Comparison of plasma ctDNA and tissue/cytology-based techniques for the detection of EGFR mutation status in advanced NSCLC: Spanish data subset from ASSESS

Purpose: The analysis of epidermal growth factor receptor (EGFR) mutations in many patients with advanced non-small-cell lung cancer (aNSCLC) has provided the opportunity for successful treatment with specific, targeted EGFR tyrosine kinase inhibitors. However, this therapeutic decision may be challenging when insufficient tumor tissue is available for EGFR mutation testing. Therefore, blood surrogate samples for EGFR mutation analysis have been suggested. Methods: Data were collected from the Spanish cohort of patients in the large, non-interventional, diagnostic ASSESS study (NCT01785888) evaluating the utility of circulating free tumor-derived DNA from plasma for EGFR mutation testing. The incidence of EGFR mutation in Spain and the level of concordance between matched tissue/cytology and plasma samples were evaluated. Results: In a cohort of 154 eligible patients, EGFR mutations were identified in 15.1 and 11.0% of tumor and plasma samples, respectively. The most commonly used EGFR mutation testing method for the tumor tissue samples was the QIAGEN Therascreen® EGFR RGQ PCR kit (52.1%). Fragment Length Analysis + PNA LNA Clamp was used for the plasma samples. The concordance rate for EGFR mutation status between the tissue/cytology and plasma samples was 88.8%; the sensitivity was 45.5%, and the specificity was 96.7%. Conclusions: The high concordance between the different DNA sources for EGFR mutation testing supports the use of plasma samples when tumor tissue is unavailable

No disponible

Comparison of plasma ctDNA and tissue/cytology-based techniques for the detection of EGFR mutation status in advanced NSCLC: Spanish data subset from ASSESS.

PURPOSE: The analysis of epidermal growth factor receptor (EGFR) mutations in many patients with advanced non-small-cell lung cancer (aNSCLC) has provided the opportunity for successful treatment with specific, targeted EGFR tyrosine kinase inhibitors. However, this therapeutic decision may be challenging when insufficient tumor tissue is available for EGFR mutation testing. Therefore, blood surrogate samples for EGFR mutation analysis have been suggested. METHODS: Data were collected from the Spanish cohort of patients in the large, non-interventional, diagnostic ASSESS study (NCT01785888) evaluating the utility of circulating free tumor-derived DNA from plasma for EGFR mutation testing. The incidence of EGFR mutation in Spain and the level of concordance between matched tissue/cytology and plasma samples were evaluated. RESULTS: In a cohort of 154 eligible patients, EGFR mutations were identified in 15.1 and 11.0% of tumor and plasma samples, respectively. The most commonly used EGFR mutation testing method for the tumor tissue samples was the QIAGEN Therascreen® EGFR RGQ PCR kit (52.1%). Fragment Length Analysis + PNA LNA Clamp was used for the plasma samples. The concordance rate for EGFR mutation status between the tissue/cytology and plasma samples was 88.8%; the sensitivity was 45.5%, and the specificity was 96.7%. CONCLUSIONS: The high concordance between the different DNA sources for EGFR mutation testing supports the use of plasma samples when tumor tissue is unavailable.

Assessment of neuronal autoantibodies in patients with small cell lung cancer treated with chemotherapy with or without ipilimumab.

Small-cell lung cancer (SCLC) is often associated with paraneoplastic syndromes. To assess the role of anti-neuronal autoantibodies (NAAs) as biomarkers of treatment outcome, we assessed NAAs in serial samples from SCLC patients treated with chemoimmunotherapy compared to chemotherapy alone. We evaluated 2 cohorts: in cohort 1 (C1), 47 patients received standard platinum/etoposide, and in cohort 2 (C2), 38 patients received ipilimumab, carboplatin and etoposide. Serum samples at baseline and subsequent time points were analyzed for the presence of NAAs. NAAs were detected at baseline in 25 patients (53.2%) in C1 and in 20 patients (52.6%) in C2 (most frequently anti-Sox1). NAA at baseline was associated with limited disease (75% vs 50%; p: 0.096) and better overall survival (15.1 m vs 11.7 m; p: 0.032) in C1. Thirteen patients (28.9%) showed 2 or more reactivities before treatment; this was associated with worse PFS (5.5 m vs 7.3 m; p: 0.005) in patients treated with chemoimmunotherapy. NAA titers decreased after therapy in 68.9% patients, with no differential patterns of change between cohorts. Patients whose NAA titer decreased after treatment, showed longer OS [18.5 m (95% CI: 15.8 - 21.2)] compared with those whose NAA increased [12.3 m (95% CI: 8.1 - 16.5; p 0.049)], suggesting that antibody levels correlate to tumor load. Our findings reinforce the role of NAAs as prognostic markers and tumor activity/burden in SCLC, warrant further investigation in their predictive role for immunotherapy and raise concern over the use of immunotherapy in patients with more than one anti-NAA reactivity.

Adecuación terapéutica en pacientes crónicos / Therapeutic appropriateness in chronic patients

La falta de adecuación terapéutica constituye un importante problema de salud en los pacientes con patologías crónicas, generalmente ancianos, por su asociación a deterioro de la salud, pérdida de capacidad funcional y de calidad de vida y aumento de la mortalidad. Aunque existen múltiples variables relacionadas con la prescripción potencialmente inapropiada, la polimedicación es el principal factor asociado. Por todo lo anterior, es necesario implementar en la práctica clínica diaria actuaciones encaminadas a mejorar la adecuación terapéutica y disminuir la prescripción inadecuada de medicamentos. Dicha estrategia debe comenzar en el momento mismo de la prescripción, existiendo distintas herramientas de ayuda para la revisión de la adecuación de la medicación previamente prescrita. Toda intervención debe partir de un análisis individualizado de la situación y contar con la aceptación del paciente, especialmente si se trata de retirada de medicamentos. Además, estas actuaciones de revisión deben ser repetidas de forma periódica dadas las circunstancias cambiantes en el estado de salud, en los objetivos terapéuticos y en la perspectiva del paciente.Se han realizado distintos estudios con el objetivo de evaluar este tipo de intervenciones, habiendo evidenciado mejoras en resultados intermedios (reducción de prescripción potencialmente inapropiada), pero con escasos datos publicados sobre resultados en términos de nivel de salud. Existe consenso en la necesidad de continuar con su implementación (AU)

Inappropriate prescribing is an important health problem in patients with chronic diseases, usually elderly, due to its association with health deterioration, loss of functional capacity and quality of life, and increased mortality. Although there are multiple variables related to potentially inappropriate prescribing, polypharmacy is the main associated factor.For all of the above, it is necessary to implement actions in daily clinical practice aimed at improving therapeutic appropriateness and reducing inappropriate drug prescription. This strategy should start at the moment of prescription, having different tools to help to review the adequacy of previously prescribed medication. Any intervention must begin with an individualized analysis of the situation, and must have the patient’s approval, especially in the case of drug withdrawal. Furthermore, these review actions should be periodically repeated, given the changing circumstances in the state of health, the therapeutic goals and the patient’s perspective. Various studies have been carried out in order to evaluate such interventions, having demonstrated improvements in intermediate outcomes (reduction of potentially inappropriate prescribing), but with little published data on outcomes in terms of health status. There is consensus on the need to continue with its implementation (AU)

Production of fructanase by a wild strain of Saccharomyces cerevisiae on tequila agave fructan.

A new wild strain of Saccharomyces cerevisiae (CF3) isolated from tequila must was evaluated for production of fructanase on Agave tequilana Weber fructan (FT). Fructanase activity (F) was assessed by a 3(3) factorial design (substrate, temperature and pH). High enzymatic activity (31.1 U/ml) was found at 30 °C, pH 5, using FT (10 g/l) as substrate. The effect of initial substrate concentration on F (FT0, 5.7-66 g/l) was studied and it was found that F was highest (44.8 U/ml) at FT0 25 g/l. A 2(2) factorial experimental design with five central points was utilized to study the effect of stirring and aeration on fructanase activity; stirring exhibited a stronger effect on F. The ratio fructanase to invertase (F/S) was 0.57, which confirms that the enzymes are fructanase. Crude fructanase reached high substrate hydrolysis (48 wt%) in 10 h. It is shown that S. cerevisiae CF3 was able to produce large amounts of fructanase by growing it on fructan from A. tequilana.

Polyakov loop and the hadron resonance gas model.

The Polyakov loop has been used repeatedly as an order parameter in the deconfinement phase transition in QCD. We argue that, in the confined phase, its expectation value can be represented in terms of hadronic states, similarly to the hadron resonance gas model for the pressure. Specifically, L(T)≈1/2[∑(α)g(α)e(-Δ(α)/T), where g(α) are the degeneracies and Δ(α) are the masses of hadrons with exactly one heavy quark (the mass of the heavy quark itself being subtracted). We show that this approximate sum rule gives a fair description of available lattice data with N(f)=2+1 for temperatures in the range 150 MeV

Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours.

BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS: In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin. RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade ≥3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. CONCLUSION: Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug-drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.

MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines.

BACKGROUND: Small cell lung carcinoma (SCLC) has poor prognosis and remains orphan from targeted therapy. MET is activated in several tumour types and may be a promising therapeutic target. METHODS: To evaluate the role of MET in SCLC, MET gene status and protein expression were evaluated in a panel of SCLC cell lines. The MET inhibitor PHA-665752 was used to study effects of pathway inhibition in basal and hepatocyte growth factor (HGF)-stimulated conditions. Immunohistochemistry for MET and p-MET was performed in human SCLC samples and association with outcome was assessed. RESULTS: In MET mutant SCLC cells, HGF induced MET phosphorylation, increased proliferation, invasiveness and clonogenic growth. PHA-665752 blocked MET phosphorylation and counteracted HGF-induced effects. In clinical samples, total MET and p-MET overexpression were detected in 54% and 43% SCLC tumours (n = 77), respectively. MET phosphorylation was associated with poor median overall survival (132 days) vs p-MET negative cases (287 days) (P < 0.001). Phospho-MET retained its prognostic value in a multivariate analysis. CONCLUSIONS: MET activation resulted in a more aggressive phenotype in MET mutant SCLC cells and its inhibition by PHA-665752 reversed this phenotype. In patients with SCLC, MET activation was associated with worse prognosis, suggesting a role in the adverse clinical behaviour in this disease.

Demencia y dolor / No disponible

El interés de los investigadores por el dolor, su evaluación e intervención en personas con demencia es creciente. Dada la tendencia demográfica a un incremento del envejecimiento poblacional, aumentando las patologías que presentan dolor y el avance en los conocimientos en el campo de las demencias, se identifican cambios que se producen en diferentes áreas cerebrales implicadas en el control del dolor. La presente revisión se centra en las modificaciones que se producen en la percepción del dolor en las personas con demencia, así como analizar los instrumentos más eficaces para reconocer, valorar y tratar el dolor en las personas con demencia. El abordaje integral del dolor debe tener en cuenta a los cuidadores, para prevenir la sobrecarga de los mismos y garantizar la máxima calidad de vida posible de los pacientes (AU)

The interest of researchers for the pain assessment and intervention in people with dementia is growing. Given the demographic trend to an increased aging population, increasing with pain conditions and progress in knowledge in the field of dementia, identify changes that occur in different brain areas involved in pain control. This review focuses on the changes that occur in the perception of pain in people with dementia as well as analyzing the most effective tools to identify, assess and treat pain in people with dementia. The comprehensive approach of pain should take into account carers, to prevent overload them and ensure the highest possible quality of life of patients (AU)

Biotin starvation with adequate glucose provision causes paradoxical changes in fuel metabolism gene expression similar in rat (Rattus norvegicus), nematode (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae).

BACKGROUND/AIM: Biotin affects the genetic expression of several glucose metabolism enzymes, besides being a cofactor of carboxylases. To explore how extensively biotin affects the expression of carbon metabolism genes, we studied the effects of biotin starvation and replenishment in 3 distantly related eukaryotes: yeast Saccharomyces cerevisiae, nematode Caenorhabditis elegans and rat Rattus norvegicus. METHODS: Biotin starvation was produced in Wistar rats, in C. elegans N2 and S. cerevisiae W303A fed with abundant glucose. High-density oligonucleotide microarrays were used to find gene expression changes. Glucose consumption, lactate and ethanol were measured by conventional tests. RESULTS: In spite of abundant glucose provision, the expression of fatty oxidation and gluconeogenic genes was augmented, and the transcripts for glucose utilization and lipogenesis were diminished in biotin starvation. These results were associated with diminished glucose consumption and glycolysis products (lactate and ethanol in yeast), which was consistent across 3 very different eukaryotes. CONCLUSION: The results point toward a strongly selected role of biotin in the control of carbon metabolism, and in adaptations to variable availability of carbon, conceivably mediated by signal transduction including soluble guanylate cyclase, cGMP and a cGMP-dependent protein kinase (PKG) and/or biotin-dependent processes.

C-MET as a new therapeutic target for the development of novel anticancer drugs.

MET is a tyrosine kinase receptor that, upon binding of its natural ligand, the hepatocyte growth factor (HGF), is phosphorylated and subsequently activates different signalling pathways involved in proliferation, motility, migration and invasion. MET has been found to be aberrantly activated in human cancer via mutation, amplification or protein overexpression. MET expression and activation have been associated with prognosis in a number of tumour types and predict response to MET inhibitors in preclinical models. Here we review the HGF/MET signalling pathway, its role in human cancer and the different inhibitory strategies that have been developed for therapeutic use.

C-MET as a new therapeutic target for the development of novel anticancer drugs

MET is a tyrosine kinase receptor that, upon binding of its natural ligand, the hepatocyte growth factor (HGF), is phosphorylated and subsequently activates different signalling pathways involved in proliferation, motility, migration and invasion. MET has been found to be aberrantly activated in human cancer via mutation, amplification or protein overexpression. MET expression and activation have been associated with prognosis in a number of tumour types and predict response to MET inhibitors in preclinical models. Here we review the HGF/MET signalling pathway, its role in human cancer and the different inhibitory strategies that have been developed for therapeutic use (AU)

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Prevalencia de dolor en pacientes geriátricos institucionalizados / Pain prevalence among the elderly in care homes

Objetivo: Valorar la presencia de dolor en población geriátrica institucionalizada. Material y método: Estudio descriptivo, transversal, que determina la prevalencia y características del dolor en el medio residencial en pacientes sin deterioro cognitivo y en aquellos con demencia, a través de la escala observacional PAINAD. Resultados: Residencia de 187 residentes con una edad media de 84 años, siendo un 74%mujeres, con una dependencia severa en un 40% de éstos, con una prevalencia de demencia en el 64% de los residentes. La prevalencia de dolor es del 61%, principalmente nociceptivo somático con relación a patologías osteoarticulares, en un 64% es diario y en un29% de intensidad severa. La escala de valoración de la intensidad más cumplimentada es la escala numérica del dolor. Hay correlación entre la presencia de dolor y la capacidad funcional como con el nivel de ansiedad. Los pacientes con demencia, en un 22%presenta puntuaciones > 4 en la escala PAINAD, objetivándose correlación entre la presencia de dolor con la capacidad funcional, estado afectivo y conductual, y hay correlación baja (r: 0.24) entre los trastornos de conducta y la presencia de dolor. Conclusiones: La detección sistemática y estructurada del dolor en pacientes geriátricos debe constituir un requisito básico de atención dada su prevalencia para alcanzar deforma real una adecuada calidad de vida y de cuidado en dicha población (AU)

Objective: To assess the presence of pain among elderly residents in care homes. Material and method: We performed a descriptive cross sectional study to establish the prevalence and characteristics of pain in residents of a care home without cognitive impairment and in those with dementia using the observational Pain Assessment in Advanced Dementia (PAINAD) scale. Results: The evaluation was performed in a care home with 187 residents with a mean age of 84 years. Seventy-four percent were women, 40% had high dependency and the prevalence of dementia was 64%. The prevalence of pain was 61%, mainly nociceptive and somatic pain related to osteoarticular disease. Daily pain was experienced by 64%and severe pain by 29%. The most frequently used pain intensity evaluation scale was the numerical pain scale. There was some correlation between the presence of pain and functional capacity and anxiety. Twenty-two percent of patients with dementia scored more than 4 points on the PAINAD scale and a correlation was found between the presence of pain and functional capacity and emotional and behavioral states. A low correlation (r:0.24) was found between behavior disorders and the presence of pain. Conclusions: Given the high prevalence of pain in elderly residents of care homes, systematic and structured pain detection may be a basic requirement to achieve adequate quality of life and quality of care in this setting (AU)

Genetic changes in small cell lung carcinoma

Small cell lung carcinoma (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. Therefore, there is a need to develop novel treatments to improve the outcome of patients with SCLC. To fulfil this need, it is critical to gain further understanding on the molecular basis of SCLC and specifically to identify novel therapeutic targets. Clinical trials with molecularly targeted agents have been performed with little success in the past, but recently many promising oncogenic pathways have been discovered and novel targeted therapies are under evaluation. In this review, we summarise the most relevant genetic and signalling pathway alterations reported to date in SCLC and discuss the potential therapeutic implications of such events (AU)

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Aromatase inhibitors and male breast cancer.

The majority of breast cancers in male patients are hormone receptor positive. Tamoxifen has proven to be successful in both adjuvant and metastatic settings and remains the standard of care. Given the improved outcomes in female patients with aromatase inhibitors (AI), these drugs have become a potential therapeutic tool for male patients. Preliminary data show effective suppression of oestradiol levels in males treated with AI and some reports have demonstrated objective responses. Here we report a case of a male patient with metastatic breast cancer treated with letrozole who achieved clinical response associated with a decrease in blood oestradiol levels.

Aromatase inhibitors and male breast cancer

The majority of breast cancers in male patients are hormone receptor positive. Tamoxifen has proven to be successful in both adjuvant and metastatic settings and remains the standard of care. Given the improved outcomes in female patients with aromatase inhibitors (AI), these drugs have become a potential therapeutic tool for male patients. Preliminary data show effective suppression of oestradiol levels in males treated with AI and some reports have demonstrated objective responses. Here we report a case of a male patient with metastatic breast cancer treated with letrozole who achieved clinical response associated with a decrease in blood oestradiol levels (AU)

Genes related to iron metabolism and susceptibility to Alzheimer's disease in Basque population.

Alzheimer's disease (AD) is the most common dementing disorder and presents with a progressive and irreversible cognitive decline of gradual onset. To date, several reports have involved iron in AD physiopathology. In this study, we have analysed TFC2 variant and HFE mutations (H63D and C282Y) in 211 AD patients and 167 controls recruited from an area of the Basque Country. Furthermore, we have studied APOE genotype as it is a well-known risk factor for AD. APOE epsilon 4 allele was associated with an increased risk of AD and an earlier age at onset, whereas no association was found between TFC2 or HFE C282Y mutation and disease susceptibility. The frequency of H63D mutation was higher in control population (29.9%) than in AD patients (18%), suggesting a protective role of this allele on AD either due to the presence of the mutation itself or through the effect of other related genes in the ancestral haplotype in which it is included.

Response to neoadjuvant therapy for rectal cancer: influence on long-term results.

OBJECTIVE: Pre-operative treatment with chemoradiotherapy (CRT) seems to improve local control and overall survival in patients with rectal cancer. The aims of the study were to analyse the impact on overall, disease free and cancer related survival of tumour response to pre-operative CRT and to analyse the influence of the degree of response on long-terms results. PATIENTS AND METHODS: Patients with a locally advanced rectal cancer, treated by pre-operative CRT were studied. A radical resection of the rectal tumour with mesorectal excision was performed within 6-8 weeks. Judged on the final TNM classification patients were considered responders when the tumour showed histologically a complete response, microscopic residual disease or a partial response. Non-responders were those in whom the extent of disease remained stable or progressed. Results Radical excision was performed in 103 patients, and a palliative resection in five. Forty-three patients underwent abdominoperineal resection and 65 anterior resection of the rectum. Seventy-one (65.7%) patients showed a response to CRT, while 37 (34.3%) did not. The overall local and distant recurrence rates were 6.8% and 21.3%. Tumour recurrence (P < 0.008) and disease free survival (P < 0.007) were significantly different in responders and nonresponders. Of the 71 responders, 16 had a pathological complete response, 27 had persisting microscopic disease and 28 had macroscopic residual disease. No differences in cancer specific outcome were observed in these groups. CONCLUSION: Pathological response to pre-operative CRT is associated with improved tumour recurrence and disease-free survival rates. Any response to pre-operative CRT appears to improve outcomes as much as a complete response.

Guía de actuación ante Staphylococcus aureus resistente a meticilina (SARM) en centros gerontológicos, sociosanitarios y unidades de media-larga estancia / Practice guidelines in methicillin-resistant Staphylococcus aureus in gerontological centres, nursing homes and medium to long-term care units

Staphylococcus aureus es una bacteria muy ubicua que se encuentra en las fosas nasales de hasta en un 30 por ciento de adultos sanos y con frecuencia coloniza también la piel (especialmente los pliegues cutáneos). Es capaz de causar gran cantidad de infecciones, sobre todo en la piel y las partes blandas (infección de heridas quirúrgicas, abscesos, etc.). La patogenicidad de las cepas de S. aureus resistente a meticilina (SARM) es muy similar a las no resistentes. En los centros gerontológicos de Gipuzkoa, la mitad de los estafilococos aislados fueron SARM en el año 2002.El mecanismo de transmisión más frecuente es a través de las manos contaminadas del personal sanitario/auxiliar que no hace un correcto lavado de éstas entre la atención a diferentes residentes. El lavado de manos es la medida más importante y eficaz para reducir los riesgos de transmisión, y debe aplicarse en el manejo de todos los residentes. El uso de guantes no suple dicha medida. No está justificado el rechazo de una persona colonizada por SARM en ningún centro o recurso social, ya que su presencia no supone en la práctica un riesgo de contagio para el resto de las personas, si se siguen unas medidas higiénicas adecuadas. La persona colonizada por SARM (excepto si es de alto riesgo: con úlceras importantes, alteraciones de la conducta o colonización respiratoria) puede compartir habitación con otro residente con el mismo microorganismo multirresistente (sin agrupar los de localización dérmica con los de localización respiratoria), o con otra persona no colonizada que no tenga úlceras, heridas, catéteres, drenajes ni sondas. La persona colonizada por SARM puede utilizar áreas comunes, debiendo guardar una higiene adecuada. Si es incontinente, se recomienda la colocación de un pañal limpio antes de la utilización de dicho espacio. En caso de heridas o úlceras colonizadas, éstas deben estar cubiertas con un apósito seco. No hay que tratar con antibióticos a las personas colonizadas por SARM. No se consigue la erradicación ni se reduce la transmisión, ni tampoco la enfermedad ni la mortalidad. Sin embargo, se selecciona un mayor número de resistencias antibióticas. La persona infectada por SARM será trasladada, a criterio médico, a un centro sanitario. La persona infectada por SARM o colonizada de alto riesgo (con úlceras importantes, alteraciones de la conducta o colonización respiratoria), si no es trasladada a un centro sanitario, puede compartir habitación con otra con la misma infección (excepto si es de localización respiratoria) o, en última instancia, con otra persona no colonizada que no tenga úlceras ni heridas, catéteres, drenajes, sondas ni esté inmunodeprimida. Sin embargo, no debería utilizar áreas comunes y las visitas serán restringidas. No es necesario realizar controles sistemáticos entre el personal sanitario que atiende a las personas colonizadas/infectadas por SARM. El personal dedicado al traslado de éstas deberá aplicar las precauciones estándar (AU)

The BCL11 gene family: involvement of BCL11A in lymphoid malignancies.

Many malignancies of mature B cells are characterized by chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus on chromosome 14q32.3 and result in deregulated expression of the translocated oncogene. t(2;14)(p13;q32.3) is a rare event in B-cell malignancies. In contrast, gains and amplifications of the same region of chromosome 2p13 have been reported in 20% of extranodal B-cell non-Hodgkin lymphomas (B-NHL), in follicular and mediastinal B-NHL, and in Hodgkin disease (HD). It has been suggested that REL, an NF-kappaB gene family member, mapping within the amplified region, is the pathologic target. However, by molecular cloning of t(2;14)(p13;q32.3) from 3 cases of aggressive B-cell chronic lymphocytic leukemia (CLL)/immunocytoma, this study has shown clustered breakpoints on chromosome 2p13 immediately upstream of a CpG island located about 300 kb telomeric of REL. This CpG island was associated with a Krüppel zinc finger gene (BCL11A), which is normally expressed at high levels only in fetal brain and in germinal center B-cells. There were 3 major RNA isoforms of BCL11A, differing in the number of carboxy-terminal zinc fingers. All 3 RNA isoforms were deregulated as a consequence of t(2;14)(p13;q32.3). BCL11A was highly conserved, being 95% identical to mouse, chicken, and Xenopus homologues. BCL11A was also highly homologous to another gene (BCL11B) on chromosome 14q32.1. BCL11A coamplified with REL in B-NHL cases and HD lymphoma cell lines with gains and amplifications of 2p13, suggesting that BCL11A may be involved in lymphoid malignancies through either chromosomal translocation or amplification.