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Benign prostatic hyperplasia (BHP) is a local disturbance in the prostate that may involve an intlammatory infiltrate predominantly composed of activated lymphocytes and macrophages. The activation and proliferative response of T lymphocytes to different mitogenic signals has been analysed in periphheral blood mononuclear cells (PMBC) from 45 patients with BHP and 55 healthy controls. The PBMC obtained from llic patients showed a significant specific impairment in proliferation, CD25 expression and lL-2 production in response to stimulation with lectins (phytohaemagglutinin (PHA), concanavalin A (Con A)), that was not corrected by the addition of IL-2 or phorbol esters (phorbol myristate)acetate (PMA)). Also, the CD28 response was defective in patient PBMC. Activation with anti-CD.1 or anti-CD2 MoAbs was normal, but the addition of PMA to these stimuli provoked a significant defective response. Only the use of transmembrane stimuli (PMA and ionomycin) elicited responses similar to those found in the control group. The results indicate that peripheral T lymphocytes from BPH patients show a functional impairment that is mainly explained by an alteration of membrane signals (PHA. CD28) and is distal to protein kinase C (PKC) activation. [ABSTRACT FROM AUTHOR]

Several 1,4-naphthoquinone derivatives having a hydrazino side chain were synthesized from 3-diazo-naphthalene-1,2,4-trione and tested as potential antimicrobial agents. These naphthoquinone derivatives 2-[N'-(1-acetyl-2-oxo-propylidene)-hydrazino]-3-hydroxy -[1,4]naphthoquinone, ethyl 2-[(3-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-hydrazono] -3-oxo-butyrate, t-butyl 2-[(3-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-hydrazono]-3-oxo -butyrate, 3-hydroxy-2-[(di-O-isopropylidene-malonate)-hydrazino]-1,4-naphthoquinone, and diethyl 2-[(3-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-hydrazono]-malonate showed greater antibacterial activity at the level of the preliminary susceptibility testing in disk than lapachol (1), a well known 1,4-naphthoquinone which has several biological activities. Studies on the minimal inhibitory concentration (MIC) for Staphylococcus aureus showed that diethyl 2-[(3-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-hydrazono]-malonate has an activity twofold greater than 1. On the other hand, optical density measurement for S. aureus indicated that this compound has similar activity compared with vancomycin at 2xMIC.

Abstract Background Gene regulatory networks have an essential role in every process of life. In this regard, the amount of genome-wide time series data is becoming increasingly available, providing the opportunity to discover the time-delayed gene regulatory networks that govern the majority of these molecular processes. Results This paper aims at reconstructing gene regulatory networks from multiple genome-wide microarray time series datasets. In this sense, a new model-free algorithm called GRNCOP2 (Gene Regulatory Network inference by Combinatorial OPtimization 2), which is a significant evolution of the GRNCOP algorithm, was developed using combinatorial optimization of gene profile classifiers. The method is capable of inferring potential time-delay relationships with any span of time between genes from various time series datasets given as input. The proposed algorithm was applied to time series data composed of twenty yeast genes that are highly relevant for the cell-cycle study, and the results were compared against several related approaches. The outcomes have shown that GRNCOP2 outperforms the contrasted methods in terms of the proposed metrics, and that the results are consistent with previous biological knowledge. Additionally, a genome-wide study on multiple publicly available time series data was performed. In this case, the experimentation has exhibited the soundness and scalability of the new method which inferred highly-related statistically-significant gene associations. Conclusions A novel method for inferring time-delayed gene regulatory networks from genome-wide time series datasets is proposed in this paper. The method was carefully validated with several publicly available data sets. The results have demonstrated that the algorithm constitutes a usable model-free approach capable of predicting meaningful relationships between genes, revealing the time-trends of gene regulation.

Nephrolithiasis has become an increasing worldwide problem during the last decades. Metabolic syndrome, its components, and related dietary factors have been pointed out as responsible for the increasing incidence. The objective of this study was to evaluate the trends in the hospitalization rates of patients with nephrolithiasis, hospitalization features, costs, and how metabolic syndrome traits influence both the prevalence and complications of lithiasic patients. An observational retrospective study was conducted by analyzing hospitalization records from the minimum basic data set, including all patient hospitalizations in Spain in which nephrolithiasis has been coded as a main diagnosis or as a comorbidity during the period 2017-2020. A total of 106,407 patients were hospitalized and coded for kidney or ureteral lithiasis in this period. The mean age of the patients was 58.28 years (CI95%: 58.18-58.38); 56.8% were male, and the median length of stay was 5.23 days (CI95%: 5.06-5.39). In 56,884 (53.5%) patients, kidney or ureteral lithiasis were coded as the main diagnosis; the rest of the patients were coded mostly as direct complications of kidney or ureteral stones, such as "non-pecified renal colic", "acute pyelonephritis", or "tract urinary infection". The hospitalization rate was 56.7 (CI95%: 56.3-57.01) patients per 100,000 inhabitants, showing neither a significant increasing nor decreasing trend, although it was influenced by the COVID-19 pandemic. The mortality rate was 1.6% (CI95%: 1.5-1.7), which was higher, if lithiasis was coded as a comorbidity (3.4% CI95%: 3.2-3.6). Metabolic syndrome diagnosis component codes increased the association with kidney lithiasis when age was higher, reaching the highest in the eighth decade of life. Age, diabetes, and hypertension or lithiasis coded as a comorbidity were the most common causes associated with the mortality of lithiasic patients. In Spain, the hospitalization rate of kidney lithiasis has remained stable during the period of study. The mortality rate in lithiasic patients is higher in elderly patients, being associated with urinary tract infections. Comorbidity conditions such as diabetes mellitus and hypertension are mortality predictors.

The relationship of sex hormones with prostate glandular activity and the evidence of the favourable impact of bilateral orchiectomy in 21 patients with locally advanced or metastatic prostate cancer (PCa), ratified by Huggins C.B. and cols. in 1941, is one of the pillars for the acceptance of androgen deprivation therapy (ADT). Its clinical relevance has withstood the passage of time and remains valid, fundamentally, in advanced PCa. ADT has expanded its use over the years and, after extensive clinical experience, substantial modifications have been incorporated into its indications and options, both of which are increasingly precise. The objective of this review is to update the therapeutic positioning of primary ADT, genetic-molecular advances and future of the developing treatments of PCa.

Urolithiasis is a worldwide problem and a risk factor for kidney injury. Oxidative stress-associated renal endothelial dysfunction secondary to urolithiasis could be a key pathogenic factor, similar to obesity and diabetes-related nephropathy. The aim of the present study was to characterize urolithiasis-related endothelial dysfunction in a hyperoxaluria rat model of renal lithiasis., Experimental Approach: Endothelial dysfunction was assessed in preglomerular arteries isolated from control rats and in which 0.75% ethylene glycol was administered in drinking water. Renal interlobar arteries were mounted in microvascular myographs for functional studies; superoxide generation was measured by chemiluminescence and mRNA and protein expression by RT-PCR and immunofluorescence, respectively. Selective inhibitors were used to study the influence of the different ROS sources, xanthine oxidase, COX-2, Nox1, Nox2 and Nox4. Inflammatory vascular response was also studied by measuring the RNAm expression of NF-κB, MCP-1 and TNFα by RT-PCR., Results: Endothelium-dependent vasodilator responses were impaired in the preglomerular arteries of the hyperoxaluric group along with higher superoxide generation in the renal cortex and vascular inflammation developed by MCP-1 and promoted by NF-κB. The xanthine oxidase inhibitor allopurinol restored the endothelial relaxations and returned superoxide generation to basal values. Nox1 and Nox2 mRNA were up-regulated in arteries from the hyperoxaluric group, and Nox1 and Nox2 selective inhibitors also restored the impaired vasodilator responses and normalized NADPH oxidase-dependent higher superoxide values of renal cortex from the hyperoxaluric group., Conclusions: The current data support that hyperoxaluria induces oxidative stress-mediated endothelial dysfunction and inflammatory response in renal preglomerular arteries which is promoted by the xanthine oxidase, Nox1 and Nox2 pathways.

Purpose: To evaluate the preoperative and intraoperative risk factors for revision after artificial urinary sphincter (AUS) implantation in male patients with stress urinary incontinence (SUI)., Methods: A retrospective analysis from a prospectively maintained database was performed. Male patients, with moderate-tosevere SUI, undergoing AUS implantation were included. All patients underwent placement of AMS 800. Cause of revision, type of revision, and time to revision were recorded. Multivariable analyzes were performed using a logistic regression to investigate the risk factors. Competing risk analysis according to Fine-Gray model was used to study time to event data., Results: A total of 70 patients were included. Revision surgery was performed in 22 of 70 patients (31.4%), after a median (interquartile range) time of 26.5 months (6.5-39.3 months). Overall, 19 of 22 repairs (86.4%) and 3 of 22 explants (13.6%) were recorded. Mechanical dysfunction, urethral erosion, urethral atrophy, and device infection were the causes of revision in 11 of 22 (50.0%), 6 of 22 (27.3%), 3 of 22 (13.6%), and 2 of 22 patients (9.1%). Vesicourethral anastomosis stenosis (P=0.02), urethral cuff size of 3.5 cm (P=0.029), and dual implantation (P=0.048) were independent predictors for revision. Vesicourethral anastomosis stenosis (P=0.01) and urethral cuff size of 3.5 cm (P=0.029) predicted a lower survival of the AUS., Conclusion: The vesicourethral anastomosis stenosis, urethral cuff size of 3.5 cm, and dual implantation are independent predictors for revision after AUS implantation. However, only the vesicourethral anastomosis stenosis and urethral cuff size of 3.5 cm predict a lower survival of AUS.

Background: Warm ischemia time and ischemia-reperfusion damage result in higher rates of delayed graft function and primary nonfunction in kidney transplants (KTs) from controlled donation after circulatory death (cDCD). This study aimed to assess early and late kidney function and patient and graft survival of KT from cDCD preserved with normothermic regional perfusion (NRP) and to compare with KT from brain death donors (DBDs) and cDCD preserved with rapid recovery (RR)., Methods: Patients who received a KT at our institution from 2012 to 2018 were included, with a minimum follow-up period of 1 y. They were categorized by donor type and conditioning methods: DBD, cDCD with NRP, and cDCD with RR. Early and late graft function, along with patient and graft survival were analyzed in all groups., Results: A total of 182 KT recipients were included in the study (98 DBD and 84 cDCD). Out of the cDCDs, 24 kidneys were recovered with the use of NRP and 62 with RR; 22 of the 24 kidneys were ultimately transplanted. The cDCD using NRP group showed lower rates of delayed graft function compared with the cDCD with RR group (36.3% versus 46.7%, P  = 0.01). Also, primary nonfunction rates were lower in the cDCD using NRP group (4.5% versus 6.4% cDCD-RR and 10.2% DBD). Patient survival rates were >90% in all groups. No differences were found in graft survival rates at 1 y., Conclusions: The use of abdominal NRP improves early function recovery of KT from cDCD, making their outcomes comparable with those of DBD., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

An increased risk of cardiovascular morbidity has been reported in lithiasic patients. In this context, endothelial dysfunction (ED), an earlier status of atherogenesis, has been identified in hyperoxaluria rat models of urolithiasis., Objective: The purpose of this study was to determine the endothelial vascular function in patients with urolithiasis in relation to systemic inflammatory, oxidative stress, and vascular function serum markers., Methods: A cross-sectional study was performed between 27 urolithiasic patients, matched for age and sex, with 27 healthy patients. Endothelial function was assessed by measuring flow-mediated dilation (Celermajer method). Fasting blood was collected to determine metabolic parameters (glucose and lipid profile), along with serum CRP, IL-6, MDA, ADMA, and VCAM-1., Results: Both the control and urolithiasis groups were homogenous in anthropometric, exploration, and general laboratory measures. Flow-mediated dilation (%FMD) was 11.85% (SE: 2.78) lower in the lithiasis group ( p < 0.001). No significant differences were achieved between groups when CRP, IL-6, MDA, ADMA, and VCAM-1 were compared, although slightly higher values of CRP, ADMA, and VCAM-1 were detected in the lithiasic group. A correlation was not reached in any of the serum markers when they were related to flow-mediated values, although a slight negative correlation trend was observed in MDA, VCAM-1, and IL-6 values., Conclusions: Endothelial dysfunction constitutes an important disorder related to urolithiasis patients. It must be considered as an early feature responsible for future cardiovascular events. Our study did not find a significant association between inflammatory, oxidative stress, endothelial serum markers, and flow-mediated dilation.

AMP-activated protein kinase (AMPK) is a cellular energy sensor activated during energy stress to stimulate ATP production pathways and restore homeostasis. AMPK is widely expressed in the kidney and involved in mitochondrial protection and biogenesis upon acute renal ischemia, AMPK activity being blunted in metabolic disease-associated kidney disease. Since little is known about AMPK in the regulation of renal blood flow, the present study aimed to assess the role of AMPK in renal vascular function. Functional responses to the selective AMPK activator A769662 were assessed in intrarenal small arteries isolated from the kidney of renal tumour patients and Wistar rats and mounted in microvascular myographs to perform simultaneous measurements of intracellular calcium [Ca 2+ ] i and tension. Superoxide (O 2 .- ) and hydrogen peroxide (H 2 O 2 ) production were measured by chemiluminescence and fluorescence and protein expression by Western blot. Activation of AMPK with A769662 increased AMPK α phosphorylation at Thr-172 and induced potent relaxations compared to AICAR in isolated human and rat intrarenal arteries, through both endothelium-dependent mechanisms involving nitric oxide (NO) and intermediate-conductance calcium-activated potassium (IK Ca ) channels, as well as activation of ATP-sensitive (K ATP ) channels and sarcoplasmic reticulum Ca 2+ -ATP ase (SERCA) in vascular smooth muscle (VSM). Furthermore, AMPK activator reduced NADPH oxidase 4 (Nox4) and Nox2-derived reactive oxygen species (ROS) production. These results demonstrate that A769662 has potent vasodilator and antioxidant effects in intrarenal arteries. The benefits of AMPK activation in rat kidney are reproduced in human arteries and therefore vascular AMPK activation might be a therapeutic target in the treatment of metabolic disease-associated kidney injury., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Surgical intervention in Peyronie's disease (PD) should ideally be delayed until the resolution of acute inflammatory phase., Aim: The objective of this review was to highlight the results of penile prosthesis to correct refractory erectile dysfunction (ED) in patients with PD, and the secondary procedures that may be required to correct the penile curvature., Methods: A systematic search on PubMed online database using Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations was done using the MeSH terms "Peyronie's disease" and "erectile dysfunction.", Main Outcome Measure: Success and satisfaction rates of various procedures., Results: The search yielded 324 language-specific (English and Spanish language) articles and 58 articles were retained for final review. The following variables were assessed in different studies: number of patients, types of secondary procedure to correct the curvature, satisfaction rates, and follow-up period., Conclusion: The aim of the surgery in PD should be to achieve a functionally straight penis (<20 degree curvature) with good erection. Patients with refractory ED in PD are candidates for penile prosthesis. Secondary procedures, like manual modeling, plication, plaque incision, or excision grafting, may be required depending on the degree of penile curvature and penile length. In quest for the best graft, TachoSil graft seems to have gained popularity in Europe. Krishnappa P, Fernandez-Pascual E, Carballido J, et al. Surgical Management of Peyronie's Disease With Co-Existent Erectile Dysfunction. Sex Med 2019;7:361-370., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The use of intraoperatory laparoscopic ultrasound for nephron sparring surgery (partial nephrectomy) in patients with technically challenging tumors has emerged during the last years. The objective of this work is to present a literature review and analysis of the published series, as well as the surgical technique of intraoperatory laparoscopic guided partial nephrectomy., Methods: Pubmed and Scopus serch was performed in January 2019 including the following keywords: "intraoperative ultrasonography", "laparoscopic ultrasonography" and "partial nephrectomy", the published series are presented. We describe the laparoscopic technique of intraoperatory ultrasound during partial nephrectomy., Results: All the published series present similar results in terms of tumour size which varies from 2.3 to 4 cm. Complications results are also very similar in the comparative series to the ones published in partial nephrectomies. They show promising oncological results during follow up with a rate superior to 90% of negative margins, comparable to those of exophytic tumor partial nephrectomies., Conclusions: The use of intraoperatory ultrasound during laparoscopic surgery to localize intraparenchymatous renal lesions can expand the indications of partial nephrectomy to more technically challenging tumors. These indications are not yet well standardized. Due to its complexity, the need of previous surgical experience is required to achieve good results and corroborate the security and feasibility of this procedure. Prospective randomized trials are needed to confirm the benefits of intraoperatory laparoscopic ultrasound for nephron sparring surgery (partial nephrectomy).

The arrival of Pfizer's blue pill Sildenafil in 1998 brought a great relief both to patient and physician signalling the start of a great era of medical therapy in sexual medicine. Since then the sexual medicine experts have been prescribing sildenafil in erectile dysfunction with acceptable minor adverse events. But the use of sildenafil in premature ejaculation (PE) is still debated. 2018 being the 20th anniversary of sildenafil, we have compiled interesting facts about the role of sildenafil in PE from various original articles, systematic reviews, meta-analyses, economic brochures and sexual medicine committee guidelines. The major issues in most of these studies were the heterogeneity in the definition of PE and estimating the exact ejaculatory latency time. This perspective article highlights the positive role of sildenafil in the management of PE (even without ED) with acceptable adverse events. Now that we have a standardised definition of PE from International Society of Sexual Medicine (ISSM) and a psychogenic component in PE definition, more randomised placebo-controlled studies are required to further establish its role.

Differentiation of B cells is a stringently controlled multi-step process, which is still incompletely understood. Here we identify and characterize a rare population of human B cells, which surprisingly carry CD8AB on their surface. Existence of such cells was demonstrated both in tonsils and in human apheresis material. Gene expression profiling and real time PCR detected however no CD8A or CD8B message in these cells. Instead, we found that surface CD8 was hijacked from activated CD8+ T cells by a transfer process that required direct cell-to-cell contact. A focused transcriptome analysis at single cell level allowed the dissection of the CD8 positive B cell population. We found that the affected cells are characteristically of the CD27+CD200- phenotype, and consist of two discrete late-stage subpopulations that carry signatures of activated memory B like cells, and early plasmablasts. Thus, there is only a restricted time window in the differentiation process during which B cells can intimately interact with CD8+ T cells. The findings point to a novel link between the T and B arms of the adaptive immune system, and suggest that CD8+ T cells have the capability to directly shape the global antibody repertoire., Competing Interests: The authors are employees of Novartis and declare no other competing interest. The commercial affiliation does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

The role of NADPH oxidase (Nox)-derived reactive oxygen species in kidney vascular function has extensively been investigated in the harmful context of oxidative stress in diabetes and obesity-associated kidney disease. Since hydrogen peroxide (H 2 O 2 ) has recently been involved in the non-nitric oxide (NO) non-prostanoid relaxations of intrarenal arteries, the present study was sought to investigate whether NADPH oxidases may be functional sources of vasodilator H 2 O 2 in the kidney and to assess their role in the endothelium-dependent relaxations of human and rat intrarenal arteries. Renal interlobar arteries isolated from the kidney of renal tumor patients who underwent nephrectomy, and from the kidney of Wistar rats, were mounted in microvascular myographs to assess function. Superoxide (O 2 .- ) and H 2 O 2 production was measured by chemiluminescence and Amplex Red fluorescence, and Nox2 and Nox4 enzymes were detected by Western blotting and by double inmunolabeling along with eNOS. Nox2 and Nox4 proteins were expressed in the endothelium of renal arterioles and glomeruli co-localized with eNOS, levels of expression of both enzymes being higher in the cortex than in isolated arteries. Pharmacological inhibition of Nox with apocynin and of CYP 2C epoxygenases with sulfaphenazol, but not of the NO synthase (NOS), reduced renal NADPH-stimulated O 2 .- and H 2 O 2 production. Under conditions of cyclooxygenase and NOS blockade, acetylcholine induced endothelium-dependent relaxations that were blunted by the non-selective Nox inhibitor apocynin and by the Nox2 or the Nox1/4 inhibitors gp91ds-tat and GKT136901, respectively. Acetylcholine stimulated H 2 O 2 production that was reduced by gp91ds-tat and by GKT136901. These results suggest the specific involvement of Nox4 and Nox2 subunits as physiologically relevant endothelial sources of H 2 O 2 generation that contribute to the endothelium-dependent vasodilatation of renal arteries and therefore have a protective role in kidney vasculature., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background Aims: Cell therapy with autologous mesenchymal stromal cells (MSCs) in patients with spinal cord injury (SCI) is beginning, and the search for its better clinical application is an urgent need., Methods: We present a phase 2 clinical trial in patients with chronic SCI who received three intrathecal administrations of 100 x 10 6 MSCs and were followed for 10 months from the first administration. Efficacy analysis was performed on nine patients, and safety analysis was performed on 11 patients. Clinical scales, urodynamic, neurophysiological and neuroimaging studies were performed previous to treatment and at the end of the follow-up., Results: The treatment was well-tolerated, without any adverse event related to MSC administration. Patients showed variable clinical improvement in sensitivity, motor power, spasms, spasticity, neuropathic pain, sexual function or sphincter dysfunction, regardless of the level or degree of injury, age or time elapsed from the SCI. In the course of follow-up three patients, initially classified as ASIA A, B and C, changed to ASIA B, C and D, respectively. In urodynamic studies, at the end of follow-up, 66.6% of the patients showed decrease in postmicturition residue and improvement in bladder compliance. At this time, neurophysiological studies showed that 55.5% of patients improved in somatosensory or motor-evoked potentials, and that 44.4% of patients improved in voluntary muscle contraction together with infralesional active muscle reinnervation., Conclusions: The present guideline for cell therapy is safe and shows efficacy in patients with SCI, mainly in recovery of sphincter dysfunction, neuropathic pain and sensitivity., (Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background Aims: Recently, clinical studies show that cell therapy with mesenchymal stromal cells (MSCs) improves the sequelae chronically established in paraplegic patients, being necessary to know which of them can obtain better benefit., Methods: We present here a phase 2 clinical trial that includes six paraplegic patients with post-traumatic syringomyelia who received 300 million MSCs inside the syrinx and who were followed up for 6 months. Clinical scales, urodynamic, neurophysiological, magnetic resonance (MR) and studies of ano-rectal manometry were performed to assess possible improvements., Results: In all the cases, MR at the end of the study showed a clear reduction of the syrinx, and, at this time, signs of improvement in the urodynamic studies were found. Moreover, four patients improved in ano-rectal manometry. Four patients improved in neurophysiological studies, with signs of improvement in evoked potentials in three patients. In the American Spinal Injury Association (ASIA) assessment, only two patients improved in sensitivity, but clinical improvement in neurogenic bowel dysfunction was observed in four patients and three patients described improvement in bladder dysfunction. Spasms reduced in two of the five patients who had them previous to cell therapy, and spasticity was improved in the other two patients. Three patients had neuropathic pain before treatment, and it was reduced or disappeared completely during the study. Only two adverse events ocurred, without relation to the cell therapy., Conclusions: Cell therapy can be considered as a new alternative to the treatment of post-traumatic syringomyelia, achieving reduction of syrinx and clinical improvements in individual patients., (Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: To move towards a more standardized approach in clinical practice to manage patients with castration-resistant prostate cancer (CRPC) in Spain., Methods: A panel of 18 Spanish experts in Urology with expertise managing CRPC followed a modified Delphi process with two rounds and a final face-to-face consensus meeting. The panel considered a total of 106 clinical questions divided into the following 6 sections: definition of CRPC, diagnosis of metastases by imaging techniques, symptoms of CRPC, progression of CRPC, M0 and M1 management and therapeutic sequencing., Results: A bone scan (BS) is recommended at diagnosis, at the onset of bone pain, and depending on PSA levels, but it is not sensitive enough to confirm or exclude bone metastases if there is bone pain. Whole-body MRI and axial MRI are more sensitive than BS and plain X-rays, but more expensive, so they have to be used in certain situations. There is CRPC progression when there is radiologic, clinical or confirmed PSA progression. Flare phenomenon appears in treatment with taxanes and abiraterone. It was agreed that in M0 CRPC patients no drug treatment is currently recommended, although in M1 CRPC patients the first-line therapy would be mainly enzalutamide/abiraterone and/or docetaxel, depending on the symptom burden., Conclusion: After the consensus, we provide a series of recommendations for Spanish physicians treating CRPC to address the disease characteristics,how to tailor patient management decisions, the use of imaging techniques, and how to handle disease progression appropriately to improve patients' quality of life.

Objective: Campylobacter is considered the most frequent agent of gastroenteritis in humans all around the world. The aim of this study was to know the incidence, trend and seasonality of notified campylobacteriosis cases in Castile and Leon, Spain, from 2008 to 2015. In addition, to describe the type of case and source of notification, and study the influence of age, sex and Campylobacter species on the hospitalization of cases., Methods: Retrospective cross-sectional study with a time series analysis. Data on notified campylobacteriosis cases were collected from the Epidemiological Surveillance System of Castile and Leon (2008-2015). Incidence rates and incidence rate ratios by age, sex and year of notification were calculated. In order to estimate trend and seasonality, a time series analysis was performed using a multiplicative method and adjusted to a linear and exponential model., Results: From 4,330 cases analyzed, 49.4% of children aged under 5 were affected. The ratio of men to women was 1.43 and 61.8% of cases were notified from secondary care. C. jejuni was isolated from 72.3% of samples (n=2,593). Incidence rate ranged from 11.42 cases per 100,000 inhabitants in 2008 to 33.53 in 2015. The seasonality range was from 71.97% (13th four-week period) to 125.54% (9th four-week period). Hospitalization reached 62.5% for people aged 60 or over., Conclusions: A growing trend of notified campylobacteriosis cases is observed in Castile and Leon (2008-2015), mainly in children aged under 5, with a peak in summer months. Males are more affected than females and hospitalization increases with age., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background Aims: Cell therapy with mesenchymal stromal cells (MSCs) offers new hope for patients suffering from spinal cord injury (SCI)., Methods: Ten patients with established incomplete SCI received four subarachnoid administrations of 30 × 10 6 autologous bone marrow MSCs, supported in autologous plasma, at months 1, 4, 7 and 10 of the study, and were followed until the month 12. Urodynamic, neurophysiological and neuroimaging studies were performed at months 6 and 12, and compared with basal studies., Results: Variable improvement was found in the patients of the series. All of them showed some degree of improvement in sensitivity and motor function. Sexual function improved in two of the eight male patients. Neuropathic pain was present in four patients before treatment; it disappeared in two of them and decreased in another. Clear improvement in bladder and bowel control were found in all patients suffering previous dysfunction. Before treatment, seven patients suffered spasms, and two improved. Before cell therapy, nine patients suffered variable degree of spasticity, and 3 of them showed clear decrease at the end of follow-up. At this time, nine patients showed infra-lesional electromyographic recordings suggesting active muscle reinnervation, and eight patients showed improvement in bladder compliance. After three administrations of MSCs, mean values of brain-derived neurotrophic factor, glial-derived neurotrophic factor, ciliary neurotrophic factor, and neurotrophin 3 and 4 showed slight increases compared with basal levels, but without statistically significant difference., Conclusions: Administration of repeated doses of MSCs by subarachnoid route is a well-tolerated procedure that is able to achieve progressive and significant improvement in the quality of life of patients suffering incomplete SCI., (Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Renal angiomyolipomas (AML) are usual manifestations of tuberous sclerosis complex (TSC) that may cause aneurism-related haemorrhages and renal impairment. Everolimus has emerged as an alternative to surgery/embolization. We provide further insight into everolimus safety and efficacy for TSC-related AML., Methods: This was a Spanish expanded access trial including patients aged ≥18 years with TSC-related AML. They received 10 mg everolimus once daily until AML progression, unacceptable toxicity, death/withdrawal, commercialisation for TSC-related AML, or 1 year after first patient enrolment. The primary outcome was dose-limiting safety according to grade 3/4 adverse events, serious adverse events, or adverse events leading to treatment modification. Secondary outcomes included overall safety and efficacy., Results: Nineteen patients were enrolled and received everolimus for a median of 6.6 (5.3-10.9) months. Eleven (57.9 %) remained on 10 mg/day throughout the study and eight (42.1 %) required treatment modifications due to adverse events; none permanently discontinued treatment. Adverse events were overall grade 1/2 and most frequently included aphthous stomatitis/mucosal inflammation, hypercholesterolaemia/hypertriglyceridaemia, urinary tract infection, hypertension, dermatitis acneiform, and insomnia. Four (21.1 %) patients experienced grade 3 adverse events, none was grade 4, and only one (5.3 %) was serious (pneumonia). AML volume was reduced ≥30 % in 11 (57.9 %) patients and ≥50 % in 9 (47.4 %); none progressed. Right and left kidney sizes decreased in 16 and 14 patients, respectively., Conclusions: These findings support the benefit of everolimus for renal AML due to a manageable safety profile accompanied by reduced AML and kidney volumes., Trial Registration: EudraCT number 2012-005397-63 ; date of registration 22 Nov 2012.

Background Aims: Cell transplantation in patients suffering spinal cord injury (SCI) is in its initial stages, but currently there is confusion about the results because of the disparity in the techniques used, the route of administration, and the criteria for selecting patients., Methods: We conducted a clinical trial involving 12 patients with complete and chronic paraplegia (average time of chronicity, 13.86 years; SD, 9.36). The characteristics of SCI in magnetic resonance imaging (MRI) were evaluated for a personalized local administration of expanded autologous bone marrow mesenchymal stromal cells (MSCs) supported in autologous plasma, with the number of MSCs ranging from 100 × 10(6) to 230 × 10(6). An additional 30 × 10(6) MSCs were administered 3 months later by lumbar puncture into the subarachnoid space. Outcomes were evaluated at 3, 6, 9 and 12 months after surgery through clinical, urodynamic, neurophysiological and neuroimaging studies., Results: Cell transplantation is a safe procedure. All patients experienced improvement, primarily in sensitivity and sphincter control. Infralesional motor activity, according to clinical and neurophysiological studies, was obtained by more than 50% of the patients. Decreases in spasms and spasticity, and improved sexual function were also common findings. Clinical improvement seems to be dose-dependent but was not influenced by the chronicity of the SCI., Conclusion: Personalized cell therapy with MSCs is safe and leads to clear improvements in clinical aspects and quality of life for patients with complete and chronically established paraplegia., (Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)