A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules

Genomic mutation profile in progressive chronic lymphocytic leukemia patients prior to first-line chemoimmunotherapy with FCR and rituximab maintenance (REM)

Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia in Western countries and is notable for its variable clinical course. This variability is partly reflected by the mutational status of IGHV genes. Many CLL samples have been studied in recent years by next-generation sequencing. These studies have identified recurrent somatic mutations in NOTCH1, SF3B1, ATM, TP53, BIRC3 and others genes that play roles in cell cycle, DNA repair, RNA metabolism and splicing. In this study, we have taken a deep-targeted massive sequencing approach to analyze the impact of mutations in the most frequently mutated genes in patients with CLL enrolled in the REM (rituximab en mantenimiento) clinical trial. The mutational status of our patients with CLL, except for the TP53 gene, does not seem to affect the good results obtained with maintenance therapy with rituximab after front-line FCR treatment

A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules

Ba+2 ion trapping using organic submonolayer for ultra-low background neutrinoless double beta detector

If neutrinos are their own antiparticles the otherwise-forbidden nuclear reaction known as neutrinoless double beta decay can occur. The very long lifetime expected for these exceptional events makes its detection a daunting task. In order to conduct an almost background-free experiment, the NEXT collaboration is investigating novel synthetic molecular sensors that may capture the Ba dication produced in the decay of certain Xe isotopes in a high-pressure gas experiment. The use of such molecular detectors immobilized on surfaces must be explored in the ultra-dry environment of a xenon gas chamber. Here, using a combination of highly sensitive surface science techniques in ultra-high vacuum, we demonstrate the possibility of employing the so-called Fluorescent Bicolor Indicator as the molecular component of the sensor. We unravel the ion capture process for these molecular indicators immobilized on a surface and explain the origin of the emission fluorescence shift associated to the ion trapping

Predicting long-term disease control in transplant-ineligible patients with multiple myeloma: impact of an MGUS-like signature

Disease control at 5 years would be a desirable endpoint for elderly multiple myeloma (MM) patients, but biomarkers predicting this are not defined. Therefore, to gain further insights in this endpoint, a population of 498 newly diagnosed transplant-ineligible patients enrolled in two Spanish trials (GEM2005MAS65 and GEM2010MAS65), has been analyzed. Among the 435 patients included in this post-hoc study, 18.6% remained alive and progression free after 5 years of treatment initiation. In these patients, overall survival (OS) rate at 10 years was 60.8% as compared with 11.8% for those progressing within the first 5 years. Hemoglobin (Hb) >= 12 g/dl (OR 2.74, p = 0.001) and MGUS-like profile (OR 4.18, p = 0.005) were the two baseline variables associated with long-term disease-free survival. Upon including depth of response (and MRD), Hb >= 12 g/dl (OR 2.27) and MGUS-like signature (OR 7.48) retained their predictive value along with MRD negativity (OR 5.18). This study shows that despite the use of novel agents, the probability of disease control at 5 years is still restricted to a small fraction (18.6%) of elderly MM patients. Since this endpoint is associated with higher rates of OS, this study provides important information about diagnostic and post-treatment biomarkers helpful in predicting the likelihood of disease control at 5 years

20 years' experience in the management of Zenker's diverticulum in a third-level hospital Experiencia de 20 años en el manejo del divertículo de Zenker en un hospital de 3er nivel

Zenker's diverticulum arises in the posterior wall of the pharynx, above the cricopharyngeal muscle, secondary to a functional cricopharyngeal disorder. We describe our experience with the management of Zenker's diverticulum from 1985 to this day in a third-level hospital. We review clinical data from 27 patients (78% males) with a mean age of 60.4 years. The most common clinical manifestations were dysphagia, regurgitation, syalorrhea, cough, and weight loss. All cases were diagnosed using an esophagogram. A diverticulectomy with cricopharingeal myotomy was performed in 74% of patients. Complications developed in 5 cases (21%), and the recurrence rate was 4% (1 of 3 cases, where myotomy was not performed)

Surgical treatment of esophageal leiomyoma: an analysis of our experience Tratamiento quirúrgico de leiomioma esofágico: análisis de nuestra experiencia

Introduction: leiomyoma is the most common benign esophageal neoplasm. Surgical treatment (enucleation) has traditionally been the therapy of choice. The advent of minimally invasive techniques has produced an increase in endoscopic approaches to the detriment of open surgery. Objective: the aim of this study was to compare the results obtained with open surgery and with laparoscopic surgery in this kind of pathology. Material and methods: we performed a retrospective study of all leiomyomas operated for in our center between 1986 and 2004, and obtained 9 cases of esophageal leiomyoma. Four were women and five men, between the ages of 40 and 70, with a mean age of 53.5 years. The most frequent symptoms were heartburn (5 cases), dysphagia (3 cases), and retrosternal pain (3 cases). Surgery was in all the cases an enucleation. An open approach was performed in 5 cases (3 thoracotomies and 2 laparotomies), and an endoscopic approach in 4 (2 thoracoscopies and 2 laparoscopies). Results: the mean postoperative hospital stay was 5.12 days (range 2-8 days). This was shorter for endoscopic approaches versus open surgery (3.25 vs. 7 days). There was no case of esophageal mucosal perforation or reconversion. No death, intraoperative complication, or tumor relapse was described. Only 2 patients had complications: post-surgical thoracic pain, and intestinal obstruction by adhesions 8 years after surgery. Conclusion: enucleation is an easier procedure and constitutes the therapy of choice for esophageal leiomyoma. This approach has to be laparoscopic. We think that muscle borders should be closed after enucleation, and that biopsy is not indicated preoperatively.Introducción: el leiomioma es el tumor benigno más frecuente del esófago. Tradicionalmente el tratamiento quirúrgico de estos pacientes consistía en la enucleación. El avance en las técnicas mínimamente invasivas ha provocado un aumento del abordaje endoscópico en detrimento de la cirugía abierta. Objetivo: el objetivo del trabajo fue comparar los resultados obtenidos por vía abierta y por vía laparoscópica en este tipo de patología. Material y métodos: realizamos un estudio retrospectivo de los leiomiomas intervenidos en nuestro centro entre 1986-2004, obteniéndose 9 leiomiomas esofágicos. Cuatro eran mujeres y cinco varones, con unas edades comprendidas entre los 40-70 años, siendo la edad media de 53,5 años. Los síntomas más frecuentes eran pirosis (5 casos), disfagia (3 casos) y dolor retroesternal (3 casos). El tratamiento quirúrgico fue en todos los casos la enucleación. En cinco pacientes se realizó un abordaje abierto (3 toracotomías y 2 laparotomías) y en 4 casos se realizó una laparoscopia (2 toracoscopias y 2 laparoscopias). Resultados: la estancia hospitalaria postoperatoria oscila entre los 2-8 días, con una media de 5,12 días, siendo esta menor en el grupo en el que se realizó cirugía laparoscópica en comparación con el grupo de cirugía abierta (3,25-7 días). No existe ningún caso de perforación de la mucosa esofágica ni de reconversión. Tampoco se describe ningún caso de mortalidad, complicación intraoperatoria ni de recidiva tumoral. Dos pacientes presentan algún tipo de complicaciones: dolor torácico post cirugía, obstrucción intestinal por bridas 8 años después de la cirugía. Conclusión: la enucleación es un procedimiento fácilmente realizable y constituye el tratamiento de elección del leiomioma esofágico. Actualmente el abordaje debe ser laparoscópico. Somos partidarios del cierre de la muscular y bajo nuestro punto de vista la biopsia preoperatoria no está indicada