Resonancia magnética multiparamétrica y cáncer de próstata: ¿qué hay de nuevo? / Multiparametric magnetic resonance imaging and prostate cancer: what's new?

La resonancia magnética multiparamétrica (RMmp) prostática ha tenido recientemente un extenso desarrollo, convirtiéndose en una herramienta clave en el diagnóstico y la toma de decisiones terapéuticas en relación al carcinoma prostático (CaP). El rápido desarrollo tecnológico, así como de lectura (PIRADS V2), exigen una permanente actualización del conocimiento en esta área. El objetivo de este artículo es presentar una revisión actualizada sobre los aspectos técnicos, los modelos de lectura y las indicaciones de la RMmp prostática en relación al CaP, en el marco de una visión multidisciplinaria. Actualmente está establecida la utilidad de la RMmp ante un antígeno específico de próstata elevado y una biopsia prostática previa negativa; para estadificación tumoral; en la evaluación de candidatos a vigilancia activa; en la planificación de tratamientos focales y para la evaluación de la recurrencia tumoral. Otras indicaciones, como su uso en pacientes con sospecha de CaP pero sin biopsia previa, aunque se realizan en algunos centros, aún requieren una exhaustiva valoración coste-beneficio para extender su empleo (AU)

Prostatic multi-parametric magnetic resonance imaging (MP-MRI) has recently had a wide development becoming a key tool in the diagnostic and therapeutic decisions in prostate cancer (Pca). The fast development both in technology and in reading (PIRADS V2) requires a continuous updating of knowledge within this area. The aim of this article is to present an updated revision of technical aspects, reading patterns and prostatic MP-MRI in Pca, with a multidisciplinary approach. Currently guidelines establish the use of the MP-MRI when there is a high PSA and a negative prostatic biopsy; tumor staging; evaluation in candidates to active surveillance; focal treatments plans and tumoral recurrence evaluation. Although it is used in other indications in some centers, like its use in patients suspicious of Pca but with no previous biopsy, there is still the need of a cost/benefit assessment for its use to be wider (AU)

Multiparametric magnetic resonance imaging and prostate cancer: what's new? / Resonancia magnética multiparamétrica y cáncer de próstata: ¿qué hay de nuevo?

Prostatic multi-parametric magnetic resonance imaging (MP-MRI) has recently had a wide development becoming a key tool in the diagnostic and therapeutic decisions in prostate cancer (Pca). The fast development both in technology and in reading (PIRADS V2) requires a continuous updating of knowledge within this area. The aim of this article is to present an updated revision of technical aspects, reading patterns and prostatic MP-MRI in Pca, with a multidisciplinary approach. Currently guidelines establish the use of the MP-MRI when there is a high PSA and a negative prostatic biopsy; tumor staging; evaluation in candidates to active surveillance; focal treatments plans and tumoral recurrence evaluation. Although it is used in other indications in some centers, like its use in patients suspicious of Pca but with no previous biopsy, there is still the need of a cost/benefit assessment for its use to be wider.

Selection of the method to appraise and compare health systems using risk stratification: the ASSEHS approach.

To face the challenge of active and healthy ageing, European Health Systems and services should move towards proactive, anticipatory and integrated care. The comparison of methods to combine results across studies and to determine an overall effect was undertaken by the EU project ASSEHS (Activation of Stratification Strategies and Results of the interventions on frail patients of Healthcare Services, EU project (No. 2013 12 04). The questions raised in ASSEHS are broad and involve a complex body of literature. Thus, systematic reviews are not appropriate. The most appropriate method appears to be scoping studies. In this paper, an updated method of scoping studies has been used to determine the questions needed to appraise the health systems and services for frailty in the ageing population. Three objectives were set (i) to detect a relevant number of risk stratification tools for frailty and identify the best-in-class, (ii) to understand the feasibility of introducing stratification tools and identify the difficulties of the process and (iii) to find evidence on the impact of risk stratification in Health Services. This novel approach may provide greater clarity about scoping study methodology and help enhance the methodological rigor with which authors undertake and report scoping studies.

Blocking the epithelial-to-mesenchymal transition pathway abrogates resistance to anti-folate chemotherapy in lung cancer.

Anticancer therapies currently used in the clinic often can neither eradicate the tumor nor prevent disease recurrence due to tumor resistance. In this study, we showed that chemoresistance to pemetrexed, a multi-target anti-folate (MTA) chemotherapeutic agent for non-small cell lung cancer (NSCLC), is associated with a stem cell-like phenotype characterized by an enriched stem cell gene signature, augmented aldehyde dehydrogenase activity and greater clonogenic potential. Mechanistically, chemoresistance to MTA requires activation of epithelial-to-mesenchymal transition (EMT) pathway in that an experimentally induced EMT per se promotes chemoresistance in NSCLC and inhibition of EMT signaling by kaempferol renders the otherwise chemoresistant cancer cells susceptible to MTA. Relevant to the clinical setting, human primary NSCLC cells with an elevated EMT signaling feature a significantly enhanced potential to resist MTA, whereas concomitant administration of kaempferol abrogates MTA chemoresistance, regardless of whether it is due to an intrinsic or induced activation of the EMT pathway. Collectively, our findings reveal that a bona fide activation of EMT pathway is required and sufficient for chemoresistance to MTA and that kaempferol potently regresses this chemotherapy refractory phenotype, highlighting the potential of EMT pathway inhibition to enhance chemotherapeutic response of lung cancer.

A breath of Twitter.

The use of online social networks among physicians and physicians-in-training is similar to that of the general population. Patients also use online social networks to communicate and exchange information with other patients who have similar conditions and with health professionals, something which is not free from ethical problems. In any case, online social networks have penetrated clinical practice irreversibly. Twitter is an effective social communication tool used for many different purposes. It has been massively adopted in many sectors including healthcare. The article explores its usefulness for respiratory physicians, focusing in four areas: 1) Access to generic and scientific information, 2) Contact with the professional community, 3) Public health, 4) Relationship with patients.

WT1 mutations may be a cause of severe renal failure due to nephroblastomatosis in Wilms' tumor patients.

Wilms' tumor suppressor gene (WT1) encodes a transcription factor required for normal development of the genitourinary system. Germline WT1 mutations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms' tumor. Here we report a 4-year-old male patient who presented with bilateral cryptorchidism, Wilms' tumor, nephroblastomatosis and renal failure without nephrotic proteinuria. Sequence analysis of the WT1 gene demonstrated a constitutional heterozygous nonsense mutation in exon 7, which leads to a truncation of the WT1 protein at the zinc-finger 1. In the DNA of the tumor, we observed the same mutation in homo/hemizygosity. Given the requirement of WT1 for normal development, the WT1 mutation is likely to be responsible for the nephroblastomatosis and, in consequence, for the severe renal failure observed in our patient. This finding extends the spectrum of kidney diseases related to WT1 mutations and points to the need to screen for this gene in children with genitourinary abnormalities and Wilms' tumor because of the associated risk of nephroblastomatosis and renal failure in those carrying WT1 mutations.

Efectos de la rapamicina en los angiomiolipomas de pacientes con esclerosis tuberosa / Effects of rapamycin on angiomyolipomas in patients with tuberous sclerosis

Introducción: La esclerosis tuberosa (ET) es una enfermedad sistémica, de herencia autosómica dominante, ocasionada por mutaciones en dos genes (TSC1 y TSC2), que causan la aparición de tumores (angiolipomas [AML], angiofibromas, astrocitomas, etc.). La proliferación inadecuada y constante que existe en la ET puede ser bloqueada por inhibidores de la kinasa mTOR (mammalian target of rapamycin), como la rapamicina. Material y métodos: Se han incluido 17 pacientes afectados de ET y, al menos, un AML mayor de 2 cm de diámetro diagnosticado por resonancia magnética (RM). Han recibido tratamiento con rapamicina durante 12 meses. Los niveles plásmáticos se han mantenido entre 4 y 8 ng/dl. El tamaño del AML se ha monitorizado semestralmente mediante RM abdominal. Resultados: A los 12 meses de la inclusión, con la RM se ha objetivado una disminución del tamaño del AML en todos los pacientes incluidos, mostrando una reducción de, al menos, un 50% en el 82,4% (14/17; intervalo de confianza [IC] 95% [56,57%, 96,20%]). El porcentaje medio de reducción fue del 66,3% (IC95 [56,9%, 75,6%]; p <0,0001). Los principales efectos secundarios observados han sido: aftas orales (5/17); hipertrigliceridemia (3/17); microcitosis e hipocromía (3/17); diarrea (2/17); acné (1/17); pielonefritis aguda (1/17), y proteinuria (1/17). Conclusiones: Los datos clínicos preliminares sugieren que la rapamicina puede desempeñar un papel beneficioso en el tratamiento de la ET. Nuestra experiencia en 17 pacientes tratados durante 12 meses demuestra seguridad y eficacia en la reducción de AML (AU)

Background: Tuberous sclerosis (TS) is a systemic disease, with an autosomal dominant pattern of inheritance caused by mutations in two genes (TSC1 and TSC2) that cause tumours (angiomyolipomas [AML], angiofibromas, astrocytomas). Constant and inadequate proliferation occurring in TS may be blocked by mTOR inhibitors (mammalian target of rapamycin), such as rapamycin. Material and methods: At present, our study includes 17 patients with TS. All had at least one AML greater than 2cm in diameter diagnosed by MRI. They received rapamycin during 12 months. Plasma levels remained stable between 4-8ng/dl. The AML size was monitored every six months by abdominal MRI. Results: At 12 months of inclusion, MRI indicated a decrease in the size of AML in all patients showing at least a 50% reduction in 82.4% (14/17, 95% CI [56.57%, 96.20%]). The mean percent reduction was 66.3% (95% CI [56.9%, 75.6%], P<.0001). The major side effects observed were: oral aphthous ulcers (5/17); hypertriglyceridemia (3/17); microcytosis and hypochromia (3/17); diarrhea (2/17); acne (1/17); acute pyelonephritis (1/17); and proteinuria (1/17). Conclusions: These preliminary clinical data suggest that rapamycin can play a beneficial role in the treatment of TS. Our experience in 17 patients treated for 12 months demonstrates safety and efficacy in reducing AML volume (AU)

Complicaciones de aterosclerosis de grandes vasos / Complications of large vessel atherosclerosis

La enfermedad renal ateroembólica es consecuencia del desprendimiento y migración a vasos distales de microémbolos de colesterol, procedentes de placas de ateroma de grandes arterias. Estos émbolos pueden ocluir pequeños vasos en el riñón, retina, cerebro, páncreas, músculos y piel. Se produce en pacientes con arterioesclerosis tras procesos endovasculares o bien se puede producir espontáneamente. Por ello ante un deterior de función renal inexplicable, en paciente con signos de arterioesclerosis, se debe sospechar siempre una enfermedad ateroembólica y buscar manifestaciones extrarrenales. En estos casos, puede ser necesaria la confirmación histológica para el diagnóstico definitivo. No existe tratamiento específico, debiendo tomar algunas medidas como, suspender los anticoagulantes, las manipulaciones aórticas y reducir la PA. De ello dependerá la evolución, ya que ésta puede ser muy variable siendo, desde formas leves, hasta potencialmente mortales. Por otro lado es conveniente remarcar; que a pesar del control estricto de los factores de riesgo vascular, la enfermedad aterosclerótica es una enfermedad progresiva, como se desprende del caso que presentamos y aconsejamos en pacientes de este tipo, con alto riesgo vascular, la toma periódica de la PA en ambas extremidades (AU)

Atheroembolic renal disease is a consequence of the detachment and migration of microemboli distal vessels of cholesterol from atherosclerotic plaques of large arteries. These emboli can occlude small vessels in the kidney, retina, brain, pancreas, muscles and skin. It occurs in patients with atherosclerosis after endovascular procedures or it may occur spontaneously. Therefore, before an unexplained deterioration of renal function, in patients with signs of atherosclerosis, an atherosclerotic disease should always be suspected and seek for extra renal manifestations. In these cases, histological confirmation may be required for definitive diagnosis. There is non specific treatment and certain measures should be taken such as suspending anticoagulants, aortic manipulation and reducing the blood pressure. The evolution will depend on this, as it can vary from being mild to life-threatening forms. On the other band, it is advisable to note, that in despite the strict control of vascular risk factors, atherosclerotic disease is a progressive disease, as shown in the case reported, and in such patients, with high vascular risk, we advise monitoring their BP regularly in both extremities (AU)

Riñón intratorácico. Caso clínico / Intrathoracic kidney. A clinical case

El riñón intratorácico es un tipo de ectopia renal poco frecuente, que presenta morfología y funcionamiento conservado, habitualmente se diagnostica de forma incidental durante el estudio de masa mediastínica y no requiere tratamiento médico ni quirúrgico (AU)

Intrathoracic kidney is an uncommon type of renal ectopy in which the kidney morphology and function is preserved. Usually the diagnosis is incidental during the study of mediastinal mass. Medical or surgery treatment is not required (AU)

Carcinoma urotelial renal en una paciente con enfermedad renal poliquística autosómico dominante: presentación de un caso y revisión de la literatura / Urothelial carcinoma in a woman with autosomal dominant polycystic kidney disease: description of a case and revision of the literature

Presentamos un caso de carcinoma urotelial de pelvis renal en una paciente de 48 años con enfermedad renal poliquística autosómico dominante (ERPAD). Se discute la dificultad del diagnóstico radiológico en estos pacientes y se revisa la incidencia de tumores renales en dicha entidad. La asociación de carcinoma urotelial y ERPAD es muy infrecuente y aparentemente sin relación causal

We describe a case of urothelial carcinoma of renal pelvis in a 48 years old woman affected of autosomal dominant polycystic kidney disease (ADPKD). We discuss the difficulty of the radiological diagnostic and we revise the incidence of renal tumors in this entity. Association between urothelial carcinoma and ADPKD is highly infrequent and without apparently causal relation

Pol eta is required for DNA replication during nucleotide deprivation by hydroxyurea.

Hydroxyurea reduces DNA replication by nucleotide deprivation, whereas UV damage generates DNA photoproducts that directly block replication fork progression. We show that the low fidelity class Y polymerase Pol eta is recruited to proliferating cell nuclear antigen at replication forks both by hydroxyurea and UV light. Under nucleotide deprivation, Pol eta allows cells to accumulate at the G1/S boundary by facilitating slow S-phase progression and promotes apoptosis. Normal cells consequently enter apoptosis at a faster rate than Pol eta-deficient cells. Coincident with hydroxyurea-induced S-phase delay, Pol eta-deficient cells undergo more replication fork breakage and accumulate more foci of the Mre11/Rad50/Nbs1 complex and phosphorylated histone H2AX. We conclude that under conditions of nucleotide deprivation, Pol eta is required for S-phase progression but is proapoptotic. However, as Pol eta is reported to require higher nucleotide concentrations than class B replicative polymerases, its recruitment by hydroxyurea requires it to function under suboptimal conditions. Our results suggest that hydroxyurea-induced apoptosis occurs at the G1/S boundary and that initiation of the S-phase requires greater nucleotide concentrations than does S-phase progression.

[Urothelial carcinoma in a woman with autosomal dominant polycystic kidney disease: description of a case and review of the literature]. / Carcinoma urotelial renal en una paciente con enfermedad renal poliquística autosómico dominante: presentación de un caso y revisión de la literatura.

We describe a case of urothelial carcinoma of renal pelvis in a 48 years old woman affected of autosomal dominant polycystic kidney disease (ADPKD). We discuss the difficulty of the radiological diagnostic and we revise the incidence of renal tumors in this entity. Association between urothelial carcinoma and ADPKD is highly infrequent and without apparently causal relation.

Cockayne syndrome exhibits dysregulation of p21 and other gene products that may be independent of transcription-coupled repair.

Cockayne syndrome (CS) is a progressive childhood neurodegenerative disorder associated with a DNA repair defect caused by mutations in either of two genes, CSA and CSB. These genes are involved in nucleotide excision repair (NER) of DNA damage from ultraviolet (UV) light, other bulky chemical adducts and reactive oxygen in transcriptionally active genes (transcription-coupled repair, TCR). For a long period it has been assumed that the symptoms of CS patients are all due to reduced TCR of endogenous DNA damage in the brain, together with unexplained unique sensitivity of specific neural cells in the cerebellum. Not all the symptoms of CS patients are however easily related to repair deficiencies, so we hypothesize that there are additional pathways relevant to the disease, particularly those that are downstream consequences of a common defect in the E3 ubiquitin ligase associated with the CSA and CSB gene products. We have found that the CSB defect results in altered expression of anti-angiogenic and cell cycle genes and proteins at the level of both gene expression and protein lifetime. We find an over-abundance of p21 due to reduced protein turnover, possibly due to the loss of activity of the CSA/CSB E3 ubiquitylation pathway. Increased levels of p21 can result in growth inhibition, reduced repair from the p21-PCNA interaction, and increased generation of reactive oxygen. Consistent with increased reactive oxygen levels we find that CS-A and -B cells grown under ambient oxygen show increased DNA breakage, as compared with xeroderma pigmentosum cells. Thus the complex symptoms of CS may be due to multiple, independent downstream targets of the E3 ubiquitylation system that results in increased DNA damage, reduced transcription coupled repair, and inhibition of cell cycle progression and growth.

Masa pelviana en paciente con adenocarcinoma de próstata / Pelvic mass in a patient with prostatic adenocarcinoma

Se presenta el caso de un paciente que tras biopsias prostáticas seriadas, por PSA persistentemente elevado, se diagnostica de ADC de próstata. En el estudio de extensión se detectan metástasis hepáticas y una masa abdominal que tras biopsia percutánea, se diagnostica de GIST

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[Intraocular lens (IOL) power calculation after keratorefractive procedures]. / Cálculo del poder dióptrico de la lente intraocular (LIO) tras cirugía refractiva.

PURPOSE: To compare various methods of estimating corneal power for IOL calculation for cataract surgery after corneal refractive surgery. METHODS: Review of the medical literature and case reports. RESULTS: For more accurate IOL power calculations we need pre- (Kpre) and post-treatment keratometry records (Kpost) if using 3rd generation formulae, or Kpost records when using 4th generation formulae. CONCLUSIONS: Prior to performing a keratorefractive procedure it is advisable to have pre-treatment refraction and keratometry (K and method) registered. 3rd generation formulae with Aramberri's double-K correction, or 4th generation formulae are recommended.

Cálculo del poder dióptrico de la lente intraocular (LIO) tras cirugía refractiva / Intraocular lens (IOL) power calculation alter keratorefractive procedures

Objetivo: Comparar los distintos métodos de estimación del poder refractivo de la córnea para el cálculo la lente intra-ocular (LIO) para la cirugía de cataratas después de cirugía refractiva corneal.Método: Revisión de la literatura médica y de series de casos clínicos.Resultados: Para el cálculo más exacto de la LIO necesitamos la queratométría previa (Kpre) y posterior (Kpost) a la cirugía refractiva si utilizamos una fórmula de 3.ª generación o solamente la Kpost si optamos por una fórmula de 4.ª generación.Conclusiones: Previamente a la cirugía refractiva es conveniente registrar la refracción y queratometría (K y método). Se recomienda utilizar fórmulas de 3.ª generación con la corrección doble-k de Aramberri o fórmulas de 4.ª generación

Purpose: To compare various methods of estimating corneal power for IOL calculation for cataract surgery after corneal refractive surgery. Methods: Review of the medical literature and case reports. Results: For more accurate IOL power calculations we need pre- (Kpre) and post-treatment keratometry records (Kpost) if using 3rd generation formulae, or Kpost records when using 4th generation formulae. Conclusions: Prior to performing a keratorefractive procedure it is advisable to have pre-treatment refraction and keratometry (K and method) registered. 3rd generation formulae with Aramberri’s double-K correction, or 4th generation formulae are recommended

Estudio descriptivo de los trastornos adaptativos en un centro de atención primaria / Descriptive study of adaptive disorders in a primary care centre

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