Clinical outcome and prognostic factors of patients with Richter syndrome: real-world study of the Spanish Chronic Lymphocytic Leukemia Study Group (GELLC).

Richter syndrome (RS) is an uncommon evolution of chronic lymphocytic leukaemia (CLL) with a dismal prognosis. Clinical-biological features predicting outcome and best therapeutic approach for these patients remain to be established. In this study, 128 patients with RS, including 112 diffuse large B-cell lymphoma (DLBCL)-type RS, 15 Hodgkin lymphoma (HL)-type RS, and one plasmablastic lymphoma, were identified in 11 centres of the Spanish CLL Study Group (GELLC). The median overall survival (OS) was 5·9 months for DLBCL-type RS and 30·8 months for HL-type RS. Eastern Cooperative Oncology Group Performance Status, haemoglobin level, platelet count, serum lactate dehydrogenase and ß2-microglobulin levels, tumour protein p53 (TP53) abnormalities in the CLL clone concomitant to RS, number of prior therapies, and clonal relationship between CLL and RS, were associated with OS in patients with DLBCL-type RS. A platelet count of <100 × 109 /l, prior CLL therapy (0 vs. ≥1), and presence of TP53 alterations maintained an independent prognostic impact in the multivariate analysis. Patients without any of these factors had a better clinical outcome, with a median OS of 75·3 months, while patients with one or two or more of these factors presented a median OS of 25·5 and 3 months, respectively. Although OS of patients with RS is generally poor, a proportion of patients achieved prolonged survival. Treatment of RS remains a medical need, and further therapeutic approaches with novel therapies are warranted.

Use of eltrombopag for secondary immune thrombocytopenia in clinical practice.

Eltrombopag is a second-line treatment in primary immune thrombocytopenia (ITP). However, its role in secondary ITP is unknown. We evaluated the efficacy and safety of eltrombopag in secondary ITP in daily clinical practice. Eighty-seven secondary ITP patients (46 with ITP secondary to autoimmune syndromes, 23 with ITP secondary to a neoplastic disease subtype: lymphoproliferative disorders [LPDs] and 18 with ITP secondary to viral infections) who had been treated with eltrombopag were retrospectively evaluated. Forty-four patients (38%) had a platelet response, including 40 (35%) with complete responses. Median time to platelet response was 15 days (95% confidence interval, 7-28 days), and was longer in the LPD-ITP group. Platelet response rate was significantly lower in the LPD-ITP than in other groups. However, having achieved response, there were no significant differences between the durable response of the groups. Forty-three patients (49·4%) experienced adverse events (mainly grade 1-2), the commonest being hepatobiliary laboratory abnormalities. There were 10 deaths in this case series, all of which were related to pre-existing medical conditions. In routine clinical practice, eltrombopag is effective and well-tolerated in unselected patients with ITP secondary to both immune and infectious disorders. However, the response rate in LPD-ITP is low.

Actualización de las guías nacionales de consenso del Grupo Español de Leucemia Linfocítica Crónica para el tratamiento y seguimiento de la leucemia linfocítica crónica / Update of the Grupo Español de Leucemia Linfocítica Crónica clinical guidelines of the management of chronic lymphocytic leukemia

Antecedentes y objetivo: El amplio arsenal terapéutico junto con la heterogeneidad biológica de los pacientes hace que sea difícil estandarizar el tratamiento de la leucemia linfocítica crónica (LLC) en la práctica clínica. Estas consideraciones han motivado la preparación del presente documento de consenso, que se trata de una actualización de la versión publicada en 2013, prestando especial atención a las estrategias de tratamiento que han aparecido en los últimos 5 años, como los inhibidores del receptor de células B (ibrutinib e idelalisib), los nuevos anticuerpos monoclonales anti-CD20 (ofatumumab y obinutuzumab) y los inhibidores de Bcl-2 (venetoclax). Material y métodos: Un grupo de expertos del Grupo Español de Leucemia Linfocítica Crónica ha revisado la bibliografía publicada entre 2010 y 2016 para poder establecer una serie de recomendaciones basadas en la evidencia clínica. En aquellas áreas donde no se encontró una evidencia científica, el grupo de expertos estableció recomendaciones por consenso con base en sus experiencias clínicas. Resultados: Como resultado del proyecto se ha establecido un conjunto de recomendaciones de carácter práctico que facilitarán el diagnóstico, el tratamiento y el seguimiento de los pacientes con LLC. Conclusiones: Existen muchos aspectos del tratamiento de la LLC que resultan ser temas controvertidos sobre los que no hay estudios apropiados para generar recomendaciones de forma consensuada (AU)

Background and objective: The broad therapeutic arsenal and the biological heterogeneity of patients with chronic lymphocytic leukemia (CLL) makes it difficult to standardize treatment for CLL patients with specific clinical settings in routine clinical practice. These considerations prompted us to elaborate the present consensus document, which constitutes an update of the previous version published in 2013, mainly focusing on novel treatment strategies that have been developed over last 5 years, namely B-cell receptor inhibitors (ibrutinib and idelalisib), anti-CD20 monoclonal antibodies (ofatumumab and obinutuzumab), and Bcl-2 inhibitors (venetoclax). Material and methods: A group of experts from the Spanish Chronic Lymphocytic Leukemia Group reviewed all published literature from January 2010 to January 2016, in order to provide recommendations based on clinical evidence. For those areas without strong scientific evidence, the panel of experts established consensus criteria based on their clinical experience. Results: The project has resulted in several practical recommendations that will facilitate the diagnosis, treatment, and follow-up of patients with CLL. Conclusions: There are many controversial issues in the management of CLL with no appropriate studies for making consensus recommendations (AU)

Update of the Grupo Español de Leucemia Linfocítica Crónica clinical guidelines of the management of chronic lymphocytic leukemia. / Actualización de las guías nacionales de consenso del Grupo Español de Leucemia Linfocítica Crónica para el tratamiento y seguimiento de la leucemia linfocítica crónica.

BACKGROUND AND OBJECTIVE: The broad therapeutic arsenal and the biological heterogeneity of patients with chronic lymphocytic leukemia (CLL) makes it difficult to standardize treatment for CLL patients with specific clinical settings in routine clinical practice. These considerations prompted us to elaborate the present consensus document, which constitutes an update of the previous version published in 2013, mainly focusing on novel treatment strategies that have been developed over last 5 years, namely B-cell receptor inhibitors (ibrutinib and idelalisib), anti-CD20 monoclonal antibodies (ofatumumab and obinutuzumab), and Bcl-2 inhibitors (venetoclax). MATERIAL AND METHODS: A group of experts from the Spanish Chronic Lymphocytic Leukemia Group reviewed all published literature from January 2010 to January 2016, in order to provide recommendations based on clinical evidence. For those areas without strong scientific evidence, the panel of experts established consensus criteria based on their clinical experience. RESULTS: The project has resulted in several practical recommendations that will facilitate the diagnosis, treatment, and follow-up of patients with CLL. CONCLUSIONS: There are many controversial issues in the management of CLL with no appropriate studies for making consensus recommendations.

Surgical and Audiologic Outcomes in Endoscopic Stapes Surgery across 4 Institutions.

OBJECTIVES: To investigate intra- and postoperative outcomes of endoscopic stapes surgery. STUDY DESIGN: Case series with chart review. SETTING: Four tertiary care otologic centers. SUBJECTS AND METHODS: Sixty-five subjects 18 years and older who underwent endoscopic stapes surgeries were analyzed. Variables analyzed included surgical techniques and intraoperative findings. Outcomes measured included postoperative hearing and complications to date. RESULTS: Fifty-one patients met inclusion and exclusion criteria. The average patient age was 48.1 years (range, 26-87 years), with 60.0% female patients. Patients had a median follow-up of 5.13 months (range, 0.8-57.4 months). Of the subjects, 71.7% required scutum removal. The chorda tympani nerve was manipulated in 94.0% of subjects and transected in 12.0%. At last follow-up visit, the median air-bone gap decreased from 34.5 dB hearing level (HL) preoperatively to 9.0 dB HL postoperatively (P < .0001). Ninety percent of subjects had closure of their air-bone gap ≤20 dB HL. Intraoperative complications included tympanic membrane tears in 8.0% of subjects, all of which resolved at first follow-up. Postoperatively, 10.0% of subjects complained of altered taste. CONCLUSIONS: The present multicentered study of endoscopic stapes surgery demonstrates similar audiometric and postoperative outcomes previously published in the literature, with a median postoperative air-bone gap of 9.0 dB HL. Future prospective endoscopic stapes surgery studies, addressing the need for scutum removal, postoperative taste changes, and pain scores, are merited.

Development of a low-dose protocol for cone beam CT examinations of the anterior maxilla in children.

OBJECTIVE: The aim of this study was to develop a low-dose protocol suitable for cone beam CT (CBCT) examination of an impacted maxillary canine in children by using a combination of dosimetry with subjective and objective image quality assessment. METHODS: Radiation dose and image quality measurements were made using a dental CBCT machine. An image quality phantom was used to investigate the relationship between objective image quality and dose-area product (DAP) for a broad range of exposure settings. Subjective image quality assessment was achieved using a paediatric skull phantom submerged in a water bath for the same range of exposure settings. Eight clinicians assessed each CBCT data set for nine aspects of image quality using a five-point rating scale of agreement. RESULTS: Acceptable image quality, defined using subjective judgements by the clinicians of the skull phantom images, was achievable with DAP values of 127 mGy cm(2) or greater and a polytetrafluoroethylene (PTFE) contrast-to-noise ratio (CNR) of 4.8 or greater. A cautious choice was made to recommend a low-dose protocol of 80 kV and 3 mA for implementation into clinical practice, corresponding to a DAP value of 146 mGy cm(2) and a PTFE CNR of 5.0. CONCLUSION: A low-dose protocol for this particular CBCT machine was established which represents as much as a 50% reduction compared with manufacturer's recommendations. ADVANCES IN KNOWLEDGE: To the authors' best knowledge, this is the first study that addresses dose optimization in paediatric clinical protocols in dental CBCT. Furthermore, this study explores the relationship between radiation dose, objective and subjective image quality.

Pharmacological profiles of acute myeloid leukemia treatments in patient samples by automated flow cytometry: a bridge to individualized medicine.

BACKGROUND: We have evaluated the ex vivo pharmacology of single drugs and drug combinations in malignant cells of bone marrow samples from 125 patients with acute myeloid leukemia using a novel automated flow cytometry-based platform (ExviTech). We have improved previous ex vivo drug testing with 4 innovations: identifying individual leukemic cells, using intact whole blood during the incubation, using an automated platform that escalates reliably data, and performing analyses pharmacodynamic population models. PATIENTS AND METHODS: Samples were sent from 24 hospitals to a central laboratory and incubated for 48 hours in whole blood, after which drug activity was measured in terms of depletion of leukemic cells. RESULTS: The sensitivity of single drugs is assessed for standard efficacy (EMAX) and potency (EC50) variables, ranked as percentiles within the population. The sensitivity of drug-combination treatments is assessed for the synergism achieved in each patient sample. We found a large variability among patient samples in the dose-response curves to a single drug or combination treatment. CONCLUSION: We hypothesize that the use of the individual patient ex vivo pharmacological profiles may help to guide a personalized treatment selection.

Implantes auditivos de conducción ósea percutáneo, transcutáneo: comparación / Percutaneous, Transcutaneous Bone Conduction Hearing Implants: comparison

Introducción: Los implantes de conducción ósea son alternativas en rehabilitación para pacientes con sordera conductiva/mixta o unilateral. Objetivo: Analizar desenlaces audiológicos, calidad de vida y percepción subjetiva de beneficios en pacientes con sordera conductiva y/o mixta o unilateral, usuarios del sistema transcutáneo Bonebridge®, o del sistema percutáneo BAHA®. Método: Estudio prospectivo en diez pacientes usuarios del sistema transcutáneo, y comparación con diez usuarios del sistema percutáneo. Evaluación audiológica, percepción de calidad de vida y satisfacción. Resultados: Con el sistema transcutáneo en sordera conductiva/mixta se registró ganancia promedio de 39 dB SPL (desviación estándar [DE] ±4; intervalo de confianza [IC] 95% 35-43), y con el sistema percutáneo, 33 dB SPL (DE ±7; IC 95% 26-40); diferencia de 6 dB SPL (EE ±3; IC 95% -1-13, p = 0,09). Discriminación de lenguaje con sistema transcutáneo 100% a 63 dB (DE ±2 dB; IC 95% 61-65) y con sistema percutáneo 100% a 58 dB (DE ±7 dB; IC 95% 51-65), diferencia de 5 dB (EE ±3 dB; IC 95% -2-12, p = 0,12). En sordera unilateral, la comparación de umbrales promedio con los dispositivos: 37 dB SPL (DE ±4; IC 95% 31-43) para el sistema transcutáneo y 32 dB SPL (DE ±3, IC 95% 27-37) para el sistema percutáneo, diferencia de 5 dB SPL (EE ±3; IC 95% -1-11, p = 0,09). Discriminación de lenguaje para sistema transcutáneo 100% a 66 dB SPL (DE ±7; IC 95% 55-77) y con sistema percutáneo 100% a 64 dB SPL (DE ±5; IC 95% 56-72), diferencia de 2 dB SPL (EE ±4; IC 95% –9-13, p = 0,7). Promedio total para percepción de beneficios con el uso de los dispositivos: 33 (DE ±18; IC 95% 20-46) para el sistema transcutáneo y 22 (DE ±12; IC 95% 13-31) en sistema percutáneo, diferencia de 11 puntos (EE ±7; IC 95% –3-25, p = 0,12). El nivel de satisfacción fue cuantificado de manera semejante, excepto en: Aspectos generales, sub-ítem Comodidad a favor del sistema transcutáneo. Conclusiones: Los beneficios audiológicos, satisfacción y calidad de vida identificados en los pacientes con el sistema Bonebridge son evidentes y comparables a los que han logrado los pacientes con el sistema BAHA...

Introduction: Hearing bone conduction implants are alternatives available for hearing rehabilitation in patients with conductive mixed hearing loss or unilateral deafness. Objective: To analyze audiological outcomes, quality of life and subjective hearing benefits perception in patients with conductive mixed hearing loss or unilateral deafness, users of percutaneous BAHA® system, or transcutaneous active bone conduction system Bonebridge®. Materials and Methods: Prospective study on 10 patients with transcutaneous system compared with 10 users of percutaneous system. Audiometries, speech recognition with and without the system, Glasgow Benefit Inventory (GBI) and Hearing Device Satisfaction Scale (HDSS) surveys tools. Results: With transcutaneous system, conductive mixed hearing loss group, achieved postoperatory mean gain of 33 dB SPL (Standard error [SE] ±3, 95% confidence interval [95% CI] 26-40, p>0.00001); with percutaneous system 38 dB SPL (SE ±6) 5% CI 25-51, p>0.00001); difference 5 dB SPL (SE ±3, 95% CI 1-11, p = 0.09). Postoperative speech discrimination, transcutaneous system 100% @63 dB (Standard deviation [SD] ±2 dB, 95% CI 61-65); percutaneous system 100% @58 dB (SD ±7 dB, 95% CI 51-65); difference 5 dB (SE ±3 dB, 95% CI -2 – 12, p = 0.12). In Single Sided Deafness (SSD), postoperative, transcutaneous system 82 dB SPL (SE ±4, 95% CI 72-92); percutaneous system 92 dB SPL (SE ±7, 95% CI 76-108); difference of 10 dB SPL (SE ±4, 95% CI 0.1-20, p = 0.047). Speech discrimination, postoperative, transcutaneous system 100% @66 dB SPL (SD ±7, 95% CI 55-77), percutaneous system 100% @64 dB (SD ±5, 95% CI 56-72); difference 2 dB (SE ±4, 95% CI -9-13, p = 0.7). For benefit perception with the devices, for transcutaneous system mean total scored 33 (SD ±18, 95% CI 20-46); for percutaneous system, 22 (SD ±12, 95% CI 13-31); difference 11 points (EE ±7, 95% CI -3-25, p = 0.12). Satisfaction with the device survey scored similarly except for the Comfort sub-item in the General Aspects favorable to the transcutaneous system. Conclusions: Audiological, satisfaction and –quality of life benefits identified in patients with Bonebridge® system are evident and comparable to those achieved by patients with the BAHA® system...

Complicaciones en el implante coclear pediátrico en la Clínica José A. Rivas. Bogotá - Colombia / Complications in pediatric cochlear implant Clinic Jose A. Rivas. Bogotá – Colombia

Introducción: La cirugía de implante coclear, como cualquier otro acto quirúrgico, puede asociarse a complicaciones inherentes al procedimiento o por un fallo atribuible al dispositivo. Objetivo: Identificar y reportar la tasa de complicaciones asociadas a la implantación coclear en menores de 18 años atendidos en el programa de implante coclear en una institución en Bogotá, Colombia. Diseño: Estudio retrospectivo. Métodos: Se incluyeron pacientes a quienes se les realizaron implantes cocleares pediátricos en el período 1994 al 2011. Se analiza en este estudio a los que recibieron implante coclear a la edad de 18 años o menos. Desenlaces principales: tasa global de complicaciones; tasa discriminada de complicaciones por tipo: médico-quirúrgica, y complicaciones atribuibles a fallo del dispositivo. Resultados: Del total de implantes cocleares (920) realizados durante el período de estudio, se selecciona el grupo con edad ≤ 18 años a la fecha del implante, 598 (65%). Total complicaciones identificadas: 49 (8,2%). Complicaciones médico-quirúrgicas: 15 (2,5%). Fallos relacionados con el dispositivo: 5,7%. Conclusiones: La tasa global de complicaciones y fallos identificada en este estudio se asemeja a la reportada por diferentes estudios, la cual varía entre el 5 y el 13% …

Introduction: Cochlear implant surgery, like any surgery, can be associated with complications inherent to the procedure or a failure attributable to the device. Objective: To identify and report the rate of complications associated with cochlear implantation in children under 18 years who presented to the cochlear implant program at a school in Bogota, Colombia. Design: Retrospective. Methods: Patients who underwent pediatric cochlear implants performed in the period 1994-2011. Is analyzed in this study who received cochlear implant at the age of 18 years or less. Main outcome measures: overall complication rate, rate of complications discriminated by type: medical-surgical complications due to device failure. Results: A total of cochlear implants (920) performed during the study period is selected age group ≤ 18 years at the time of implantation, 598 (65%). Total complications identified: 49 (8.2%). Medical-surgical complications: 15 (2.5%). Device-related failures: 5.7%. Conclusions: The overall rate of complications and failures identified in this study is similar to that reported by different studies, which varies between 5 and 13%…

Chronic lymphocytic leukaemia with 17p deletion: a retrospective analysis of prognostic factors and therapy results.

Patients with chronic lymphocytic leukaemia (CLL) whose tumour cells harbour a 17p deletion (17p-) are universally considered to have a poor prognosis. The deletion can be detected at diagnosis or during the evolution of the disease, particularly in patients who have received chemotherapy. We sought to evaluate the natural history of patients with 17p- CLL, identify predictive factors within this prognostic subgroup, and evaluate the results of different therapeutic approaches. Data from 294 patients with 17p- CLL followed up at 20 different institutions was retrospectively collected and analysed. Median age was 68 (range 27-98) years at the time of fluorescence in situ hybridization analysis. After 17p- documentation, 52% received treatment, achieving an overall response rate of 50%. Median overall survival was 41 months, and was significantly shorter in patients with elevated beta(2)-microglobulin concentration (P < 0·001), B symptoms (P = 0·016), higher percentage of cells with deletion (P < 0·001), and acquired deletions (P = 0·012). These findings suggest that patients with 17p- CLL have a variable prognosis that can be refined using simple clinical and laboratory features, including 17p- clone size, beta2-microglobulin concentration, presence of B symptoms and type of deletion (de novo versus acquired).

Ictus isquémico tras infarto de miocardio fibrinolisado en paciente con hipercoagulabilidad / Ischemic stroke after fibrinolytic therapy myocardial infarction in a patient with hypercoagulability

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Los ejercicios específicos para el desarrollo de la rapidez del voleibolista / Specific exercises for developing speed in voleyball players

El trabajo realizado tiene como objetivo demostrar la eficacia de los ejercicios de rapidez especial por medio de diferentes figuras geométricas y su contribución a la preparación física con balones en el terreno del jugador de v/b sala. Dada la necesidad, de establecer un orden metodológico respecto al tratamiento y entrenamiento de la rapidez, tanto general como especial, se seleccionó un grupo de figuras geométricas, que de acuerdo con su recorrido y número de metros, tributaron de la mejor forma a la rapidez que se manifiesta en el juego de voleibol por parte de los jugadores. Los métodos utilizados fueron el experimento, la medición y la observación.