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Objetivos: Evaluar la prevalencia de calcificación vascular y fracturas vertebrales en una cohorte de pacientes sometidos a trasplante renal, y su asociación con mortalidad por todas las causas y disfunción del injerto, así como la relación con parámetros bioquímicos del metabolismo óseo y mineral. Material y métodos: Estudio prospectivo, observacional, unicéntrico, en el que se incluyeron 405 pacientes sometidos a trasplante renal, con recogida de parámetros clínicos, bioquímicos, epidemiológicos y de calcificación vascular radiológica y fracturas vertebrales mediante radiografía simple en el momento del trasplante, con un seguimiento mínimo de dos años, evaluando mortalidad cardiovascular y por todas las causas y descenso del filtrado glomerular. Se dispuso además de 39 estudios de densitometría ósea realizados en los meses previos al trasplante. Resultados: La supervivencia de los pacientes fue significativamente menor en el grupo de pacientes con calcificación vascular (131±1,5 meses sin calcificación frente a 110±3,5 meses con calcificación vascular, p

Patients with non-muscle-invasive bladder cancer (NMIBC) in the intermediate and high-risk groups must receive adjuvant treatment with intravesical Bacillus Calmette-Guérin (BCG) following transurethral resection (TUR), as it reduces the risk of recurrence and presumably the risk of progression as well. Optimization of BCG efficacy is achieved by administering maintenance therapy. However, since many immunological aspects of the mechanism of action of BCG in the bladder remain unknown, the implementation of the optimal dose, number of instillations, strains and adequate maintenance regimen over the last decades has been heterogeneous. Additionally, this has hindered the interpretation of efficacy in terms of oncologic outcomes. This, together with the shortages of BCG in recent years, have forced scientific societies to adapt their clinical practice guidelines and modify their protocols of adjuvant treatment with BCG. This includes changes to strains, doses, and maintenance during this period of time. This consensus document evaluates the current status of adjuvant BCG treatment and the implications of BCG supply availability in the treatment of patients with NMIBC. It also addresses the implementation of novel therapies that will improve cancer prognosis and the quality of life of patients with NMIBC in the future., (Copyright © 2024 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: We report the results of the 2023 Spanish catheter ablation registry., Methods: Procedural data were collected and incorporated into the REDCap platform by all participating centers through a specific form., Results: There were 104 participating centers in 2023 compared with 103 in 2022. In 2023, the total number of ablation procedures was 26 207, indicating a stabilization of the increase observed in 2022 following the pandemic. The increase was mainly due to procedures for atrial fibrillation (AF), with a total of 9942 ablations, representing 38% of all substrates. Notably, pulse-field ablation represented 10.3% of all AF ablation procedures, leading single-shot ablation strategies to outnumber point-by-point AF ablation for the first time in the history of the registry. Cavotricuspid isthmus ablation remained the second most targeted substrate (19% of all substrates, n=5067). The overall acute success rate remained high (97%), with a downward trend in the complication rate (1.6% vs 1.8% in 2022) and mortality rate (0.03%; n=7). Compared with 2022, there was a significant increase in procedures performed using electro-anatomical mapping and zero-fluoroscopy techniques for cavotricuspid isthmus ablation (52% vs 26%), AV node re-entrant tachycardia (48% vs 34%), and accessory pathways (62% vs 22%). We registered 466 ablations in pediatric patients., Conclusions: The data indicate a stabilization in the post-pandemic increase in ablation procedures, with an absolute and relative increase in AF as the predominant substrate. Success rates remained stable with a modest reduction in complication and mortality rates., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Vascular calcification has a global health impact that is closely linked to bone loss. The Receptor Activator of Nuclear Factor Kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, fundamental for bone metabolism, also plays an important role in vascular calcification. The Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a novel receptor for RANKL, regulates bone remodeling, and it appears to be involved in vascular calcification. Besides RANKL, LGR4 interacts with R-spondins (RSPOs), which are known for their roles in bone but are less understood in vascular calcification. Studies were conducted in rats with chronic renal failure fed normal or high phosphorus diets for 18 weeks, with and without control of circulating parathormone (PTH) levels, resulting in different degrees of aortic calcification. Additionally, vascular smooth muscle cells (VSMCs) were cultured under non-calcifying (1 mM phosphate) and calcifying (3 mM phosphate) media with different concentrations of PTH. To explore the role of RANKL in VSMC calcification, increasing concentrations of soluble RANKL were added to non-calcifying and calcifying media. The effects mediated by RANKL binding to its receptor LGR4 were investigated by silencing the LGR4 receptor in VSMCs. Furthermore, the gene expression of the RANK/RANKL/OPG system and the ligands of LGR4 was assessed in human epigastric arteries obtained from kidney transplant recipients with calcification scores (Kauppila Index). Increased aortic calcium in rats coincided with elevated systolic blood pressure, upregulated Lgr4 and Rankl gene expression, downregulated Opg gene expression, and higher serum RANKL/OPG ratio without changes in Rspos gene expression. Elevated phosphate in vitro increased calcium content and expression of Rankl and Lgr4 while reducing Opg . Elevated PTH in the presence of high phosphate exacerbated the increase in calcium content. No changes in Rspos were observed under the conditions employed. The addition of soluble RANKL to VSMCs induced genotypic differentiation and calcification, partly prevented by LGR4 silencing. In the epigastric arteries of individuals presenting vascular calcification, the gene expression of RANKL was higher. While RSPOs show minimal impact on VSMC calcification, RANKL, interacting with LGR4, drives osteogenic differentiation in VSMCs, unveiling a novel mechanism beyond RANKL-RANK binding.

Background: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of chronic kidney disease-mineral and bone disorders (CKD-MBD) and bone fragility fractures in the COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) project., Methods: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 haemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and parathyroid hormone (PTH) (exposure), was assessed using standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables., Results: During a median follow-up of 24 months, 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months, respectively. Baseline serum phosphate >6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models {hazard ratio (HR) 1.53 [95% confidence interval (CI) 1.10-2.13] and HR 1.44 (95% CI 1.02-2.05)}. The significant association persisted after competitive risk analysis [subHR 1.42 (95% CI 1.02-1.98)] but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH >800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis., Conclusions: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in haemodialysis patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Metabolic bone diseases cover a broad spectrum of disorders that share alterations in bone metabolism that lead to a defective skeleton, which is associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, with TP53 being one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke, and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in humanized Tp53 Arg72Pro knock-in mice. This work reports on the influence of the TP53 Arg72Pro polymorphism in bone microarchitecture, OPG expression, and apoptosis bone status. The results show that the proline variant of the TP53 Arg72Pro polymorphism (Pro72-p53) is associated with deteriorated bone tissue, lower OPG/RANK ratio, and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker that can be used to identify individuals with an increased risk of suffering metabolic bone alterations.

Background: Electrical isolation of pulmonary veins (PV) with high-power short-duration (HPSD) radiofrequency application (RFa) may reduce the duration of atrial fibrillation (AF) ablation, without compromising the procedural efficacy and safety in comparison with the conventional approach. This hypothesis has been generated in several observational studies; the POWER FAST III will test it in a randomized multicenter clinical trial., Methods: It is a multicenter randomized, open-label and non-inferiority clinical trial with two parallel groups. AF ablation using 70 W and 9-10 s RFa is compared with the conventional technique using 25-40 W RFa guided by numerical lesion indexes. The main efficacy objective is the incidence of atrial arrhythmia recurrences electrocardiographically documented during 1-year follow-up. The main safety objective is the incidence of endoscopically detected esophageal thermal lesions (EDEL). This trial includes a substudy of incidence of asymptomatic cerebral lesions detected by magnetic resonance imaging (MRI) after ablation., Results: A randomized clinical trial compares for the first time high-power short-duration and conventional ablation in order to obtain data about the efficacy and safety of the high-power technique in an adequate methodological context., Conclusions: The results of the POWER FAST III could support the use of the high-power short-duration ablation in clinical practice., Registration: ClinicalTrials.gov: NTC04153747., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Vascular calcification (VC) is a common complication in patients with chronic kidney disease which increases their mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some of the main redox regulators, such as catalase, the main scavenger of H 2 O 2 , remains unclear. In the present study, epigastric arteries of kidney transplant recipients, a rat model of VC, and an in vitro model of VC exhibiting catalase (Cts) overexpression were analysed. Pericalcified areas of human epigastric arteries had increased levels of catalase and cytoplasmic, rather than nuclear runt-related transcription factor 2 (RUNX2). In the rat model, advanced aortic VC concurred with lower levels of the H 2 O 2 -scavenger glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in total levels of RUNX2. However, Cts VMSCs also exhibited a lower percentage of the nucleus stained for RUNX2 in response to calcifying media. In this early model of VC, we did not observe a dysregulation of the mitochondrial redox state; instead, an increase in the general redox state was observed in the cytoplasm. These results highlight the complex role of antioxidant enzymes as catalase by regulation of RUNX2 subcellular location delaying the onset of VC.

Background: Cardiac resynchronization therapy (CRT) via permanent His bundle pacing (pHBP) has gained acceptance globally, but robust studies comparing pHBP-CRT with classic CRT are lacking. In this study, we aimed to compare the improvement in left ventricular ejection fraction (LVEF) after pHBP-CRT versus classic CRT., Methods: This was a single-center study comparing a prospective series of pHBP-CRT with a historical series of CRT via classic biventricular pacing (BVP). Patients with non-ischemic cardiomyopathy, baseline LVEF < 35%, left bundle branch block (LBBB), and CRT indications were selected., Results: Fifty-one patients underwent classic CRT and 52 patients underwent pHBP-CRT. In the classic CRT group, the median (interquartile range) basal LVEF was 30% (IQR, 29-35%) before implantation and 40% (35-48%) at follow-up. In the pHBP-CRT group, the median basal LVEF was 30% (28-34%) before implantation and 55% (45-60%) at follow-up, with significant differences between both modalities at follow-up (p = 0.001). The median long term His recruitment threshold with LBBB correction was 1.25 (1-2.5) V at 0.4 ms in cases of pHBP-CRT, compared to a left ventricular coronary sinus threshold of 1.25 (1-1.75) V in cases of classic CRT (p = 0.48). After CRT, the median paced QRS was 135 (120-145) ms for pHBP-CRT versus 140 (130-150) ms for BVP-CRT (p = 0.586)., Conclusions: The improvement in LVEF was superior with pHBP-CRT than with classic CRT. The thresholds at follow-up were similar in both groups., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Usually, after an abnormal level of serum prostate-specific antigen (PSA) or digital rectal exam, men undergo a prostate needle biopsy. However, the traditional sextant technique misses 15-46% of cancers. At present, there are problems regarding disease diagnosis/prognosis, especially in patients' classification, because the information to be handled is complex and challenging to process. Matrix metalloproteases (MMPs) have high expression by prostate cancer (PCa) compared with benign prostate tissues. To assess the possible contribution to the diagnosis of PCa, we evaluated the expression of several MMPs in prostate tissues before and after PCa diagnosis using machine learning, classifiers, and supervised algorithms. A retrospective study was conducted on 29 patients diagnosed with PCa with previous benign needle biopsies, 45 patients with benign prostatic hyperplasia (BHP), and 18 patients with high-grade prostatic intraepithelial neoplasia (HGPIN). An immunohistochemical study was performed on tissue samples from tumor and non-tumor areas using specific antibodies against MMP -2, 9, 11, and 13, and the tissue inhibitor of MMPs -3 (TIMP-3), and the protein expression by different cell types was analyzed to which several automatic learning techniques have been applied. Compared with BHP or HGPIN specimens, epithelial cells (ECs) and fibroblasts from benign prostate biopsies before the diagnosis of PCa showed a significantly higher expression of MMPs and TIMP-3. Machine learning techniques provide a differentiable classification between these patients, with greater than 95% accuracy, considering ECs, being slightly lower when considering fibroblasts. In addition, evolutionary changes were found in paired tissues from benign biopsy to prostatectomy specimens in the same patient. Thus, ECs from the tumor zone from prostatectomy showed higher expressions of MMPs and TIMP-3 compared to ECs of the corresponding zone from the benign biopsy. Similar differences were found for expressions of MMP-9 and TIMP-3, between fibroblasts from these zones. The classifiers have determined that patients with benign prostate biopsies before the diagnosis of PCa showed a high MMPs/TIMP-3 expression by ECs, so in the zone without future cancer development as in the zone with future tumor, compared with biopsy samples from patients with BPH or HGPIN. Expression of MMP -2, 9, 11, and 13, and TIMP-3 phenotypically define ECs associated with future tumor development. Also, the results suggest that MMPs/TIMPs expression in biopsy tissues may reflect evolutionary changes from prostate benign tissues to PCa. Thus, these findings in combination with other parameters might contribute to improving the suspicion of PCa diagnosis.

Prostate cancer (PCa) is a common cancer among males globally, and its occurrence is growing worldwide. Clinical decisions about the combination of therapies are becoming highly relevant. However, this is a heterogeneous disease, ranging widely in prognosis. Therefore, new approaches are needed based on tumor biology, from which further prognostic assessments can be established and complementary strategies can be identified. The knowledge of both the morphological structure and functional biology of the PCa stroma compartment can provide new diagnostic, prognostic or therapeutic possibilities. In the present review, we analyzed the aspects related to the tumor stromal component (both acellular and cellular) in PCa, their influence on tumor behavior and the therapeutic response and their consideration as a new therapeutic target.

Recent investigations point at the stromal microenvironment to assess additional diagnostic information and provide new therapeutic targets in cancer. The aim of the study was to contribute to the characterization of the phenotype of cancer-associated fibroblasts (CAFs) in prostate cancer (PCa) compared with normal prostate-associated fibroblasts (NAFs) and fibroblasts from benign prostatic hyperplasia (BPH). Three patient populations were prospectively recruited: 23 patients with new localized PCa, 14 patients with advanced PCa treated with androgenic deprivation therapy (ADT), and 7 patients with BPH. Gene expression of 20 stroma-derived factors, including the androgen receptor (AR), chaperones (HSPA1A and HSF1), growth factors (FGF2, FGF7, FGF10, HGF, PDGFB, and TGFβ), proteins implicated in invasion (MMP2, MMP9, and MMP11), inflammation (IL6, IL17RB, NFκB, and STAT3), and in-stroma/epithelium interaction (CDH11, CXCL12, CXCL14, and FAP), was evaluated. Localized PCa CAFs showed a significant higher expression of FGF7, IL6, MMP2, and MMP11 compared with NAFs or IL17RB compared with BPH fibroblasts, but significantly lower expression of FGF10 and IL17RB compared with NAFs or CXCL14 compared with BPH fibroblasts. In addition, CAFs from ADT-resistant PCa showed significantly higher MMP11 and NFκB but significant lower TGFβ expression compared with CAFs from ADT-sensitive tumors. Our results contribute to defining the CAFs phenotypes associated to PCa progression, which may contribute to the diagnosis and design of alternative therapies in PCa.

Bone is crucial for the support of muscles and the protection of vital organs, and as a reservoir of calcium and phosphorus. Bone is one of the most metabolically active tissues and is continuously renewed to adapt to the changes required for healthy functioning. To maintain normal cellular and physiological bone functions sufficient oxygen is required, as evidence has shown that hypoxia may influence bone health. In this scenario, this review aimed to analyze the molecular mechanisms involved in hypoxia-induced bone remodeling alterations and their possible clinical consequences. Hypoxia has been associated with reduced bone formation and reduced osteoblast matrix mineralization due to the hypoxia environment inhibiting osteoblast differentiation. A hypoxic environment is involved with increased osteoclastogenesis and increased bone resorptive capacity of the osteoclasts. Clinical studies, although with contradictory results, have shown that hypoxia can modify bone remodeling.

We investigated changes in symptoms and quality of life (QoL) in men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) receiving the hexanic extract of Serenoa &nbsp; repens (HESr) and compared results with a matched group on watchful waiting (WW). Data was from a real-world, open-label, prospective, multicenter study. This sub-group analysis included patients with moderate-to-severe symptoms receiving either the HESr 320 mg/daily for six months (HESr) or who remained untreated for LUTS/BPH (WW). Changes in urinary symptoms and QoL were measured by IPSS and BII questionnaires. Two statistical approaches (iterative matching and propensity score pairing) were used to maximize between-group comparability at baseline. Tolerability was assessed in the HESr group. After iterative matching, data for analysis was available for 783 patients (102 WW, 681 HESr). IPSS scores improved by a mean (SD) of 3.8 (4.4) points in the HESr group and by 2.2 (4.5) points in the WW group ( p = 0.002). Changes in BII score were 1.8 (2.4) points and 1.0 (2.2) points, respectively ( p < 0.001). Three patients (0.9%) treated with the HESr reported mild adverse effects. Moderate-severe LUTS/BPH patients treated for six months with the HESr showed greater improvements in symptoms and QoL than matched patients on WW, with a very low rate of adverse effects.

The vitamin D receptor (VDR), a member of the nuclear receptor superfamily of transcriptional regulators, is crucial to calcitriol signalling. VDR is regulated by genetic and environmental factors and it is hypothesised that the response to vitamin D supplementation could be modulated by genetic variants in the VDR gene. The best studied polymorphisms in the VDR gene are Apal (rs7975232), BsmI (rs1544410), Taql (rs731236) and Fokl (rs10735810). We conducted a systematic review and meta-analysis to evaluate the response to vitamin D supplementation according to the BsmI, TaqI, ApaI and FokI polymorphisms. We included studies that analysed the relationship between the response to vitamin D supplementation and the genotypic distribution of these polymorphisms. We included eight studies that enrolled 1038 subjects. The results showed no significant association with the BsmI and ApaI polymorphisms ( p = 0.081 and p = 0.63) and that the variant allele (Tt+tt) of the TaqI polymorphism and the FF genotype of the FokI variant were associated with a better response to vitamin D supplementation ( p = 0.02 and p < 0.001). In conclusion, the TaqI and FokI polymorphisms could play a role in the modulation of the response to vitamin D supplementation, as they are associated with a better response to supplementation.

Introduction and Objective: The COVID-19 pandemic has brought about changes in the management of urology patients, especially those with prostate cancer. The aim of this work is to show the changes in the ambulatory care practices by individualized telematic care for each patient profile., Materials and Methods: Articles published from March 2020 to January 2021 were reviewed. We selected those that provided the highest levels of evidence regarding risk in different aspects: screening, diagnosis, treatment and follow-up of prostate cancer., Results: We developed a classification system based on priorities, at different stages of the disease (screening, diagnosis, treatment and follow-up) to which the type of care given, in-person or telephone visits, was adapted. We established 4 options, as follows: in priority A or low, care will be given by telephone in all cases; in priority B or intermediate, if patients are considered subsidiary of an in-person visit after telephone consultation, they will be scheduled within 3 months; in priority C or high, patients will be seen in person within a margin from 1 to 3 months and in priority D or very high, patients must always be seen in person within a margin of up to 48 h and considered very preferential., Conclusions: Telematic care in prostate cancer offers an opportunity to develop new performance and follow-up protocols, which should be thoroughly analyzed in future studies, in order to create a safe environment and guarantee oncologic outcomes for patients., (Copyright © 2021. Published by Elsevier España, S.L.U.)

In a subset analysis of data from a 6-month, multicenter, non-interventional study, we compared change in symptoms and quality of life (QoL), and treatment tolerability, in men with moderate to severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) receiving tamsulosin (TAM, 0.4 mg/day) or the hexanic extract of Serenoa repens (HESr, 320 mg/day) as monotherapy. Symptoms and QoL were assessed using the IPSS and BII questionnaires, respectively. Patients in the treatment groups were matched using two statistical approaches (iterative and propensity score matching). Within the iterative matching approach, data was available from a total of 737 patients (353 TAM, 384 HESr). After 6 months, IPSS scores improved by a mean (SD) of 5.0 (4.3) points in the TAM group and 4.5 (4.7) points in the HESr group (p = 0.117, not significant). Improvements in QoL were equivalent in the two groups. TAM patients reported significantly more adverse effects than HESr patients (14.7% vs 2.1%; p < 0.001), particularly ejaculation dysfunction and orthostatic hypotension. These results show that HESr is a valid treatment option for men with moderate/severe LUTS/BPH; improvements in urinary symptoms and QoL were similar to those observed for tamsulosin, but with considerably fewer adverse effects., (© 2021. The Author(s).)

Introduction: In patients with uncontrolled atrial fibrillation, atrioventricular (AV) node ablation after permanent His bundle pacing (p-HBP) could be a therapeutic option for heart rate (HR) control. We aimed to demonstrate the advantages of AV node ablation with p-HBP, and to describe its effectiveness and safety., Methods: This descriptive observational study included patients with uncontrolled permanent atrial arrhythmias who were candidates for HR control (January 2019 to July 2020) and underwent p-HBP and AV node ablation., Results: A total of 39 patients were included. The median left ventricular ejection fraction (LVEF) was 55% (45-60); 46.1% in NYHA class II and 43.6% in NYHA class III. p-HBP was achieved in 92.3% (n = 36), and AV node ablation was successfully performed in all patients. The LVEF improved in patients with reduced LVEF (baseline, 35% [23.8-45.3%]; follow-up, 40% [35-56.5%], p < 0.05); the NYHA class also showed improvement (baseline, 71.4% patients in class III and 7.1% in class II, and at follow-up, 78.6% patients in class II and 14.3% in class I). In patients with previously normal LVEF, LVEF remained stable; nevertheless, a significant NYHA class improvement was observed (baseline, 63.6% class II and 31.8% class III patients; follow-up, 54.5% class I and 45.5% class II patients). The His thresholds and lead parameter values did not significantly change during the follow-up and remained stable., Conclusions: In patients with uncontrolled atrial arrhythmias who underwent AV node ablation after p-HBP, the NYHA class improved and the LVEF increased in those with reduced baseline LVEF. The values of pacing parameters were acceptable and remained stable during the follow-up., (© 2021 Wiley Periodicals LLC.)

The treatment of choice for high-risk non-muscle invasive bladder cancer (NMIBC) is bacillus Calmette-Guérin (BCG). However, when this fails, the indicated treatment is radical cystectomy. In recent years, trials are being developed with various drugs to avoid this surgery in patients with BCG failure. The aim of this article is to update the treatments under study for bladder preservation in this patient population. Non-systematic review, searching PubMed with the terms "Bladder cancer", "Non-muscle invasive bladder cancer", "NMIBC", "BCG", "BCG-refractory", "Mitomycin C", "MMC", "Hyperthermia", "Electromotive Drug Administration", "EMDA". We used the search engines clinicaltrials.gov and clinicaltrialsregister.eu to find clinical trials. The only intravesical drug approved by the Food and Drug Administration (FDA) for carcinoma in situ (CIS) after failure to BCG is Valrubicin. Recently, the FDA has approved intravenous Pembrolizumab, following the publication of preliminary data from the KEYNOTE-057 study. Atezolizumab has demonstrated similar preliminary efficacy results. Only microwave-induced chemohyperthermia and EMDA-MMC (Electromotive Drug Administration) are recognized as alternatives in European guidelines. Other options under investigation are taxanes and gemcitabine, alone or in combination, recombinant viruses and device-assisted intravesical chemohyperthermia. The results of new drugs are promising, with a large number of trials underway. Knowing the mechanisms of resistance to BCG is essential to explore new therapeutic options., (Copyright © 2020 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Permanent His bundle pacing (p-HBP) could be an alternative for traditional cardiac resynchronization therapy (CRT), but an important limitation is that p-HBP cannot always correct the left bundle branch block (LBBB). The purpose of this article is to assess electrocardiographic patterns of LBBB that can predict electrocardiographic response (QRS narrowing) to His bundle pacing., Methods: We designed a prospective descriptive study of patients with LBBB and CRT indication proposed for CRT by p-HBP. We analyzed the correlation between the different electrocardiographic patterns and the correction of conduction disturbance (LBBB)., Results: We included 70 patients. Pacing at the location where His bundle electrogram was recorded narrowed the QRS in 81.4% (n = 57). Basically, we identified two electrocardiographic patterns in lead V1: QS or rS. The QS pattern was a sensitivity of 56%, a specificity of 84.6%, and a positive predictive value (PPV) of 94.1% to predict the correction of the LBBB (area under the curve [AUC] = .70). In patients with rS pattern, a ratio between the descending and the ascending S wave component duration ≥0.64 was a very good predictor of the correction of the LBBB (AUC = .968); with a value ≥0.64, the sensitivity, specificity, and PPV was 92%, 100%, and 100%, respectively., Conclusions: In patients with LBBB and CRT indication, the QS pattern in lead V1 predicts the correction of the QRS with HBP. In the case of rS pattern in lead V1, the ratio descending/ascending S wave component duration has a strong correlation with the LBBB correction., (© 2020 Wiley Periodicals LLC.)

To investigate whether tamsulosin (TAM) and the hexanic extract of Serenoa repens (HESr) are more effective in combination than as monotherapy in men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Subset analysis of data from a 6-month, multicenter observational study. Patients received either tamsulosin (0.4 mg/day) or HESr (320 mg/day) alone or in combination. Primary endpoints were change in symptoms and quality of life. Tolerability was also assessed. Seven hundred and nine patients were available for intention to treat (ITT) analysis, 263 treated with tamsulosin, 262 with HESr, and 184 with TAM + HESr. After 6 months, International Prostate Symptom Score (IPSS) scores improved by a mean (standard deviation) of 7.2 (5.0) points in the TAM + HESr group compared to 5.7 (4.3) points with TAM alone and 5.4 (4.6) points with HESr ( p < 0.001). Quality of life showed greatest improvement with combination therapy ( p < 0.02). Adverse effects were reported by 1.9% of patients receiving HESr, 13.3% receiving TAM, and 12.0% receiving TAM + HESr ( p < 0.001). In men with moderate/severe LUTS/BPH, combination treatment with TAM + HESr produced more effective symptom relief and greater improvement in quality of life than with either treatment alone, with acceptable tolerability.

Background: Insulin may play a key role in bone metabolism, where the anabolic effect predominates. This study aims to analyze the relationship between insulin resistance and bone quality using the trabecular bone score (TBS) and three-dimensional dual-energy X-ray absorptiometry (3D-DXA) in non-diabetic postmenopausal women by determining cortical and trabecular compartments., Methods: A cross-sectional study was conducted in non-diabetic postmenopausal women with suspected or diagnosed osteoporosis. The inclusion criteria were no menstruation for more than 12 months and low bone mass or osteoporosis as defined by DXA. Glucose was calculated using a Hitachi 917 auto-analyzer. Insulin was determined using an enzyme-linked immunosorbent assay (EIA). Insulin resistance was estimated using a homeostasis model assessment of insulin resistance (HOMA-IR). DXA, 3D-DXA, and TBS were thus collected. Moreover, we examined bone parameters according to quartile of insulin, hemoglobin A1C (HbA1c), and HOMA-IR., Results: In this study, we included 381 postmenopausal women. Women located in quartile 4 (Q4) of HOMA-IR had higher values of volumetric bone mineral density (vBMD) but not TBS. The increase was higher in the trabecular compartment (16.4%) than in the cortical compartment (6.4%). Similar results were obtained for insulin. Analysis of the quartiles by HbA1c showed no differences in densitometry values, however women in Q4 had lower levels of TBS. After adjusting for BMI, statistical significance was maintained for TBS, insulin, HOMA-IR, and HbA1c., Conclusions: In non-diabetic postmenopausal women there was a direct relationship between insulin resistance and vBMD, whose effect is directly related to greater weight. TBS had an inverse relationship with HbA1c, insulin, and insulin resistance unrelated to weight. This might be explained by the formation of advanced glycosylation products (AGEs) in the bone matrix, which reduces bone deformation capacity and resistance, as well as increases fragility.

Metalloproteases (MMPs) and tissue inhibitor of metalloprotease-3 (TIMP-3) have been associated to the risk of having cancer and tumor aggressiveness. When facing the difficulties of prostate cancer diagnosis, the expression of MMPs and TIMP-3 in negative biopsies could be helpful to evaluate a diagnostic suspicion. Our objective is to carry out a comparative study of the expression of MMPs and TIMP-3 in previous negative biopsies and radical prostatectomies (RP)., Material and Methods: Retrospective analysis of a hospital-based cohort including 21 patients with suspicion of prostate carcinoma, whose expressions of MMP-2, 9, 11 and 13 and TIMP-3 were evaluated by immunohistochemistry in the tumor area from previous negative biopsies and RP., Results: Immunohistochemical staining values (Score) for MMPs (-11 and -13) and TIMP-3 showed no significant differences when comparing the areas of negative biopsies where tumors subsequently developed with those of the RP. However, we did observe a significant difference in the increased expression of MMP-2 (P=.002) and MMP-9 (P=.001) in the tumor area of the RP with respect to the corresponding area of the previous negative biopsy., Conclusions: Our data indicate a higher overall expression of MMP-2 and MMP-9 in the tumor area of the RP compared to the corresponding areas of the negative previous biopsy, which seems to be associated to the process of malignant transformation., (Copyright © 2019 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: Permanent His bundle pacing (p-HBP) can correct intraventricular conduction disorders and could be an alternative to traditional cardiac resynchronization therapy (CRT) via the coronary sinus. We describe the short-term impact of HBP on left ventricular ejection fraction (LVEF) and improvement of left intraventricular synchrony., Methods and Results: This prospective descriptive study, performed from January 2018 to February 2019, included patients with left bundle branch block (LBBB) and an CRT indication who were resynchronized by p-HBP. We used the Medtronic C315 His catheter or a combination of the CPS-Direct-Universal introducer, CPS-AIM™-Universal subselector (Abbot), and SelectSecure™ MRI-SureScan™ 3830 lead. Correction of the LBBB by HBP had been previously checked. At 1 month of follow-up, we analysed the quantification of LVEF and measurement of the delay of the septal wall with the posterior wall as a parameter of intraventricular synchrony. We included 48 patients with LBBB and an indication for CRT. With HBP, we corrected the LBBB in 81% of patients (n = 39), and we achieved cardiac resynchronization through permanent HBP in 92% of these patients (n = 36). Left ventricular ejection fraction and intraventricular mechanical resynchronization improved in all patients, which was demonstrated by echocardiography through the improvement of the delay of the septal wall with the posterior wall from 138 ms (range 131-151) to 41 ms (19-63)., Conclusion: There is early improvement after p-HBP in LVEF and left ventricular electromechanical synchronization in patients with LBBB, heart failure, and an indication for CRT., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: The increase of healthcare pressure in Emergency Departments compels us to have a better understanding of patients' characteristics and the pathology they consult for. This is the first study that estimates the waiting time in the emergency room and the factors that are independently related with hospital admission., Methods: Descriptive and retrospective study of 2.741 patients who were admitted to the Emergency Department with genitourinary symptoms in 2011. Clinical and epidemiological features were reviewed. A multivariable study was performed to identify the factors related with the final resolution of patients, recurrence emergency attendance, and waiting time in the emergency room., Results: Most of the patients were male (60.3%), being diagnosed with hematuria, acute urinary retention and genital pathology. Females complained more frequently for pyelonephritis, urinary tract infection and low-back pain. Male were hospitalized in greater proportion. Age, diagnosis of infection/sepsis or low-back pain, and yellow or orange MTS level were independent features for hospital admission. Also, in the univariate and multivariate study, age > 60 years (311 vs 220 min.), UTI/sepsis related diagnoses (300 vs 250 min.), and hospital admission as final resolution (440 vs 240 min.) had a significant influence in the waiting time in the Emergency Department., Conclusions: Age over 60 years, hospital admission as final resolution and infection/sepsis diagnosis were independent features for further waiting time in the Emergency Department. Persistent pain and symptoms of infection/sepsis behaved as independent features for hospital admission.

Introduction: New imaging studies have appeared in recent years for the diagnosis and follow-up of metastatic urological tumours., Material and Methods: A total of 41 patients were reviewed with suspected recurrence of a urothelial or kidney tumour, analysing the diagnostic performance of PET-CT scans undertaken between 2013 and 2016., Results: We collected 17 urothelial tumours and 24 renal tumours, with a median follow-up of 30 months. A total of 39.3% of the urothelial tumours were high grade and 29.3% of the kidney tumours were clear cell Fuhrman II. As a whole, the imaging studies detected recurrences in 34 patients. CT was positive in 83% of the patients, while the PET scan was positive in 75.6%, CT/PET coincidence was 50%. The PET scan detected further disease in 41% of the cases compared to 5% by CT. This resulted in a change of therapeutic strategy in 40% of the patients. Sensitivity, specificity, positive predictive value and negative predictive value for the CT and the PET scans were 92% and 92%, 57% and 100%, 92% and 100%, and 57% and 70% respectively., Conclusion: The PET scan showed similar sensitivity for urological tumours to the standard imaging techniques but with higher specificity, positive predictive value and negative predictive value. This led to a change in treatment strategy for 40% of the patients in our series. The PET scan will probably become the standard test in the extension and follow-up studies of most urological tumours., (Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens (HESr, Permixon ® ; Pierre Fabre Médicament, Castres, France), at a dose of 320 mg daily, as monotherapy for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH)., Materials and Methods: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective observational studies in patients with LUTS/BPH identified through searches in Medline, Web of Knowledge (Institute for Scientific Information), Scopus, the Cochrane Library, and bibliographic references up to March 2017. Articles studying S. repens extracts other than Permixon were excluded. Data were collected on International Prostate Symptom Score (IPSS), maximum urinary flow rate (Q max ), nocturia, quality of life, prostate volume, sexual function, and adverse drug reactions (ADRs). Data obtained from RCTs and observational studies were analysed jointly and separately using a random effects model. A sub-group analysis was performed of studies that included patients on longer-term treatment (≥1 year)., Results: Data from 27 studies (15 RCTs and 12 observational studies) were included for meta-analysis (total N = 5 800). Compared with placebo, the HESr was associated with 0.64 (95% confidence interval [CI] -0.98 to -0.31) fewer voids/night (P < 0.001) and an additional mean increase in Q max of 2.75 mL/s (95% CI 0.57 to 4.93; P = 0.01). When compared with α-blockers, the HESr showed similar improvements on IPSS (weighted mean difference [WMD] 0.57, 95% CI -0.27 to 1.42; P = 0.18) and a comparable increase in Q max to tamsulosin (WMD -0.02, 95% CI -0.71 to 0.66; P = 0.95). Efficacy assessed using the IPSS was similar after 6 months of treatment between the HESr and 5α-reductase inhibitors (5ARIs). Analysis of all available published data for the HESr showed a mean improvement in IPSS from baseline of -5.73 points (95% CI -6.91 to -4.54; P < 0.001). HESr did not negatively affect sexual function and no clinically relevant effect was observed on prostate-specific antigen. Prostate volume decreased slightly. Similar efficacy results were seen in patients treated for ≥1 year (n = 447). The HESr had a favourable safety profile, with gastrointestinal disorders being the most frequent ADR (mean incidence of 3.8%)., Conclusion: The present meta-analysis, which includes all available RCTs and observational studies, shows that the HESr (Permixon) reduced nocturia and improved Q max compared with placebo and had a similar efficacy to tamsulosin and short-term 5-ARI in relieving LUTS. HESr (Permixon) appears to be an efficacious and well-tolerated therapeutic option for the long-term medical treatment of LUTS/BPH., (© 2018 The Authors BJU International Published by John Wiley & Sons Ltd on behalf of BJU International.)

Introduction and Objective: This systematic review of the literature has been focused on determining the clinical usefulness of random bladder biopsies (RB) in the diagnosis of carcinoma in situ. A meta-analysis was performed to establish the clinic and pathological factors associated to positive biopsies., Evidence Acquisition: A systematic review was performed using Pubmed/Medline database according to the PRISMA guidelines. Thirty-seven articles were included, recruiting a total of 12,657 patients, 10,975 were submitted to RB., Evidence Synthesis: The overall incidence of positive RB was 21.91%. Significant differences were found in the incidence of positive RB when patients were stratified according to urine cytology result, tumor multiplicity, tumor appearance, stage and grade. The results of the meta-analysis revealed that the presence of positive cytology, tumor multiplicity, non-papillary appearance tumors, stage T1 and histological grades G2 and G3 represent the risk factors to predict abnormalities in RB., Conclusions: The incidence of positive RB in patients with non-muscle invasive bladder cancer was 21.91%. The maximum usefulness of RB was observed when these are performed in a standardized way. The results of the meta-analysis showed that besides positive cytology and non-papillary appearance tumors, tumor multiplicity and histological grades G2 and G3 represent risk factors associated to positive RB, suggesting that the use of RB might be extensive to the intermediate risk group of the European Organization for Research and Treatment of Cancer (EORTC)., (Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: Bladder cancer (BC) in the transplanted population can represent a challenge owing to the immunosuppressed state of patients and the higher rate of comorbidities. The objective was to analyze the treatment of BC after renal transplant (RT), focusing on the mode of presentation, diagnosis, treatment options and predictive factors for recurrence., Material and Methods: We conducted an observational prospective study with a retrospective analysis of 88 patients with BC after RT at 10 European centers. Clinical and oncologic data were collected, and indications and results of adjuvant treatment reviewed. The Kaplan-Meier method and uni- and multivariate Cox regression analyses were performed., Results: A total of 10,000 RTs were performed. Diagnosis of BC occurred at a median of 73 months after RT. Median follow-up was 126 months. Seventy-one patients (81.6%) had non-muscle invasive bladder cancer, of whom 29 (40.8%) received adjuvant treatment; of these, six (20.6%) received bacillus Calmette-Guérin and 20 (68.9%) mitomycin C. At univariate analysis, patients who received bacillus Calmette-Guérin had a significantly lower recurrence rate (P=.043). At multivariate analysis, a switch from immunosuppression to mTOR inhibitors significantly reduced the risk of recurrence (HR 0.24, 95% CI: 0.053-0.997, P=.049) while presence of multiple tumors increased it (HR 6.31, 95% CI: 1.78-22.3, P=.004). Globally, 26 patients (29.88%) underwent cystectomy. No major complications were recorded. Overall mortality (OM) was 32.2% (28 patients); the cancer-specific mortality was 13.8%., Conclusions: Adjuvant bacillus Calmette-Guérin significantly reduces the risk of recurrence, as does switch to mTOR inhibitors. Multiple tumors increase the risk., (Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: To assess the adherence to European Association of Urology (EAU) guidelines in the management of prostate cancer (PCa) in Spain., Patients and Methods: Epidemiological, population-based, study including a national representative sample of 3,918 incident patients with histopathological confirmation during 2010; 95% of the patient's sample was followed up for at least one year. Diagnosis along with treatment related variables (for localized PCa -low, intermediate, high and locally-advanced by D'Amico risk stratification) was recorded. Differences between groups were tested with Chi-squared and Kruskal-Wallis tests., Results: Mean (SD) age of PCa patients was 68.48 (8.18). Regarding diagnostic by biopsy procedures, 64.56% of all patients had 8-12 cores in first biopsy and 46.5% of the patients over 75 years, with PSA<10ng/mL were biopsied. Staging by Computer Tomography (CT) or Bone Scan (BS) was used for determining tumor extension in 60.09% of high-risk cases and was applied differentially depending on patients' age; 3,293 (84.05%) patients received a treatment for localized PCa. Radical prostatectomy was done in 1,277 patients and 206 out of these patients also had a lymphadenectomy, being 4.64% low-risk, 22.81% intermediate-risk and 36.00% high-risk patients; 86.08% of 1,082 patients who had radiotherapy were treated with 3D or IMRT and 35.77% received a dose ≥75Gy; 419 patients were treated with brachytherapy (BT): 54.81% were low-risk patients, 22.84% intermediate-risk and 12.98% high-risk. Hormonotherapy (HT, n=521) was applied as single therapy in 9.46% of low-risk and 17.92% of intermediate-risk patients. Additionally, HT was combined with RT in 14.34% of lower-risk patients and 58.26% of high-risk patients, and 67.19% low-intermediate risk with RT and/or BT received neoadjuvant/concomitant/adjuvant HT. Finally, 83.75% of high-risk patients undergoing RT and/or BT also received HT., Conclusions: Although EAU guidelines for PCa management are easily available in Europe, the adherence to their recommendations is low, finding the highest discrepancies in the need for a prostate biopsy and the diagnostic methods. Improve information and educational programs could allow a higher adherence to the guidelines and reduce the variability in daily practice. (Controlled-trials.com: ISRCTN19893319)., (Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Systemic treatment for metastatic renal cell carcinoma (mRCC) has changed with the new therapies, and it is not clear if nephrectomy (NEP) has a survival benefit in this kind of patients., Objective: To investigate if NEP associated to systemic treatment improves overall survival (OS) and progression-free survival (PFS)., Material and Methods: A retrospective, observational, descriptive study of 45 patients with diagnosis of mRCC between 2006-2014. Advanced cases with only palliative care were excluded, also patients with solitary metastasis who were managed with surgical resection., Results: Finally 34 patients were treated with systemic treatment. Twenty-six also with surgery associated. Seventy percent were intermediate/low risk at the Motzer classification and>80% Karnofsky performance status. PFS was 7m. NEP improves PFS (10 vs. 4m). High risk Motzer decreased PFS (P<.001). The OS was 11.5m. Patients with Karnofsky performance status>80, intermediate or low risk Motzer treated with NEP and mTOR as second line treatment, increased the OS (14 vs. 3m, P=.0001; 14 vs. 6m, P=.001; and 9 vs. 5m, P=.003, respectively). In the multivariate analysis only NEP (P=0,006; HR 4.5) and intermediate/low risk at the Motzer classification(P=.020; HR 8.9) demonstrated significant improvement in OS., Conclusions: Patients treated with NEP associated to systemic treatment and with an intermediate/low risk in the Motzer classification had a better PFS and OS. The OS also improves in patients treated with mTOR in second line, and Karnofsky performance status>80%in the univariate study, but not in the multivariable one., (Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: In Spanish public hospital Reproduction Units it is very problematic to perform programmed intrauterine insemination (IUI) on weekends, if indicated. Small previous pilot studies suggest that using a GnRH antagonist to avoid an LH weekend surge would allow to perform IUI on the following Monday, not impairing the expected pregnancy rate., Methods: Between 1st January 2007 and 31st December 2015, 4.782 intrauterine inseminations were performed at Valladolid University Clinic, Spain, corresponding to 1.650 women. Of them, 911, corresponding to 695 women, should ideally have been performed during the weekend. If it happened that a member of the Reproduction Unit was on duty during that particular weekend, the standard protocol was not interrupted, and the IUI performed as planned (control group, 685 IUIs). If the former was not the case, the weekend gap was bridged by administering 0.25 mg GnRH antagonist (GnRHa). Ovulation was induced by means of 250 ug recombinant HCG (rHCG) 36 h prior to IUI on the following Monday (study group, 226 IUIs)., Results: There were no differences in the clinical pregnancy rate (13.7 cc vs. 16.2 %, p = 0.371) or in the ongoing pregnancy rate between groups (11.9 % vs. 14.9 %, p = 0.271). The multiple pregnancy rate was also comparable in both groups (14.7 % vs. 18.5 %, p = 0.77)., Conclusions: Women with a planned IUI which cannot be performed at the ideal date can be offered postponement for two days with the support of GnRHa treatment, with results that are not inferior to those expected applying the regular protocol.

Objectives: To describe the established therapies for localised prostate cancer (PC) in Spain and to assess compliance with the 2010 UAE guidelines., Patients and Methods: This was an epidemiological, observational, prospective and multicentre study. Of the 3,918 patients diagnosed with PC during 2010, only those patients with localised PC were included. Follow-up was ultimately conducted for a minimum of one year from the diagnosis for 3,713 patients (94.77%). The treatment groups assessed were as follows: radical prostatectomy, radiation therapy, hormone therapy, brachytherapy, active surveillance or observation and experimental local treatment (cryotherapy or other treatment). Compliance with the recommendations of the EAU guidelines was studied, describing the treatment groups according to D'Amico risk stratification criteria (localised [low, intermediate and high risk] and locally advanced), age, PSA and Gleason score., Results: By applying the D'Amico criteria, we included 3,641 (92.93%) patients. Based on the UAE recommendations: 1) 68.87% of the patients at low-intermediate risk aged≤65 years underwent radical prostatectomy; 2) 34.51% of the patients>65 years at high risk with locally advanced disease were administered radiation therapy and hormone therapy; 3) 30.36% of the patients at high risk with locally advanced disease were only treated with hormone therapy; 4) 15.20% of the patients at low risk were only treated with brachytherapy; 5) active surveillance or observation was selected for 2.44% of the patients aged≤65 years and for 10.63% of the patients at low-intermediate risk who were>65 years. Lastly, 86.5% of the patients at low risk underwent a single treatment, and 43.62% of the patients at high risk with locally advanced disease underwent combined treatments., Conclusions: This is the first national European study to evaluate the therapeutic management of localised PC based on the risk group to which the patient belonged. Most young patients (≤65 years) with low-intermediate risk localised PC were treated with surgery, which adheres to the recommendations of the 2010 UAE guidelines. Various therapeutic combinations have been employed for patients with high-risk, locally advanced localised tumours, revealing the need for a multidisciplinary approach (Controlled-trials.com number: ISRCTN19893319)., (Copyright © 2015. Publicado por Elsevier España, S.L.U.)

The role of epigenetics in distinguishing pathological and clinical subgroups in bladder cancer is not fully characterized. We evaluated whether methylation of tumor-suppressor genes (TSGs) would classify non-muscle-invasive (NMI) bladder cancer subgroups and predict outcome. A retrospective design included the following paraffin-embedded primary NMI tumor types (n = 251): pTa low grade (LG) (n = 79), pT1LG (n = 81), and pT1 high grade (HG) (n = 91). Methylation of 25 TSGs was measured using methylation-specific, multiplex, ligation-dependent probe amplification. The TSGs most frequently methylated in the overall series were STK11 (96.8%), MGMT2 (64.5%), RARB (63.0%), and GATA5 (63.0%). TSG methylation correlated to clinicopathological variables in each subgroup and in the overall NMI series. Methylation of RARB, CD44, PAX5A, GSTP1, IGSF4 (CADM1), PYCARD, CDH13, TP53, and GATA5 classified pTa versus pT1 tumors whereas RARB, CD44, GSTP1, IGSF4, CHFR, PYCARD, TP53, STK11, and GATA5 distinguished LG versus HG tumors. Multivariate analyses indicated that PAX5A, WT1, and BRCA1 methylation independently predicted recurrence in pTaLG, PAX6, ATM, CHFR, and RB1 in pT1LG disease; PYCARD, in pT1HG disease; and PAX5A and RB1, in the overall series. Methylation of TSGs provided a molecular classification of NMI disease according to clinicopathological factors. Furthermore, TSG methylation predicted recurrence in NMI subgroups., (Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Nonfluoroscopic mapping systems have demonstrated significant reduction of radiation exposure in radiofrequency (RF) catheter ablation procedures. However, their use as only imaging guide is still limited., Objective: To evaluate the usefulness of a completely nonfluoroscopic approach to catheter ablation of supraventricular arrhythmias using the Ensite-NavX™ electroanatomical navigation system., Methods: During 6 years, all consecutive patients referred for RF catheter ablation of regular supraventricular tachycardia (SVT) were admitted for a "zero-fluoroscopy" approach and studied prospectively. The only exclusion criterion was the need to perform a transseptal puncture., Results: A total of 340 procedures were performed on 328 patients (179 men, age 55.7 ± 18.6 years). One hundred fifty-three patients had typical atrial flutter (AFL), 146 had AV nodal reentrant tachycardia (AVNRT), 35 had AV reciprocating tachycardia (AVRT), 4 patients had incisional atrial flutter (IAF), and 2 had focal atrial tachycardia (AT). Procedural success was achieved in 337 of the cases (99.1%). In 322 (94.7%), the procedure was completed without any fluoroscopy use. Mean procedure time was 110.5 ± 51.8 minutes. Mean RF application time was 9.8 ± 12.8 minutes and the number of RF lesions was 16.43 ± 15.8. Only 1 major complication related to vascular access was recorded. During follow-up, there were 12 recurrences (3.5%) (8 patients from the AVNRT group, 4 patients from the AP group)., Conclusion: RF catheter ablation of SVT with an approach completely guided by the NavX system and without use of fluoroscopy is feasible, safe, and effective., (© 2014 Wiley Periodicals, Inc.)

Objectives: Despite the uncertain value of adjuvant chemotherapy after radical nephroureterectomy (RNU) it is clear that impaired renal function represents a contraindication to its administration. The objective of this study was to identify possible predictive clinical factors for impaired renal function following RNU in patients with upper urinary tract urothelial cell carcinoma (UUT-UCC)., Patients and Methods: A retrospective analysis was conducted of 546 patients who underwent RNU between 1992 and 2008 at our institution. Data of interest for this study included estimated glomerular filtration rate (eGFR), age, pathological stage and preoperative hydronephrosis (HN). The predictive value of HN, age and pathological stage for impaired renal function after RNU was calculated by multivariate linear regression analysis., Results: In total, 138 patients met the criteria for inclusion, including 108 men (78%). Mean age at surgery was 67 ± 10 years. There was a significant correlation (p < 0.001) between pre- and postoperative eGFR (decrease of 21% after NU). Preoperative HN was present in 51 patients (37%). On linear regression analysis, preoperative eGFR ≤60 ml/min (p = 0.012; OR = 4.60) and HN (p = 0.027; OR = 10.34) were confirmed to be predictive factors for a postoperative eGFR ≤60 ml/min. When postoperative eGFR ≤45 ml/min was used as the criterion for impaired renal function, predictive factors proved to be preoperative eGFR ≤45 ml/min (p < 0.0001; OR = 18.53), HN (p = 0.038; OR = 0.380) and age ≥70 years (p < 0.0001; OR = 0.169)., Conclusions: Preoperative HN, older age and preoperative eGFR <60 ml/min were proven to be predictive factors for impaired renal function after RNU. In these settings, neoadjuvant chemotherapy may be considered., (2013 S. Karger AG, Basel.)

Context: Since June 2012, the has been a worldwide lack of available of the Connaught strain. In December 2012, a group of experts met in the Spanish Association of Urology to analyze this situation and propose alternatives., Objective: To present the work performed by said committee and the resulting recommendations., Acquisition of Evidence: An update has been made of the principal existing evidence in the treatment of middle and high risk tumors. Special mention has been made regarding the those related with the use of BCG and their possible alternative due to the different availability of BCG., Evidence Synthesis: In tumors with high risk of progression, immediate cystectomy should be considered when BCG is not available, with dose reduction or alternating with chemotherapy as methods to economize on the use of BCG when availability is reduced. In tumors having middle risk of progression, chemotherapy can be used, although when it is associated to a high risk of relapse, BCG would be indicated if available with the mentioned savings guidelines. BCG requires maintenance to maintain its effectiveness, it being necessary to optimize the application of endovesical chemotherapy and to use systems that increase its penetration into the bladder wall (EMDA) if they are available., Conclusions: Due to the scarcity of BCG, it has been necessary to agree on a series of recommendations that have been published on the web page of the Spanish Association of Urology., (Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.)

Background: Biventricular pacing through the coronary sinus (CS) is effective for the treatment of patients with heart failure and left bundle-branch block. However, this approach is not always feasible. Although surgical epicardial lead implantation is an alternative, the technique may be deleterious in some patients. Thus, direct left ventricular (LV) endocardial pacing under local anesthesia may be an option., Objective: We describe our technique and analyze the results of direct LV endocardial pacing., Method: Fourteen patients with failed resynchronization via CS (April 2006-September 2011) were selected. Using a femoral approach, we performed transseptal puncture and LV mapping, then fixed the active lead where the longest electrical delay was observed; the generator was placed in the anterior thigh. For resynchronization, eight patients with a device previously implanted through the upper veins received a single-chamber generator that was set to the VVT mode to sense the subclavian pacing spike. Six patients received a complete femoral resynchronization system with either a defibrillator or pacemaker. Patients were followed for 6-54 months., Results: The LV lead was successfully implanted in all cases. Two patients experienced excessive bleeding and two died during follow-up. All except one improved at least one New York Heart Association class and experienced improved left ventricle ejection fraction. One patient with recurrent episodes of ventricular fibrillation was asymptomatic., Conclusion: Direct LV endocardial pacing is safe and may be a less risky, more efficient alternative than surgical epicardial lead implantation for resynchronization via CS., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Background: Bacillus Calmette-Guérin (BCG) is a standard treatment to reduce tumor recurrence and delay progression of high-risk non-muscle-invasive (NMI) bladder tumors. However, it is not clear yet which patients are more likely to respond to BCG., Objective: The aim was to evaluate the role of polyamine-modulated factor-1 (PMF-1) methylation in predicting clinical outcome of T1 high-grade (T1HG) bladder tumors treated with BCG., Design, Setting, and Participants: In a retrospective design, PMF-1 methylation was analyzed on tumor specimens belonging to 108 patients with T1HG NMI bladder cancer undergoing BCG treatment. Median follow-up was 77 mo (range: 5-235 mo)., Outcome Measurements and Statistical Analysis: PMF-1 methylation was assessed by methylation-specific polymerase chain reactions. Recurrence, progression into muscle-invasive tumors, and disease-specific survival rates were analyzed using competing risks regression analysis., Results and Limitations: Among the 108 patients analyzed, 35 had recurring disease (32.4%), 21 progressed (19.4%), and 16 died of disease (14.8%); 71.3% of tumors had PMF-1 methylation. Univariate analyses using cumulative incidence curves revealed that an unmethylated PMF-1 was significantly associated with increased recurrence (p=0.026), progression (p=0.01), and shorter disease-specific survival (log-rank, p=0.03). Multivariate analyses indicated that among sex, age, focality, tumor size, and concomitant carcinoma in situ, only PMF-1 methylation provided significant hazard ratios (HRs) for recurrence of (HR: 2.032; p=0.042), and progression (HR: 2.910; p=0.020). Limitations of the study include its retrospective design, lymphovascular invasion status not available, short maintenance BCG, and that a second transurethral resection was not performed., Conclusions: Epigenetic analyses revealed that the methylation status of PMF-1 was associated with the clinical outcome of patients with T1HG tumors undergoing BCG treatment. An unmethylated PMF-1 correlated to recurrence and progression in T1HG disease using univariate and multivariate analyses. Thus, assessing the methylation status of PMF-1 may serve to distinguish patients responding to BCG from those who may require more aggressive therapeutic approaches., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)