Royal Decree 601/2019 on justification and optimization: Practical aspects.

The Royal Decree 601/2019 of 18th October is the result of the partial transposition into the Spanish legal system of the Euratom Directive 59/2013. This Royal Decree includes the mandates of the Directive related to the need to justify and optimize medical exposure, including that of asymptomatic people, proposal of stricter requirements regarding the information that must be provided to the patient, registration and notification of the doses of medical-radiological procedures, use of reference levels for diagnosis and the availability of dose-indicating devices. The article reviews the most relevant aspects and novelties related to the principles of justification, optimization, dose control and the obligations derived from the right to information and consent. This Royal Decree considers essential for radiologists to develop a high level of competence and a new list of responsibilities and functions, which are detailed and analysed in this article.

Micafungin as antifungal prophylaxis in non-transplanted haemotological patients.

OBJECTIVE: Fungal infections are a major cause of morbidity and mortality in the haematological patients. These infections are mainly due to Candida spp. and Aspergillus spp. Mortality by these infections is high, but rates have descended in the latest series due to better antifungal agents. Echinocan-dins are, in vitro, very active against Candida and Aspergillus spp. The objective of the study is to analyse the efficacy and safety of micafungin in the antifungal prophylaxis of haema-tological patients on chemotherapy. METHODS: A multicentre, observational retrospective study was performed in 7 Haematology Depart-ments in Spain. Patients admitted to these departments with chemotherapy or immunosuppressive treatment, and who had received antifungal prophylaxis with micafungin between 1 January 2009 and 31 December 2014 were included. RESULTS: There were 5 cases of probable or proven fun-gal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 as-pergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity. CONCLUSIONS: Micafungin is an antifungal agent which, used in prophylaxis, has demonstrated good efficacy and an excellent toxicity profile, making it an apparently interesting option in patients requiring antifungal prophylaxis during their hospitalisation episode.

Establishing a baseline for a national paediatric antimicrobial stewardship programme.

BACKGROUND: The majority of antimicrobial stewardship programmes focus on prescribing in adult populations; however, there is a recognized need for targeted paediatric antimicrobial stewardship to improve the quality and safety of prescribing amongst this patient group. OBJECTIVES: To describe the current epidemiology of antimicrobial prescribing in paediatric inpatient populations in Scotland to establish a baseline of evidence and identify priority areas for quality improvement to support a national paediatric antimicrobial stewardship programme. METHODS: A total of 559 paediatric inpatients were surveyed during the Scottish national point prevalence survey of healthcare-associated infections and antimicrobial prescribing, 2016. The prevalence of antimicrobial prescribing was calculated and characteristics of antimicrobial prescribing were described as proportions and compared between specialist hospitals and paediatric wards in acute hospitals. RESULTS: Prevalence of antimicrobial use in paediatric inpatients was 35.4% (95% CI = 31.6%-39.4%). Treatment of community- and hospital-acquired infections accounted for 47.1% and 20.7% of antimicrobial use, respectively, with clinical sepsis being the most common diagnosis and gentamicin the most frequently prescribed antimicrobial for the treatment of infection. The reason for prescribing was documented in the notes for 86.5% of all prescriptions and, of those assessed for compliance against local policy, 92.9% were considered compliant. CONCLUSIONS: Data from national prevalence surveys are advantageous when developing antimicrobial stewardship programmes. Results have highlighted differences in the prescribing landscape between paediatric inpatient populations in specialist hospitals and acute hospitals, and have informed priorities for the national antimicrobial stewardship programme, which reinforces the need for a targeted paediatric antimicrobial stewardship programme.

[Drug using risks screening in primary care patients using the ASSIST test: Cross sectional study]. / Cribado de riesgos derivados del consumo de drogas utilizando la herramienta ASSIST (Alcohol, smoking and substances involvement screening test) en pacientes de atención primaria: estudio transversal.

OBJECTIVE: The aim of this study is to estimate risky-drug use patterns of consumption of primary care patients. DESIGN: Multicentric descriptive cross-sectional study. SETTING: five primary health care centers of the South of Madrid. PARTICIPANTS: all patients between 16-100 year-old consulting with their family physician. MEASUREMENTS: Spanish-validated World Health Organization ASSIST test was use to screen risky drug use in primary care. Total points scored at the test were obtained. RESULTS: A sum of 441 screening test were collected. Mean age was 51,3 years and 51.6% of patients presented a moderate-severe risky drug use out of the nine drugs tested. The more frequent drug use screened were tobacco (41.7%) followed by alcohol (15.4%), hypnotics (13.7%) and cannabis (5.7%). Differences were found between genders in the patterns: men had higher risky drug uses compared to women regarding alcohol and cannabis. Women had higher sedatives/hypnotics consumption prevalence. A 16% of patients presented with polyconsumption drug use patterns. CONCLUSIONS: There is risk derived from drug misuse in primary care for tobacco, alcohol, hypnotics and cannabis as detected by the ASSIST test. There is a higher rate of hypnotics than expected.

Results from the third Scottish National Prevalence Survey: is a population health approach now needed to prevent healthcare-associated infections?

BACKGROUND: Healthcare-associated infections (HCAIs) are a major public health concern and a significant cause of morbidity and mortality. A robust and current evidence base that is specific to local, national and Europe-wide settings is necessary to inform the development of strategies to reduce HCAI and contain antimicrobial resistance. AIM: To measure the prevalence of HCAI and antimicrobial prescribing and identify key priority areas for interventions to reduce the burden of infection. METHODS: A national rolling point-prevalence survey (PPS) in National Health Service (NHS) acute, NHS non-acute, NHS paediatric, and independent hospitals was carried out between September and November 2016 using the European Centre for Disease Prevention and Control protocol designed for the European PPS. FINDINGS: The prevalence of HCAI was 4.6%, 2.7%, and 3.2% in acute adults, paediatric and non-acute patient groups, respectively. The most frequent HCAI types reported in adult patients were urinary tract infection and pneumonia. The prevalence of antimicrobial prescribing was 35.7%, 29.3%, and 13.8% in acute adults, paediatric, and non-acute patient groups, respectively. Respiratory, skin and soft tissue, gastrointestinal, and urinary tract infections were the most common infections being treated at the time of survey. CONCLUSION: HCAI continues to be a public health concern in Scotland. Urinary tract infection and pneumonia continue to place a significant burden on patients and on healthcare delivery, including those that develop in the community and require hospital admission. A broader population health approach which focuses on reducing the risk of infection upstream would reduce these infections in both community and hospital settings.

Neuroprotective Effects of Selected Microbial-Derived Phenolic Metabolites and Aroma Compounds from Wine in Human SH-SY5Y Neuroblastoma Cells and Their Putative Mechanisms of Action.

Moderate wine consumption has shown the potential to delay the onset of neurodegenerative diseases. This study investigates the molecular mechanisms underlying the protective effects of wine-derived phenolic and aroma compounds in a neuroinflammation model based on SIN-1 stress-induced injury in SH-SY5Y neuroblastoma cells. Cell pretreatment with microbial metabolites found in blood after wine consumption, 3,4-dihydroxyphenylacetic (3,4-DHPA), 3-hydroxyphenylacetic acids and salicylic ß-d-O-glucuronide, at physiologically concentrations (0.1-10 µM) resulted in increased cell viability versus SIN-1 control group (p < 0.05). Results also showed significant decreases in mitogen-activated protein kinase (MAPK) p38 and ERK1/2 activation as well as in downstream pro-apoptotic caspase-3 activity by some of the studied compounds. Moreover, pretreatment with p38, MEK, and ERK1/2-specific inhibitors, which have a phenolic-like structure, also resulted in an increase on cell survival and a reduction on caspase-3 activity levels. Overall, these results contribute with new evidences related to the neuroprotective actions of wine, pointing out that wine-derived human metabolites and aroma compounds may be effective at protecting neuroblastoma cells from nitrosative stress injury by inhibiting neuronal MAPK p38 and ERK1/2, as well as downstream caspase 3 activity.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

[Traumatic spinal cord injury in children and adolescents in Asturias]. / Lesion medular traumatica en la infancia y adolescencia en Asturias.

INTRODUCTION: Traumatic spinal cord injury (TSCI) is rare in childhood, but it has serious complications. AIM: To assess incidence, causes and socio-demographic aspects of TSCI among children and adolescents in Asturias. PATIENTS AND METHODS: It was made a census of children among aged 0-17 years codified as 'TSCI with or without vertebral fracture' in Asturias between 1934 and 2013. Socio-demographic, hospital and clinical variables were picked up. RESULTS: In total 72 patients were registered, most of them males (79.2%), with an average age of 16 (range: 5-17). The estimated incidence in 2011 was found to be 7.3/million children/year for children aged 0-17 years. Complete TSCIs (68.1%) and dorsal localization (44.4%) were found to be more common. There was bone injury in 95.8% with two or more vertebras affected in a half of the cases. The main cause was traffic accidents (52.1%) mainly the four wheels vehicles (63.4%), most of them males with an average age of 17 and dorsal localization (46.3%). On second and third place were work-related injuries and sports-related injuries, with the same number of cases. In work related injuries, males were the majority, with dorsal level (77.8%) and the direct blow was the fundamental mechanism. In sports there were males also the dominant, being diving the most important cause, with cervical level. CONCLUSIONS: It is necessary to carry out studies focused on this population group in order to indentify the own characteristics, to establish care and preventive programs, adapted to their necessities.

TITLE: Lesion medular traumatica en la infancia y adolescencia en Asturias.Introduccion. La lesion medular traumatica es rara en la infancia, pero con graves complicaciones. Objetivo. Conocer la incidencia, etiologia y caracteristicas sociodemograficas de los pacientes pediatricos y adolescentes con lesion medular traumatica en Asturias. Pacientes y metodos. Censo de pacientes entre 0-17 años codificados como 'lesion medular traumatica con o sin fractura vertebral' en Asturias entre 1934 y 2013. Se recogen variables sociodemograficas, hospitalarias y clinicas. Resultados. Se registran 72 pacientes, la mayoria varones (79,2%), con una edad media de 16 años (rango: 5-17 años). La incidencia en 2011 fue de 7,3 por millon. Predominaron las lesiones completas (68,1%) y la localizacion dorsal (44,4%). Hubo lesion osea en el 95,8%, y en la mitad de ellos, afectacion de dos o mas vertebras. La etiologia predominante fueron los accidentes de trafico (52,1%), sobre todo de vehiculos de cuatro ruedas (63,4%), con una mayoria de varones con una edad media de 17 años y una localizacion dorsal (46,3%). En segundo y tercer lugar se situaron la etiologia laboral y la deportiva, con el mismo numero de casos. En la laboral predominaron los varones y el nivel toracico (77,8%), y el mecanismo fundamental fue el golpe directo. En la deportiva, la mayoria fueron varones, y la zambullida fue la causa mas importante, de predominio cervical. Conclusiones. Son necesarios estudios centrados en este grupo poblacional que permitan determinar sus caracteristicas diferenciadoras para establecer programas de cuidados adaptados a sus necesidades, asi como las medidas preventivas mas oportunas para reducir las posibilidades de una lesion con tan graves repercusiones.

MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.

Bone marrow WT1 levels at diagnosis, post-induction and post-intensification in adult de novo AML.

We retrospectively assessed whether normalized bone marrow WT1 levels could be used for risk stratification in a consecutive series of 584 acute myeloid leukemia (AML) patients. A cutoff value of 5065 copies at diagnosis identified two prognostic groups (overall survival (OS): 44 ± 3 vs 36 ± 3%, P=0.023; leukemia-free survival (LFS): 47 ± 3 vs 36 ± 4%, P=0.038; and cumulative incidence of relapse (CIR): 37 ± 3 vs 47 ± 4%, P=:0.043). Three groups were identified on the basis of WT1 levels post-induction: Group 0 (WT1 between 0 and 17.5 copies, 134 patients, OS: 59 ± 4%, LFS:59 ± 4% and CIR: 26 ± 4%); Group 1 (WT1 between 17.6 and 170.5 copies, 160 patients, OS: 48 ± 5%, LFS:41 ± 4% and CIR: 45 ± 4%); and Group 2 (WT1 >170.5 copies, 71 patients, OS: 23 ± 6%, LFS: 19 ± 7% and CIR: 68 ± 8%) (P<0.001). Post-intensification samples distinguished three groups: patients with WT1 >100 copies (47 patients, 16%); an intermediate group of patients with WT1 between 10 and 100 copies (148 patients, 52%); and a third group with WT1 <10 copies (92 patients, 32%). Outcomes differed significantly in terms of OS (30 ± 7%, 59 ± 4%, 72 ± 5%), LFS (24 ± 7%, 46 ± 4%, 65 ± 5%) and relapse probability (CIR 72 ± 7%, 45 ± 4%, 25 ± 5%), all P<0.001. WT1 levels in bone marrow assayed using the standardized ELN method provide relevant prognostic information in de novo AML.

Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy.

Risk associated to FLT3 internal tandem duplication (FLT3-ITD) in patients with acute myeloid leukemia (AML) may depend on mutational burden and its interaction with other mutations. We analyzed the effect of FLT3-ITD/FLT3 wild-type (FLT3wt) ratio depending on NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated with intensive chemotherapy. Among NPM1mut patients, FLT3wt and low ratio (<0.5) subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas high ratio (≥0.5) patients had a worse outcome. In NPM1wt AML, FLT3-ITD subgroups showed a comparable outcome, with higher risk of relapse and shortened overall survival than FLT3wt patients. Allogeneic stem cell transplantation in CR1 was associated with a reduced relapse risk in all molecular subgroups with the exception of NPM1mut AML with absent or low ratio FLT3-ITD. In conclusion, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.

Public health response to an outbreak of Legionnaires' disease in Edinburgh, United Kingdom, June 2012.

We report an outbreak comprising 50 confirmed cases of Legionnaires' disease in Edinburgh, Scotland, June 2012. In addition, there were 49 suspected cases. Epidemiological evidence suggests that a common outdoor airborne exposure occurred over south-west Edinburgh. This probably emanated from cooling towers in the north-east of the affected area, although not yet clearly linked by scientific evidence. The co-ordinated public health, environmental and clinical response helped prevent ongoing exposure and mitigated associated mortality and morbidity.

Insuficiencia ovárica primaria familiar asociada a una translocación X;autosoma / Familial primary ovarian insuffciency associated with X;autosomal translocation

La insuficiencia ovárica primaria (IOP) es una condición clínica que describe un estado de disfunción ovárica que se presenta antes de los 40 años. En el 8-9 % de las pacientes se han descripto anomalías del cromosoma X, tanto familiares como esporádicas. Estas incluyen anomalías numéricas como la monosomía o trisomía X, aneuploidías parciales como deleciones o isocromosomas, y anomalías estructurales como las translocaciones X;autosoma (TXA). Presentamos una paciente con diagnóstico de hipogonadismo hipergonadotrófico efectuado a los 18 años, en la que el estudio citogenético reveló un cariotipo 46,X,t(X;11)(q23;q22), interpretándose como una translocación X;autosoma balanceada con punto de ruptura en la región crítica para la función ovárica normal. A los 25 años de edad, bajo tratamiento hormonal sustitutivo cursó un embarazo. Nació una niña con crecimiento y desarrollo normales, con telarca y pubarca a los 11 años. A los 13 años y 3 meses, debido a una detención en el desarrollo puberal, se le diagnosticó un hipogonadismo hipergonadotrófico. El estudio citogenético detectó la traslocación X;autosoma balanceada heredada de su madre. Las mujeres con translocaciones X;autosoma balanceadas frecuentemente desarrollan falla ovárica prematura por interrupción de la región crítica del cromosoma X que se extiende entre Xq13 a Xq27. En conclusión, presentamos dos pacientes (madre e hija) con diagnóstico de una TXA balanceada, y discutimos los aspectos vinculados con las alteraciones de los segmentos del cromosoma X involucrados en el funcionamiento ovárico, así como las consecuencias para su eventual descendencia.

Primary Ovarian Insufficiency (POI) is a clinical condition characterized by ovarian dysfunction before 40 years of age. In 8-9 % of patients, both familial and sporadic chromosome abnormalities have been reported. These include numerical abnormalities such as monosomy or trisomy X, partial aneuploidies, such as deletions or isochromosomes, and structural abnormalities such as X;autosomal translocation (XAT). We report the case of a patient diagnosed with hypergonadotropic hypogonadism at the age of 18, whose cytogenetic study revealed a formula 46,X,t(X;11)(q23;q22), interpreted as an X;autosome balanced translocation with breakpoint in the critical region for normal ovarian differentiation. At the age of 25, under hormone replacement therapy, the patient became pregnant. She gave birth to a girl with normal growth and development, with thelarche and menarche at 11 years old. At the age of 13 years and 3 months, because of an arrest of pubertal development, she was diagnosed with hypergonadotropic hypogonadism. The cytogenetic study detected the X;autosome balanced translocation inherited from her mother. Women with X;autosome balanced translocation frequently develop premature ovarian failure because of breakpoints in the critical region of the X chromosome from Xq13 to Xq27. In conclusion, we report the case of two patients (mother and daughter) with a diagnosis of XAT, and discuss molecular genetics issues related to alterations of X chromosome segments involved in ovarian function, as well as the consequences for potential offspring.

[Cavernous haemangioma of the skull]. / Hemangioma cavernoso intraóseo craneal.

INTRODUCTION: Cavernous haemangiomas are benign tumours that rarely affect the skull. A correct suspicion diagnosis is seldom obtained when typical radiological signs are lacking. In this way a definite diagnosis is only obtained after a surgical procedure in most cases. CASE REPORT: A 52-year-old female presented a painless, slow-growing tumoration in her right forehead. Skull CT showed an osteolytic lesion located within the right frontal bone. On suspicion of a metastatic origin of the lesion, a systemic research for a primary tumour was performed without significative findings. Finally, en bloc resection of the lesion was performed followed by cranioplasty. Microscopically, the lesion proved to be a cavernous haemangioma of the frontal bone. CONCLUSION: Despite their low frequency, cavernous haemangiomas must be included in the differential diagnosis of slow-growing osteolytic lesions located within the skull. The elective treatment of this tumours includes a complete resection by craniectomy, with safe bony margins.

Hiperprolactinemia en la población infantojuvenil: un tema vigente / Hyperprolactinaemia in child an adolescent population: a current issue

La hiperprolactinemia constituye la altelaración endocrina más común del eje hipotálamo-hipofisario, aunque su prevalencia en la población infantojuvenil no está aún claramente definida. Además de la Prolactina (PRL) nativa (23Kda), se han descripto numerosas variantes moleculares, algunas de ellas con menor o ausente actividad biológica. Todo proceso que interrumpa la secreción de dopamina, interfiera con su liberación hacia los vasos portales hipofisarios o bloquee los receptores dopaminérgicos de las células lactotróficas, puede causar hiperprolactinemia. Si bien la patología tumoral constituye el diagnóstico de mayor relevancia, los prolactinomas son poco frecuentes en nios y adolescentes, aunque tienen en general una particular presentación clínica: de acuerdo con nuestra experiencia, el retraso puberal puede observarse en aproximadamente el 50% de las pacientes de sexo femenino. En pacientes con hiperprolactinemia asintomática debe evaluarse la presencia de proporciones alteradas de isoformas de PRL. La cromatografía en columna con sephadex G100, la precipitación con suspención de proteína A o con PEG y la ultracentrifugación constituyen los métodos más frecuentemente empleados para la detección de las distintas isoformas de PRL. En nuestra experiencia la B PRL constituyó el 6,6 - 32,6% de la PRL total y la BB PRL contituyó el 40 y el 72% de çesta en este gruo de pacientes. En cuanto al tratamiento por su efectividad y tolerancia, los agonistas dopaminérgicos constituyen la terapia inicial de elección en pacientes en edad pediátrica. La bromocriptina y la cabergolina han sido empleadas y con resultados similares a los de los pacientes adultos.