Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors.

The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) in type 2 diabetes (T2D). We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. Oral treatment with FIN (10 mg/kg/day in rat chow) in diabetic animals (D-FIN) was compared to a group of D rats receiving no treatment and a group of non-diabetic untreated MWF rats (C) (n = 7-10 animals per group). After 6 weeks, D and D-FIN exhibited significantly elevated blood glucose levels (271.7 ± 67.1 mg/dl and 266.3 ± 46.8 mg/dl) as compared to C (110.3 ± 4.4 mg/dl; p < 0.05). D showed a 10-fold increase of kidney damage markers Kim-1 and Ngal which was significantly suppressed in D-FIN. Blood pressure, pulse wave velocity (PWV) and arterial collagen deposition were lower in D-FIN, associated to an improvement in endothelial function due to a reduction in pro-contractile prostaglandins, as well as reactive oxygen species (ROS) and inflammatory cytokines (IL-1, IL-6, TNFα and TGFß) in perivascular and perirenal adipose tissue (PVAT and PRAT, respectively). In addition, FIN restored the imbalance observed in CKD between the procalcifying BMP-2 and the nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. Our data show that treatment with FIN improves kidney and vascular damage in a new rat model of DKD with T1D associated with a reduction in inflammation, fibrosis and osteogenic factors independently from changes in glucose homeostasis.

Bioactive injectable hydrogels for on demand molecule/cell delivery and for tissue regeneration in the central nervous system.

Currently there are no potential curative therapies that can improve the central nervous system (CNS) regeneration after traumatic injuries or diseases. Indeed, the regeneration of CNS is greatly impaired by limited drug penetration across the blood brain barrier (BBB), poor drug targeting, deficient progenitor neural cells and limited proliferation of mature neural cells. To overcome these limitations, bioengineered injectable hydrogels in combination with drug and cell therapy have been proposed to mimic the complexity of the CNS microenvironment and architecture. Additionally, to enhance relevant CNS regeneration, proper biophysical and biochemical cues are needed. Recently, great efforts have been devoted to tailor stimuli-responsive hydrogels as novel carrier systems which are able to guide neural tissue regeneration. This review provides an extensive overview on the most promising injectable hydrogels for neural tissue engineering. A special emphasis is made to highlight the ability of these hydrogels to deliver bioactive compounds/cells upon the exposure to internal and external stimuli. Bioactive injectable hydrogels have a broad application in central nervous system's (CNS) regeneration. This review gives an overview of the latest pioneering approaches in CNS recovery using stimuli-responsive hydrogels for several neurodegenerative disorders. STATEMENT OF SIGNIFICANCE: This review summarizes the latest innovations on bioactive injectable hydrogels, focusing on tailoring internal/external stimuli-responsive hydrogels for the new injectable systems design, able to guide neural tissue response. The purpose is to highlight the advantages and the limitations of thermo-responsive, photo responsive, magnetic responsive, electric responsive, ultrasound responsive and enzymes-triggered injectable hydrogels in developing customizable neurotherapies. We believe that this comprehensive review will help in identifying the strengths and gaps in the existing literature and to further support the use of injectable hydrogels in stimulating CNS regeneration.

Caloric restriction induces H2O2 formation as a trigger of AMPK-eNOS-NO pathway in obese rats: Role for CAMKII.

Caloric restriction (CR) improves endothelial function through the upregulation of adenosine monophosphate-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). Moreover, hydrogen peroxide (H2O2) is upregulated in yeast subjected to CR. Our aim was to assess if mild short-term CR increases vascular H2O2 formation as a link with AMPK and eNOS activation. Twelve-week old Zucker obese (fa/fa) and control Zucker lean male rats were fed a standard chow either ad libitum (AL, n=10) or with a 20% CR (CR, n=10) for two weeks. CR significantly improved relaxation to ACh in fa/fa rats because of an enhanced endogenous production of H2O2 in aortic rings (H2O2 levels fa/faAL=0.5 ±â€¯0.05 nmol/mg vs. H2O2 levels fa/faCR=0.76 ±â€¯0.07 nmol/mg protein; p<0.05). Expression of mitochondrial superoxide dismutase (Mn-SOD) and total SOD activity were increased in aorta from fa/fa animals after CR. In cultured aortic endothelial cells, serum deprivation or 2-deoxy-d-glucose induced a significant increase in: i) superoxide anion and H2O2 levels, ii) p-AMPK/AMPK and p-eNOS/eNOS expression and iii) nitric oxide levels. This effect was reduced by catalase and strongly inhibited by Ca2+/calmodulin-dependent kinase II (CamkII) silencing. In conclusion, we propose that mild short-term CR might be a trigger of mechanisms aimed at protecting the vascular wall by the increase of H2O2, which then activates AMPK and nitric oxide release, thus improving endothelium-dependent relaxation. In addition, we demonstrate that CAMKII plays a key role in mediating CR-induced AMPK activation through H2O2 increase.

Using Clinical Signs and Symptoms for Medical Management of Radiation Casualties - 2015 NATO Exercise.

The utility of early-phase (≤5 days) radiation-induced clinical signs and symptoms (e.g., vomiting, diarrhea, erythema and changes in blood cell counts) was examined for the prediction of later occurring acute radiation syndrome (ARS) severity and the development of medical management strategies. Medical treatment protocols for radiation accident victims (METREPOL) was used to grade ARS severities, which were assigned response categories (RCs). Data on individuals (n = 191) with mild (RC1, n = 45), moderate (RC2, n = 19), severe (RC3, n = 20) and fatal (RC4, n = 18) ARS, as well as nonexposed individuals (RC0, n = 89) were generated using either METREPOL (n = 167) or the system for evaluation and archiving of radiation accidents based on case histories (SEARCH) database (n = 24), the latter comprised of real-case descriptions. These data were converted into tables reflecting clinical signs and symptoms, and submitted to eight teams representing five participating countries. The teams were comprised of medical doctors, biologists and pharmacists with subject matter expertise. The tables comprised cumulated clinical data from day 1-3 and day 1-5 postirradiation. While it would have reflected a more realistic scenario to provide the data to the teams over the course of a 3- or 5-day period, the logistics of doing so proved too challenging. In addition, the team members participating in this exercise chose to receive the cumulated reports of day 1-3 and 1-5. The teams were tasked with predicting ARS incidence, ARS severity and the requirement for hospitalization for multiple cases, as well as providing the certainty of their diagnosis. Five of the teams also performed dose estimates. The teams did not employ harmonized methodologies, and the expertise among the members varied, as did the tools used and the means of analyzing the clinical data. The earliest report time was 3 h after the tables were sent to the team members. The majority of cases developing ARS (89.6% ± 3.3 SD) and requiring hospitalization (88.8% ± 4.6 SD) were correctly identified by all teams. Determination of ARS severity was particularly challenging for RC2-3, which was systematically overestimated. However, RC4 was correctly predicted at 94-100% by all teams. RC0 and RC1 ARS severities were more difficult to discriminate. When reported RCs (0-1 and 3-4) were merged, on average 89.6% (±3.3 SD) of all cases could be correctly classified. Comparisons on frequency distributions revealed no statistically significant differences among the following: 1. reported ARS from different teams (P > 0.2); 2. cases generated based on METREPOL or SEARCH (P > 0.5); or 3. results reported at day 3 and 5 postirradiation (P > 0.1). Dose estimates of all teams increased significantly along with ARS severity (P < 0.0001) as well as with dose estimates generated from dicentric chromosomal-aberration measurements available for SEARCH cases (P < 0.0001). In summary, early-phase radiation-induced clinical signs and symptoms proved to be useful for rapid and accurate assessment, with minor limitations, toward predicting life-threatening ARS severity and developing treatment management strategies.

Genome-based study of a spatio-temporal cluster of invasive meningococcal disease due to Neisseria meningitidis serogroup C, clonal complex 11.

OBJECTIVES: To describe a spatio-temporal cluster of invasive meningococcal disease (IMD) due to serogroup C meningococci, occurred in a restricted area of Tuscany between January and October 2015, and the results of whole genome sequencing (WGS). METHODS: Surveillance activities and public health measures were implemented in the Region. Bacterial isolates from IMD cases were characterized by the National Reference Laboratory of the Istituto Superiore di Sanità (ISS), and WGS was performed on available strains. The kSNP software was used to identify core genome SNPs. RESULTS: Overall, 28 IMD cases due to meningococcus C were identified up to 31st October, 2015. Of them, 26 were due to meningococcus C:P1.5-1,10-8: F3-6:ST-11 (cc11) and 2 to C:P1.5-1,10-8: F3-6:ST-2780 (cc11). WGS of 13 meningococci isolated during the outbreak occurred in Tuscany in 2015 showed higher similarity when compared with those of 47 C: P1.5-1,10-8: F3-6:ST-11 (cc11) invasive strains from sporadic cases previously detected in Italy. CONCLUSIONS: A highly aggressive meningococcal C strain was involved in the cluster of severe IMD occurred in Tuscany, a Region with high vaccine coverage among children. Whether this was due to low herd immunity related to the short duration of vaccine protection needs further investigation.

Draft Genome Sequence of a Bordetella pertussis Strain with the Virulence-Associated Allelic Variant ptxP3, Isolated in Italy.

Despite a universal immunization program, pertussis has persisted and resurged, and is of particular concern for infants in terms of morbidity and mortality. Here, we report the genome sequence of a Bordetella pertussis strain with the virulence-associated allelic variant ptxP3, isolated from a 45-day-old infant.

Draft Genome Sequence of Neisseria gonorrhoeae Sequence Type 1407, a Multidrug-Resistant Clinical Isolate.

Gonorrhea may become untreatable due to the spread of resistant or multidrug-resistant strains. Cefixime-resistant gonococci belonging to sequence type 1407 have been described worldwide. We report the genome sequence of Neisseria gonorrhoeae strain G2891, a multidrug-resistant isolate of sequence type 1407, collected in Italy in 2013.

Whole-Genome Sequencing of Mycoplasma mycoides subsp. mycoides Italian Strain 57/13, the Causative Agent of Contagious Bovine Pleuropneumonia.

Mycoplasma mycoides subsp. mycoides is generally considered one of most pathogenic Mycoplasma species, and it is the etiological agent of contagious bovine pleuropneumonia (CBPP). Here, we present the annotated genome sequence of M. mycoides subsp. mycoides Italian strain 57/13, isolated in 1992 during CBPP outbreaks in Italy.

La resonancia magnética multiparamétrica predice la presencia de cáncer de próstata en pacientes con biopsia prostática negativa / Multiparametric magnetic resonance imaging predicts the presence of prostate cancer in patients with negative prostate biopsy

Objetivo: Evaluar el papel del estudio multiparamétrico mediante imagen por resonancia magnética (mpMRI) de próstata para detectar cáncer de próstata en pacientes con biopsia prostática transrectal (BPTR) negativa previa. Material y métodos: Se practicó una mpMRI (secuencias TSE-T2-w, DWI y DCE) de la próstata con equipo de 1.5 T (Magnetom Avanto; Siemens Healthcare Solutions) a 150 pacientes con sospecha previa de cáncer de próstata y BPTR negativa. Se aplicaron criterios de European Society of Urogenital Radiology (ESUR) (1: muy posiblemente benigno, 2: posiblemente benigno, 3: dudoso, 4: posiblemente maligno, y 5: muy posiblemente maligno). A todos los pacientes se les realizó PSA (total y libre), tacto rectal (TR), ecografía transrectal (ETR) y segunda BPTR de, al menos, 14 cilindros. Las variables fueron analizadas de forma ciega independiente. Se estudió la exactitud de cada prueba y se evaluó un modelo de selección de variables stepwise para predecir cáncer en la segunda BPTR. Resultados: La edad media ± desviación estándar fue 66,2 ± 5 (51-77) años, el PSA 11,3 ± 9,6 (0,9-75) ng/mL y el volumen prostático 82,2 ± 42 (20-250) cc. El TR fue sospechoso en 11(7,3%) pacientes. La segunda BPTR muestreó 17,6 ± 2,7 (14-22) cilindros por caso y resultó positiva en 28 (18,7%) pacientes. La mpMRI se consideró positiva (3-5) en 102 (68%), siendo la sensibilidad de la prueba del 92,9% y el VPN del 95,8%. Modifican riesgo de cáncer en segunda BPTR: velocidad de PSA > 0,75 (OR 1,04 [0,99-1,08]); p = 0,06), PSA libre/total < 15% (OR 0,37 [0,13-1,05]; p = 0,06), cada cc de volumen prostático (OR 0,98 [0,97-1]; p = 0,017) y mpMRI 3-5 (OR 7,87 [1,78-34,7]; p = 0,006). El análisis multivariante reveló que mpMRI (OR 7,41 [1,65-33,28]; p = 0,009) y volumen prostático (OR 0,31 [0,12-0,78]; p = 0,01) definen riesgo de cáncer de forma independiente. Conclusiones: La mpMRI según criterios ESUR es una herramienta de gran valor para predecir la presencia de cáncer en la segunda BPTR en pacientes con biopsia previa negativa y resulta más fiable en próstatas de menor volumen

Objective: To assess the ability of multiparametric prostate magnetic resonance imaging (mpMRI) to detect prostate cancer in patients with prior negative transrectal prostate biopsy (TPB). Material and methods: mpMRI (TSE-T2-w, DWI and DCE sequences) was performed on 1.5 T (Magnetom Avanto; Siemens Healthcare Solutions) in 150 patients suspicious of prostate cancer and with negative TPB. European Society of Urogenital Radiology (ESUR) criteria were used (score 1: clinically significant disease is highly unlikely to be present; score 2: clinically significant cancer is unlikely to be present; score 3: clinically significant cancer is equivocal; score 4: clinically significant cancer is likely to be present; score 5: clinically significant cancer is highly likely to be present). PSA measurement (total and free), digital rectal examination (DRE), transrectal ultrasound (TRU) and a second TPB (at least 14 cylinders) were performed in all patients. Variables were submitted for independent blind analysis. The accuracy of each test was measured. Stepwise selection model for prediction of prostate cancer in second TPB was developed. Results: Mean age was 66.2± 5 years (51-77), mean PSA 11.3± 9.6 ng/mL (0.9-75) and mean prostatic volume 82.2 ± 42 (20-250) cc. DRE was suspicious in 11 (7.3%) patients. The mean number of cylinders per patient sampled in second TRB was 17.6 ± 2.7(14-22). Second TRB was positive in 28 patients (18.7%). mpMRI was positive (score 3-5) in 102 (68%), test sensibility was 92.9% and the NPV was 95.8%. The risk of prostate cancer diagnosis in second TPB is modified by: PSA velocity > 0.75 (OR 1.04 [0.99-1.08]; P=0.06), free/total ratio PSA <15% (OR 0.37 [0.13-1.05]; P=0.06), each cc. of prostate volume (OR 0.98 [0.97-1]; P=0.017) and mpMRI 3-5 (OR 7.87 [1.78-34.7]; P=0.006). Multivariate analysis reveals that mpMRI (OR 7.41 [1.65-33.28]; P=0.009) and prostatic volume (OR 0.31 [0.12-0.78]; P=0.01) are independent risk predictors of prostate cancer. Conclusions: According to ESUR guidelines and in patients with prior negative prostate biopsy, mpMRI is a valuable tool for the prediction of prostate cancer in second TPB. Lower prostate volume, the higher reliability

Multiparametric magnetic resonance imaging predicts the presence of prostate cancer in patients with negative prostate biopsy.

OBJECTIVE: To assess the ability of multiparametric prostate magnetic resonance imaging (mpMRI) to detect prostate cancer in patients with prior negative transrectal prostate biopsy (TPB). MATERIAL AND METHODS: mpMRI (TSE-T2-w, DWI and DCE sequences) was performed on 1.5T (Magnetom Avanto; Siemens Healthcare Solutions) in 150 patients suspicious of prostate cancer and with negative TPB. European Society of Urogenital Radiology (ESUR) criteria were used (score 1: clinically significant disease is highly unlikely to be present; score 2: clinically significant cancer is unlikely to be present; score 3: clinically significant cancer is equivocal; score 4: clinically significant cancer is likely to be present; score 5: clinically significant cancer is highly likely to be present). PSA measurement (total and free), digital rectal examination (DRE), transrectal ultrasound (TRU) and a second TPB (at least 14 cylinders) were performed in all patients. Variables were submitted for independent blind analysis. The accuracy of each test was measured. Stepwise selection model for prediction of prostate cancer in second TPB was developed. RESULTS: Mean age was 66.2± 5 years (51-77), mean PSA 11.3± 9.6ng/mL (0.9-75) and mean prostatic volume 82.2±42 (20-250) cc. DRE was suspicious in 11 (7.3%) patients. The mean number of cylinders per patient sampled in second TRB was 17.6±2.7(14-22). Second TRB was positive in 28 patients (18.7%). mpMRI was positive (score 3-5) in 102 (68%), test sensibility was 92.9% and the NPV was 95.8%. The risk of prostate cancer diagnosis in second TPB is modified by: PSA velocity > 0.75 (OR 1.04 [0.99-1.08]; P=0.06), free/total ratio PSA <15% (OR 0.37 [0.13-1.05]; P=0.06), each cc. of prostate volume (OR 0.98 [0.97-1]; P=0.017) and mpMRI 3-5 (OR 7.87 [1.78-34.7]; P=0.006). Multivariate analysis reveals that mpMRI (OR 7.41 [1.65-33.28]; P=0.009) and prostatic volume (OR 0.31 [0.12-0.78]; P=0.01) are independent risk predictors of prostate cancer. CONCLUSIONS: According to ESUR guidelines and in patients with prior negative prostate biopsy, mpMRI is a valuable tool for the prediction of prostate cancer in second TPB. Lower prostate volume, the higher reliability.

Draft Genome Sequence of C:P1.5-1,10-8:F3-6:ST-11 Meningococcal Clinical Isolate Associated with a Cluster on a Cruise Ship.

Meningococcal serogroup C strains, in particular those belonging to the ST-11 clonal complex, are known to cause invasive diseases worldwide. We report the genome sequence of a Neisseria meningitidis strain linked to a cluster of cases of invasive meningococcal disease on a cruise ship that was described in 2012.

Simulador de realidad virtual para el entrenamiento en vaporización fotoselectiva de la próstata con láser de diodo 980 nm y curva de aprendizaje de la técnica / Virtual reality simulator for training on photoselective vaporization of the prostate with 980 nm diode laser and learning curve of the technique

Objetivo: Se investiga la utilidad de un simulador de realidad virtual para el entrenamiento de la vaporización fotoselectiva de la próstata con láser de diodo. Material y método: Se han practicado 2 experimentos con un simulador (VirtaMed AG, Zürich, Suiza) con software para entrenamiento específico en vaporización prostática modo de contacto con fibra Twister (Biolitec AG, Jena, Alemania). Dieciocho cirujanos realizaron ablación prostática (55 cc) por duplicado y se comparó la puntuación obtenida (190 puntos eficacia y 80 seguridad) en la segunda de ellas por grupos de experiencia (alumnos médicos, residentes, especialistas). También realizaron prueba de orientación espacial con puntuaciones de 0 a 6. Posteriormente 6 de estos cirujanos repitieron 15 ablaciones prostáticas (55 y 70 ml). Se evalúa la mejora de los parámetros obtenidos para definir la curva de aprendizaje y cómo influye la experiencia, las habilidades de orientación espacial y el tipo de secuencia realizada. Resultados: La puntuación global de eficacia y seguridad fue diferente según el grado de experiencia (p = 0,005). Al comparar por pares se detectaron diferencias especialista-alumno (p = 0,004), pero no especialista-residente (p = 0,12) o residente-alumno (p = 0,2). Con respecto a la eficacia del procedimiento se detectan diferencias especialista-alumno (p = 0,0026) y residente-alumno (p = 0,08). Los indicadores parciales diferentes en términos de eficacia fueron tasa de ablación (p = 0,01), tiempo de procedimiento (p = 0,03) y cantidad de cápsula no expuesta (p = 0,03). No se observaron diferencias entre grupos en seguridad (p = 0,5). Con respecto a la curva de aprendizaje la mediana del porcentaje sobre la puntuación total superó el 90% tras realizar 4 procedimientos para próstatas de 55 ml y 10 para glándulas de 70 ml. Esta evolución no se modificó por experiencia previa (residente-especialista; p = 0,6), pero sí según la secuencia de repetición (progresiva-aleatoria; p = 0,007). Los cirujanos con orientación espacial inferior a la mediana del grupo (valor 2,5) no superaron el 90% de puntuación a pesar de la repetición del procedimiento. Conclusión: La simulación para la ablación prostática con láser de diodo de contacto es un buen modelo de aprendizaje con validez discriminativa, al correlacionar resultados métricos con niveles de experiencia y habilidades. La repetición secuencial del procedimiento en niveles crecientes de dificultad favorece el aprendizaje

Objective: The utility of a virtual reality simulator for training of the photoselective vaporization of the prostate with diode laser was studied. Materials and methods: Two experiments were performed with a simulator (VirtaMed AG, Zürich, Switzerland) with software for specific training in prostate vaporization in contact mode with Twister fiber (Biolitec AG, Jena, German). Eighteen surgeons performed ablation of the prostate (55 cc) twice and compared the score obtained (190 points efficacy and 80 safety) in the second one of them by experience groups (medical students, residents, specialists). They also performed a spatial orientation test with scores of 0-6. After, six of these surgeons repeated 15 ablations of the prostate (55 and 70 ml). Improvement of the parameters obtained was evaluated to define the learning curve and how experience, spatial orientation skills and type of sequences performed affects them. Results: Global efficacy and safety score were different according to the grade of experience (P = 0.005). When compared by pairs, specialist-student differences were detected (p = 0.004), but not specialist-resident (P = 0.12) or resident-student (P = 0.2). Regarding efficacy of the procedure, specialist-student (p = 0.0026) and resident-student (P = 0.08) differences were detected. The different partial indicators in terms of efficacy were rate of ablation (P = 0.01), procedure time (P = 0.03) and amount of unexposed capsule (p = 0.03). Differences were not observed between groups in safety (P = 0.5). Regarding the learning curve, percentage median on the total score exceeded 90% after performing four procedures for prostates of 55 ml and 10 procedures for prostate glands of 70 ml. This course was not modified by previous experience (resident-specialist; P = 0.6). However, it was modified according to the repetition sequence (progressive-random; P = 0.007). Surgeons whose spatial orientation was less than the median of the group (value 2.5) did not surpass 90% of the score in spite of repetition of the procedure. Conclusion: Simulation for ablation of the prostate with contact diode laser is a good learning model with discriminative validity, as it correlates the metric results with levels of experience and skills. The sequential repetition of the procedure on growing levels of difficulty favors learning

Eficacia y seguridad de fosfomicina-trometamol en la profilaxis de la biopsia transrectal de la próstata: estudio prospectivo aleatorizado comparativo con ciprofloxacino / Efficacy and safety of Fosfomycin-trometamol in the prophylaxis for transrectal prostate biopsy. Prospective randomized comparison with ciprofloxacin

Objetivo: La biopsia de próstata constituye el estándar de diagnóstico del cáncer de próstata. No existe un protocolo estandarizado, pero sí recomendaciones que ayudan a disminuir la incidencia de complicaciones. El objetivo de este trabajo es evaluar la eficacia y seguridad de la profilaxis antibiótica en biopsia prostática comparando 2 dosis de fosfomicina-trometamol (FMT) 3 g (cada 48 h) con 10 de ciprofloxacino oral 500 mg (cada 12 h, 5 días). Material y métodos: Estudio prospectivo aleatorizado con 671 pacientes sometidos a biopsia prostática transrectal ecodirigida ambulante. El grupo A (n = 312) recibió ciprofloxacino y el B (n = 359) FMT. Se comparó la eficacia de ambos regímenes y tolerabilidad del tratamiento. Se practicó cultivo de orina a las 2 semanas de la biopsia. Los pacientes con bacteriuria asintomática no recibieron tratamiento antibiótico inicialmente, y se les practicó un nuevo cultivo de orina al mes, tratándose la bacteriuria persistente según el antibiograma. Resultados: No existieron diferencias entre grupos respecto a la edad (p = 0,78), presencia de cáncer (p = 0,9) o número de cilindros (p = 0,93). El número medio de cilindros obtenidos fue 11,3 + 3,25 (rango: 6-20). Nueve pacientes (2,9%) en A y 10 (2,8%) en B presentaron intolerancia digestiva. Un caso (0,3%) en A presentó reacción alérgica severa. En total 167 (24,6%) presentaron complicaciones: 16 (2,4%) fiebre, 47 (6,9%) hemospermia, 81 (11,9%) hematuria, 7 (1%) rectorragia y 16 (2,4%) retención urinaria. No se detectaron diferencias entre grupos (27,6 vs. 22,6%; p = 0,17), pero sucedió más hemospermia en A (9,9 vs. 4,5%; p = 0,006). En 44 (6,6%) se detectó bacteriuria tras la biopsia, más frecuente en B (4,2 vs. 8,6%; p = 0,02), aunque sin precisar mayor número de segundos tratamientos (53,9 vs. 29%; p = 0,17). La probabilidad de resistencia a ciprofloxacino en pacientes con bacteriuria en A fue mayor que la de FMT en B (69,2 vs. 41,9%; p = 0,0004). Conclusiones: La profilaxis antibiótica en la biopsia prostática con FMT (2 dosis de 3 g) es una opción igual de eficaz y segura que ciprofloxacino (10 dosis de 500 mg), que conlleva menor tasa de resistencias. En nuestra experiencia la profilaxis con este fármaco es una opción segura, bien tolerada y de cómoda administración, lo que facilita su cumplimiento. Se necesitan estudios multicéntricos prospectivos que confirmen estos hallazgos

Objective: Prostate biopsy is the standardized diagnostic method for prostate cancer. However, although there is not a standardized protocol, there are recommendations in order to reduce the incidence of complications. The objective of the present work is to assess the efficacy and safety of antibiotic prophylaxis in the prostate biopsy by comparing two antibiotic regimes: two doses of fosfomycin-trometamol 3 g (FMT) every 48 h with 10 doses of oral ciprofloxacin 500 mg every 12 h for 5 days. Material and methods: Randomized prospective study was performed with 671 patients who had undergone to walking transrectal ultrasound guided prostate biopsy. Patients of group A (n = 312) were treated with ciprofloxacin, and patients of group B (n = 359) with FMT. Efficacy and tolerability of two prophylactic regimes were compared. Urine culture was carried out at 2 weeks after biopsy. Initially, patients with asymptomatic bacteriuria were not treated with antibiotics; urine culture was repeated after 1 month, persistent bacteriuria was treated according to antibiogram. Results: No differences between groups were found in age (p = 0.78), cancer presence (p = 0.9) or number of biopsy cylinders (p = 0.93). The mean number of cores obtained was 11.3 ± 3.25 (range 6-20). Digestive intolerance was observed for 9 patients (2.9%) of group A and 10 patients (2.8%) in group B. One patient (0.3%) of group A showed severe allergic reaction. In total, 167 patients (24.6%) had complications: 16 (2.4%) fever, 47 (6.9%) hemospermia, 81 (11.9%) hematuria, 7 (1%) rectal bleeding and 16 (2.4%) urinary retention. No statistically differences between groups were observed (27.6% vs. 22.6%; p = 0.17). However, hemospermia was more frequent in group A (9.9% vs. 4.5%; p = 0.006). Bacteriuria after biopsy was detected in 44 patients (6.6%), being more frequent in group B patients (4.2% vs. 8.6%; p = 0.02) although a higher number of second treatment cycles were not needed (53.9% vs. 29%; p = 0.17). The likelihood of resistance to ciprofloxacin in patients with bacteriuria in A was greater than that of FMT in B (69.2% vs. 41.9%; p = 0.0004). Conclusions: Antibiotic prophylaxis with FMT (2 doses of 3 g) in prostate biopsy is an alternative as effective and safe as ciprofloxacin (10 doses of 500 mg), which carries lower rate of resistance. According to our experience, this drug is a safe, well-tolerated, and easily manageable prophylactic option, facilitating patient compliance. More prospective multicenter studies are necessary to confirm these findings

Evaluación de la invasión extracapsular y otros parámetros de estadificación mediante resonancia nuclear magnética multiparamétrica en pacientes con cáncer de próstata candidatos a prostatectomía radical / Multiparametric Magnetic Resonance Imaging for the Assessment of Extracapsular Invasion and Other Staging Parameters in Patients With Prostate Cancer Candidates for Radical Prostatectomy

Introducción: La correcta evaluación de la extensión extracapsular (EEC), la invasión de las vesículas seminales y de los ganglios linfáticos regionales es necesaria para planificar el tratamiento a seguir en el cáncer de próstata localizado. Se define un modelo que evalúa el riesgo de EEC en el espécimen considerando los hallazgos clínicos, histopatológicos y de imagen. Material y métodos: Estudio prospectivo en 85 pacientes con cáncer de próstata tratados mediante prostatectomía radical. La biopsia de próstata se realizó 4 semanas antes del estudio multiparamétrico (mpMRI). Este incluyó resonancia magnética con antena endorrectal balanceada en T2 (MRI-T2W), secuencias balanceadas con difusión (MRI-DW) y secuencias balanceadas con perfusión (MRI-DCE). Se calculó también el coeficiente de difusión aparente (ADC). Se evaluó la consistencia de los estudios (k), comparándose las curvas de características receptor operador (ROC) y el área bajo la curva (ABC) obtenida en cada caso (Z). Finalmente se realizó un modelo de regresión para predecir EEC. Resultados: La edad media fue 63,7 + 6,9 años y el valor medio de PSA 12,6 + 13,8. El tacto rectal resultó sospechoso de malignidad en el 31,7% de los casos. El espécimen de prostatectomía mostró pT2a en 12 (14%), pT2b 3 (3%), pT2c 37 (43%), pT3a 19 (22%) y pT3b 14 (17%) casos. Se evidenció EEC en 33 (39%) de los especímenes, invasión de vesículas seminales en 14 (16,5%) y afectación de ganglios pélvicos en 5 (6%). La consistencia en la evaluación de EEC entre imagen y anatomía patológica fue 0,35 en el caso de MRI (sensibilidad 0,33; especificidad 0,96) y 0,62 para mpMRI (sensibilidad 0,58; especificidad 0,98). El valor medio de ADC para los pacientes con EEC fue 0,76 + 0,2. Este valor no se asoció con la puntuación de Gleason (p = 0,2) o con el valor de PSA (p = 0,6). El ABC para predecir EEC fue 65% para MRI, 78% para mpMRI y 50% para ADC (Z = 0,008). El análisis univariante mostró que por cada punto del valor de Gleason aumenta 5,1 veces la probabilidad de EEC, mientras que por cada unidad de PSA dicha probabilidad aumenta 1,06 veces y por cada punto de ADC la reduce 0,3 veces. El análisis multivariante confirmó que el valor ADC es un factor protector leve para EEC (OR = 0,01; IC 95%: 0,002-0,14), mientras que el índice Gleason aumenta abiertamente dicho riesgo (OR = 4,92; IC 95%: 2,1-11,4). La consistencia en la evaluación de la invasión de vesículas seminales fue 0,43 para MRI y 0,67 para mpMRI. El ABC respectivo fue 69 y 82% (Z = 0,02). La consistencia en la evaluación de ganglios positivos fue 0,4 para MRI y 0,7 para mpMRI, con un ABC respectivo de 68 y 88% (Z = 0,36). Conclusiones: El estudio multiparamétrico permite llevar a cabo una mejor evaluación preoperatoria de EEC que MRI convencional. MRI-DW asociada a MRI-DCE, el coeficiente ADC y la puntuación de Gleason son los factores más fiables para predecir EEC. La superioridad de mpMRI también se demuestra a la hora de evaluar la invasión de las vesículas seminales, pero no para la evaluación de ganglios linfáticos

Introduction: The proper evaluation of the extracapsular extension (ECE), the invasion of seminal vesicles and regional lymph nodes are necessary to plan the treatment of localized prostate cancer. A model that assesses the risk of ECE in the specimen considering the clinical, histological and imaging findings is defined. Material and methods: Prospective study in 85 patients with prostate cancer treated with radical prostatectomy. Prostate biopsy was performed 4 weeks before multiparametric study (mpMRI). mpMRI included T2-weighted endorectal magnetic resonance imaging (T2W-MRI), diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The apparent diffusion coefficient (ADC) was also measured. A study of consistency (k) was assessed comparing receiver operating characteristic (ROC) curve and area under the curve (AUC), which were obtained in each case (Z). Finally, a regression model was performed to predict ECE. Results: The mean age was 63.7 ± 6.9 years and the mean value of PSA 12.6 ± 13.8. In 31.7% of cases, digital rectal examination was suspicious for malignancy. Prostatectomy specimen showed pT2a in 12 cases (14%), pT2b in 3 (3%), pT2c in 37 (43%), pT3a in 19 (22%) and pT3b 14 cases (17%). ECE was evidenced in 33 (39%) of the specimens, seminal vesicle invasion in 14 (16.5%) and pelvic node involvement in 5 patients (6%). The consistency in the evaluation of ECE (image and pathological studies) was 0.35 for MRI (sensitivity 0.33, specificity 0.96) and 0.62 for mpMRI (sensitivity 0.58, specificity 0.98). Mean value of ADC was .76 ± .2 in patients with ECE. This value was not associated with Gleason score (p = 0.2) or with PSA value (p = 0.6). AUC value as predictor of ECE was of 65% for MRI, 78% for mpMRI and 50% ADC (Z = 0.008). Univariate analysis demonstrated that ECE probability increases with each Gleason score point, whilst this probability increases 1.06 times with each PSA point, and decreases 0.3 times with each point of ADC. Multivariate analysis confirmed that ADC value is a slight protective factor against ECE (OR = 0.01; CI 95% 0.002-0.14). The consistency in the evaluation of seminal vesicles was 0.43 for MRI and 0.67 for mpMRI. AUC was 69% and 82% respectively (Z = 0.02). The consistency in the evaluation of positive lymph nodes was 0.4 for MRI and 0.7 for mpMRI. AUC was 68% and 88% respectively (Z = 0.36). Conclusions: Multiparametric study allows to carry out a more proper preoperative evaluation of ECE than convectional MRI. The most reliable predictors of ECE are DW-MRI combined with DCE-MRI, ADC coefficient and Gleason score. The superiority of mpMRI is also demonstrated for the detection of seminal vesicles invasion, but not for the evaluation of lymph nodes invasion

Cytokinesis-block micronucleus assay by manual and automated scoring: calibration curves and dose prediction.

The cytokinesis-block micronucleus assay in peripheral blood lymphocytes is one of the best standardized and validated techniques for individual radiation dose assessment. This method has been proposed as an alternative to the dicentric chromosome assay, which is considered the "gold standard" in biological dosimetry because it requires less time and cytogenetic expertise. Nevertheless, for application as a biodosimetry tool in large-scale nuclear or radiological accidents, the manually performed cytokinesis-block micronucleus assay needs further strategies (e.g., the automation of micronucleus scoring) to speed up the analysis. An essential prerequisite for radiation dose assessment is to establish a dose-effect curve. In this study, blood samples of one healthy subject were irradiated with seven increasing doses of x-ray (240 kVp, 1 Gy min⁻¹) ranging from 0.25-4.0 Gy to generate calibration curves based on manual as well as on automated scoring mode. The quality of the calibration curves was evaluated by determination of the dose prediction accuracy after the analysis of 10 blood samples from the same donor exposed to unknown radiation doses. The micronucleus frequencies in binucleated cells were scored manually as well as automatically and were used to assess the absorbed radiation doses with reference to the respective calibration curve. The accuracy of the dose assessment based on manual and automatic scoring mode was compared.

Virtual reality simulator for training on photoselective vaporization of the prostate with 980 nm diode laser and learning curve of the technique.

OBJECTIVE: The utility of a virtual reality simulator for training of the photoselective vaporization of the prostate with diode laser was studied. MATERIAL AND METHOD: Two experiments were performed with a simulator (VirtaMed AG, Zürich, Switzerland) with software for specific training in prostate vaporization in contact mode with Twister fiber (Biolitec AG, Jena, German). Eighteen surgeons performed ablation of the prostate (55 cc) twice and compared the score obtained (190 points efficacy and 80 safety) in the second one of them by experience groups (medical students, residents, specialists). They also performed a spatial orientation test with scores of 0 to 6. After, six of these surgeons repeated 15 ablations of the prostate (55 and 70 ml). Improvement of the parameters obtained was evaluated to define the learning curve and how experience, spatial orientation skills and type of sequences performed affects them. RESULTS: Global efficacy and safety score was different according to the grade of experience (P=.005). When compared by pairs, specialist-student differences were detected (p=0.004), but not specialist-resident (P=.12) or resident-student (P=.2). Regarding efficacy of the procedure, specialist-student (p=0.0026) and resident-student (P=.08) differences were detected. The different partial indicators in terms of efficacy were rate of ablation (P=.01), procedure time (P=.03) and amount of unexposed capsule (p=0.03). Differences were not observed between groups in safety (P=.5). Regarding the learning curve, percentage median on the total score exceeded 90% after performing 4 procedures for prostates of 55 ml and 10 procedures for prostate glands of 70 ml. This course was not modified by previous experience (resident-specialist; P=.6). However, it was modified according to the repetition sequence (progressive-random; P=.007). Surgeons whose spatial orientation was less than the median of the group (value 2.5) did not surpass 90% of the score in spite of repetition of the procedure. CONCLUSION: Simulation for ablation of the prostate with contact diode laser is a good learning model with discriminative validity, as it correlates the metric results with levels of experience and sills. The sequential repetition of the procedure on growing levels of difficulty favors learning.

Efficacy and safety of fosfomycin-trometamol in the prophylaxis for transrectal prostate biopsy. Prospective randomized comparison with ciprofloxacin.

OBJECTIVE: Prostate biopsy is the standardized diagnostic method for prostate cancer. However, although there is not a standardized protocol, there are recommendations in order to reduce the incidence of complications. The objective of the present work is to assess the efficacy and safety of antibiotic prophylaxis in the prostate biopsy by comparing two antibiotic regimes: two doses of fosfomycin-trometamol 3g (FMT) every 48 hours with 10 doses of oral ciprofloxacin 500 mg every 12 hours during 5 days. MATERIAL AND METHODS: Randomized prospective study was performed with 671 patients who had undergone to walking transrectal ultrasound guided prostate biopsy. Patients of group A (n=312) were treated with ciprofloxacin, and patients of group B (n=359) with FMT. Efficacy and tolerability of two prophylactic regimes were compared. Urine culture was carried out at 2 weeks after biopsy. Initially, patients with asymptomatic bacteriuria were not treated with antibiotics; urine culture was repeated after 1 month, persistent bacteriuria was treated according to antibiogram. RESULTS: No differences between groups were found in age (P=.78), cancer presence (P=.9) or number of biopsy cylinders (P=.93). The mean number of cores obtained was 11.3 ± 3.25 (range 6-20). Digestive intolerance was observed for 9 patients (2.9%) of group A and 10 patients (2.8%) in group B. One patient (.3%) of group A showed severe allergic reaction. In total, 167 patients (24.6%) had complications: 16 (2.4%) fever, 47 (6.9%) hemospermia, 81 (11.9%) hematuria, 7 (1%) rectal bleeding and 16 (2.4%) urinary retention. No statistically differences between groups were observed (27.6% vs. 22.6%; P=.17). However, hemospermia was more frequent in group A (9.9% vs. 4.5%; P=.006). Bacteriuria after biopsy was detected in 44 patients (6.6%), being more frequent in group B patients (4.2% vs. 8.6%; P=.02) although a higher number of second treatment cycles were not needed (53.9% vs. 29%; P=.17). The likelihood of resistance to ciprofloxacin in patients with bacteriuria in A was greater than that of FMT in B (69.2% vs. 41.9%; P=.0004). CONCLUSIONS: Antibiotic prophylaxis with FMT (2 doses of 3g) in prostate biopsy is an alternative as effective and safe as ciprofloxacin (10 doses of 500 mg), which carries lower rate of resistance. According to our experience, this drug is a safe, well-tolerated, and easily manageable prophylactic option, facilitating patient compliance. More prospective multicenter studies are necessary to confirm these findings.

Multiparametric magnetic resonance imaging for the assessment of extracapsular invasion and other staging parameters in patients with prostate cancer candidates for radical prostatectomy.

INTRODUCTION: the proper evaluation of the extracapsular extension (ECE), the invasion of seminal vesicles and regional lymph nodes are necessary to plan the treatment of localized prostate cancer. A model that assesses the risk of ECE in the specimen considering the clinical, histological and imaging findings is defined. MATERIAL AND METHODS: prospective study in 85 patients with prostate cancer treated with radical prostatectomy. Prostate biopsy was performed 4 weeks before multiparametric study (mpMRI). mpMRI included T2-weighted endorectal magnetic resonance imaging (T2W-MRI), diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The apparent diffusion coefficient (ADC) was also measured. A study of consistency (k) was assessed comparing receiver operating characteristic (ROC) curve and area under the curve (AUC), which were obtained in each case (Z). Finally, a regression model was performed to predict ECE. RESULTS: the mean age was 63.7 ± 6.9 years and the mean value of PSA 12.6 ± 13.8. In 31.7% of cases, digital rectal examination was suspicious for malignancy. Prostatectomy specimen showed pT2a in 12 cases (14%), pT2b in 3 (3%), pT2c in 37 (43%), pT3a in 19(22%) and pT3b 14 cases (17%). ECE was evidenced in 33 (39%) of the specimens, seminal vesicle invasion in 14 (16.5%) and pelvic node involvement in 5 patients (6%). The consistency in the evaluation of ECE (image and pathological studies) was .35 for MRI (sensitivity .33, specificity .96) and .62 for mpMRI (sensitivity .58, specificity .98). Mean value of ADC was .76 ± .2 in patients with ECE. This value was not associated with Gleason score (P = .2) or with PSA value (P = .6). AUC value as predictor of ECE was of 65% for MRI, 78% for mpMRI and 50% ADC (Z = .008). Univariate analysis demonstrated that ECE probability increases with each Gleason score point, whilst this probability increases 1.06 times with each PSA point, and decreases .3 times with each point of ADC. Multivariate analysis confirmed that ADC value is a slight protective factor against ECE (OR = .01; CI 95% .002-.14). The consistency in the evaluation of seminal vesicles was .43 for MRI and .67 for mpMRI. AUC was 69% and 82% respectively (Z = .02). The consistency in the evaluation of positive lymph nodes was .4 for MRI and .7 for mpMRI. AUC was 68% and 88% respectively (Z = .36). CONCLUSIONS: multiparametric study allows to carry out a more proper preoperative evaluation of ECE than convectional MRI. The most reliable predictors of ECE are DW-MRI combined with DCE-MRI, ADC coefficient and Gleason score. The superiority of mpMRI is also demonstrated for detection of seminal vesicles invasion, but not for the evaluation of lymph nodes invasion.

Prediction of extracapsular disease with multiparametric magnetic resonance imaging in high risk localized prostate cancer patient.

OBJECTIVES: To assess the usefulness of multiparametric magnetic resonance imaging (MRI) in the staging of patients with localized prostate cancer (PC) and high risk of extracapsular disease (ECD). METHODS: Retrospective study including 30 patients with localized PC and high risk of ECD. Pathologist and radiologist established an ECD suspicion according to the evaluation of the prostatic biopsy specimens and the multiparametric MRI analysis, respectively. Radical prostatectomy (RP) specimen analysis was used as a definitive confirmatory reference. Kappa (k)test was used to assess the degree of consistency between the initial suspicion provided by both specialists and the reference RP specimen. RESULTS: When the prostatic gland was analyzed as a single unit, the pathological evaluation of the biopsy specimens did not correctly detect the risk of ECD in 46.6% of the patients (14/30; 10 FN; k=-0.035, 95%CI [-0.29-0.36]), while multiparametric MRI did not do in 36% of the cases (11/30, 9 FP; k=0.27, 95%CI [-0.03-0.61]). Whereas, if each side of the prostate (i.e. right and left) was considered as an independent observation, the pathologist wrongly predicted the risk of ECD in 35% of the cases (21/60; 18 FN; k=0.19, 95%CI [-0.03-0.40]), while the radiologist erred only in 18.3% of the cases (11/60; 7 FN and 4 FP; k=0, 61, 95%CI [0.40-0.81]). CONCLUSIONS: Data from our experience suggest an added value of multiparametric MRI in the clinical staging of localized PC in cases of high risk of ECD. Multiparametric MRI may be used as a helpful tool in the surgical planning and the decision-making process regarding the management of this entity.

Predicción de la presencia de enfermedad extracapsular en pacientes con cáncer de próstata de alto riesgo mediante análisis multiparamétrico de resonancia magnética / Prediction of extracapsular disease with multiparametric magnetic resonance imaging in high risk localized prostate cancer patients

OBJETIVO: Evaluar la utilidad del análisis multiparamétrico de resonancia magnética (RM) en la estadificación de pacientes con cáncer de próstata (CP) localizado y alto riesgo de enfermedad extracapsular (E-EC). MÉTODOS: Estudio retrospectivo que incluyó un total de 30 pacientes diagnosticados de CP localizado y alto riesgo de E-EC. El patólogo y el radiólogo establecieron un diagnóstico de sospecha de acuerdo con la evaluación de los especímenes de biopsia prostática y el análisis multiparamétrico de RM, respectivamente. El análisis de la pieza de prostatectomía radical (PR) fue empleado como referencia confirmatoria definitiva. El estadístico kappa (k) se utilizó para determinar el grado de consistencia entre la sospecha inicial proporcionada por ambos especialistas y la pieza de PR utilizada como referencia. RESULTADOS: Cuando se analizó la glándula globalmente, la evaluación patológica de los especímenes procedentes de la biopsia no detectó correctamente la presencia de E-EC en el 46.6% de los pacientes (14/30; 10 FN; k=-0.035, IC95% (-0.29-0.36)), mientras que la RM multiparamétrica no lo consiguió en el 36% de los casos (11/30, 9 FP; k=0.27, IC95% (- 0.03-0.61)). Sin embargo, si cada lado de la próstata (derecho e izquierdo) se tomaba como una observación independiente, el patólogo predijo erróneamente el riesgo de E-EC en el 35% de los casos (21/60; 18 FN; k=0.19, IC95% (- 0.03-0.40)), mientras que el radiólogo solo erró en el 18.3% de los casos (11/60; 7 FN y 4 FP; k=0, 61, IC95% (0.40-0.81)). CONCLUSIONES: Los datos derivados de nuestra experiencia sugieren un valor diagnóstico añadido de la RM multiparamétrica para la estadificación clínica del CP localizado con alto riesgo de E-EC. El análisis de RM multiparamética puede emplearse como una herramienta útil en el proceso de toma de decisiones acerca del tratamiento y la planificación quirúrgica de ésta entidad (AU)

OBJECTIVES: To assess the usefulness of multiparametric magnetic resonance imaging (MRI) in the staging of patients with localized prostate cancer (PC) and high risk of extracapsular disease (ECD). METHODS: Retrospective study including 30 patients with localized PC and high risk of ECD. Pathologist and radiologist established an ECD suspicion according to the evaluation of the prostatic biopsy specimens and the multiparametric MRI analysis, respectively. Radical prostatectomy (RP) specimen analysis was used as a definitive confirmatory reference. Kappa (k) test was used to assess the degree of consistency between the initial suspicion provided by both specialists and the reference RP specimen. RESULTS: When the prostatic gland was analyzed as a single unit, the pathological evaluation of the biopsy specimens did not correctly detect the risk of ECD in 46.6% of the patients (14/30; 10 FN; k=-0.035, 95%CI [- 0.29-0.36]), while multiparametric MRI did not do in 36% of the cases (11/30, 9 FP; k=0.27, 95%CI [- 0.03-0.61]). Whereas, if each side of the prostate (i.e. right and left) was considered as an independent observation, the pathologist wrongly predicted the risk of ECD in 35% of the cases (21/60; 18 FN; k=0.19, 95%CI [- 0.03-0.40]), while the radiologist erred only in 18.3% of the cases (11/60; 7 FN and 4 FP; k=0, 61, 95%CI [0.40-0.81]). CONCLUSIONS: Data from our experience suggest an added value of multiparametric MRI in the clinical staging of localized PC in cases of high risk of ECD. Multiparametric MRI may be used as a helpful tool in the surgical planning and the decision-making process regarding the management of this entity (AU)