Individualized dose of anti-thymocyte globulin based on weight and pre-transplantation lymphocyte counts in pediatric patients: a single center experience.

Anti-thymocyte globulin (ATG) has become a standard in preventing GVHD in related and unrelated donor transplantation, but there is no consensus on the best administration schedule. The PARACHUTE trial reported excellent CD4 immune reconstitution (CD4 IR) using a dosing schedule based on the patient's weight and pre-conditioning absolute lymphocyte count (ALC). In 2015 we introduced the PARACHUTE dosing schedule for pediatric patients at our center. One hundred one patients were transplanted for malignant and non-malignant diseases. In this non-concurrent cohort CD4 IR+, defined by a single CD4 count >50/µL on day 90, was seen in 81% of patients. The incidence of grade II-IV and III to IV aGvHD was 26.6% and 15.3% and 5% for cGvHD with no severe cases. We found no difference in aGvHD between donor type and stem cell sources. Five-year EFS and OS were 77.5% and 83.5%. Grade III-IV GFRS was 75.2%. CD4 IR+ patients had better EFS (93.1% vs. 77.7%, p = 0.04) and lower non-relapse mortality (2.7% vs. 22.2%, p = 0.002). The PARACHUTE ATG dosing schedule individualized by weight and ALC results in good early immune reconstitution, low incidence of cGvHD, and favorable survival for patients with different disease groups, donor types, and stem cell sources.

Crown-Root Angle Measurement in Permanent Central Incisors

The anatomical variations of teeth are directly related to the esthetics achieved in orthodontic treatment. These variations include the dental axes, such as the long crown axis and the long root axis. For this reason, these axes and the angle formed by their intersection, or crown-root angle, have been studied using several methodologies, mainly in central incisors. This study aimed to propose the visual- spatial processing as a method to determine the long crown axis and the long root axis, and thus measure the angle between these axes (crown-root angle) in the permanent upper and lower central incisors. The study had a quantitative, descriptive, observational and cross- sectional approach. The study sample consisted of 100 Cone-beam computed tomography (CBCT) images: 50 of permanent upper central incisors and 50 of permanent lower central incisors. The crown-root angle was measured considering the long crown axis and the long root axis. The mean crown root angle in the upper central incisors was 21.34 °, with a standard deviation (SD) of 4.41º; for the lower central incisors, the mean value was 20.05º with a SD of 4.18º. This study suggests that the visual-spatial processing can be a valid method to determine the long crown axis and the long root axis, also with the advantage of not requiring specific instruments and anatomical reference points, which simplifies the tracing of axes and thus measurement of the crown-root angle.

Las variaciones anatómicas de los dientes tienen directa relación con la estética lograda en el tratamiento de ortodoncia. Dentro de estas variaciones se encuentran los ejes dentarios, como el eje mayor de la corona y el eje mayor radicular. Por esta razón, se ha estudiado mediante diversas metodologías estos ejes y el ángulo formado por dicha intersección o ángulo corono radicular, principalmente en los incisivos centrales. El objetivo del presente estudio es plantear la percepción viso espacial como método para determinar el eje mayor de la corona y el eje mayor radicular, y así medir el ángulo entre estos ejes (ángulo corono radicular) en los incisivos centrales superiores e inferiores definitivos. La investigación es de enfoque cuan- titativo, descriptivo, observacional y transversal. La muestra del estudio fueron 100 imágenes de CBCT: 50 de incisivos centrales superiores definitivos y 50 de incisivos centrales inferiores definitivos. Se midió el ángulo corono radicular considerando el eje mayor de la corona y el eje mayor radicular. El promedio del ángulo corono radicular en los incisivos centrales superiores fue de 21.34° con desviación estándar (DS) de 4. 41º y para los incisivos centrales inferiores se obtuvo como valor promedio 20.05º con DS de 4.18º. Este estudio plantea que la percepción viso espacial puede ser válido como método para determinar el eje mayor de la corona y el eje mayor radicular, teniendo además la ventaja de prescindir de instrumentos específicos y de puntos anatómicos de referencia, lo cual simplifica el trazado de los ejes y por ende la medición del ángulo corono radicular.

Asociación entre enfermedad de von Willebrand y angiodisplasia: ¿casualidad o causalidad? / Association between von Willebrand disease and angiodysplasia

Von Willebrand factor (vWf) is a fundamental multimeric plasma glycoprotein in the coagulation process. Its function is to mediate platelet adhesion and to stabilize circulating factor VIII. A functional or quantitative alteration of vWf gives rise to von Willebrand disease (vWD). The association between vWD and angiodysplasia was described in 1967, but it was only until 2011 that Starke et al demonstrated the in vitro and in vivo role of vWf in angiogenesis. Congenital or acquired vWf deficiency, especially of high molecular weight multimeters, not only favors bleeding, but also contributes to increased angiogenesis in these patients. The treatment should be focused both on the control of the acute episode of gastrointestinal bleeding, with vWf replacement therapy and local endoscopic treatment, as well as on the prevention of the progression of angiodysplasia and future bleeding. There are different published therapeutic approaches using vWf replacement that are not effective in all patients. Recently, angiogenesis inhibitor medications have been used.

[Association between von Willebrand disease and angiodysplasia]. / Asociación entre enfermedad de von Willebrand y angiodisplasia: ¿casualidad o causalidad?

Von Willebrand factor (vWf) is a fundamental multimeric plasma glycoprotein in the coagulation process. Its function is to mediate platelet adhesion and to stabilize circulating factor VIII. A functional or quantitative alteration of vWf gives rise to von Willebrand disease (vWD). The association between vWD and angiodysplasia was described in 1967, but it was only until 2011 that Starke et al demonstrated the in vitro and in vivo role of vWf in angiogenesis. Congenital or acquired vWf deficiency, especially of high molecular weight multimeters, not only favors bleeding, but also contributes to increased angiogenesis in these patients. The treatment should be focused both on the control of the acute episode of gastrointestinal bleeding, with vWf replacement therapy and local endoscopic treatment, as well as on the prevention of the progression of angiodysplasia and future bleeding. There are different published therapeutic approaches using vWf replacement that are not effective in all patients. Recently, angiogenesis inhibitor medications have been used.

El trasplante de hígado es un procedimiento plausible, efectivo y seguro en pacientes con hemofilia: caso clínico / Liver transplantation in hemophilia A: report of one case

Due to blood derivative requirements, many patients with hemophilia were exposed to Hepatitis C virus infection (HCV) before the availability of HCV testing. We report a 46-year-old male with Hemophilia A with a hepatitis virus C infection since 2004 causing a cirrhosis. Due to a hepatopulmonary syndrome, he received a liver allograph using a factor VIII replacement protocol, after eradicating the virus C. He had a good postoperative evolution, and no more factor VIII was required after transplantation until his last assessment.

El sangrado menstrual excesivo afecta la calidad de vida en adolescentes / Heavy menstrual bleeding affects quality of life in adolescents

Resumen Introducción: El sangrado menstrual excesivo (SME) se presenta aproximadamente en 37% de las adolescentes y afecta en distinto grado su calidad de vida. Objetivo: Medir la magnitud del impacto del SME en la calidad de vida en adolescentes. Pacientes y Método: Se entrevistó a adolescentes con diagnóstico de SME entre 10 y 18 años y a uno de sus tutores. Se aplicó el cuestionario de calidad de vida PedsQL 4.0 escala genérica, su versión Proxy PedsQL 4.0 al tutor, más 3 preguntas sobre limitación de actividades diarias. La concordancia entre la percepción de calidad de vida del tutor y adolescente se evaluó con el gráfico de Bland y Altman. Resultados: 46 adolescentes y tutores fueron evaluados. El puntaje total promedio PedsQL 4.0 para las adolescentes fue 64,48 (DS 14,54), con un rango de 18,48 a 88,04 con mayor compromiso en la dimensión emocional. Un 50% de las adoles centes falta al colegio, 80,4% a educación física y 65,2% a actividades al aire libre o fiestas. No hubo concordancia entre la percepción de las adolescentes y sus tutores. Conclusiones: Se evidenció un deterioro de la calidad de vida de las adolescentes encuestadas, siendo la dimensión emocional la más afectada. El desempeño en el cuestionario fue incluso más bajo que en patologías crónicas publicadas con esta misma herramienta.

Abstract Introduction: Heavy menstrual bleeding (HMB) occurs in 37% of adolescents and compromise their quality of life. Objective: To measure the magnitude of the impact of the SME on the quality of life in adolescents. Patients and Method: We interviewed adolescents diagnosed with HMB between 10 and 18 years old and one of their guardians. PedsQL 4.0 generic core scale was applied to measure quality of life, its Proxy PedsQL 4.0 version was applied to the guardian and 3 more questions to adolescents about limitation of daily activities. The concordance between the guardian's perception of the adolescent quality of life and the adolescent's perception was evaluated with the Bland and Altman graph. Results: 46 adolescents and guardians were evaluated. The total average PedsQL 4.0 score for adolescents was 64.48 (SD 14.54), with a range of 18.48 to 88.04 with a greater involvement in the emotional dimension. 50% of adolescents missed school, 80.4% physical education and 65.2% outdoor activities or parties. There was no agreement between the perception of the girls and guar dians. Conclusions: We evidence a deterioration in the quality of life of the surveyed adolescents, being the emotional dimension most affected. The performance in the questionnaire was also lower than in samples of chronic diseases published with this same tool.

Bleeding risk of surgery and its prevention in patients with inherited platelet disorders.

Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. We rated the outcome of 829 surgical procedures carried out in 423 patients with well-defined forms of inherited platelet disorders: 238 inherited platelet function disorders and 185 inherited platelet number disorders. Frequency of surgical bleeding was high in patients with inherited platelet disorders (19.7%), with a significantly higher bleeding incidence in inherited platelet function disorders (24.8%) than in inherited platelet number disorders (13.4%). The frequency of bleeding varied according to the type of inherited platelet disorder, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%). Frequency of bleeding was predicted by a pre-operative World Health Organization bleeding score of 2 or higher. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urological surgery. The use of pre-operative pro-hemostatic treatments was associated with a lower bleeding frequency in patients with inherited platelet function disorders but not in inherited platelet number disorders. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with the lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in inherited platelet disorders is substantial, especially in inherited platelet function disorders, and bleeding history, type of disorder, type of surgery and female sex are associated with higher bleeding frequency. Prophylactic pre-operative pro-hemostatic treatments appear to be required and are associated with a lower bleeding incidence.

Factors associated with thrombotic complications in pediatric patients with vascular malformations.

BACKGROUND AND OBJECTIVES: Thrombosis is an uncommon disorder in children. Patients with slowflow vascular malformations have higher risk of developing localized intravascular coagulation, which is closely related to the presence of thrombotic events. These episodes cause pain, can be recurrent and determine a clear deterioration in the quality of life. Moreover, serious complications such as pulmonary thromboembolism and eventually death have been described. The aim of the present study is to identify clinical and laboratory risk factors associated with thrombotic events in pediatric patients with vascular malformations. METHODS: Case-Control study. Clinical records of patients who consulted the vascular anomalies study group (VASG). This group carries out interdisciplinary assessment of patients with vascular malformations. From June 2008 to December 2014, 110 patients were assessed of whom 46 patients met the inclusion criteria, with half of them presenting a thrombotic complication and the others not, these latter serving as controls. Statistical analysis included multivariate logistic regression analysis to determine major risk factors for thrombosis. RESULTS: In the bivariate analysis we found a significant association between increased levels of Ddimer and thrombotic complications (OR 17.1 [95% CI 3.95-73.95; p<0.01]). In addition, a surface area≥10cm2 (OR 6.18 [95% CI 1.59-23.99; p<0.01]) and the presence of palpable phleboliths (OR 20.17 [95% CI 2.32-165.77; p<0.01]) were associated with a significant higher risk of thrombosis. Multivariate analysis identified older age (OR 1.33; p=0.013), a surface area≥10cm2 (OR 8.19; p=0.042) and palpable phleboliths (OR 85.29; p<0.01) as significant risk factors. CONCLUSIONS: Our study suggests the existence of clinical factors associated with higher risk of thrombotic complications, such as the extent of the malformation, palpable phleboliths and increased age among children with vascular malformations.

Correlación de valores de TTPa con anti factor Xa para establecer rango terapéutico en tratamiento anticoagulante con heparina sódica / Correlation between aPTT and antifactor Xa to determine therapeutic ranges for unfractionated heparin

Background: The therapeutic range (TR) of activated partial thromboplastin time (aPTT) for unfractionated heparin (UFH) dosing was established in the 1970 decade. Since then aPTT determination has changed. Current TR may be sub or supra-therapeutic depending on the reagents of the test, and therefore, responsible for complications of therapy. Aim: To establish the TR for UFH dosing in our institution using antifactor Xa analysis as reference standard. Material and Methods: After obtaining an informed consent, 43 blood samples were obtained for aPTT determination and antifactor Xa assay in 23 patients treated with intravenous UFH. Samples were processed at Emergency and Hemostasis Labs. We excluded patients receiving other anticoagulants, with thrombophilia, pregnancy or liver disease. Results: Mean aPTT values in the Hemostasis and Emergency labs ​​were 57.1 ± 18.9 and 56.6 ± 18.3 seconds, respectively (p = 0.77). The squared correlation coefficients between aPTT and antifactor Xa at hemostasis and emergency labs were R2 0.5 and 0.45 respectively, p < 0.001. Using a linear regression analysis, therapeutic aPTT range values ​​in our laboratory were established between 50 and 80 seconds, corresponding to antifactor Xa values of 0.3 to 0.7 IU/mL. Conclusions: According to current recommendations, validation of aPTT determination with reference techniques should be done in every institution.

Lactancia materna exclusiva y enfermedades prevalentes de la infancia en menores de seis meses / Exclusive breastfeeding and childhood illness in under six months infants

Objetivo: Determinar la asociación entre lactancia materna exclusiva (LME) y enfermedades prevalentes de la infancia en niños menores de seis meses en Perú el año 2012. Métodos: Análisis secundario de la Encuesta Demográfica de Salud Familiar (ENDES) 2012. Se definen variables y establece asociación de LME con enfermedad diarreica aguda (EDA), infecciones respiratorias agudas (IRA), infección inespecífica (fiebre) y problema de salud infeccioso. Análisis estad¡stico univariado, bivariado con Chi-cuadrado, OR (IC95%) y multivariado con regresión logística binaria con p<0,05 en SPSS 20, según procedimiento de ponderación del INEI. Resultados: Se incluyó a 829 niños peruanos menores de seis meses. 97,4% de niños se encontraba actualmente lactando, solo 48,7 % recib¡a LME. Se encontró un OR ajustado (ORa) de 0,37 IC95% 0,22 – 0,62) entre LME y EDA, ORa de 0,57 (IC95% 0,37 – 0,89) entre LME e infección inespecífica y ORa de 0,46 (IC95% 0.31 – 0.69) entre LME y problema de salud infeccioso en comparación a quienes no recib¡an LME. No se encontró asociación entre LME e IRA. Conclusiones: La lactancia materna exclusiva se asoció a menor probabilidad de presentar enfermedad diarreica aguda, infección inespecífica y algún problema de salud infeccioso en niños peruanos menores de seis meses.

Objective: To determine the association between exclusive breastfeeding (EBF) and infectious diseases in infants younger than 6 months in Peru in 2012. Methods: Secondary analysis of “Encuesta Demogr fica de Salud Familiar” (ENDES) survey database of 2012. Variables were defined on the database and association established based between EBF and fever (non-specific infection), acute diarrhea (AD), respiratory tract infections (RTI) and infectious health problem. Univariate and bivariate analysis performed with Chi-squared test and Odds Ratio (IC95%); multivariate analysis with binary logistic regression, p<0.05 using SPSS 20, according to weighing procedures of INEI. Results: 829 peruvian children under 6 months were included in the study. 97,4% of infants received breastfeeding, and only 48,7% received EBF. Compared with non-EBF infants, EBF infants presented lower risks of AD (adjusted OR [aOR]= 0,38; 95%CI 0,23-0,63); non-specific infection (aOR=0,60; 95%CI 0,39-0,93) and infectious health disease (aOR=0,47; 95%CI 0,32-0,69). No association was found between RTI and EBF. Conclusion: Exclusive breastfeeding was associated with lower risk of presenting acute diarrhea, non-specific infection and infectious health problems.

[Use of desmopressin in children with inherited platelet dysfunctions undergoing adenotonsillar procedures]. / Uso de desmopresina en niños con disfunción plaquetaria congénita sometidos a adeno y/o amigdalectomía.

INTRODUCTION AND GOALS: Adenotonsillar surgery represents a major haemostatic challenge in paediatric patients with mild inherited platelet dysfunction. While there are recommendations for perioperative haemostatic management, there are no reports of the outcomes with the different recommendations in these children when undergoing adenotonsillectomy. Our objective was to evaluate the management of perioperative bleeding with desmopressin in children with mild platelet dysfunctions who underwent adenotonsillar surgery in our hospital. METHODS: We performed a retrospective study aimed at determining the perioperative bleeding and complication rate in children with mild inherited platelet dysfunction in whom desmopressin was used while undergoing adenotonsillar procedures. RESULTS: Between 2004 and 2010, 27 children with mild inherited platelet dysfunction underwent adenotonsillar procedures in our hospital and were treated with desmopressin. One patient developed perioperative bleeding (3.7%) and there was 1 child (3.7%) who presented transitory hypotension as a side effect of desmopressin. CONCLUSIONS: The use of desmopressin allowed adequate perioperative bleeding prophylaxis management in children with mild inherited platelet dysfunction who underwent adenotonsillar procedures without presenting severe complications.

Nuevos anticoagulantes orales / New oral anticoagulant drugs

Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.

Análisis de las inversiones del intrón 1 y 22 y secuenciación del gen F8 para el diagnóstico genético-molecular de hemofilia A en Chile / Introns 1 and 22 inversions and F8 gene sequencing for molecular diagnosis of hemophilia A in Chile

Background: Hemophilia A is an inherited disorder caused by alterations in factor VIII gene (F8) located on the X-chromosome, the intron 22 inversion being the most common mutation. The rest are predominantly point mutations distributed along this large gene of 26 exons. Aim: To implement a molecular diagnostic test to detect mutations in the F8 gene in Chilean patients with Hemophilia A. Material and Methods: To validate the testing methods, we analyzed samples with intron 22 and intron 1 inversion, and with point mutations previously studied, as well as one subject without Hemophilia. We also studied unrelated Chilean patients with Hemophilia A and their female relatives for carrier testing. Intron 22 and intron 1 inversions were studied by long distance polymerase chain reaction (PCR) and point mutations by sequencing the coding and promoter regions of the F8 gene. Results: The results obtained in all samples used for validation were concordant with those obtained previously. In the Chilean patients, the intron 22 inversion and point mutations previously described were observed. In 6 out of 9 patients with mild Hemophilia A we found the same mutation (Arg2159Cys) in exon 23, which has been described as prevalent in mild Hemophilia A. Conclusions: The analysis of intron 22 and intron 1 inversions, as well as of point mutations in the F8 gene will help us to confirm the diagnosis in patients with severe, moderate and mild Hemophilia A, and also it will allow us to perform carrier testing and to provide better genetic counseling.