Post-CART-T Cell Infection: Etiology, pathogenesis, and therapeutic approaches.

Chimeric antigen receptor (CAR) T cell therapy targeting CD-19 has revolutionized the treatment of refractory B-cell malignancies. However, patients undergoing this therapy face an increased risk of infections due to compromised immune function, lymphodepleting chemotherapy, hospitalization, and therapy-related complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. Patients with systemic corticosteroid use, low immunoglobulin levels, and severe CRS, are at higher risk of infection. This review article highlights the spectrum of infections encountered in CAR T cell therapy, including bacterial, viral, and fungal infections. Following consensus guidelines for vaccination and immunoglobulin replacement is recommended. Clear criteria for antibiotic usage and vaccinating household members against respiratory viruses are crucial. Understanding the risk factors, spectrum of infections, and implementing appropriate prophylactic measures are essential to optimize outcomes in patients undergoing CAR T cell therapy. By prioritizing infection prevention strategies, healthcare professionals can effectively improve patient care.

Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.

Dermoscopy of inverted follicular keratosis: study of 12 cases.

BACKGROUND: Inverted follicular keratosis (IFK) is an uncommon benign tumour of the follicular infundibulum, which is often misdiagnosed clinically as other keratinizing tumours, and commonly diagnosed correctly by histopathology. There are few reports about the dermoscopic findings of this lesion. AIM: To evaluate the dermoscopic features of IFK. METHODS: The dermoscopic structures and patterns in digital dermoscopic images of 12 histopathologically confirmed cases of IFK collected from 5 hospitals in Spain were evaluated. RESULTS: A keratoacanthoma (KA)-like pattern composed of central keratin surrounded by hairpin vessels in a radial arrangement was the most common pattern in IFK (58.3%). The second most common pattern was composed of a yellowish-white amorphous central area surrounded by vascular structures in a radial arrangement (33.3%). The remaining case showed a pattern composed of a yellowish-white amorphous central area with milky red globules. Vascular structures were present in all cases, with a monomorphic pattern in seven cases and a polymorphic pattern in five, mainly with radial arrangement. Arborizing vessels, linear irregular vessels, corkscrew vessels and milky red globules were present in some cases. CONCLUSIONS: We describe the two main patterns of IFK. Lesions with a KA-like pattern are clinically and dermoscopically undistinguishable from KA and squamous cell carcinoma. Cases with a polymorphic vascular pattern could be confused with malignant tumours, including basal cell carcinoma and amelanotic melanoma.

Resultados oncológicos y funcionales en prostatectomía radical laparoscópica en grupo de bajo riesgo vs riesgo intermedio y alto / Oncological and functional results OF radical laparoscopic prostatectomy in low-risk group vs intermediate and high risk

INTRODUCCIÓN: La prostatectomía radical (PR) es el tratamiento de elección en pacientes con cáncer de próstata organoconfinado y esperanza de vida mayor a 10 años. Dentro de este grupo se pueden distinguir pacientes de riesgo bajo, intermedio y alto según D'Amico. Parámetros oncológicos y funcionales, como la continencia inmediata o precoz y potencia sexual sirven para evaluar el resultado de este procedimiento. OBJETIVO: Evaluar parámetros oncológicos y funcionales entre el grupo de riesgo bajo Vs Intermedio alto. PACIENTES Y MÉTODOS: Estudio prospectivo de carácter descriptivo. 132 Pacientes sometidos aprostatectomía radical laparoscópica entre 2003-2013 por un único cirujano. Datos recopilados en el momento de la cirugía y controles postoperatorios. Se agruparon según edad, Score de Gleason, PSA y estadio clínico en pacientes de riesgo bajo e intermedio-alto. En controles se realizó encuesta de continencia, potencia sexual y evaluación de biopsia. Los datos se analizaron considerando p<0,05 estadísticamente significativo según prueba Xi Square. RESULTADOS: Se incluyeron en total 132 pacientes, edad promedio 64,2(±7)años (48-75). PSA promedio 8,4(±6)ng/dl (1,5-37). El grupo de riesgo bajo(G1) corresponde a 92 pacientes (70 %), Promedio 64 años, PSA 6, 83 por ciento T1c. El grupo de riesgo intermedio-alto (G2) 40 pacientes (30 %), Promedio 64,9 años, PSA 13,7; 86 por ciento T1c. Márgenes positivos en G1 13(14 por ciento )pacientes Vs 11(26 por ciento) pacientes en G2. En G1 41 (45 por ciento ) están continentes al mes, 73 por ciento al tercer mes y 92 por ciento al año Vs 35 (41 por ciento ) están continentes al mes, 65 por ciento al tercer mes y 825 al año en G2. De los pacientes con seguimiento mayor a un año y erección satisfactoria previa, en G1 un 53 por ciento logró erección de igual calidad al octavo mes Vs G2 un (53 por ciento ) lo logró al mes 11. No hubo diferencia significativa en márgenes (+), continencia y potencia postoperatoria entre ambos grupos con (P>0.05). CONCLUSIONES: Los resultados oncológicos y funcionales no difieren en pacientes de bajo riesgo VS riesgo mayor. No hubo diferencias significativas en los parámetros estudiados, aunque se necesitan estudios de mayor cantidad de pacientes y revisiones sistemáticas para comparar series de distintos centros.(AU)

INTRODUCTION: Radical prostatectomy is the treatment of choice for patients with localized prostate cancer and life expectancy over 10 years. Within this group we can distinguish patients with low, intermediate and high risk according to D'Amico. Oncological and functional parameters, such as immediate or early continence and sexual potency are useful to evaluate the outcome of this procedure. OBJECTIVE: To evaluate oncological and functional parameters among low-risk group vs. intermediate. PATIENTS AND METHODS: Prospective descriptive clinical study. 132 patients underwent laparoscopic radical prostatectomy between the years 2003-2013 performed by a single surgeon. Data collected that at the time of surgery and postoperative controls. They were grouped according to age, Gleason Score, PSA and clinical stage in patients with risk low- and intermediate-high. During controls, a survey was performed in relation to continence, sexual potency and evaluation of biopsy. Data were analyzed considering p <0.05 statistically significant according Xi Square test. RESULTS: 132 patients participated, with an average age of 64.2 (± 7) years (48-75). PSA average 8.4 (± 6) ng / dl (1.5 to 37). The low risk group (G1) corresponds to 92 patients (70 pertrcent), average 64 years, PSA 6.83 pertcent T1c. The intermediate-high risk group G2) consisted of 40 patients (30 pertcent), average 64.9 years, PSA 13.7; 86 pertcent T1c. G1 positive margins in 13 (14 percent) patients vs 11 (26 pertcent) patients in G2. In G1 41 (45 pertcent) are continent in a month, 73 pertcent in the third month and 92 pertcent in one year vs 35 (41 pertcent)are continent in a month, 65 pertcent in the third month and 825 in a year in G2. Of patients with follow-up longer than a year and satisfactory prior erection in G1, a 53 pertcent achieved erection of equal quality in eighth month vs. G2 one (53 pertcent) did it achieved it in month 11. There was no significant difference in margins (+), postoperative continence or potency between the two groups (P> 0.05). CONCLUSIONS: oncological and functional results do not differ in low-risk patients vs. higher risk. There were no significant differences in the parameters studied, althoug. (AU)

Prevalencia de anemia y estado nutricional de escolares del área periurbana de Sucre, Bolivia / Anemia prevalence and nutritional status in children of a suburban area of Sucre, Bolivia

Background: There is limited data on the nutritional status and the prevalence of anemia among school children of Bolivia. This study aimed to determine the prevalence of anemia, iron deficiency and nutritional status by anthropometry in children of a suburban area in the Municipality of Sucre, Bolivia. Subjects and methods: A cross-sectional observational study was conducted involving all school children aged 6 to 10years (n=195) of a suburban school of Sucre-Bolivia (2750 m over sea level). We measured weight and height and calculated Z score for weight/age, height/age, and BMI/age indices using WHO standards. Blood samples were drawn to determine hemoglobin (Hb) and mean corpuscular volume (MCV). Anemia was defined using cut-offs points adjusted for age and corrected for altitude (Hb < 13.4 d/dl). Results: The prevalence of malnutrition observed by Z scores of height/age and weight/age were 20% and 8, 7%, respectively, and mean BMIz score was -0,07. Of these children, 17.9% showed anemia (17.4% iron deficiency anemia), 22.6% iron deficiency without anemia and 19.5% depleted iron stores. Conclusions: The school age children from the suburban area of Sucre-Bolivia presented a mild prevalence of anemia and medium prevalence of stunting.

Introducción: Existen escasos datos sobre el estado nutricional y la prevalencia de la anemia entre los escolares de Bolivia. Este estudio tuvo como objetivo determinar la prevalencia de anemia, deficiencia de hierro y el estado nutricional por antropometría en niños de una zona suburbana de la Municipalidad de Sucre, Bolivia. Sujetos y métodos: Se realizó un estudio observacional transversal en que participaron todos los escolares de 6 a 10 años (n=195) de una escuela suburbana de Sucre-Bolivia (2750 msnm). Se midió el peso y la talla y se calculó puntaje Z peso/edad, talla/edad, e IMC utilizando tablas de la OMS. Se extrajo una muestra de sangre para determinar hemoglobina, volumen corpuscular medio y ferritina sérica. La anemia se definió utilizando un punto de corte por edad y corregidos por la altitud (Hb <13.4 d/dl). Resultados: La prevalencia de malnutrición observado por las puntuaciones Z de talla/edad y peso/edad fueron de 20% y 9%, respectivamente, y la media del z de IMC fue -0,07. De estos niños, 17, 9% presentó anemia (17,4 anemia por deficiencia de hierro), 22,6% deficiencia de hierro sin anemia y 19,5% depósitos de hierro depletados. Conclusiones: Los niños en edad escolar de la zona suburbana de Sucre-Bolivia presentaron una prevalencia leve de anemia, y una moderada prevalencia de retraso del crecimiento.

Calcium as a nutrient involved in the synthesis and localization of proteins that facilitate iron uptake and efflux in enterocytes / El calcio como nutriente implicado en la síntesis y localización de proteínas que participan en la captación y eflujo del hierro en los enterocitos

Iron deficiency is the most common type of nutritional deficiency in the world, and calcium intake is low in many populations. Developing a supplement that contains both micronutrients would be an excellent method to prevent iron deficiency and increase calcium intake. Human and cellular studies have shown that calcium inhibits iron absorption. Currently, the mechanisms underlying this inhibitory effect have not been elucidated. Because calcium is involved in cell signaling pathways, it may affect the regulation of the expression or localization of proteins involved in iron uptake and efflux in enterocytes. The aim of this review was to describe the processes involved in the absorption of dietary iron and the regulation of the expression and activity of proteins involved in this absorption. Additionally, the potential mechanisms by which calcium affects the expression and localization of these proteins are also discussed.

La deficiencia de hierro es la deficiencia nutricional más común en el mundo y la ingesta de calcio es baja en la mayoría de poblaciones. El desarrollo de un suplemento que contenga ambos micronutrientes sería una excelente estrategia para prevenir la deficiencia de hierro y aumentar la ingesta de calcio. Estudios en humanos y en células han demostrado que el calcio inhibe la absorción del hierro. Actualmente los mecanismos que explican este efecto inhibitorio no están claramente dilucidados. Dado que el calcio está implicado en la señalización celular, podría afectar la regulación de la expresión y localización de proteínas implicadas en la captación y eflujo de hierro en los enterocitos. El objetivo de esta revisión es describir los procesos implicados en la absorción del hierro dietario y la regulación de la expresión y actividad de las proteínas implicadas en esta absorción. Además, se discutirán los posibles mecanismos por los cuales el calcio afecta la expresión y localización de esas proteínas.

El cerdo como modelo experimental para la nutrición de hierro / The pig as an experimental model for iron nutrition

Disorders due to iron (Fe) deficiency are quite common in the world population, especially in developing countries. This has generated a considerable increase of research related to the Fe homeostasis on rats and mice animal models in the last years. For several decades the pig model has been used for Fe nutritional studies due to its physiological similarities with the human gastrointestinal tract, and several types of Fe supplementation have been tested on them. However, differences on the effects of some dietary compounds, which could enhance or inhibit the non-heme Fe absorption have been reported between pigs and humans. The newborn pig usually develops Fe deficiency anemia in the perinatal period, being an ideal model for Fe nutrition studies. Therefore, the aim of this review was to update concepts about the absorption of heme and non-heme Fe, its homeostasis in pigs, and to establish similarities and differences with Fe human metabolism. Recent investigations that use the pig as a model for studies in Fe nutrition are also reviewed.

Los trastornos por deficiencia de hierro (Fe) son bastantes comunes en la población mundial sobre todo en países en vías de desarrollo, lo que ha generado un aumento considerable de la investigación relacionada con la homeostasis de este metal, realizada en modelos animales como ratas y ratones. Desde hace varias décadas se ha utilizado ampliamente al cerdo como modelo en los estudios de nutrición de Fe debido a sus similitudes fisiológicas de su tracto gastrointestinal al humano, en los cuales se han probado varios tipos de intervenciones de suplementación con Fe. Sin embargo, se han identificado algunas diferencias en relación al efecto de ciertos compuestos dietarios que pueden aumentar o inhibir la absorción de Fe del tipo no-hemínico (Fe no-hemo) en el cerdo respecto al humano. El cerdo neonato presenta de manera habitual anemia por deficiencia de Fe en el período perinatal, convirtiéndose en el modelo ideal para estudios de nutrición de Fe. Por tanto, el objetivo de esta revisión fue actualizar conceptos sobre absorción de Fe no-hemo y Fe hemínico (Fe-hemo), y su homeostasis en el cerdo, y establecer sus similitudes y diferencias con el humano. También se revisan algunas de las investigaciones recientes que han utilizado al cerdo como modelo de estudio de la nutrición de Fe.

Distribución de polimorfismos del gen del antígeno-4 del linfocito T citotóxico en población chilena con diabetes mellitus tipo 1 / Distribution of cytotoxic T lymphocyte antigen-4 gene polymorphisms in Chilean population with type 1 diabetes mellitus

Background: Cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule is an important regulator of T cell activation involved in the down-regulation of immune response. Their polymorphisms +49 A/G and CT60 have been suggested to confer susceptibility to autoimmune endocrine disorders. The aim of this study was to determine the association of CTLA-4 gene polymorphisms with T1D in the Chilean population. We also wanted to study if the combined haplotypes of +49 A/G and CT60 had an impact on risk for T1D. Methods: To evaluate the impact of allelic variants CT60 and +49 A/G SNPs were studied in a Chilean population, including 248 T1D patients and 160 controls. Genotypes of both polymorphisms of CTLA-4 gene were determinate by PCR-restriction fragment polymorphism (PCRRFLP).Results: No statistical differences were observed when comparing patients with diabetes and controls for both CTLA-4 genotypes. However, the haplotype analysis between CT60 and +49 A/G showed an interesting combination of risk conformed by G*G combination with an OR of 1.648 [1.19- 2.28], (p = 0.002). Conclusions: The G*G haplotype could be a risk marker in patients with T1D in Chilean population.

Estado nutricional de hierro, cobre y zinc en relación con el uso de método anticonceptivo hormonal / Iron, copper and zinc status in relation with the hormonal contraceptive method

Childbearing age women are part of a vulnerable group to present micronutrient deficiencies. It has been associated the contraceptive method (CM) with iron (Fe) status, and the hormonal CM (HCM) with the alteration of copper (Cu) and zinc (Zn) biomarkers. The aim of this study was to assess the effect of CM over the biomarkers of Fe, Cu and Zn status, and the prevalence of micronutrient deficiency on 81 Chilean childbearing age women. We evaluated mean corpuscular volume (MCV), hemoglobin (Hb), zinc protoporphyrin (Zpp), serum Fe (FeS) , transferrin saturation (TS), total Fe binding capacity (TIBC), transferrin receptor (Tfr), serum ferritin (SF), serum copper (CuS), ceruloplasmin (Cp) mass, activity and specific activity and serum zinc (ZnS). From the total women, 40% used HCM and 49% did not use HCM. Women using HCM showed higher values of FeS, ST, CuS, Cp mass and activity (p<0.05) and lower Zpp (p<0.05) compared with those that did not use HCM. Not statistical differences were found on MCV, Hb, TIBC, Tfr, SF, ZnS and Cp specific activity values between groups. HCM utilization did not affect Fe, Cu and Zn status in the studied population.

Las mujeres en edad reproductiva conforman un grupo vulnerable de presentar deficiencia de micronutrientes. Se ha relacionado el método anticonceptivo (MA) con el estatus de hierro (Fe), y al MA hormonal (MAH) con la alteración de bio-marcadores de cobre (Cu) y zinc (Zn). El objetivo del presente estudio fue evaluar el efecto del MA sobre los biomarcadores del estatus de Fe, Cu y Zn y la prevalencia de deficiencia de éstos, en 81 mujeres chilenas en edad reproductiva. Se evaluó el volumen corpuscular medio (VCM), hemoglobina (Hb), Zinc protoporfirina (Zpp), Fe sérico (FeS), saturación de tranferrina (ST), capacidad total de unión de Fe (TIBC), receptor de transferrina (rTf), ferritina sérica (FS), cobre sérico (CuS), ceruloplasmina (Cp) masa, actividad y actividad específica y zinc sérico (ZnS). El 40% utilizó MAH y 49% no utilizaba MAH. Las mujeres que utilizaban MAH presentaron valores más altos de FeS, ST, CuS, Cp masa y actividad (p<0,05) y menor Zpp (p<0,05) que aquellas que no utilizaban MAH. No se encontraron diferencias en el VCM, Hb, TIBC, rTf, FS, ZnS, y Cp actividad específica entre ambos grupos. Se concluye que el uso de MAH no afectó el estatus de Fe, Cu y Zn en la población estudiada.

Consejería nutricional incrementa el consumo de alimentos ricos en calcio, pero la ingesta se mantiene por debajo del requierimiento diario / Nutritional counseling increases consumption of calcium-rich foods, but mean intake remains below the daily requirement

Calcium (Ca) plays a crucial role in the regulation of metabolic processes, especially neuromuscular function and bone health. In Chile, calcium intake in women of childbearing age does not meet the dietary requirement. Objective: To determine whether standard and virtual nutritional counseling increases the dietary calcium intake in Chilean women of childbearing age. Subjects and Methods: Dietary calcium intake in 20 women (mean age 39 ± 5 years) before and after a nutritional education intervention was compared. Nutritional counseling was provided to promote daily consumption of calcium-rich foods. Subsequently, a virtual space was provided to enhance standard counseling. On days 1, 30 and 62 a semi-quantitative food frequency questionnaire was completed by the women. Calcium intake significantly increased post intervention (ANOVA F = 4.43, P= 0.02). Dietary calcium intake was 308 ± 116mg/d at baseline, 354 ± 138mg/d at 30 days, and 412 ± 188mg/d after 62 days. Post intervention, 95% of the participants did not meet the daily intake requirement for calcium; the average percent of adequate intake of calcium was 68 ± 19%. Conclusion: Nutritional counseling increased dietary calcium intake in women of reproductive age, but the increase was not enough to meet the daily calcium requirements.

El calcio juega un rol crucial en la regulación de procesos metabólicos, especialmente en la función neuromuscular y en la salud ósea. Sin embargo, la ingesta dietaria de calcio en mujeres en edad fértil de Chile no cubre los requerimientos. Objetivo: determinar sí la consejería nutricional presencial y virtual incrementa la ingesta dietaria de calcio en mujeres chilenas de edad fértil. Sujetos y métodos: la ingesta dietaria de calcio en 20 mujeres (edad media de 39 ± 5 años) antes y después de una intervención de educación alimentaria y nutricional fue comparada. La consejería nutricional fue impartida para promover el consumo diario de alimentos ricos en calcio. Además, se habilitó un espacio virtual para reforzar la consejería nutricional. En el día 1, 30 y 62 se aplicaron cuestionarios de frecuencia de consumo semi-cuantitativos. La ingesta dietaria de calcio incrementó significativamente (ANOVA F = 4.43, P= 0.02) después de la intervención. La ingesta dietaria de calcio fue 308 ± 116mg/d al día 1, 354 ± 138mg/d al día 30, e incrementó a 412 ± 188mg/d después de 62 días. Al final de la intervención, el 95% de las participantes no cubrieron sus requerimientos diarios de calcio; la media del porcentaje de adecuación para la ingesta de calcio fue 68 ± 19%. La consejería nutricional podría incrementar la ingesta dietaria de calcio en mujeres de edad media en Chile. Sin embargo, el aumento no es suficiente para cubrir los requerimientos de calcio.

Efecto de la estacionalidad sobre el estado nutricional de Hierro, Zinc y Cobre / Effect of seasonality on nutritional status of Iron, Zinc and Copper

Food consumption and therefore the nutritional status of micro-nutrients are influenced by various factors such as seasonality. This study aimed to determine the effect of seasonality on the nutritional status of Fe, Zn and Cu in adult subjects. A longitudinal study was conducted during the months of September 2005 and August 2006. Fifty subjects of both sexes belonging to the urban area of the city of Santiago de Chile were evaluated. Blood samples were drawn during the first week of each month; serum iron, copper and zinc, hemoglobin, mean cell volume, serum ferritin, zinc-protophorphyrin and ceruloplasmin were determined. Serum copper and zinc levels showed significant seasonal variations but not serum iron. Mean cell volume, hemoglobin and ceruloplasmins were significantly lower during spring and summer while serum ferritin and zinc-protophorphyrin showed lower concentrations during autumn and winter. We conclude that during the spring and summer levels of serum iron, copper and zinc could be diminished by reduced food intake.

El consumo de alimentos y por lo tanto el estado de nutrición de los micronutrientes está condicionado por diferentes factores como la estacionalidad. El presente estudio tuvo como objetivo determinar el efecto de la estacionalidad sobre el estado nutricional de hierro, zinc y cobre de sujetos adultos habitantes de la ciudad de Santiago de Chile. Un estudio longitudinal en 50 sujetos de ambos sexos se realizó entre los meses de septiembre del 2005 y agosto del 2006. Durante la primera semana de cada mes se extrajo muestras de sangre para la determinación de hierro, zinc y cobre sérico, hemoglobina, volumen corpuscular medio, ferritina sérica zinc-protoporfirina y ceruloplasmina. Los niveles de cobre, zinc, hemoglobina, volumen corpuscular medio, y ceruloplasmina fueron significativamente menores durante primavera y verano mientras ferritina sérica y zinc-protoporfirina presentaron niveles más bajas durante otoño e invierno. Concluimos que la estacionalidad es un factor a considerar cuando se realicen mediciones de estado de nutrición de los microminerales hierro, zinc y cobre.

Human chorionic gonadotropin (hCG) modulation of TIMP1 secretion by human endometrial stromal cells facilitates extravillous trophoblast invasion in vitro.

STUDY QUESTION: Are secreted extracellular matrix (ECM) remodelling elements, relevant to embryo implantation and placentation, modified by hCG in endometrial stromal cells (ESCs)? SUMMARY ANSWER: hCG decreases tissue inhibitor of metalloproteinase 1 (TIMP-1) secretion in ESCs, thereby facilitating extravillous trophoblast invasion in vitro. WHAT IS KNOWN ALREADY: Successful embryo implantation and placentation depend on the appropriate invasion of the trophoblast into the maternal endometrial stroma. hCG is one of the earliest embryo-derived secreted signals in the endometrium which abundantly expresses hCG receptors. However, there is little data concerning the effects of hCG on endometrial ECM remodelling with respect to embryo implantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted in an academic research laboratory within a tertiary-care hospital. Samples were collected from 36 women undergoing benign gynaecological surgery during the mid-secretory phase. ESCs were isolated and stimulated with hCG (10 UI/ml) or vehicle. Conditioned media (CM) were analysed to determine changes in the secreted profile of nine matrix metalloproteinases (MMPs) and three tissue-specific inhibitors of MMPs (TIMPs) using an ELISA array. Data were confirmed by gelatine zymography, western blot and ELISA. The HTR8/SVneo cell line served as a model for trophoblast cells. The invasive potential of trophoblast cells was assessed using Transwell invasion assays under CM or co-culture conditions with ECS and the role of regulated molecules was examined by using immunoprecipitation in CM prior to the assessment of invasive potential. MAIN RESULTS AND THE ROLE OF CHANCE: MMP-2 levels increased 30%, whereas TIMP-1 levels decreased 20% in CM from ESCs stimulated with hCG (P < 0.05). Gelatine zymography confirmed an increase in MMP-2 activity (P < 0.05). ELISA and western blotting also confirmed the reduction in TIMP-1 upon hCG treatment (P < 0.05). Invasion assays revealed a ∼50% increase in invading HTR8/SVneo cells in chambers with hCG-stimulated ESCs compared with the control (P < 0.05). Immunodepletion of TIMP-1 from control ESC-CM partially resembled the effect of CM from hCG-stimulated ESCs in the trophoblast invasion assays. LIMITATIONS, REASONS FOR CAUTION: The assays were performed in vitro and ESCs were not decidualized, therefore they reflected the very early stages of embryo implantation or the advanced stages when decidualization fails. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that hCG induces endometrial stromal extracellular remodelling by modulating secreted MMP-2 and TIMP-1. This regulation may be physiologically relevant because it increases the invasive potential of trophoblast-derived cells. At present, few data exist concerning the implications of hCG and endometrial ECM remodelling in embryo implantation. Hence, our results should be confirmed by further in vivo studies. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by FONDECYT 11100443, PBCT-PSD51 (IDIMI) and FONDAP 15010006. None of the authors have any conflicts of interest to declare.

Consenso chileno sobre Abobotulinumtoxina A (Dysport®): indicaciones, técnicas / Chilean Consensus for on abobotulinumtoxin A (Dysport®): indications, techniques

Botulinum neurotoxin is widely used to treat a variety of movement disorders, especially dystonia and spasticity. There botúlica different preparations of botulinum type A, that because biologics are difficult to compare. AbobotulinumtoxinA (Dysport ®) has recently been introduced in Chile for treating dystonia and spasticity. The aim of this paper is to provide a review by experts on the existing evidence and propose a practical guide to the use of the drug. Methods and Results: A group of Chilean experts met on 6 and 7 July 2012 to review AbobotulinumtoxinA doses along with injection protocols for dystonia, spasticity and other movement disorders. We worked in two groups, one composed of neurologists who reviewed the on dystonias and other by physiatrists who reviewed the indications for spasticity. Conclusions: Finally, there is a proposal in terms of dose, injection points and recommendations for dystonia and spasticity...

La neurotoxina botulínica es ampliamente usada para tratar una variedad de trastornos del movimiento, especialmente la distonía y la espasticidad. Existen diferentes preparados de toxina botúlica tipo A, que por ser productos biológicos resultan difícilmente comparables. La abobotulinumtoxinA (Dysport®) ha sido introducida en Chile recientemente para el tratamiento de la distonía y la espasticidad. El objetivo de este trabajo es entregar una revisión hecha por expertos sobre la evidencia existente y plantear una guía práctica para el uso del medicamento. Métodos y Resultados: Un grupo de expertos chilenos se reunieron el 6 y 7 julio de 2012 para revisar las dosis abobotulinumtoxin A, junto con los protocolos de inyección para la distonía, la espasticidad y otros trastornos del movimiento. Se trabajó en dos grupos, uno compuesto por neurólogos que revisaron las indicaciones en distonías y otro por fisiatras que revisaron las indicaciones para espasticidad. Conclusiones: Finalmente, se realiza una propuesta en cuanto a dosis, puntos a inyectar y recomendaciones para la distonia y espasticidad...