Comprehensive detection of CRLF2 alterations in acute lymphoblastic leukemia: a rapid and accurate novel approach.

Introduction: Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer with high cure rate, but poses a significant medical challenge in adults and relapsed patients. Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype, with approximately half of cases characterized by CRLF2 overexpression and frequent concomitant IKZF1 deletions. Methods: To address the need for efficient, rapid, and cost-effective detection of CRLF2 alterations, we developed a novel RT-qPCR technique combining SYBR Green and highresolution melting analysis on a single plate. Results: The method successfully identified CRLF2 expression, P2RY8::CRLF2 fusions, and CRLF2 and JAK2 variants, achieving a 100% sensitivity and specificity. Application of this method across 61 samples revealed that 24.59% exhibited CRLF2 overexpression, predominantly driven by IGH::CRLF2 (73.33%). High Resolution Melting analysis unveiled concurrent CRLF2 or JAK2 variants in 8.19% of samples, as well as a dynamic nature of CRLF2 alterations during disease progression. Discussion: Overall, this approach provides an accurate identification of CRLF2 alterations, enabling improved diagnostic and facilitating therapeutic decision-making.

Cytogenetic Assessment and Risk Stratification in Myelofibrosis with Optical Genome Mapping.

Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow. In this study, peripheral blood samples from a series of 21 myelofibrosis patients were analyzed via OGM. We assessed the clinical impact of the application of OGM for disease risk stratification using the DIPSS-plus, GIPSS, and MIPSS70+v2 prognostic scores compared with the standard-of-care approach. OGM, in combination with NGS, allowed for risk classification in all cases, compared to only 52% when conventional techniques were used. Cases with unsuccessful karyotypes (n = 10) using conventional techniques were fully characterized using OGM. In total, 19 additional cryptic aberrations were identified in 9 out of 21 patients (43%). No alterations were found via OGM in 4/21 patients with previously normal karyotypes. OGM upgraded the risk category for three patients with available karyotypes. This is the first study using OGM in myelofibrosis. Our data support that OGM is a valuable tool that can greatly contribute to improve disease risk stratification in myelofibrosis patients.

Design and Validation of a Custom Next-Generation Sequencing Panel in Pediatric Acute Lymphoblastic Leukemia.

The molecular landscape of acute lymphoblastic leukemia (ALL) is highly heterogeneous, and genetic lesions are clinically relevant for diagnosis, risk stratification, and treatment guidance. Next-generation sequencing (NGS) has become an essential tool for clinical laboratories, where disease-targeted panels are able to capture the most relevant alterations in a cost-effective and fast way. However, comprehensive ALL panels assessing all relevant alterations are scarce. Here, we design and validate an NGS panel including single-nucleotide variants (SNVs), insertion-deletions (indels), copy number variations (CNVs), fusions, and gene expression (ALLseq). ALLseq sequencing metrics were acceptable for clinical use and showed 100% sensitivity and specificity for virtually all types of alterations. The limit of detection was established at a 2% variant allele frequency for SNVs and indels, and at a 0.5 copy number ratio for CNVs. Overall, ALLseq is able to provide clinically relevant information to more than 83% of pediatric patients, making it an attractive tool for the molecular characterization of ALL in clinical settings.

The role of next-generation sequencing in acute myeloid leukemia.

PURPOSE OF REVIEW: The development of high-throughput techniques like next-generation sequencing (NGS) has unraveled the genetic profile of cancer. In this review, we discuss the role of NGS on the diagnostic, risk stratification, and follow-up of patients with acute myeloid leukemia (AML). RECENT FINDINGS: NGS has become an essential tool in clinical practice for AML management. Therefore, efforts are being made to improve its applications, automation, and turnaround time. Other high-throughput techniques, such as whole genome sequencing or RNA-sequencing, can be also used to this end. However, not all institutions may be able to implement these approaches. NGS is being investigated for measurable residual disease (MRD) assessment, especially with the development of error-correction NGS. New data analysis approaches like machine learning are being investigated in order to integrate genomic and clinical data and develop comprehensive classifications and risk scores. SUMMARY: NGS has proven to be a useful approach for the analysis of genomic alterations in patients with AML, which aids patient management. Current research is being directed at reducing turnaround time and simplifying processes so that these techniques can be universally integrated into clinical practice.

Relaciones entre los estilos de crianza actuales, el empleo de las técnicas de orientación del comportamiento y su enseñanza en Odontopediatría. Revisión bibliográfica. / Relações entre os estilos de criação atuais, a utilização das técnicas de orientação comportamental e seu ensino em Odontopediatria. Revisão bibliográfica. / Relationships between current parenting styles, the use of behavioral guidance techniques and their teaching in Pediatric Dentistry. A bibliographic review.

Introducción: Los cambios en los estilos de crianza de los últimos 25 años han llevado a desestimar en Odontopediatria algunas técnicas de orientación conductual (TODC) clásicas porque los padres las consideran poco apropiadas para sus hijos. Esto ha generado cambios en los programas de formación en Odontopediatría. Objetivo: Revisar las TODC más empleadas actualmente por odontopediatras, las más enseñadas en los programas de Odontología y la influencia de la aceptación parental en ello. Material y método: se realizó una revisión descriptiva de la literatura. Para establecer la base documental, constituida por 42 artículos, se realizó una búsqueda en las bases de datos: Cochrane, SciElo, Medline y Google Academy. Resultados:La familia ha experimentado un proceso de transformación con nuevos modelos de relaciones familiares y de crianza. Aunque los odontopediatras reconocen que la crianza autoritativa es la que favorece un comportamiento más positivo en el consultorio, perciben una tendencia parental hacia la permisividad. Eso ha favorecido que el empleo de algunas TODC clásicas, como control de voz o la estabilización física activa haya disminuido y la formación y entrenamiento al respecto también. Conclusiones:La formación de los odontopediatras está influenciada por el entorno socio-cultural y por aspectos ético-legales cambiantes. Ante la tendencia actual a un patrón de crianza más permisivo las TODC más enseñadas en los programas de Odontopediatría y, las más empleadas por los odontopediatras son las de comunicación. Conocer el patrón de crianza parental puede orientar al profesional para sugerir las TODC más adecuadas a cada entorno familiar

Introdução: As mudanças nos estilos de criação dos últimos 25 anos levaram a rejeitar algumas técnicas de orientação comportamental (TOC) clássicas em Odontopediatria porque os pais as consideravam inapropriadas para seus filhos. Isto gerou mudanças nos programas de formação em Odontopediatria. Objetivo: Revisar as TOC mais utilizadas atualmente pelos odontopediatras, as mais ensinadas nos programas de Odontologia e a influência da aceitação parental em todo isso. Material e método: Foi feita uma revisão descritiva da literatura. Para estabelecer a base documental, composta por 42 artigos, realizou-se uma pesquisa nas bases de datos: Cochrane, SciElo, Medline y Google Academy. Resultados: A família passou por um processo de transformação com novos modelos de relacionamento familiar e parental. Embora os odontopediatras reconheçam que a criação autoritativa é a que favorece um comportamento mais positivo no consultório, percebem também uma tendência dos pais à permissividade. Isso tem favorecido que o emprego de algumas TOC clássicas, como controle de voz ou a estabilização física ativa, tenha diminuído e a formação e treinamento a esse respeito também. Conclusões: A formação dos odontopediatras é influenciada pelo entorno sócio-cultural e por aspetos ético-legais mutáveis. Dada a tendência atual para um modelo de criação mais permissivo as TOC mais ensinadas nos programas de Odontopediatria e, as mais empregadas pelos odontopediatras são as de comunicação. Conhecer o modelo parental pode orientar o profissional para sugerir as TOC mais adequadas a cada ambiente familiar

Introduction: The changes in parenting styles in the last 25 years have led to the dismissal in pediatric dentistry of some classic behavioral guidance techniques (BGT) because parents consider them inappropriate for their children. This has generated changes in the training programs in Pediatric Dentistry. Objective: To review the BTG most currently used by pediatric dentists, the most taught in Dentistry programs and the influence of parental acceptance on it. Material and method: A descriptive review of the literature was carried out. To establish the documentary base, consisting of 42 articles, a search was carried out in the databases: Cochrane, SciElo, Medline and Google Academy. Results: The family has undergone a process of transformation with new models of family and parenting relationships. Although pediatric dentists recognize that authoritative parenting is the one that favors a more positive behavior in the dental office, they perceive a parental tendency towards permissiveness that has favored the decrease in the use of some classic BGT, such as voice control or active physical stabilization, and the learning and training about them as well. Conclusions: The training of pediatric dentists is influenced by the socio-cultural environment and by the changing ethical-legal aspects. Given the current trend towards a more permissive parenting pattern, the most taught and most used BGT in Pediatric Dentistry programs are communication techniques. Knowing the parental upbringing pattern can guide the professional to suggest the most appropriate BGT for each family environment

Basic behavior guidance techniques: A survey of members of the Spanish Society of Paediatric Dentistry.

BACKGROUND: Over the last 20-30 years social trends, educational and parenting patterns, and the ethical and legal factors guiding them have led to the revaluation and even abandonment of some traditionally used behavior guidance techniques (BGTs). AIMS: To profile the professionals providing specialized pediatric treatments in Spain and understand changes in their preferences and use of basic BGTs, and the evolution of these preferences. SETTINGS AND DESIGN: A cross-sectional, descriptive, and correlational study was designed. METHODS: One hundred and twenty-six dentists completed a previously validated survey. STATISTICAL ANALYSIS: Descriptive statistics and Chi-square tests were performed to analyze the questionnaire data. RESULTS: The most common BGTs were "Tell/Show/Do" (98%) and positive reinforcement (92.1%), and the most abandoned BGT was: "hand-over-mouth" (15%), because it was rejected by parents and because of potential legal problems and psychological consequences for the patients. Of note, 37% of the professionals allowed the patient's parents to be present during the treatment. CONCLUSIONS: There has been a notable decrease in the use of certain BGTs in Spain, especially hand-over-mouth and voice control, because they are becoming less socially acceptable as the way society relates to and educates children changes.

The use of Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 on oral health indexes in a school population: A pilot randomized clinical trial.

To assess the effects of a probiotic upon oral health indices in adolescents and to establish relationships between these indices and dietary habits and oral hygiene. Twenty-seven adolescents between 12 and 18 years of age were randomized into two groups. The study group received tablets containing Lactobacillus reuteri DSM 17938/ATCC 5289 for 28 days, while the control group received tablets without any bacteria. Streptococcus mutans, Lactobacillus sp., and salivary pH were assessed at baseline and at 7, 14, 21, 28, and 45 days. The plaque, gingivitis, and bleeding indices were recorded at baseline and at 14, 28, and 45 days. Dietary and oral hygiene habits were also evaluated by means of a questionnaire. A less marked rise in S. mutans was recorded in the study group. Improvements were observed in terms of plaque, gingivitis, and bleeding, though statistical significance was not reached. Oral pH increased in the study group, though not to a significant degree. Poorer eating habits were significantly correlated to increased plaque. The study parameters decreased with the two strains of L. reuteri DSM 17938 and ATCC PTA 5289, though the results failed to reach statistical.

Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML project

Next-Generation Sequencing has recently been introduced to efficiently and simultaneously detect genetic variations in acute myeloid leukemia. However, its implementation in the clinical routine raises new challenges focused on the diversity of assays and variant reporting criteria. To overcome this challenge, the PETHEMA group established a nationwide network of reference laboratories aimed to deliver molecular results in the clinics. We report the technical cross-validation results for next-generation sequencing panel genes during the standardization process and the clinical validation in 823 samples of 751 patients with newly diagnosed or refractory/relapse acute myeloid leukemia. Two cross-validation rounds were performed in seven nationwide reference laboratories in order to reach a consensus regarding quality metrics criteria and variant reporting. In the pre-standardization cross-validation round, an overall concordance of 60.98% was obtained with a great variability in selected genes and conditions across laboratories. After consensus of relevant genes and optimization of quality parameters the overall concordance rose to 85.57% in the second cross-validation round. We show that a diagnostic network with harmonized next-generation sequencing analysis and reporting in seven experienced laboratories is feasible in the context of a scientific group. This cooperative nationwide strategy provides advanced molecular diagnostic for acute myeloid leukemia patients of the PETHEMA group.

Conocimientos de erosión en adolescentes españoles / Conhecimento sobre a erosão dentaria em adolescentes espanhóisArtigo originale-220178Vol 11 N° 1 Enero - Junio 2021 / Erosion knowledge in Spanish adolescents

Objetivos: Determinar en una muestra de adolescentes españoles sus conocimientos sobre la erosión dental y los alimentos, bebidas y hábitos alimenticios que la producen. Material y métodos: Se llevó a cabo un estudio transversal. La muestra estuvo constituida por 348 adolescentes entre 12 y 17 años. Se valoró su conocimiento sobre la erosión dental y sus factores etiológicos mediante un cuestionario. Resultados: El 17,82% refirió conocer la erosión dental, el 26,44% solo había oído hablar de ella y el 62,35% pensaba erróneamente que los términos erosión y caries eran equivalentes. Al relacionar el conocimiento sobre los alimentos que producen erosión dental y la edad de los participantes se observó que el grupo de 16-17 años conocía en un porcentaje significativamente mayor la capacidad erosiva de la naranja (p<0,05), el limón (p<0,05), la fresa (p<0,01) y el kiwi (p<0,01). Esto se observó también con las bebidas gaseosas (p<0,01) y las isotónicas (p<0,01). Conclusiones: El nivel de conocimientos sobre la erosión dental es en general bajo, aumentando con la edad. La capacidad erosiva de los cítricos y de las bebidas gaseosas es más conocida entre los adolescentes que la de otros alimentos o bebidas.

Objetivos: Determinar em uma amostra de adolescentes espanhóis seu conhecimento sobre a erosão dentaria e os alimentos, as bebidas e os hábitos alimentares que a produzem. Material e métodos: Foi realizado um estudo transversal. A amostra foi composta por 348 adolescentes entre 12 e 17 anos. O conhecimento sobre erosão dentaria e seus fatores etiológicos foi avaliada por meio de um questionário. Resultados: 17,82% relataram conhecer erosão dentaria; 26,44% tinham ouvido falar dela e 62,35% pensavam erroneamente que os termos erosão e càrie eram equivalentes. Ao relacionar o conhecimento sobre os alimentos que produzem erosão dentaria y a idade dos participantes observou-se que o grupo de 16-17 anos conhecia em uma porcentagem significativamente maior a capacidade erosiva da laranja (p<0,05), do limão (p<0,05), do morango (p<0,01) e do kiwi (p<0,01). Isto também foi observado com refrigerantes (p<0,01) e bebidas isotônicas (p<0,01). Concluções: O conhecimento sobre erosão dentaria foi geralmente baixo, aumentando com a idade. Os adolescentes conhecem melhor a capacidade erosiva de frutas cítricas e refrigerantes do que outros alimentos ou bebidas.

Objectives: To determine in a sample of Spanish adolescents their knowledge of dental erosion and the food, drinks and eating habits that produce it. Material and methods: A cross-sectional study was carried out. The sample consisted of 348 adolescents between 12 and 17 years old. Their knowledge of dental erosion and its etiological factors was assessed through a questionnaire. Results: 17.82% reported knowing dental erosion, 26.44% had only heard of it and 62.35% mistakenly thought that the terms erosion and caries were equivalent. When relating knowledge about the foods that cause dental erosion and the age of the participants, it was observed that the group of 16-17 years knew in a significantly higher percentage the erosive capacity of the orange (p <0.05), the lemon ( p <0.05), strawberry (p <0.01) and kiwi (p <0.01). This was also observed with soft drinks (p <0.01) and isotonic drinks (p <0.01). Conclusions: The level of knowledge about dental erosion was generally low, increasing with age. The erosive capacity of citrus fruits and soft drinks is better known among adolescents than that of other foods or drinks.

Helpful Criteria When Implementing NGS Panels in Childhood Lymphoblastic Leukemia.

The development of Next-Generation Sequencing (NGS) has provided useful diagnostic, prognostic, and therapeutic strategies for individualized management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Consequently, NGS is rapidly being established in clinical practice. However, the technology's complexity, bioinformatics analysis, and the different available options difficult a broad consensus between different laboratories in its daily routine introduction. This collaborative study among Spanish centers was aimed to assess the feasibility, pros, and cons of our customized panel and other commercial alternatives of NGS-targeted approaches. The custom panel was tested in three different sequencing centers. We used the same samples to assess other commercial panels (OncomineTM Childhood Cancer Research Assay; Archer®FusionPlex® ALL, and Human Comprehensive Cancer Panel GeneRead Panel v2®). Overall, the panels showed a good performance in different centers and platforms, but each NGS approach presented some issues, as well as pros and cons. Moreover, a previous consensus on the analysis and reporting following international guidelines would be preferable to improve the concordance in results among centers. Our study shows the challenges posed by NGS methodology and the need to consider several aspects of the chosen NGS-targeted approach and reach a consensus before implementing it in daily practice.

Analysis of SNP Array Abnormalities in Patients with DE NOVO Acute Myeloid Leukemia with Normal Karyotype.

Nearly 50% of patients with de novo acute myeloid leukemia (AML) harbor an apparently normal karyotype (NK) by conventional cytogenetic techniques showing a very heterogeneous prognosis. This could be related to the presence of cryptic cytogenetic abnormalities (CCA) not detectable by conventional methods. The study of copy number alterations (CNA) and loss of heterozygozity (LOH) in hematological malignancies is possible using a high resolution SNP-array. Recently, in clinical practice the karyotype study has been complemented with the identification of point mutations in an increasing number of genes. We analyzed 252 de novo NK-AML patients from Hospital La Fe (n = 44) and from previously reported cohorts (n = 208) to identify CCA by SNP-array, and to integrate the analysis of CCA with molecular alterations detected by Next-Generation-sequencing. CCA were detected in 58% of patients. In addition, 49% of them harbored CNA or LOH and point mutations, simultaneously. Patients were grouped in 3 sets by their abnormalities: patients carrying several CCA simultaneously, patients with mutations in FLT3, NPM1 and/or DNMT3A and patients with an amalgam of mutations. We found a negative correlation between the number of CCA and the outcome of the patients. This study outlines that CCA are present in up to 50% of NK-AML patients and have a negative impact on the outcome. CCA may contribute to the heterogeneous prognosis.

Measurable Residual Disease Assessed by Flow-Cytometry Is a Stable Prognostic Factor for Pediatric T-Cell Acute Lymphoblastic Leukemia in Consecutive SEHOP Protocols Whereas the Impact of Oncogenetics Depends on Treatment.

Robust and applicable risk-stratifying genetic factors at diagnosis in pediatric T-cell acute lymphoblastic leukemia (T-ALL) are still lacking, and most protocols rely on measurable residual disease (MRD) assessment. In our study, we aimed to analyze the impact of NOTCH1, FBXW7, PTEN, and RAS mutations, the measurable residual disease (MRD) levels assessed by flow cytometry (FCM-MRD) and other reported risk factors in a Spanish cohort of pediatric T-ALL patients. We included 199 patients treated with SEHOP and PETHEMA consecutive protocols from 1998 to 2019. We observed a better outcome of patients included in the newest SEHOP-PETHEMA-2013 protocol compared to the previous SHOP-2005 cohort. FCM-MRD significantly predicted outcome in both protocols, but the impact at early and late time points differed between protocols. The impact of FCM-MRD at late time points was more evident in SEHOP-PETHEMA 2013, whereas in SHOP-2005 FCM-MRD was predictive of outcome at early time points. Genetics impact was different in SHOP-2005 and SEHOP-PETHEMA-2013 cohorts: NOTCH1 mutations impacted on overall survival only in the SEHOP-PETHEMA-2013 cohort, whereas homozygous deletions of CDKN2A/B had a significantly higher CIR in SHOP-2005 patients. We applied the clinical classification combining oncogenetics, WBC count and MRD levels at the end of induction as previously reported by the FRALLE group. Using this score, we identified different subgroups of patients with statistically different outcome in both Spanish cohorts. In SHOP-2005, the FRALLE classifier identified a subgroup of high-risk patients with poorer survival. In the newest protocol SEHOP-PETHEMA-2013, a very low-risk group of patients with excellent outcome and no relapses was detected, with borderline significance. Overall, FCM-MRD, WBC count and oncogenetics may refine the risk-stratification, helping to design tailored approaches for pediatric T-ALL patients.

Development, Implementation and Assessment of Molecular Diagnostics by Next Generation Sequencing in Personalized Treatment of Cancer: Experience of a Public Reference Healthcare Hospital.

The establishment of precision medicine in cancer patients requires the study of several biomarkers. Single-gene testing approaches are limited by sample availability and turnaround time. Next generation sequencing (NGS) provides an alternative for detecting genetic alterations in several genes with low sample requirements. Here we show the implementation to routine diagnostics of a NGS assay under International Organization for Standardization (UNE-EN ISO 15189:2013) accreditation. For this purpose, 106 non-small cell lung cancer (NSCLC) and 102 metastatic colorectal cancer (mCRC) specimens were selected for NGS analysis with Oncomine Solid Tumor (ThermoFisher). In NSCLC the most prevalently mutated gene was TP53 (49%), followed by KRAS (31%) and EGFR (13%); in mCRC, TP53 (50%), KRAS (48%) and PIK3CA (16%) were the most frequently mutated genes. Moreover, NGS identified actionable genetic alterations in 58% of NSCLC patients, and 49% of mCRC patients did not harbor primary resistance mechanisms to anti-EGFR treatment. Validation with conventional approaches showed an overall agreement >90%. Turnaround time and cost analysis revealed that NGS implementation is feasible in the public healthcare context. Therefore, NGS is a multiplexed molecular diagnostic tool able to overcome the limitations of current molecular diagnosis in advanced cancer, allowing an improved and economically sustainable molecular profiling.

RNA Sequencing Analysis for the Identification of a PCM1/PDGFRB Fusion Gene Responsive to Imatinib.

The platelet-derived growth factor receptor ß (PDGFRB) gene translocations lead to a spectrum of chronic myeloid neoplasms, frequently associated with eosinophilia. Clinical heterogeneity is associated with a molecular one. Here, we report a novel case of a patient harboring a t(5;8)(q33;p22) translocation, resulting in the PCM1/PDGFRB fusion. Conventional cytogenetics and RNA sequencing were performed to identify the chromosomes and the genes involved in the rearrangement, respectively. This study shows that the combination of different strategies is pivotal to fine-tune the diagnosis and the clinical management of the patient. After 1 year of treatment with imatinib, the patient achieves hematological and molecular remission. We present an attractive strategy to identify novel and/or cryptic fusions, which will be relevant for clinicians dealing with the diagnosis of the patients with myelodysplastic syndrome/myeloproliferative diseases with atypical manifestations.

Clinical Utility of a Next-Generation Sequencing Panel for Acute Myeloid Leukemia Diagnostics.

Next-generation sequencing (NGS) has redefined the genetic landscape of acute myeloid leukemia (AML), providing new molecular markers for diagnostic and prognostic classifications. However, its application in the clinical setting is still challenging. We hypothesized that a 19-gene AML-targeted NGS panel could be a valid approach to obtain clinically relevant information. Thus, we assessed the ability of this panel to classify AML patients according to diagnostic and prognostic indexes in a cohort of 162 patients. The assay yielded a median read depth >2000×, with 88% of on-target reads and a mean uniformity >93% without significant global strand bias. The method was sensitive and specific, with a valid performance at the clinical variant allele frequency cutoff of 3% for point mutations and 5% for insertions or deletions (INDELs). Three-hundred thirty-nine variants were found (36% INDELs and 64% single nucleotide variants). Concordance between NGS and other conventional techniques was 100%, but the NGS approach was able to identify more clinically relevant mutations. Finally, all patients could be classified into one of the 2016 World Health Organization diagnostic categories and virtually all into the recently proposed prognostic indexes (2017 European LeukemiaNet and Genomic classification). To sum up, we validate a reliable and reproducible method for AML diagnosis and demonstrate that small, well-designed NGS panels are sufficient to guide clinical decisions according to the current standards.

Efectividad de dos anestésicos tópicos para la colocación de la grapa. Estudio clínico aleatorizado

Objetivos: Valorar la eficacia de la mezcla eutéctica de lidocaína y prilocaína al 4% comparándola con el gel de benzocaína al 20% en el control del dolor generado por la colocación de una grapa para el aislamiento absoluto previo a la realización de un sellante de fisuras y valorar el efecto psicológico placebo del uso del anestésico tópico. Material y métodos: Se llevó a cabo un estudio clínico aleatorizado. La muestra estuvo constituida por 96 primeros molares permanentes con fosas y fisuras profundas y retentivas, pertenecientes a 24 pacientes. Los molares fueron distribuidos aleatoriamente en 3 grupos de estudio, benzocaína 20%, lidocaína y prilocaína al 4%, vaselina y un grupo control. Antes y después de la colocación de la grapa se registró la escala de dolor de caras-revisada y la frecuencia cardíaca. Resultados: La mezcla eutéctica de lidocaína y prilocaína al 4% obtuvo valores significativamente más bajos en la escala de dolor de caras-revisada, seguida de la benzocaína al 20% y la vaselina (p<0,05). La mezcla eutéctica de lidocaína y prilocaína al 4% presentó menor modificación de la frecuencia cardíaca (p<0,05) en relación con los otros grupos, entre los que no se encontró diferencias estadísticamente significativas. Conclusiones: La mezcla eutéctica de lidocaína y prilocaína al 4% demostró mayor efectividad que el gel de benzocaína al 20% en la prevención del dolor generado por la colocación de una grapa. Del mismo modo se confirmó el efecto psicológico placebo de la anestésica tópica.

Focal Adhesion Genes Refine the Intermediate-Risk Cytogenetic Classification of Acute Myeloid Leukemia.

In recent years, several attempts have been made to identify novel prognostic markers in patients with intermediate-risk acute myeloid leukemia (IR-AML), to implement risk-adapted strategies. The non-receptor tyrosine kinases are proteins involved in regulation of cell growth, adhesion, migration and apoptosis. They associate with metastatic dissemination in solid tumors and poor prognosis. However, their role in haematological malignancies has been scarcely studied. We hypothesized that PTK2/FAK, PTK2B/PYK2, LYN or SRC could be new prognostic markers in IR-AML. We assessed PTK2, PTK2B, LYN and SRC gene expression in a cohort of 324 patients, adults up to the age of 70, classified in the IR-AML cytogenetic group. Univariate and multivariate analyses showed that PTK2B, LYN and PTK2 gene expression are independent prognostic factors in IR-AML patients. PTK2B and LYN identify a patient subgroup with good prognosis within the cohort with non-favorable FLT3/NPM1 combined mutations. In contrast, PTK2 identifies a patient subgroup with poor prognosis within the worst prognosis cohort who display non-favorable FLT3/NPM1 combined mutations and underexpression of PTK2B or LYN. The combined use of these markers can refine the highly heterogeneous intermediate-risk subgroup of AML patients, and allow the development of risk-adapted post-remission chemotherapy protocols to improve their response to treatment.

The modular network structure of the mutational landscape of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to this significant heterogeneity, it has been suggested that different molecular mechanisms may trigger the disease with diverse prognostic implications. We performed whole-exome sequencing (WES) of tumor-normal matched samples of de novo AML-NK patients lacking mutations in NPM1, CEBPA or FLT3-ITD to identify new gene mutations with potential prognostic and therapeutic relevance to patients with AML. Novel candidate-genes, together with others previously described, were targeted resequenced in an independent cohort of 100 de novo AML patients classified in the cytogenetic intermediate-risk (IR) category. A mean of 4.89 mutations per sample were detected in 73 genes, 35 of which were mutated in more than one patient. After a network enrichment analysis, we defined a single in silico model and established a set of seed-genes that may trigger leukemogenesis in patients with normal karyotype. The high heterogeneity of gene mutations observed in AML patients suggested that a specific alteration could not be as essential as the interaction of deregulated pathways.

NEDD9, an independent good prognostic factor in intermediate-risk acute myeloid leukemia patients.

Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated. Nevertheless, previous work has established an important role for the CAS family members NEDD9 or BCAR1 in the migratory and dissemination capacities of myeloid cells. On this basis, we hypothesized that NEDD9 or BCAR1 expression levels could associate with survival in IR-AML patients and become new prognostic markers. To that purpose, we assessed BCAR1 and NEDD9 gene expression in a cohort of 73 adult AML patients validating the results in an independent cohort (n = 206). We have identified NEDD9, but not BCAR1, as a new a marker for longer overall and disease-free survival, and for lower cumulative incidence of relapse. In summary, NEDD9 gene expression is an independent prognostic factor for favourable prognosis in IR-AML patients.

Contaminación ambiental por ruido / Environmental contamination caused by noise

Los sonidos indeseados constituyen el estorbo público más generalizado en la sociedad actual. La contaminación sonora, representa un problema ambiental para el hombre por las afectaciones a la salud que pueden ocasionar, los peligros por ruido actualmente están identificados como un gran problema a resolver por la salud ambiental, son las formas de energía potencialmente nocivas en el ambiente, que pueden resultar en peligrosidad inmediata o gradual de adquirir un daño cuando se transfiere en cantidades suficientes a individuos expuestos. La liberación de energía física puede ser súbita y no controlada, como el caso de un ruido fuerte explosivo o mantenido y más o menos bajo control como en las condiciones de trabajo con la exposición a largo plazo a niveles inferiores de ruido constante. Con la vigencia de la actualización de los lineamientos de la política económica y social del partido y la Revolución para el período 2016-2021, los autores se han motivado a incursionar en la problemática haciendo una valoración del ruido como uno de los ejemplos más comunes de peligro físico que ocasiona efectos en la salud (AU).

Unwanted sounds are the most generalized public hindrance in the current society. Sound contamination is an environmental problem for people because of the health disorders it could cause. Dangers by noise are nowadays identified as a big problem to solve for the environmental health because they are the forms of energy potentially noxious in the environment that could result in an immediate or gradual risk of causing damage when they are transferred to the exposed individuals in enough quantity. The physical energy release could be unexpected and non-controlled as in the case of a strong explosive noise, or sustained and more or less under control as in working conditions with the long-term exposition to lower levels of constant noise. In force of the Party and Revolution social and economic politics up-dating for the period 2016-2021, the authors have been motivated to deal with this problem, stating that noise is one of the most common examples of physical danger causing effects on human health (AU).