Search

Estimates of the spectrum and frequency of pathogenic variants in Parkinson's disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson's disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10-34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10-35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10-4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10-14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Gaucher disease (GD) is a rare autosomal recessive disorder arising from bi-allelic variants in the GBA1 gene, encoding glucocerebrosidase. Deficiency of this enzyme leads to progressive accumulation of the sphingolipid glucosylsphingosine (lyso-Gb1). The international, multicenter, observational "Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease"-LYSO-PROOF study succeeded in enrolling a cohort of 160 treatment-naïve GD patients from diverse geographic regions and evaluated the potential of lyso-Gb1 as a specific biomarker for GD. Using genotypes based on established classifications for clinical presentation, patients were stratified into type 1 GD ( n = 114) and further subdivided into mild ( n = 66) and severe type 1 GD ( n = 48). Due to having previously unreported genotypes, 46 patients could not be classified. Though lyso-Gb1 values at enrollment were widely distributed, they displayed a moderate and statistically highly significant correlation with disease severity measured by the GD-DS3 scoring system in all GD patients (r = 0.602, p < 0.0001). These findings support the utility of lyso-Gb1 as a sensitive biomarker for GD and indicate that it could help to predict the clinical course of patients with undescribed genotypes to improve personalized care in the future.

Introduction: Active surveillance (AS) is considered a suitable management practice for those patients with low-risk prostate cancer (PCa). At present, however, the role of multiparametric magnetic resonance imaging (mpMRI) in AS protocols has not yet been clearly established., Outcomes: To determine the role of mpMRI and its ability to detect significant prostate cancer (SigPCa) in PCa patients enrolled in AS protocols., Materials and Methods: There were 229 patients enrolled in an AS protocol between 2011 and 2020 at Reina Sofía University Hospital. MRI interpretation was based on PIRADS v.1 or v.2/2.1 classification. Demographics, clinical, and analytical data were collected and analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for mpMRI in different scenarios. We defined SigPCa and reclassification/progression as a Gleason score (GS) ≥ 3 + 4, a clinical stage ≥T2b, or an increase in PCa volume. Kaplan-Meier and log-rank tests were used to estimate progression-free survival time., Results: Median age was 69.02 (±7.73) at diagnosis, with a 0.15 (±0.08) PSA density (PSAD). Eighty-six patients were reclassified after confirmatory biopsy, with a suspicious mpMRI an indication for a clear reclassification and risk-predictor factor in disease progression (p < 0.05). During follow-up, 46 patients were changed from AS to active treatment mainly due to disease progression. Ninety patients underwent ≥2mpMRI during follow-up, with a median follow-up of 29 (15-49) months. Thirty-four patients had a baseline suspicious mpMRI (at diagnostic or confirmatory biopsy): 14 patients with a PIRADS 3 and 20 patients with ≥PIRADS 4. From 14 patients with a PIRADS 3 baseline mpMRI, 29% progressed radiologically, with a 50% progression rate versus 10% (1/10 patients) for those with similar or decreased mpMRI risk. Of the 56 patients with a non-suspicious baseline mpMRI (PIRADS < 2), 14 patients (25%) had an increased degree of radiological suspicion, with a detection rate of SigPCa of 29%. The mpMRI NPV during follow-up was 0.91., Conclusion: A suspicious mpMRI increases the reclassification and disease progression risk during follow-up and plays an important role in monitoring biopsies. In addition, a high NPV at mpMRI follow-up can help to decrease the need to monitor biopsies during AS., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Gaucher disease is a rare inherited disorder caused by a deficiency of the lysosomal acid beta-glucocerebrosidase enzyme. Metabolomic studies by our group targeted several new potential urinary biomarkers. Apart from lyso-Gb 1 , these studies highlighted lyso-Gb 1 analogs -28, -26, -12 (A/B), +2, +14, +16 (A/B), +30, and +32 Da, and polycyclic lyso-Gb 1 analogs 362, 366, 390, and 394 Da. The main objective of the current study was to develop and validate a robust UPLC-MS/MS method to study the urine distribution of these biomarkers in patients., Method: Urine samples were purified using solid-phase extraction. A 12 min UPLC-MS/MS method was developed., Results: Validation assays revealed high precision and accuracy for creatinine and lyso-Gb 1 . Most lyso-Gb 1 analogs had good recovery rates and high intra- and interday precision assays. Biomarker-estimated LOD and LOQ levels ranged from 56-109 pM to 186-354 pM, respectively. Comparison between GD patients and healthy controls showed significant differences in most biomarker levels. Typically, treated GD patients presented lower biomarker levels compared to untreated patients., Conclusions: These data suggest that the metabolites investigated might be interesting GD biomarkers. More studies with a larger cohort of patients will be needed to better understand the clinical significance of these GD biomarkers.

Gaucher disease (GD) is a lysosomal storage disorder resulting from a biallelic mutation in the gene GBA1 , leading to deficiencies in the enzyme β-glucocerebrosidase (Gcase). Inabilities of the Gcase to catabolize its substrate result in the accumulation of sphingolipids in macrophages, which impairs the cell functions and ultimately leads to multisystemic clinical manifestations. Important variability in symptoms and manifestations may lead to challenging diagnosis and patient care. Plasma glucosylsphingosine (lyso-Gb 1 ) is a biomarker frequently used for prognosis, monitoring, and patient follow-up. While lyso-Gb 1 appears to be a valid biomarker, few studies have investigated other matrices for potential GD biomarkers. The main objective of this study was to investigate the urine matrix as a potential source of new GD biomarkers by performing a metabolomic study using time-of-flight mass spectrometry. Our study highlighted a significant increase of eight urinary lyso-Gb 1 analogues. Moreover, a novel class of biomarkers, named polycyclic lyso-Gb 1 analogues, was identified. These four new molecules were more elevated than lyso-Gb 1 and related analogues in urine specimens of GD patients. Further investigations are warranted to validate the efficiency of these newly found biomarkers on a larger cohort of Gaucher patients and to compare them with plasma biomarkers currently quantified in clinical laboratories.

Background: Sphingolipidoses are caused by a defective sphingolipid catabolism, leading to an accumulation of several glycolipid species in tissues and resulting in neurotoxicity and severe systemic manifestations. Methods & results: Urine samples from controls and patients were purified by solid-phase extraction prior to the analysis by ultra-high-performance liquid chromatography (UPLC) combined with MS/MS. A UPLC-MS/MS method for the analysis of 21 urinary creatinine-normalized biomarkers for eight diseases was developed and validated. Conclusion: Considering the growing demand to identify patients with different sphingolipidoses early and reliably, this methodology will be applied for high-risk screening to target efficiently patients with various sphingolipidoses.

Aim: Gaucher disease (GD) is caused by a deficiency of the lysosomal enzyme acid β-glucocerebrosidase. Recent metabolomic studies highlighted several new metabolites increased in the plasma of GD patients. We aimed to develop and validate a UPLC-MS/MS method allowing a relative quantitation of lyso-Gb 1 and lyso-Gb 1 analogs -28, -12, -2, +14, +16 and +18 Da in addition to sphingosylphosphorylcholine, N -palmitoyl- O -phosphocholine to study potential correlations with clinical manifestations. Methodology & results: Following solid-phase extraction, plasma samples were evaporated and resuspended in 100 μl of resuspension solution. Three microliter is injected into the UPLC-MS/MS for analysis. Conclusion: All biomarkers studied were increased in GD patients. Significant correlations were observed between specific analogs and hematological, and visceral complications, as well as overall disease severity.

Speech is our most natural and efficient form of communication and offers a strong potential to improve how we interact with machines. However, speech communication can sometimes be limited by environmental (e.g., ambient noise), contextual (e.g., need for privacy), or health conditions (e.g., laryngectomy), preventing the consideration of audible speech. In this regard, silent speech interfaces (SSI) have been proposed as an alternative, considering technologies that do not require the production of acoustic signals (e.g., electromyography and video). Unfortunately, despite their plentitude, many still face limitations regarding their everyday use, e.g., being intrusive, non-portable, or raising technical (e.g., lighting conditions for video) or privacy concerns. In line with this necessity, this article explores the consideration of contactless continuous-wave radar to assess its potential for SSI development. A corpus of 13 European Portuguese words was acquired for four speakers and three of them enrolled in a second acquisition session, three months later. Regarding the speaker-dependent models, trained and tested with data from each speaker while using 5-fold cross-validation, average accuracies of 84.50% and 88.00% were respectively obtained from Bagging (BAG) and Linear Regression (LR) classifiers, respectively. Additionally, recognition accuracies of 81.79% and 81.80% were also, respectively, achieved for the session and speaker-independent experiments, establishing promising grounds for further exploring this technology towards silent speech recognition.

Background: Genetic stratification of Parkinson's disease (PD) patients facilitates gene-tailored research studies and clinical trials. The objective of this study was to describe the design of and the initial data from the Rostock International Parkinson's Disease (ROPAD) study, an epidemiological observational study aiming to genetically characterize ~10,000 participants., Methods: Recruitment criteria included (1) clinical diagnosis of PD, (2) relative of participant with a reportable LRRK2 variant, or (3) North African Berber or Ashkenazi Jew. DNA analysis involved up to 3 successive steps: (1) variant (LRRK2) and gene (GBA) screening, (2) panel sequencing of 68 PD-linked genes, and (3) genome sequencing., Results: Initial data based on the first 1360 participants indicated that the ROPAD enrollment strategy revealed a genetic diagnostic yield of ~14% among a PD cohort from tertiary referral centers., Conclusions: The ROPAD screening protocol is feasible for high-throughput genetic characterization of PD participants and subsequent prioritization for gene-focused research efforts and clinical trials. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

The Coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in economic and social lockdowns in most countries all over the globe. Early identification of infected individuals is regarded as one of the most important prerequisites for fighting the pandemic and for returning to a 'New Normal'. Large-scale testing is therefore crucial, but is facing several challenges including shortage of sample collection tools and of molecular biological reagents, and the need for safe electronic communication of medical reports. We present the successful establishment of a holistic SARS-CoV-2 testing platform that covers proband registration, sample collection and shipment, sample testing, and report issuing. The RT-PCR-based virus detection, being central to the platform, was extensively validated: sensitivity and specificity were defined as 96.8% and 100%, respectively; intra-run and inter-run precision were <3%. A novel type of sample swab and an in-house-developed RNA extraction system were shown to perform as good as commercially available products. The resulting flexibility guarantees independence from the current bottlenecks in SARS-CoV-2 testing. Based on our technology, we offered testing at local, national, and global levels. In the present study, we report the results from approx. 18,000 SARS-CoV-2 tests in almost 10,000 individuals from a low-frequency SARS-CoV-2 pandemic area in a homogenous geographical region in north-eastern Germany for a period of 10 weeks (21 March to 31 May 2020). Among the probands, five SARS-CoV-2 positive cases were identified. Comparative analysis of corresponding virus genomes revealed a diverse origin from three of the five currently recognized SARS-CoV-2 phylogenetic clades. Our study exemplifies how preventive SARS-CoV-2 testing can be set up in a rapid and flexible manner. The application of our test has enabled a safe maintenance/resume of critical local infrastructure, e.g., nursing homes where more than 5000 elderlies and caretakers got tested. The strategy outlined by the present study may serve as a blueprint for the implementation of large-scale preventive SARS-CoV-2 testing elsewhere.

Invadosomes are specialised actin-based dynamic microdomains of the plasma membrane. Their occurrence has been associated with cell adhesion, matrix degrading and mechanosensory functions that make them crucial regulators of cell migration and invasion. Monocytic, cancer cell and Src-transformed cell invadosomes have been extensively described. Less well defined are the structures which form in other cell types, i.e., non-haematopoietic and non-transformed cells, exposed to specific stimuli. We herein describe the specificities of podosomes induced in aortic endothelial cells stimulated with TGFβ in vitro and in conditions that more closely resemble the in vivo situation. These podosomes display the typical architecture of monocytic podosomes. They organise into large rosette-shape superstructures where they exhibit collective dynamic behavior consisting in cycles of formation and regression. At the ultrastructural level, microfilament arrangements in individual podosomes were revealed. Oxygen levels and hemodynamic forces, which are key players in endothelial cell biology, both influence the process. In 3D environment, podosomes appear as globular structures along cellular extensions. A better characterization of endothelial podosomes has far-reaching implications in the understanding and, possibly, in the treatment of some vascular diseases., Competing Interests: Declaration of Competing Interest The authors do not disclose any competing interests., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Objective: To describe the technique of transrectal biopsy with a new device that fuses multiparametric magnetic resonance (mpMRI) and ultrasound images in real time to guide target biopsies and to evaluate our initial experience., Methods: Patients with persistent suspicion of prostate cancer despite a previous negative biopsy and who had an mpMRI before the biopsy were selected. All patients underwent target biopsy plus standard systematic biopsy. Significant prostate cancer (sig PCa) was defined according to the Epstein criteria for standard biopsy and Gleason grade of ≥7 and a positive core length of ≥5 mm for target biopsy., Results: The first 40 patients were evaluated. The median age was 65 years old. In a sagittal isotropic sequence, the fusion process was started. The fusion can be improved by using different tools such as concordant points and Global Positioning System corrections tools. In the target biopsy, a median of 4 cores was taken, whereas in the standard biopsy, 12 cores were taken. Twenty-two patients were diagnosed with prostate cancer; of these patients, 17 were diagnosed with sig PCa. The fusion target biopsy diagnosed more sig PCa than the standard biopsy; however, it was not statistically significant (37.5% vs 25%, P=.08). The probability of being diagnosed with cancer increased in correlation with the Prostate Imaging Reporting and Data System score, without reaching statistical significance (k=0.45, P=.08)., Conclusions: This new device is a useful tool to guide biopsy in patients with target lesions in an mpMRI to increase the detection of sig PCa. A larger cohort would be required to show significant differences., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Protein kinase D (PKD) is a family of serine/threonine kinases that is required for the structural integrity and function of the Golgi complex. Despite its importance in the regulation of Golgi function, the molecular mechanisms regulating PKD activity are still incompletely understood. Using the genetically encoded PKD activity reporter G-PKDrep we now uncover a Rho signaling network comprising GEF-H1, the RhoGAP DLC3, and the Rho effector PLCε that regulate the activation of PKD at trans-Golgi membranes. We further show that this molecular network coordinates the formation of TGN-derived Rab6-positive transport carriers delivering cargo for localized exocytosis at focal adhesions., Competing Interests: SE, FC, GL, SS, MN, MS, MO, AH No competing interests declared, (© 2018, Eisler et al.)

Objective: To assess the effect of vision in three dimensions (3D) versus two dimensions (2D) on mental workload and laparoscopic performance during simulation-based training., Materials and Methods: A prospective, randomized crossover study on inexperienced students in operative laparoscopy was conducted. Forty-six candidates executed five standardized exercises on a pelvitrainer with both vision systems (3D and 2D). Laparoscopy performance was assessed using the total time (in seconds) and the number of failed attempts. For workload assessment, the validated NASA-TLX questionnaire was administered., Results: 3D vision improves the performance reducing the time (3D = 1006.08 ± 315.94 vs. 2D = 1309.17 ± 300.28; P < .001) and the total number of failed attempts (3D = .84 ± 1.26 vs. 2D = 1.86 ± 1.60; P < .001). For each exercise, 3D vision also shows better performance times: "transfer objects" (P = .001), "single knot" (P < .001), "clip and cut" (P < .05), and "needle guidance" (P < .001). Besides, according to the NASA-TLX results, less mental workload is experienced with the use of 3D (P < .001). However, 3D vision was associated with greater visual impairment (P < .01) and headaches (P < .05)., Conclusion: The incorporation of 3D systems in laparoscopic training programs would facilitate the acquisition of laparoscopic skills, because they reduce mental workload and improve the performance on inexperienced surgeons. However, some undesirable effects such as visual discomfort or headache are identified initially., (Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: Simultaneous pancreas-kidney transplantation is the gold standard treatment for patients with end-stage renal failure secondary to insulin-dependent diabetes mellitus. This kind of transplantation is a complex operation associated with a high incidence of surgical complications and mortality risk which could influence graft survival. The aim of this study was to establish the influence of different grades of postoperative complications, classified according to Clavien-Dindo, on the rate of kidney graft loss., Methods: We performed an observational retrospective review of all simultaneous transplantations performed between February 1989 and May 2012. Factors examined were related to recipient and donor characteristics, surgical procedures, and postoperative outcomes. For this purpose, Kaplan-Meier analyses and Cox-Regression tests are used., Results: One hundred thirty-nine transplantations were performed. Complications grades I, II, and IIIa were experienced in 81 (58.3%) patients, and grades IIIb and IVa-b in 55 (39.6%). Multivariate analysis showed an influence of panel reactive antibody (hazard ratio [HR]: 10.79; P = .003), incidence of acute rejection (HR: 2.55; P = .03), and complications grouped into grades IIIb and IVa-b (HR: 3.63; P = .02). Kaplan Meier analysis showed worse kidney graft survival rate in groups grades IIIb and IVa-b compared to grades I, II, and IIIa (86.6% vs 98.7% at 1 year and 81.8% vs 97.3% at 5 years; P = .001)., Conclusions: Despite being the gold standard treatment for these patients, pancreas and kidney transplantations have numerous complications which could influence the prognosis of graft kidney survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Transforming growth factor β (TGF-β) and related cytokines play a central role in the vascular system. In vitro, TGF-β induces aortic endothelial cells to assemble subcellular actin-rich structures specialized for matrix degradation called podosomes. To explore further this TGF-β-specific response and determine in which context podosomes form, ALK5 and ALK1 TGF-β receptor signaling pathways were investigated in bovine aortic endothelial cells. We report that TGF-β drives podosome formation through ALK5 and the downstream effectors Smad2 and Smad3. Concurrent TGF-β-induced ALK1 signaling mitigates ALK5 responses through Smad1. ALK1 signaling induced by BMP9 also antagonizes TGF-β-induced podosome formation, but this occurs through both Smad1 and Smad5. Whereas ALK1 neutralization brings ALK5 signals to full potency for TGF-β-induced podosome formation, ALK1 depletion leads to cell disturbances not compatible with podosome assembly. Thus, ALK1 possesses passive and active modalities. Altogether, our results reveal specific features of ALK1 and ALK5 signaling with potential clinical implications., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Context: Prostate cancer treatment remains a challenge for the urologist. Medical control in locally advanced or metastatic prostate cancer is usually performed with LHRH analogues and/or antiandrogens. Different treatments have been proposed when there is biochemical and clinical progression of the disease and other new ones have changed the patients' perspective and life expectancy., Objective: This review has aimed to establish the current role of Abiraterone Acetate in the treatment of castration-resistant prostate cancer and facilitate decision-making by the Urologist by means of a Treatment Algorithm., Acquisition of the Evidence: A search of current evidence on Abiraterone treatment in patients with castration- resistant metastatic prostate cancer was performed in PubMed, mainly analyzing those studies designed as clinical trials. In addition, we reviewed and updated the role of hormone therapy and androgen receptors in prostate cancer., Evidence Synthesis: There are currently basically two clinical trials that demonstrate the effectiveness of Abiraterone in metastatic prostate cancer compared to placebo. The study COU-AA 302 shows a clear benefit with Abiraterone prior to chemotherapy in patients with castration-resistant prostate cancer, this making it possible to establish an algorithm for initial treatment that facilitates decision-making by the urologist., Conclusion: Abiraterone is a pre-chemotherapy treatment option in selected patients with castration resistant metastatic prostate cancer, although it is necessary to improve the cost and to design more multicenter clinical trials to optimize the cost/benefit ratio., (Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.)

Objective: The aim was to study the relation between same-donor renal biopsies and analyze whether the score influences graft survival., Methods: We retrospectively reviewed histologic results of expanded-criteria donors and the graft survival in patients followed at Reina Sofia Hospital (Cordoba, Spain) from January 2004 to October 2012. We analyzed clinical and demographic variables from the donors, as well the association between the scores of same-donor biopsies who had different scores for each kidney and the graft survival with a t test for paired data. A Kaplan-Meier with log-rank test was performed between the higher-score and the lower-score groups. We excluded retransplantation and those who received a combined transplantation (liver or pancreas)., Results: We analyzed 168 kidneys that had been biopsied, from 84 donors. Of the whole sample, 35.7% (n = 30) had the same score for each kidney, whereas 64.3% (n = 54) had discrepancies. In this second group, 81.8% (n = 44) had a difference of 1 point, and the remaining 18.2% (n = 10) had a larger difference. Both kidneys were suitable for transplantation in 72.7% of cases (n = 40), only 1 in 14.5% (n = 8), and none in 12.7% (n = 7). For analyzing the survival of the paired kidneys there were 48 kidneys from 24 donors with a different score for each kidney. We observed a difference in favor of the better scores, with a difference of 11 months up to the time of the analysis (P = .045). We found no significant differences in the log-rank test between the survival rate for the group with a less favorable score (95% confidence interval [CI], 61.26-95.67) versus those with a more favorable score (95% CI, 66.76-93.03)., Conclusions: A high percentage of biopsies had a different score for the 2 kidneys from the same donor. This difference was important for graft survival. We therefore recommend doing a biopsy of both kidneys., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Technical and medical advances over the past few years have produced an important increase in the functionality of renal allografts. The aim of this study was to identify the factors associated with allograft survival 15 years after transplantation in our series., Methods: A retrospective study of kidney transplantations was carried out at Reina Sofia Hospital in Cordoba from February 1979 to December 1997, with follow-up through June 2012. A subanalysis of the series was undertaken, and Kaplan-Meier analysis and Cox proportional hazards model regression used to achieve the main objective of the study., Results: A total of 487 renal allografts with a mean follow-up of 114 months were studied, of which 37% (n = 180) survived for >15 years. Of the 180 patients, the main causes of graft failure were chronic allograft nephropathy in 29 (66%) and patient death in 13 (29.5%). Multivariate analysis identified the number of HLA mismatches (hazard ratio [HR] 1.25, 95% CI 1.01-1.56), panel reactive antibodies (HR 2.61, 95% CI 1.28-5.26), and delayed graft function (HR 11.25, 95% CI 1.33-95.28) as being significantly associated with graft loss after 15 years., Conclusions: The high immunologic risk of the patients was independently associated with graft loss. Delayed graft function was the most important factor in the speed of graft failure beyond 15 years., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Numerous factors have been associated with early delay in kidney function and thence the graft survival. However, few data are derived from different types of donation: single or multiorgan. Our goal was to analyze the association of type of retrieval with the early function of the renal graft., Methods: A retrospective analysis of transplantations performed in the Reina Sofia Hospital from January 2004 to June 2012 from local deceased donors was carried out. We performed a descriptive analysis of the variables and univariate and multivariate analyses with the use of logistic regression to determine the association of type of retrieval (kidney-only [KO], kidney-liver [KL], and multiorgan [MO]) with delayed graft function (DGF) and early graft failure (EGF)., Results: We analyzed 287 kidney transplantations from 182 deceased donors, of which 25 (13.7%) were KO, 80 (43.9%) KL, and 77 (42.3%) MO. DGF was higher in MO retrievals compared with KL and KO (25.8% vs 24% vs 20.5%), though without reaching significance (P = .81). EGF at 3 months was 17.6% in KO compared with 10.5% in KL and 5.3% in MO (P = .2). Regarding DGF, in the multivariate analysis, donor age (P = .049) and donor sex (P = .029) appeared to be related to DGF. There were no differences by type of retrieval. Multivariate logistic regression analysis established a significant relationship between KO retrieval and EGF at 3 months (P = .005) compared with MO., Conclusions: Early graft function at 3 months decreases when the allograft is from KO retrievals compared with MO, probably related to the more unfavorable characteristics of these donors and their corresponding recipients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: This present study has aimed to assess the state of acute phase markers and oxidative stress in patients with kidney stones., Material and Methods: A prospective study was carried out on 100 patients with kidney stones and 25 healthy controls. Albumin, ß2 microglobulin, Gamma-glutamyl transpepsidase, Lactate dehydrogenase, Tumor necrosis factor alpha, Interleukin 1 and Interleukin-6 were evaluated as acute phase markers and lipid peroxidation products, Superoxide dismutase and Glutathione peroxidase levels acted as oxidative stress markers., Results: An increase in renal cell damage markers as expressed by the ß2 microglobulin (p=0.04), albumin (p=0.004), Lactate dehydrogenase (p=0.001) and Gamma glutamyl transpepsidasa (p=0.01) was observed in the patient group. There was a direct correlation between levels of ß2 microglobulin and stone size (r=0.3, p=0.03). The association between stone size and cytokine activation was observed to be stronger in patients with staghorn calculi. In these patients, Tumor necrosis factor alpha (p=0.011), Interleukin 1 (p=0.004) and Interleukin 6 (p=0.004) were significantly higher. Patients with stones in the urinary tract showed data of significantly higher oxidative stress, expressed as an increase in levels of lipid peroxidation products (p=0.03) and a decrease in the antioxidant activity of Superoxide dismutase (p=0.03) and Glutathione peroxidase (p=0.002)., Conclusions: Patients undergoing urolithiasis showed an elevation of acute phase markers, associated with oxidative stress as expressed by an increase in lipid peroxidation products and a decrease in the antioxidant enzyme activity., (Copyright © 2011 AEU. Published by Elsevier Espana. All rights reserved.)

Objectives: Many factors affect the graft and patient survival on the renal transplant outcome. These factors depend so much of the recipient and donor. We accomplished a study trying to circumvent factors that depend on the donor. We checked the paired kidneys originating of a same donor cadaver., Patients and Method: We examined the risk factors in the evolution and follow-up in 278 couples of kidney transplant. We describe their differences, significance, the graft and patient survival, their functionality in 3 and 5 years and the risk factors implicated in their function. We study immunogenic and no immunogenic variables, trying to explain the inferior results in the grafts that are established secondly. We regroup the paired kidneys in those that they did not show paired initial function within the same couple., Results: The results yield a discreet deterioration in the graft and patient survival for second group establish, superior creatinina concentration, without obtaining statistical significance. The Cox regression study establishes the early rejection (inferior to three months) and DR incompatibility values like risk factors., Conclusions: This model of paired kidneys would be able to get close to best-suited form for risk factors analysis in kidney transplant from cadaver donors, if more patients examine themselves in the same way. The paired kidneys originating from the same donor do not show the same function in spite of sharing the same conditions of the donor and perioperative management.

Background: Fine-needle aspiration cytology is frequently used for differential diagnosis of neck masses of unknown origin. Inconclusive and even false-negative results are not uncommon., Aim: To evaluate the utility of thyroglobulin (Tg) measurement in fine-needle aspirates (FNA-Tg) for detecting cervical lymph node (CLNs) metastases from differentiated thyroid carcinomas., Methods: An ultrasound-guided fine-needle aspiration was done in 67 patients with 83 suspicious enlarged CLNs to obtain material for cytology and Tg measurement in the needle washout, using an immunometric chemiluminescent assay. Measurement of anti-Tg antibodies (FNA-TgAb) was also carried out in half of all the aspirates. Subjects were divided into two groups: one of 16 patients awaiting thyroidectomy and the other of 51 patients in follow-up after surgery., Results: The first group of patients had positive FNA biopsy (FNAB-Tg) in 14 out of the 18 studied CLNs with a range of 3.2-43 352 ng/ml, while FNAB-cytology indicated metastasis in only 8 out of the 14 CLNs with positive histology. A total of 65 CLNs were studied in the follow-up group. Lymphadenectomy was performed in 23 patients and 28 aspirated CLNs were removed. Histology confirmed the diagnosis of metastasis suggested by FNAB-Tg in 20 CLNs and of reactive lymphadenitis in the remaining 8 CLNs. FNAB-cytology was positive in only 11 CLNs. Sensitivity of FNAB-Tg was not affected by the studied FNAB-TgAb., Conclusions: The FNAB-Tg achieved a sensitivity of 100% in both groups. FNAB-Tg is an easy and inexpensive technique which proved to increase the diagnostic of cytology in the early diagnosis of papillary carcinoma recurrence to CLN even in the presence of serum TgAb.

Objective: We retrospectively review the patients treated at our institution for renal cell carcinoma (RCC). We compare the patients classified in TNM state T1N0M0 in the 1997 revision with the 1992 one in order to determine survival differences. We divide patients in three size related groups and compare its survival rates., Material and Methods: We review 168 surgically treated patients. 72 of them were classified into T1N0M0 stage. We compare cancer-free survival in patients included in 1997 and 1992 T1 stage. We divide patients in three groups: 1-3 cm, 3-5 cm, 5-7 cm and compare respective cancer-free survival., Results: There is a survival difference between T1(1997)-T2(1992) (p = 0.478). There is an inferior survival in size group 5-7 cm compared with 1-3 cm and 3-5 cm ones (p = 0.02/0.0465)., Conclusions: In our patients, 1997 revision of T1 size supposes a descent of cancer-free survival compared with 1992 one. We consider a better stage limit under 5 cm, instead of actual 7 cm.

Objective: To assess the effectiveness of the combination of colchicine and vitamin E (which has anti-fibrotic, anti-mitotic and anti-inflammatory effects) in modifying the early stages of Peyronie's disease, by evaluating pain relief, correction of deformities and plaque size., Patients and Methods: In all, 45 patients were divided into two groups and treated from January 1998 to November 2001. Their mean (range) age was 53.4 (40-62) years, the time from onset of the disease < 6 months and they had penile deformity of < 30 degrees; no patient had erectile dysfunction. Twenty-two patients were given ibuprofen 400 mg/day for 6 months, whilst 23 received a combination of vitamin E 600 mg/day plus colchicine 1 mg every 12 h. Pain, plaque size and penile deformity were assessed at 6 months., Results: There were no statistically significant differences between the groups at baseline in age, time from onset of the disease until the initial evaluation or plaque size. Although the proportion of patients reporting pain relief was higher amongst those receiving colchicine plus vitamin E (91% vs 68%) this was not significantly different, but differences in plaque size and penile curvature were significant., Conclusions: The use of colchicine plus vitamin E during the early stages of Peyronie's disease (time from onset < 6 months) in patients with penile curvature of < 30 degrees and no erectile dysfunction is an effective and well-tolerated way to stabilize the disease. A more extensive study is needed, comparing these results with other oral therapies.

We report on two new cases of encrusted pielitis, a lithiasic disease of infectious ethiology--Corynebacterium of D group-. The clinic diagnostic is difficult and this disease develops in immunosuppressed patients, mainly in renal transplanted ones. One of our two cases is diagnosed in a patient with a transplanted kidney and the other one develops the disease within her native kidneys. We remark on the clinic features and therapeutic options.

Objective: To determine if the morphologic subgrouping of grade I bladder tumors between papillary neoplasm of low malignant potential and low grade papillary carcinoma is of clinical and survival value., Material and Methods: All 257 consecutive patients diagnosed of superficial bladder cancer between 1990 and 1995 in HU Reina Sofia of Cordoba were reviewed and further reclassified according to WHO/ISUP consensus classification of urothelial neoplasms of the bladder. Of the tumors 12 were urothelial papilloma, 51 were papillary neoplasm of low malignant potential, 43 were low grade papillary carcinoma Ta, 65 were low grade papillary carcinoma T1 and 37 were high grade papillary carcinoma. Eleven patients were reevaluated as T2 tumors and 38 (14.8%) were lost of control. All patients were reviewed with a follow-up at least of 5 years. We compare the results between groups with Fisher test and the risk factors for recurrence and progression are analyzed by multivariate analysis (Odds ratio). The survival function was calculated using Kaplan-Meier estimates and compared with the log-rank test., Results: There are no differences between groups respect the age or sex distribution. The differences in the multiplicity are not significant and only the mean size is higher in papillary low grade carcinoma. About the risk factors for recurrence and progression of the disease, only is significative the tumor size. Rarely, the use of chemotherapy seems to play a role in the recurrence. There are no differences in recurrence and progression between the groups, although the percentages are always higher in the papillary low grade carcinoma group., Conclusions: There are enough clinical differences between the two groups and we consider them as distinct pathologic entities. Only the higher tumoral size is prognostic factor in each group. We think that the use of chemotherapy must be avoided in this low grade bladder tumors.

Objective: To assess the safety and efficacy of sildenafil citrate in renal transplant patients with erectile dysfunction, as up to half of men with renal failure may be affected and only 60-75% recover potency after transplantation., Patients and Methods: Fifty patients with erectile dysfunction and a functioning renal transplant were treated using sildenafil (mean age 54 years, mean time on dialysis 35 months, mean time from transplantation 20 months). The hypogastric artery was not used during transplantation in any patient. Sildenafil citrate was prescribed at doses of 25 or 50 mg depending on baseline creatinine values and on the response, and plasma levels of cyclosporin/FK506 were monitored., Results: Thirty patients (60%) had a satisfactory response, with a mean time on dialysis of 23 months. Six patients (12%) did not take the sildenafil and in 14 (28%) the drug was ineffective. The mean time on dialysis in this group was 43 months. Six patients (12%) had side-effects that in no case led to withdrawal of treatment. Plasma levels of cyclosporin/FK506 remained within the safety and efficacy limits in all patients., Conclusions: Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction is an effective and safe option, with few side-effects. Plasma levels of immunosuppressants are unchanged. The response was more effective in patients with a shorter time on dialysis, as penile vascular disease is less advanced.

Renal abscess is a very rare complication of HIV infection, usually occurs in patients with severe immune deficiency. The immune status is the main factor that predict disease advancement. Highly activate antiretroviral therapy (HAART) improve the CD4 cell count. We present a case of renal abscess for Aspergillus niger in a HIV+ patient who complained of right flank mass and fever. We review relevant literature and the management of these patients.

We report on a case of fully gas-filled bladder with no evidence of intramural gas, fistula between bladder and gastrointestinal tract or instrumentation. The patient is diagnosed of a diabetic neurogenic bladder. We comment the causes of this rare finding and its relation with emphysematous cystitis.

We report on new case of a rare vesical tumour. We result the importance of immunohistochemistry and ultrastructural study to support the diagnosis of malignant fibrous histiocytoma of the urinary bladder. There has been described another 16 cases of this tumour in the literature, however, only four of them -five with ours- reports an extensive immunohistochemical and ultrastructural study. The rarity of vesical localization of this tumour may delay its diagnosis. It must be supported by a immunohistochemistry and/or ultrastructural study, in order to differentiate from other tumours with fibrohistiocytoma-like pattern: leiomyosarcoma and sarcomatoid carcinoma of the bladder. After radical removal of tumour, adjuvant therapy is recommended both systemic chemotherapy and local radiotherapy, although survival rates are over 5.3 months after first therapeutical actuation.

Objectives: We report on four new cases of Wolfram's Syndrome. We emphasize in urological aspects of this disease., Patients and Methods: Three male siblings. The other patient is also a male, without familiar relation with the other ones. All four patients presents different levels of urological alterations, mainly urinary collecting system dilation and decrease in detrusor muscle contractility., Conclusions: Urological findings are cardinal aspects in Wolfram syndrome. Due to its high frequency and prognostic value in natural history of disease. Urological disease seems to be within a systemic neurological tissues affectation of etiology that remains unknown.

High grade (PIN AG) intraepithelial neoplasia of the prostate is a likely precursor of prostate adenocarcinoma (PA) because of their association. Since the risk to suffer PA increases in patients with no previous PIN AG, its finding requires an arduous search for PA. This paper reviews the incidence of PIN AG in 499 histological studies in prostate transrectal biopsies, prostate TUR and adenomectomy specimens and radical prostatectomy (RP) sections. Evaluation of data obtained, type of presentation and association to prostate carcinoma, indicating the approach taken in the various cases.

We describe a case report in which is shown an extensive extravasation of contrast media from urethra lumen following a retrograde urethrocystography. It is shown filling of cavernous system and, at once, iliac vessels and inferior cava. Later X ray plates demonstrates entire collecting system due to the renal contrast excretion.

The emergence of acquired immunodeficiency syndrome has changed the natural history of tuberculosis which has now become the second most common infection associated to human immunodeficiency virus infection. It is only rarely that a tuberculous infection has an urogenital location, and extrapulmonary locations are generally related to severe immunosuppression. This paper presents one case of tuberculous orchitis that presented as the clinical onset of acquired immunodeficiency syndrome. Discussion of the clinical evolution and the therapeutic approach that consisted in orchiectomy associated to treatment with tuberculostatics.

Extragonadal primary tumors are uncommon and account for 3 to 5% of all germ cells neoplasias. Preferentially found in middle line structures, such tumors are frequently in an advanced stage when diagnosed. Differentiation between primary extragonadal tumors and metastasis of testicular primary tumors is essential, but may be difficult in many instances.

In our setting, the association between bilharziasis and bladder cancer is uncommon. However, the presence of recurrent haematuria in a patient from an endemic area of bilharziasis (east of Africa and Middle East), is highly suspicious of this disease. Lack of an adequate treatment by using anthelminthic drugs during the acute phase of disease, might lead to the onset of chronic bladder lesions and, on occasion, bladder cancer, of the epidermoid type in the majority of cases. Because of the high mortality and aggressivity of this type of cancer, an early diagnosis and appropriate treatment of acute lesions is mandatory. We report a 40-year-old black male from Senegal, presenting chronic bladder schistosomiasis and infiltrative epidermoid carcinoma of the bladder, diagnosed and treated in our department by palliative cystectomy.

The hydatid disease is a common condition in endemic countries, generally involving the liver or the lungs. Genitourinary tract involvement is quite uncommon, and the organ most usually affected is the kidney. A retrovesical location is even more rare. The present paper contributes one case with no evidence of hydatidosis in any other abdominal organ and describes the diagnostic and therapeutic protocol followed.

Renal trauma accounts for more than 50% of all genitourinary trauma cases, nearly 90% of them corresponding to blunt trauma. Incidence is higher in male (3:1 ratio); is more frequent between the second and third decades; and predominantly affects the left side. Our group analyzed 89 cases of blunt renal trauma seen in our service between 1983 and 1996 with the purpose of determining the choice imaging studies, indications and type of management. Based on severity, injuries were rated in 5 grades using the classification of the Organic Injuries Survey Committee (OIS) from the American Association of Surgery in Trauma (AAST). We analyzed the etiology, clinical findings, prior renal conditions, associated injuries, radiologic studies and treatment instituted. CAT was considered the choice diagnostic technique for trauma rating since it permits greater definition of renal injury grade, as well as the associated abdominal and thoracic injuries. Most renal traumas were mild in severity, and evolved favourably with conservative treatment. In renal trauma grades IV and V, surgery is the recommended therapeutic approach, always preferring the most conservative criteria.

Neonatal renal candidiasis is a rare complication but serious, associated with prematurity, immunodeficiency, parenteral nutrition and other risk factors, with a mortality rate until 50%. We describe a neonate premature of 28 weeks who developed septicaemia by Candida, complicated with bilateral ureterohydronephrosis and intrapelvic fungus ball. The patient was managed by bilateral nephrostomy drainage and amphotericin B local irrigation, anyway with systemic amphotericin B together with oral fluconazol, needing subsequently bilateral open surgery and external drainage. The infection was eradicated, reaching the patient a gradual healing.