In vitro antifungal activity of polymeric nanoparticles loaded with Euphorbia tirucalli extract.

The therapeutic potential of medicinal plants is known as an alternative in treatment of human affections; in effect, the conventional application of these medicinal sources has several limitations like low bioavailability, solubility and stability, which affect its pharmacological efficacy. In recent decades, extraordinary advances have been made in new drug delivery systems using nanocarriers. This work consisted in determining the in vitro antifungal activity of the methanolic extract of Euphorbia tirucalli formulated in polymeric nanoparticles. The antifungal activity was determined by the microdilution method in 96-well microplates, applying nanoparticles loaded with plant extract (NP-Ext) obtained by nanoprecipitation on clinical isolates of Trichophyton rubrum and T. interdigitalis. Regarding the nanoparticles, the lots used did not present significant differences in their physicochemical characteristics, with a size of 91.885 ± 1.621nm, polydispersity index of 0.152 ± 0.025 and Z-potential of -6.047 ± 0.987. The quantification of the extract in the polymeric matrix was determined by infrared spectroscopy (FTIR), where an efficiency and encapsulation percentage of 22.15 ± 0.82 and 2.95 ± 0.11, respectively, were obtained. The in vitro antifungal activity of the crude and formulated extract was obtained calculating the Minimum Inhibitory Concentration (MIC) of each one; a MIC of 125 µg/mL was obtained against T. rubrum and T. interdigitalis with the crude extract, while a MIC value of 55.55 and 0.1 µg/mL was obtained with NP-Ext, respectively, against these same. Conclusions: biological activity is closely linked to the phytochemical profile of the extract; while the improvement of said potential with the NP-Ext with the dosage form was directly related to the physicochemical characteristics of the nanocarrier.

Deep brain stimulation in Parkinson's disease: analysis of brain fractional anisotropy differences in operated patients. / Estimulación cerebral profunda en la enfermedad de Parkinson: análisis de la anisotropía fraccional cerebral en pacientes intervenidos mediante estimulación cerebral profunda.

INTRODUCTION: Deep brain stimulation (DBS) of the subthalamic nucleus is currently an evidence-based therapeutic option for motor symptoms in patients with Parkinson's disease (PD), although other non-motor symptoms can be affected by stimulation. AIM: Our objective is to evaluate the global changes in the connectivity of the large-scale structural network in PD patients that have obtained a benefit from subthalamic DBS. SUBJECTS AND METHODS: Retrospective study of 31 subjects: 7 PD patients with subthalamic DBS (group A), 12 age and gender-matched non-operated PD (B) and 12 healthy controls (C). All subjects had undergone a 1.5 T brain MRI with DTI. DICOM images were processed with the FSL5.0 software and TBSS tool. RESULTS: The study group comprised 23 men and 8 women. No statistically significant differences in age, gender, scores on the HandY scale and mean follow-up between group A and B were found, and in age and gender between groups A and C. Statistical analysis revealed differences in the fractional anisotropy of the different groups in certain areas: bilateral corticospinal tract, anterior thalamic radiations, bilateral fronto-occipital fascicle, both superior longitudinal fascicles, and left inferior longitudinal fascicle. CONCLUSIONS: In our series, PD patients treated with bilateral subthalamic DBS showed a significantly higher fractional anisotropy in widespread areas of the cerebral white matter; suggesting that neuromodulation produces connectivity changes in different neural networks.

TITLE: Estimulación cerebral profunda en la enfermedad de Parkinson: análisis de la anisotropía fraccional cerebral en pacientes intervenidos mediante estimulación cerebral profunda.Introducción. La estimulación cerebral profunda (ECP) del núcleo subtalámico actualmente es una opción terapéutica basada en la evidencia para los síntomas motores en pacientes con enfermedad de Parkinson (EP), aunque otros síntomas no motores pueden verse afectados por la estimulación. Objetivo. Nuestro objetivo es evaluar los cambios globales en la conectividad de la red estructural a gran escala en pacientes con EP que han obtenido un beneficio de la ECP subtalámica. Sujetos y métodos. Estudio retrospectivo de 31 sujetos: siete pacientes con EP con ECP subtalámica (grupo A), 12 pacientes con EP no operados de la misma edad y sexo (B) y 12 controles sanos (C). Todos los sujetos se habían sometido a una resonancia magnética cerebral de 1,5 T con imagen del tensor de la difusión. Las imágenes DICOM se procesaron con el software FSL5.0 y la herramienta estadística espacial basada en el tracto. Resultados. El grupo de estudio estuvo compuesto por 23 hombres y ocho mujeres. No se encontraron diferencias estadísticamente significativas en edad, sexo, puntuación en la escala de Hoehn y Yahr y seguimiento medio entre el grupo A y B, y en edad y sexo entre los grupos A y C. El análisis estadístico reveló diferencias en la anisotropía fraccional de los diferentes grupos en ciertas áreas: tracto corticoespinal bilateral, radiaciones talámicas anteriores, fascículo frontooccipital bilateral, ambos fascículos longitudinales superiores y fascículo longitudinal inferior izquierdo. Conclusiones. En nuestra serie, los pacientes con EP tratados con ECP subtalámica bilateral mostraron una anisotropía fraccional significativamente mayor en áreas extensas de la sustancia blanca cerebral, lo que sugiere que la neuromodulación produce cambios de conectividad en diferentes redes neuronales.

Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019.

OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.

Long-term safety and efficacy of trifarotene 50 µg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne.

BACKGROUND: Treatment for both facial and truncal acne has not sufficiently been studied. OBJECTIVES: To evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne. METHODS: In a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne received trifarotene 50 µg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET. RESULTS: Of 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene-related treatment-emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter. At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit. CONCLUSION: In this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne.

Invasive pneumococcal disease in hospitalised children from Lima, Peru before and after introduction of the 7-valent conjugated vaccine.

The objective of this study was to determine the serotype distribution and antibiotic resistance of invasive pneumococcal disease (IPD) strains in children from Lima, Peru, before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), which was introduced in the national immunisation program on 2009. We conducted a prospective, multicentre, passive surveillance IPD study during 2006-2008 and 2009-2011, before and right after the introduction of PCV7 in Peru. The study was performed in 11 hospitals and five private laboratories in Lima, Peru, in patients <18 years old, with sterile site cultures yielding Streptococcus pneumoniae. In total 159 S. pneumoniae isolates were recovered. There was a decrease in the incidence of IPD in children <2 years old after the introduction of PCV7 (18.4/100 000 vs. 5.1/100 000, P = 0.004). Meningitis cases decreased significantly in the second period (P = 0.036) as well as the overall case fatality rate (P = 0.025), including a decreased case fatality rate of pneumonia (16.3% to 0%, P = 0.04). PCV7 serotypes showed a downward trend. Vaccine-preventable serotypes caused 78.9% of IPD cases, mainly 14, 6B, 5, 19F and 23F. A non-significant increase in erythromycin resistance was reported. Our findings suggest that the introduction of PCV7 led to a significant decrease of IPD in children under 2 years old and in the overall case fatality rate.

Self-organized criticality and pattern emergence through the lens of tropical geometry.

Tropical geometry, an established field in pure mathematics, is a place where string theory, mirror symmetry, computational algebra, auction theory, and so forth meet and influence one another. In this paper, we report on our discovery of a tropical model with self-organized criticality (SOC) behavior. Our model is continuous, in contrast to all known models of SOC, and is a certain scaling limit of the sandpile model, the first and archetypical model of SOC. We describe how our model is related to pattern formation and proportional growth phenomena and discuss the dichotomy between continuous and discrete models in several contexts. Our aim in this context is to present an idealized tropical toy model (cf. Turing reaction-diffusion model), requiring further investigation.

Limit on Excitation and Stabilization of Atoms in Intense Optical Laser Fields.

Atomic excitation in strong optical laser fields has been found to take place even at intensities exceeding saturation. The concomitant acceleration of the atom in the focused laser field has been considered a strong link to, if not proof of, the existence of the so-called Kramers-Henneberger (KH) atom, a bound atomic system in an intense laser field. Recent findings have moved the importance of the KH atom from being purely of theoretical interest toward real world applications; for instance, in the context of laser filamentation. Considering this increasing importance, we explore the limits of strong-field excitation in optical fields, which are basically imposed by ionization through the spatial field envelope and the field propagation.

Assessing the variability in transmission of bovine tuberculosis within Spanish cattle herds.

In Spain, despite years of efforts to eradicate bovine tuberculosis (bTB), the disease is still endemic, with some areas of high prevalence. In this context, the surveillance and control plans may need to be re-evaluated, and understanding the dynamics of bTB spread within Spanish herds may help to develop new strategies for reducing the time for detection of infected herds and for the elimination of bTB from the herds already infected. Here, we developed a compartmental stochastic model to simulate bTB within-herd transmission, fed it with epidemiological data from 22 herds (obtained from a previous work) and carried out parameter inference using Approximate Bayesian Computing methods We also estimated the "Within-herd transmission potential Number" (Rh), i.e. the average number of secondary cases generated by a single animal infected introduced into a totally susceptible herd, considering different scenarios depending on the frequency of controls. The median global values obtained for the transmission parameters were: for the transmission coefficient (ß), 0.014 newly infected animals per infectious individual per day (i.e. 5.2 per year), for the rate at which infected individuals become infectious (α), 0.01 per day (equivalent to a latent period of 97 days), and for the rate at which infected individuals become reactive to the skin test (α1), 0.08 per day (equivalent to a period of 12 days for an infected animal to become reactive). However, the results also evidenced a great variability in the estimates of those parameters (in particular ß and α) among the 22 herds. Considering a 6-month interval between tests, the mean Rh was 0.23, increasing to 0.82 with an interval of 1 year, and to 2.01 and 3.47 with testing intervals of 2 and 4 years, respectively.

[Medullar thoracic compression by tophaceous gout: presentation of a case and review of the literature]. / Compresion medular dorsal por tofos gotosos: presentacion de un caso y revision de la bibliografia.

INTRODUCTION: Spine involvement in gout is an extremely uncommon complication. Dorsalgia and quadriplegia are some manifestations that may occur, although these symptoms are seen more frequently in other more prevalent pathologies, such as spinal tumors. CASE REPORT: We present an unusual case of thoracic spinal cord compression at T10-T11 level caused by the extradural deposit of tophaceous material in a 52-year-old woman with uncontrolled chronic tophaceous gout. In addition to intensive medical treatment, the patient required surgery (hemilaminectomy and spinal decompression) and subsequent rehabilitation. Overall and neurological evolution were satisfactory.

TITLE: Compresion medular dorsal por tofos gotosos: presentacion de un caso y revision de la bibliografia.Introduccion. La afectacion de la columna vertebral en la gota es una complicacion extremadamente infrecuente. La dorsalgia y la cuadriplejia son algunas manifestaciones que se pueden presentar, aunque estos sintomas se ven con mas frecuencia en otras patologias mas prevalentes, como los tumores medulares. Caso clinico. Se presenta un caso inusual de compresion medular dorsal en D10-D11 causado por el deposito extradural de material tofaceo en una paciente de 52 años con gota tofacea cronica incontrolada. Ademas de un tratamiento medico intensivo, la paciente requirio cirugia (hemilaminectomia y descompresion medular) y rehabilitacion posterior. La evolucion general y neurologica fue satisfactoria.

Central nervous system manganese induced lesions and clinical consequences in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Around 47-74% of patients with hereditary hemorrhagic telangiectasia (HHT) have hepatic vascular malformations (HVMs); magnetic resonance images (MRI) of the central nervous system (CNS) might show in T1 sequences a hyper-intensity signal in different areas, mainly in the basal ganglia (BG) as consequence of manganese (Mn) deposits as observed in cirrhotic patients. These patients might suffer from different neuropsychiatric disorders (hepatic encephalopathy). In HHT patients, even in the presence of hepatic shunts, hepatocellular function is usually preserved. Additionally, Mn shares iron absorption mechanisms, transferrin and CNS transferrin receptors. In iron deficiency conditions, the Mn may harbor transferrin and access BG. The objectives were to describe frequency of BG Mn deposit-induced lesions (BGMnIL) in HHT patients, its relationship with iron deficiency anemia (IDA) and HVMs. Finally, explore the association between neuropsychological and motor consequences. We performed a cross-sectional study. We determined HHT patients with or without BG-MnIL by the MRI screening of the CNS. We included all patients with lesions and a random sample of those without lesions. All patients underwent standardized and validated neuropsychological assessment to evaluate BG actions. Results were analyzed with multiple logistic regression, adjusting for potential confounders. RESULTS: Among 307 participants from a cohort included in the Institutional HHT Registry, 179 patients had MRI performed and Curaçao Criteria ≥3. The prevalence of BG-MnIL was 34.6% (95%CI 27.69-42.09). While neuropsychological symptoms were present in all patients, BG-MnIL patients performed poorly in three of the neuropsychological tests (serial dotting, line tracing time, number connection test A). HVMs frequency in BG-MnIL was 95.1%, versus 71.4% in those without lesions (p < 0.001). IDA frequency was 90.3% versus 54% (p < 0.001). When IDA is present, estimated risk for BG-MnIL is remarkably high (OR 7.73, 95%CI 2.23-26.73). After adjustment for possible confounders (gender, age, presence of HVMs), IDA was still associated with increased risk of BG-MnIL (adjusted OR 6.32, 95% CI 2.32-17.20; p < 0.001). CONCLUSIONS: Physicians should assess BG-MnIL in HHT patients in CNS-MRI. IDA and HVMs present increased risk of lesions. Patients with BG-MnIL have neuropsychological impairment, and they might benefit from sparing IDA, or undergoing future therapeutic options. TRIAL REGISTRATION: NCT01761981 . Registered January 3rd 2013.

[Bromocriptine: could it be the cure for post-surgical akinetic mutism?] / Bromocriptina: podria ser la cura para el mutismo acinetico posquirurgico?

INTRODUCTION: Akinetic mutism is considered as an alteration of the motivational state of the person, which the patient is unable to initiate verbal or motor responses voluntary, even with preserved sensorimotor and surveillance functions. CASE REPORT: A 43 year-old male involved in a cerebellum arteriovenous fistula complicated with hydrocephalus, who responded dramatically to treatment with bromocriptine. CONCLUSION: Typically, akinetic mutism is described as a transient surgeries posterior fossa. However, it can also occur after multiple valvular failure in patients with hydrocephalus.

TITLE: Bromocriptina: podria ser la cura para el mutismo acinetico posquirurgico?Introduccion. El mutismo acinetico se considera una alteracion del estado motivacional de la persona, por el cual el paciente es incapaz de iniciar respuestas verbales o motoras de caracter voluntario, aun teniendo preservadas las funciones sensomotoras y de vigilancia. Caso clinico. Varon de 43 años, intervenido de una fistula arteriovenosa del cerebelo complicada con hidrocefalia, que respondio espectacularmente al tratamiento con bromocriptina. Conclusion. Tipicamente se ha descrito el mutismo acinetico como una complicacion transitoria de las cirugias de la fosa posterior. Sin embargo, tambien puede aparecer tras multiples fallos valvulares en pacientes con hidrocefalia.

Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study.

It is important to know the spectrum of the microbial aetiology of prosthetic joint infections (PJIs) to guide empiric treatment and establish antimicrobial prophylaxis in joint replacements. There are no available data based on large contemporary patient cohorts. We sought to characterize the causative pathogens of PJIs and to evaluate trends in the microbial aetiology. We hypothesized that the frequency of antimicrobial-resistant organisms in PJIs has increased in the recent years. We performed a cohort study in 19 hospitals in Spain, from 2003 to 2012. For each 2-year period (2003-2004 to 2011-2012), the incidence of microorganisms causing PJIs and multidrug-resistant bacteria was assessed. Temporal trends over the study period were evaluated. We included 2524 consecutive adult patients with a diagnosis of PJI. A microbiological diagnosis was obtained for 2288 cases (90.6%). Staphylococci were the most common cause of infection (1492, 65.2%). However, a statistically significant rising linear trend was observed for the proportion of infections caused by Gram-negative bacilli, mainly due to the increase in the last 2-year period (25% in 2003-2004, 33.3% in 2011-2012; p 0.024 for trend). No particular species contributed disproportionally to this overall increase. The percentage of multidrug-resistant bacteria PJIs increased from 9.3% in 2003-2004 to 15.8% in 2011-2012 (p 0.008), mainly because of the significant rise in multidrug-resistant Gram-negative bacilli (from 5.3% in 2003-2004 to 8.2% in 2011-2012; p 0.032). The observed trends have important implications for the management of PJIs and prophylaxis in joint replacements.

Estimation of the individual slaughterhouse surveillance sensitivity for bovine tuberculosis in Catalonia (North-Eastern Spain).

The achievement of the Officially Tuberculosis Free (OTF) status in regions with low bovine Tuberculosis (bTB) herd prevalence, as is the case of North-Eastern Spain (Catalonia), might be a likely option in the medium term. In this context, risk-based approaches could be an alternative surveillance strategy to the costly current strategy. However, before any change in the system may be contemplated, a reliable estimate of the sensitivity of the different surveillance components is needed. In this study, we focused on the slaughterhouse component. The probability of detection of a bTB-infected cattle by the slaughterhouses in Catalonia was estimated as the product of three consecutive probabilities: (P1) the probability that a bTB-infected animal arrived at the slaughterhouse presenting Macroscopically Detectable Lesions (MDL); (P2) the probability that MDL were detected by the routine meat inspection process and (P3) the probability that the veterinary officer suspected bTB and sent the sample for laboratory confirmation. The first probability was obtained from data collected through the bTB eradication program carried out in Catalonia between 2005 and 2008, while the last two were obtained through the expert opinion of the veterinary officers working at the slaughterhouses who fulfilled a questionnaire administered during 2014. The bTB surveillance sensitivity of the different cattle slaughterhouses in Catalonia obtained in this study was 31.4% (CI 95%: 28.6-36.2), and there were important differences among them. The low bTB surveillance sensitivity was mainly related with the low probability that a bTB-infected animal arrived at the slaughterhouse presenting MDL (around 44.8%). The variability of the sensitivity among the different slaughterhouses could be explained by significant associations between some variables included in the survey and P2. For instance, factors like attendance to training courses, number of meat technicians and speed of the slaughter chain were significantly related with the probabilities that a MDL was detected by the meat inspection procedure carried out in the slaughterhouse. Technical and policy efforts should be focused on the improvement of these factors in order to maximize the slaughterhouse sensitivity.

[Multiple sclerosis and verbal episodic memory: Critical review of cognitive processes and their assessment]. / Atteinte de la mémoire épisodique verbale dans la sclérose en plaques: revue critique des processus cognitifs concernés et de leur exploration.

Memory impairment, especially verbal episodic memory (VEM), represents a common ground for cognitive complaint in patients with multiple sclerosis (MS). Beyond the difficulty caused in daily life, these deficits may impact on occupational activities. Neuropsychological assessment of these patients has to include VEM tests, to describe the level of dysfunction of the different processes contributing to VEM and, if required, to guide adapted cognitive rehabilitation. The objective of the present paper is to propose a critique review of the literature on VEM abilities in MS. This review will present the conceptual references and the psychometric characteristics of the main VEM tests applied in MS (isolated tests or included within more general batteries developed specifically for MS). In a second phase, we propose an inventory of work on MS presented as a function of the cognitive processes involved. This approach provides an approach to the limitations of each conception and possible terminological ambiguities. Contributions to knowledge of MS memory impairments will be clarified, as well as the impact of the disease characteristics (MS forms, disease duration, EDSS).

Targeting HER3 by interfering with its Sec61-mediated cotranslational insertion into the endoplasmic reticulum.

There is increasing evidence implicating human epidermal growth factor receptor 3 (HER3) in several types of cancer. However, the development of targeted therapies to inactivate HER3 function has been a challenging endeavor. Its kinase domain functions in allostery not catalysis, and the classical ATP-analog class of tyrosine kinase inhibitors fail to inactivate it. Here we describe a novel approach that eliminates HER3 expression. The small-molecule cotransin CT8 binds the Sec61 translocon and prevents the signal peptide of the nascent HER3 protein from initiating its cotranslational translocation, resulting in the degradation of HER3 but not the other HER proteins. CT8 treatment suppresses the induction of HER3 that accompanies lapatinib treatment of HER2-amplified cancers and synergistically enhances the apoptotic effects of lapatinib. The target selectivities of cotransins are highly dependent on their structure and the signal sequence of targeted proteins and can be narrowed through structure-function studies. Targeting Sec61-dependent processing identifies a novel strategy to eliminate HER3 function.

Clindamycin phosphate 1·2%-benzoyl peroxide 3·0% fixed-dose combination gel has an effective and acceptable safety and tolerability profile for the treatment of acne vulgaris in Japanese patients: a phase III, multicentre, randomised, single-blinded, active-controlled, parallel-group study.

BACKGROUND: A topical fixed-dose clindamycin phosphate 1·2% and benzoyl peroxide 3·0% combination gel (CLNP/BPO 3%) is known to be effective and safe in white people with acne. OBJECTIVES: To evaluate the efficacy and safety of CLNP/BPO 3·0% topically applied once or twice daily vs. CLNP twice daily in Japanese patients with acne. METHODS: Eight hundred patients were randomized to receive CLNP/BPO 3·0% once daily, CLNP/BPO 3·0% twice daily or CLNP twice daily for 12 weeks. Primary endpoints were absolute change in number of total lesions (TLs) from baseline to week 12 to demonstrate the superiority of CLNP/BPO 3·0% twice daily and noninferiority of CLNP/BPO 3·0% once daily vs. CLNP twice daily. Secondary endpoints were absolute and percentage changes in TLs, inflammatory lesions (ILs), noninflammatory lesions (non-ILs) and Investigator's Static Global Assessment (ISGA) score. Safety assessments included adverse events (AEs), laboratory tests, vital signs and local skin tolerability. RESULTS: Change in TL counts from baseline to week 12 for CLNP/BPO 3·0% twice daily was superior to CLNP twice daily (difference -11·0; P < 0·01); CLNP/BPO 3·0% once daily was not inferior to CLNP twice daily (difference -10·3; P < 0·01). Absolute and percentage reductions in TL, IL and non-IL counts and ISGA score were greater for CLNP/BPO 3·0% once or twice daily than for CLNP twice daily with significant differences seen from early on. Most AEs were mild or moderate. The incidence of adverse drug reactions was higher for CLNP/BPO 3·0% once (24·0%) or twice (35·1%) daily than for CLNP twice daily (9·0%). CONCLUSIONS: Compared with CLNP twice daily, CLNP/BPO 3·0% once daily was more effective and CLNP/BPO 3·0% twice daily at least as effective, with an early onset of action and an acceptable safety and tolerability profile in Japanese patients.

Prognostic factors for relapse in stage I seminoma: a new nomogram derived from three consecutive, risk-adapted studies from the Spanish Germ Cell Cancer Group (SGCCG).

BACKGROUND: We aimed to analyze prognostic factors for relapse in stage I seminoma managed by either active surveillance or adjuvant chemotherapy, and to describe the long-term patterns of recurrence in both groups. PATIENTS AND METHODS: From 1994 to 2008, 744 patients were included in three consecutive, prospective risk-adapted studies by the Spanish Germ Cell Cancer Group. Low-risk patients were managed by surveillance and high-risk patients were given two courses of adjuvant carboplatin. Relapses were treated mainly with chemotherapy. Patient age, tumor size, histological variant, pT staging, rete testis invasion, and preoperative serum BHCG levels were assessed for prediction of disease-free survival (DFS). RESULTS: After a median follow-up of 80 months, 63 patients (11.1%) have relapsed: 51/396 (14.8%) on surveillance and 12/348 (3.2%) following adjuvant carboplatin. Actuarial overall 5-year DFS was 92.3% (88.3% for surveillance versus 96.8% for chemotherapy, P = 0.0001). Median time to relapse was 14 months. Most recurrences were located at retroperitoneum (86%), with a median tumor size of 26 mm. All patients were rendered disease-free with chemotherapy (92%), radiotherapy (5%), or surgery followed by chemotherapy (3%). A nomogram was developed from surveillance patients that includes two independent, predictive factors for relapse: rete testis invasion and tumor size (as a continuous variable). CONCLUSION: Long-term follow-up confirms the risk-adapted approach as an effective option for patients with stage I seminoma. The pattern of relapses after adjuvant chemotherapy is similar to that observed following surveillance. A new nomogram for prediction of DFS among patients on surveillance is proposed. Rete testis invasion and tumor size should be taken into account when considering the administration of adjuvant carboplatin. Prospective validation is warranted.

Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study.

The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18-5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23-5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09-0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis.

Risk factors for bovine tuberculosis persistence in beef herds of Southern and Central Spain.

In order to assess risk factors related to bovine tuberculosis (bTB) persistence, a case-control study, comparing persistent versus transient bTB infected beef farms from Central and Southern Spain, was conducted. Farms were matched by herd size and geographical location (county). A questionnaire administered by personal interview was conducted on 150 herds (80 controls and 70 cases) from Andalucia and Castilla La Mancha regions. The questionnaire included questions related to the personnel involved in routine diagnostics, structure of the farm and of the herd, management, presence of other domestic species and of wildlife reservoirs. According to the results of our study, farms with large pasture areas and bTB infected neighbors had more difficulties in eradicating the disease, and therefore, were more likely to suffer a persistent bTB infection. The odds of bTB persistence were between 1.2 and 5.1 (i.e., 95% confidence interval of the OR) times higher in those herds that had a neighbor infected herd. Farms with large pasture areas had odds between 1.2 and 12.7 (i.e., 95% confidence interval of the OR) times higher of having a persistent bTB episode than farms with small pasture areas.

Synchronous versus metachronous brain metastasis from testicular germ cell tumors (TGCT): an analysis from the Spanish Germ Cell Cancer Group data base.

BACKGROUND: Brain metastases of testicular germ cell tumor (TGCT) are a rare event. Prognostic is poor and there is not much evidence on optimal management of these patients. PATIENTS AND METHODS: A review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group data base from 1994 to 2012 was conducted. RESULTS: Thirty-three out of 6,200 cases (0.5 %). Nineteen patients (57 %) group 1: synchronous, 13 (40 %) group 2: metachronous and only one developed brain metastasis during cisplatin-based chemotherapy (excluded from the analysis). Median serum BHCG levels at initial diagnosis was higher in group 1, whereas elevated AFP serum levels were more common in group 2. Histology in the primary tumor: chorionic carcinoma for group 1 versus embryonal carcinoma for group 2. Mainly solitary brain metastasis in group 2 (54 versus 21 %, respectively). The median overall survival from the diagnosis of central nervous system involvement was 16 months for group 1 (CI 95 % 13.9-18) and 23 months (95 % CI 0-165) for group 2 (log rank p = 0.84). Long-term survivors were practically identical in the two groups (38.9 % group 1 versus 38.5 % group 2). Regardless of the timing of brain metastasis, those patients that achieved complete response to the treatment had better survival (log rank p 0.003). CONCLUSION: Although some distinctive clinical characteristics have been found between patients with synchronous versus metachronous brain metastasis from TGCT, the timing of brain metastasis did not seem to have prognostic influence, but due to the retrospective nature of the analysis and the results should be interpreted with caution.