results show that Sox2 repression by pRb is a relevant mechanism of tumor suppression.

Background: Icatibant, a selective bradykinin B2 receptor antagonist for the treatment of acute hereditary angio-oedema (HAE) attacks in adults, can be administered by health care professionals (HCPs) or self-administered. This analysis compared characteristics and outcomes of acute HAE attacks treated with self-administered and HCP-administered icatibant in a real-world setting. Methods: The Icatibant Outcome Survey (Shire, Zug, Switzerland; NCT01034969) is an international observational study monitoring the safety and effectiveness of icatibant treatment. Descriptive retrospective analyses were performed (February 2008 to December 2012). Results: Icatibant was used in 652 attacks in 170 patients with HAE type I/II. Most icatibant injections were self-administered (431/652, 68.5%). The proportion of self-treated attacks increased over time (40.3% in 2009 vs. 89.7% in 2012). The median time to administration was significantly shorter in self-versus HCP-treated attacks (1.5 vs. 2.4 h; p = 0.016). Earlier treatment (

Acute urticaria and angio-oedema are common in primary care and in the emergency unit. Food allergy is one possible cause. We describe gastric anisakiasis, in which symptoms are often not obviously related to eating raw fish. A study was made of patients presenting at the emergency department who had allergic symptoms such as urticaria or angio-oedema and had recently eaten raw or undercooked fish. They were divided into two groups. Patients in group A (n = 13) also had abdominal symptoms and were diagnosed as having gastric anisakiasis by fibre-optic gastroscopy where third-stage larvae of Anisakis simplex were visualized and extracted. Skin prick tests and specific IgE to A. simplex were positive. Patients in group B (n = 13) had only allergic symptoms after eating raw fish. Eleven of 13 patients had positive skin prick tests and specific IgE to A. simplex. Three of 15 control subjects had positive skin prick tests and specific IgE to A. simplex. Allergic symptoms appeared from 2 to 20 h (mean 5.0) after ingestion in group A and from 20 min to 23 h (mean 4.3 h) in group B. Gastric symptoms in group A disappeared rapidly after extraction of the larvae. Allergic symptoms disappeared in most cases within the first 24 h. We suggest that the allergic symptoms in group A as well as in group B were mainly due to parasitization by A. simplex in sensitized patients. Gastric anisakiasis may be a widely underdiagnosed clinical entity.

Nesfatin-1, a satiety-inducing peptide identified in hypothalamic regions that regulate energy balance, is an integral regulator of energy homeostasis and a putative glucose-dependent insulin coadjuvant. We investigated its production by human cardiomyocytes and its effects on glucose uptake, in the main cardiac glucose transporter GLUT-4 and in intracellular signaling. Quantitative RT-PCR, Western blots, confocal immunofluorescence microscopy, and ELISA of human and murine cardiomyocytes and/or cardiac tissue showed that cardiomyocytes can synthesize and secrete nesfatin-1. Confocal microscopy of cultured cardiomyocytes after GLUT-4 labeling showed that nesfatin-1 mobilizes this glucose transporter to cell peripherals. The rate of 2-deoxy-D-[(3)H]glucose incorporation demonstrated that nesfatin-1 induces glucose uptake by HL-1 cells and cultured cardiomyocytes. Nesfatin-1 induced dose- and time-dependent increases in the phosphorylation of ERK1/2, AKT, and AS160. In murine and human cardiac tissue, nesfatin-1 levels varied with diet and coronary health. In conclusion, human and murine cardiomyocytes can synthesize and secrete nesfatin-1, which is able to induce glucose uptake and the mobilization of the glucose transporter GLUT-4 in these cells. Nesfatin-1 cardiac levels are regulated by diet and coronary health.

Aims: To study liver lesions in morbidly obese patients who underwent liver biopsy at the time of bariatric surgery to define histological lesions, especially inflammatory infiltrate, diagnostic categories and the possible influence of gender in this respect. Methods and results: 110 biopsies (36 males-M- and 76 females -F-) were evaluated and categorised, according to the NAS (NAFLD -non alcoholic fatty liver disease- Activity Score) system and other criteria, as non-NAFLD (15.5%, F predominance), non-alcoholic steatohepatitis (NASH) (16.5%, M predominance), non-alcoholic hepatosteatosis (NAHS) (21%, F predominance) and, the most numerous group, NASH-borderline (NASH-BORD) (47%), with three subgroups, characterised by centrozonal lesions, portal area preferential involvement or affecting both areas. The predominant form of hepatocytesteatosis was mixed with a multivesicular component that was present in most cases with fibroinflammatory portal involvement. Nuclear glycogenosomes were found in greater number of biopsies in patients in the third and sixth decades. Portal inflammation was present in a large number of cases (M predominance); the application of immunohistochemical techniques (myeloperoxidase and CD68 antibodies) to evaluate lobular inflammation revealed “surgical hepatitis” in one third of the cases, and the presence of microgranulomas (CD68+) (M predominance), which were more abundant with increasing lesion severity. Conclusions: Portal inflammation and multivesicular hepatocytesteatosis are highly prevalent in morbidly obese patients. This study identifies a new subtype of NASH-BORD characterized by centrizonal and porto-periportal area involvement and the existence of liver biopsies without steatosis. CD68+ microgranulomas constitute an unequivocal marker of lobular inflammation in surgical biopsies and of lesion severity, which is gender-related

Angioedema owing to hereditary deficiency of C1 inhibitor (HAE) is a rare, life-threatening, disabling disease. In the last 2 years, the results of well-designed and controlled trials with existing and new therapies for this condition have been published, and new treatments reached the market. Current guidelines for the treatment for HAE were released before the new trials and before the new treatments became available and were essentially based on observational studies and expert opinion. To provide evidence-based HAE treatment guidelines supported by the new studies, a conference was held in Gargnano del Garda, Italy, from September 26 to 29, 2010. The meeting hosted 58 experienced HAE expert physicians, representatives of pharmaceutical companies and representatives of HAE patients' associations. Here, we report the topics discussed during the meeting and evidence-based consensus about management approaches for HAE in adult/adolescent patients.

Presentamos la descripción del diagnóstico y manejo de una secuencia anemia-policitemia (SAP) que se presenta como complicación de una terapia láser exitosa en un embarazo gemelar monocorial cursando una transfusión feto-fetal (TFF) severa. Describimos la manifestación de esta complicación tardía de la terapia láser de la TFF severa y realizamos una revisión de la literatura internacional al respecto. A pesar del éxito de la introducción de la terapia láser en cuanto a la sobrevida y secuelas neonatales, recientemente se han descrito una serie de complicaciones de presentación tempranas o tardías. Entre las tardías, destacan la muerte de uno o ambos gemelos, recidiva de la TFF, y aparición de una SAP. Varios autores han descrito que la SAP sería secundaria a la presencia, o persistencia, de comunicaciones vasculares extremadamente pequeñas de flujo lento, las cuales llevan a una discordancia en los niveles de hemoglobina entre ambos gemelos, sin diferencias en sus volúmenes sanguíneos. We describe the diagnosis and management of twin anemia-polycythemia sequence (TAPS), which occurs as a late complication of successful laser therapy in twin monochorionic pregnancies developing severetwin to twin transfusion syndrome (TTTS). We offer a description of this late complication of laser therapy in this condition and a review of the related medical literature. Despite the successful introduction of laser therapy on the survival and neonatal sequelae, various early and late complications related to this procedure have been recently described. Among the late, stands out the death of one or both twins, recurrence of TTTS, and the appearance of TAPS. With regards TAPS, several authors have reported that it would be secondary to the presence, o persistence, of extremely small slow flow vascular communications, which lead to discre-pancies in the hemoglobin levéis between the twins, with no differences in blood volume.

Experimental research was made in compressed soil block (BTC) piles. These specimens were reinforced with hexagonal mesh and welded wire mesh to determinate its mechanics characteristics by means of axial and diagonal compression, and flexion tests. We made experimental assays in accord with Mexican Code specifications of NTCM(1) and UNAM(2) Engineering Institute researchers. In axial compression test, the piles reinforced with welded wire mesh had a significant increase in maxim admissible load (39%) but had not in masonry strength (4%). In diagonal compression test, the reinforced groups had significant increases in both, load capacity (90-125%) and masonry strength (60-83%). The strength and deformation capacity were higher in specimens reinforced with welded wire mesh. In the flexion test had similar results. Although the compression, shear and flexion design parameters was determinate, it’s important and necessary to make more tests to corroborate these results. Se realizó una investigación experimental en pilas de bloques de tierra compactados (BTC) reforzadas con malla hexagonal y malla electrosoldada para determinar la influencia del refuerzo, mediante ensayes de compresión axial, compresión diagonal y flexión lateral, según lo especifican las Normas Técnicas Complementarias para Mampostería (NTCM(1) y UNAM(2)) del DF, en México. En el ensayo a compresión axial, se determinó que la carga máxima admisible se incrementó significativamente en el grupo reforzado con malla electrosoldada (39%), no así la resistencia (4%). En el ensaye a compresión diagonal, el incremento en la carga máxima admisible y resistencia fue significativo para los dos grupos reforzados, de 90 a 125% y de 60 a 83% respectivamente. A flexión lateral los incrementos fueron altamente significativos para el grupo reforzado con malla electrosoldada. Aunque se determinaron los parámetros de diseño a compresión, cortante y flexión del BTC, es importante realizar mas ensayes para corroborar estos resultados.

Objectives: Analyze the existence of factors that are associated to a major adherence and effectiveness of vocal therapy.Study Design: Prospective.Material and Methods: We carried out an analysis in 67 patients who underwent vocal therapy in our hospital during a year by functional or organic-functional dysphonia.Results: The average percentage of attendance to the programmed sessions was of 70,42%.We find associations between a greater percentage of attendance and a greater age, feminine sex and a greater score of the anxiety scale. Vocal therapy was effective in 75% of the patients. If we grouped the patients according to use the voice or not in the work, the first one obtain a greater benefit of the treatment.Conclusion: The professionals of the voice are those that greater benefit obtain in the vocal therapy, since their interest and motivation by the treatment are greater, reason why we must give priority to them. Objetivos: Analizar la existencia de factores que se asocian a la mayor adherencia y eficacia de la reeducación vocal.Diseño del estudio: Prospectivo.Material y Métodos: Realizamos un análisis en 67 pacientes sometidos a reeducación vocal en nuestro hospital durante un año por disfonías funcionales u órganico-funcionales.Resultados: El porcentaje medio de asistencia a las sesiones programadas fue del 70,42%. Encontramos asociaciones entre un mayor porcentaje de asistencia y una mayor edad, el sexo femenino y una mayor puntuación de la escala de ansiedad. La reeducación fue eficaz en el 75% de los pacientes. Si agrupamos a los pacientes según utilicen la voz o no en el trabajo, los primeros obtienen un mayor beneficio del tratamiento.Conclusiones: Los profesionales de la voz son los que mayor beneficio obtienen en la terapia vocal, dado que su interés y motivación por la curación es mayor, por lo que debemos darle prioridad.

The dynamic posturography (PD) is an amply diffused method for the study of balance. Its principal utility is the design of therapeutic strategies based on the vestibular rehabilitation. In determined patients and with the help of other elements of rehabilitation the PD favour the compensation of the degradation ofthe secondary balance to determinated pathologic entities that affect the vestibular peripheric or central system. Normally individualized strategies for each patient are employed and although this is the more correct, we consider necessary to propose global mesures that facilitate the rehabilitation program and the comparison of the results of different authors.

Antecedentes. La evaluación gráfica del parto fue descrito originalmente por Friedman, sin embargo, una descripción de la evolución del trabajo de parto con un manejo médico contemporáneo no ha sido completamente evaluado. Objetivo: Analizar el efecto de un manejo médico estandarizado del trabajo de parto, que incluye anestesia regional, rotura artificial de membranas y conducción ocitócica, sobre la fase activa del trabajo de parto en multíparas. Método. Análisis retrospectivo de 130 multíparas en trabajo de parto espontáneo, que ingresaron con 3 a 4 cm de dilatación. Resultados. Se observó una duración de la fase activa del trabajo de parto de aproximadamente 3,5 horas, con una progresión promedio de 1,5 cm/ h, produciéndose la mayor progresión entre los 7 y 9 cm de dilatación con 1,9 cm/h. La segunda fase del trabajo de parto presento una duración promedio de 28 minutos. Conclusiones. Nuestros resultados muestran que el manejo "médico estandarizado" del trabajo de parto no reduce los tiempos de la fase activa ni de la segunda fase en multíparas. Creemos que es necesario implementar estudios randomizados para determinar la influencia de este tipo manejo del trabajo de parto en la incidencia de cesáreas Objective. To analyze the influence of a standardised protocol for the management of labour applied during the active phase of labour. Method. The graphic partograms of 130 multiparous women with spontaneous onset of labor were retrospectively analysed. A standardised protocol was defined by use of regional anaesthesia, early rupture of membranes and oxytocin acceleration during the active phase of labour. Results. The mean duration of the active phase of labour and the mean cervical rate dilatation were approximately 3.5 hours and 1.5 cm/h, respectively. The maximum mean rate of dilatation was 1.9 cm/h at the range of 7 to 9 cm, being the mean duration of the second phase of labour only 28 minutes. Conclusions. This study shows that the application of this standardised protocol of management of labour do not appear to be associated with a shortenning in the duration of the active dilatation and second stage of labour. Therefore, it would be necessary to set up a randomized control trial to evaluate the influence of this kind of managements in the caesarean section rate

Objetivo: Conocer si la divulsión del polo inferior, realizada semanalmente desde las 38 semanas de gestación en pacientes de bajo riesgo, es un método seguro y eficaz para disminuir la incidencia de partos mayores de 41 semanas. Método: 110 embarazadas de bajo riesgo y de edad gestacional segura fueron randomizadas a divulsión de polo (casos) y no divulsión (controles). Desde las 38 semanas, tanto a las controles como las intervenidas, se les realizó tactos vaginales para evaluar pelvimetría, puntaje de Bishop y divulsión de polo en aquellas gestantes aleatorizadas y que cumplían las condiciones para poder realizar el procedimiento. El objetivo primario fue determinar la incidencia de parto espontáneo antes de las 41 semanas y el secundario fue evaluar la morbimortalidad materna y neonatal. Los datos fueron analizados por Chi cuadrado, test exacto de Fisher, test t de Student y test Wilcoxson rank-sum según correspondiera. Resultados: La población estudiada en ambos grupos fueron demográficamente similares. Las gestantes divulsionadas tuvieron significativamente (p

Growth hormone releasing hormone receptor (GHRH-R) mRNA and protein was first localized to the anterior pituitary gland, consequent with the action of its ligand on GH synthesis and release. Subsequent studies found GHRH-R also expressed in the hypothalamus and in systemic tissues including those of the reproductive system. In the present work, we studied the distribution of GHRH-R in human reproductive system of males and females by immunohistochemical method. GHRH-R immunostaining was localized in male reproductive system: Leydig cells, Sertoli and basal germ cells of the seminiferous tubules and prostate secretory cells. GHRH-R immunostaining was also demonstrated in the ovary: oocytes, follicular cells, granulosa, thecal and corpus luteum cells. Endometrial glands, placenta and normal mammary glands also showed GHRH-R immunostaining. Our results demonstrate the localization of GHRH-R in the reproductive system, which may mediate the direct action of GHRH in these tissues. Moreover, GHRH-R was demonstrated in prostate and breast carcinomas, opening a variety of possibilities for the use of GHRH antagonists in the treatment of prostatic and mammary tumors.