Curvature-induced stabilization and field-driven dynamics of magnetic hopfions in toroidal nanorings.

Three dimensional magnetic textures are a cornerstone in magnetism research. In this work, we analyze the stabilization and dynamic response of a magnetic hopfion hosted in a toroidal nanoring with intrinsic Dzyaloshinskii-Moriya interaction simulating FeGe. Our results evidence that unlike their planar counterparts, where perpendicular magnetic anisotropies are necessary to stabilize hopfions, the shape anisotropy originated on the torus symmetry naturally yields the nucleation of these topological textures. We also analyze the magnetization dynamical response by applying a magnetic field pulse to differentiate among several magnetic patterns. Finally, to understand the nature of spin wave modes, we analyze the spatial distributions of the resonant mode amplitudes and phases and describe the differences among bulk and surface modes. Importantly, hopfions lying in toroidal nanorings present a non-circularly symmetric poloidal resonant mode, which is not observed in other systems hosting hopfions.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Magnetic and electrical characterization of nickel-rich NiFe thin films synthesized by atomic layer deposition and subsequent thermal reduction.

Nickel-rich NiFe thin films (Ni92Fe8, Ni89Fe11 and Ni83Fe17) were prepared by combining atomic layer deposition (ALD) with a subsequent thermal reduction process. In order to obtain Ni x Fe1-x O y films, one ALD supercycle was performed according to the following sequence: m NiCp2/O3, with m = 1, 2 or 3, followed by one FeCp2/O3 cycle. The supercycle was repeated n times. The thermal reduction process in hydrogen atmosphere was investigated by in situ x-ray diffraction studies as a function of temperature. The metallic nickel iron alloy thin films were investigated and characterized with respect to crystallinity, morphology, resistivity, and magnetism. As proof-of-concept magnetic properties of an array of Ni83Fe17, close to the perfect Permalloy stoichiometry, nanotubes and an isolated tube were investigated.

A soft/hard magnetic nanostructure based on multisegmented CoNi nanowires.

In this paper we have introduced a new soft/hard nanostructure based on multisegmented CoNi nanowire arrays having diameters of around 110 nm and made of five segments with nominal compositions of Co, Co66Ni33, Co50Ni50, Co33Ni66 and Ni, each of which has a length of 800 nm, so that the total length of the multisegmented nanowire is 4 µm. These arrays have been synthesized by means of potentiostatic electrodeposition into the pores of hard-anodic alumina templates. The morphology, chemical composition and microstructure of the multisegmented CoNi nanowires were determined by high-resolution scanning electron microscopy, energy dispersive X-ray microanalysis, and powder X-ray diffraction method, respectively. The room temperature magnetic behavior of the multisegmented nanowire arrays is also studied and compared with CoNi nanowire arrays with homogeneous composition (non-segmented nanowires), synthesized in the same templates and having the same dimensions as the segmented ones. These nanostructures could be used to control the movement of magnetic domain walls. In this way, these nanostructures can be an alternative to store information or even perform logic functions.

Multidisciplinary consensus document on the current treatment of bacille Calmette-Guérin-unresponsive non-muscle invasive bladder tumor.

Radical cystectomy is the current treatment of choice for patients with BCG-unresponsive non-muscle invasive bladder tumor (NMIBC). However, the high comorbidity of this surgery and its effects on the quality of life of patients require the investigation and implementation of bladder-sparing treatment options. These must be evaluated individually by the uro-oncology committee based on the characteristics of the BCG failure, type of tumor, patient preferences and treatment options available in each center. Based on FDA-required oncologic outcomes (6-month complete response rate for CIS: 50%; duration of response in responders for CIS and papillary: 30% at 12 months and 25% at 18 months), there is not currently a strong preference for one treatment over another, although the intravesical route seems to offer less toxicity. This work summarizes the evidence on the management of BCG-unresponsive NMIBC based on current scientific evidence and provides consensus recommendations on the most appropriate treatment.

[Non-invasive diagnosis of prostate cancer: serum and urine markers]. / Diagnóstico no invasivo del cáncer de próstata; marcadores séricos y en orina.

The great number of biomarkers basic research is presenting in different clinical scenarios of prostate cancer demands the scientific community rigor in their molecular and clinical development for the selection of those which could supply diagnostic and prognostic information for the established nomograms of clinical-pathological factors. Prostate cancer, due to its prevalence and heterogeneity, needs a more directed diagnosis, characterization of malignant potential and monitoring of its multiple therapies. In this review article we try to go over the recent incorporation of new serum and urine markers in the clinical management of this tumor, emphasizing those with greater clinical development.

Magnonic key based on skyrmion clusters.

In this work, we report the excitation of spin-waves modes in skyrmion clusters hosted in Co/Pt nanodots by applying an in-plane magnetic field pulse. The direction at which the magnetic field is applied enables the excitation of five main spin-waves modes that are understood in terms of only azimuthal-like modes, which are shown to be strongly dependent on the number of skyrmions stabilized in the system. This feature converts the present system in a mechanism to activate and suppress a set of given modes, which in turn we propose to be utilized as a magnonic key based skyrmion cluster. Our results could be useful in manufacturing potential magnonic logic devices based in skyrmionic textures.

Current treatments for BCG failure in non-muscle invasive bladder cancer (NMIBC). / Tratamientos actuales tras fracaso a BCG en cáncer de vejiga no músculo-invasivo.

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.

Dynamic and static properties of stadium-shaped antidot arrays.

In this work we performed a detailed numerical analysis on the static and dynamic properties of magnetic antidot arrays as a function of their geometry. In particular, we explored how by varying the shape of these antidot arrays from circular holes to stadium-shaped holes, we can effectively control the magnetic properties of the array. Using micromagnetic simulations we evidenced that coercivity is very sensitive to the shape of antidots, while the remanence is more robust to these changes. Furthermore, we studied the dynamic susceptibility of these systems, finding that it is possible to control both the position and the number of resonance peaks simply by changing the geometry of the holes. Thus, this work provides useful insights on the behavior of antidot arrays for different geometries, opening routes for the design and improvement of two-dimensional technologies.

Magnetic phase diagrams of barcode-type nanostructures.

The magnetic configurations of barcode-type magnetic nanostructures consisting of alternate ferromagnetic and nonmagnetic layers arranged within a multilayer nanotube structure are investigated as a function of their geometry. Based on a continuum approach we have obtained analytical expressions for the energy which lead us to obtain phase diagrams giving the relative stability of characteristic internal magnetic configurations of the barcode-type nanostructures.

Asymmetric hysteresis loop in magnetostatic-biased multilayer nanowires.

The hysteresis of multilayer nanowires composed by a soft magnetic cylindrical wire, a non-magnetic spacer layer and an external hard magnetic shell is investigated. The external magnetic shell originates a non-homogeneous magnetic field on the inner wire, which is responsible for a displacement and a change of the width of the hysteresis curve of the wire. Moreover, different reversal modes occur at each branch of the hysteresis loop, which can be understood by analyzing the interaction magnetostatic field along the wire. Our results open the possibility of controlling two parameters of the hysteresis loop, the coercivity and the bias, providing an interesting system to be investigated.

[Role of laparoscopy in the presence of a renal mass under 4 cm in size]. / Papel de la laparoscopia ante la masa renal menor de 4 cm.

The increasingly common incidental diagnosis of small renal masses (SRMs) (measuring under 4 cm in size) has led to the consideration of applying minimally invasive techniques to deal with them--particularly in view of the high percentage of non-malignant conditions of this size that are radiologically indistinguishable from tumor lesions. Accordingly, laparoscopic access has gained great importance in the management of these masses, in an attempt to lessen the morbidity associated with lumbotomy. Laparoscopic partial nephrectomy (LPN) is an evolving technique in most centers; on one hand it competes with open partial nephrectomy as the technique of choice, and on the other it will compete in the future with the non-excisional management techniques. These latter procedures in turn have become more precise thanks to laparoscopy. Based on a standardized review of the abundant literature on the treatment of SRMs, the present study examines the technical innovations and improvements afforded by the laparoscopic approach, not only for excision purposes but also a vehicle for minimally invasive treatments. Likewise, the requirements of Services of Urology and the improvements that could be introduced in health systems for advancing the application of LPN in the management of SRMs are commented. Progressive fine-tuning of the technique, with improvement of the laparoscopic repertoire and availability of hemostatic agents, will contribute to increase the indications for LPN in the future. The limited frequency of the disorder and the need to optimize the technique will require health care supervisors to centralize this type of pathology in centers with experience in laparoscopy and open partial nephrectomy.

Selective Indication of T-Tube in Liver Transplantation: Prospective Validation of the Results of a Randomized Controlled Trial.

BACKGROUND AND AIMS: T-tube placement during choledochocholedochostomy (CCS) associated with liver transplantation (LT) remains controversial. This study was designed to validate the results of an earlier prospective randomized controlled trial (RCT) on use versus nonuse of the T-tube during CCS associated with LT. METHODS: Prospective cohort study. The primary outcome was the overall incidence of biliary complications (BCs). RESULTS: In total, 405 patients were included, and the median overall monitoring period was 29 months (interquartile range: 13-47 months). Selective use of the T-tube reduced BCs (23% vs 13%; P = .003), of which 75% were type IIIa or less in the Clavien-Dindo classification. The overall BC rate did not differ between patients with versus without T-tube placement. CONCLUSIONS: We confirmed that selective use of a rubber T-tube during CCS associated with LT, following the principles established in our prospective RCT, reduced the rate of BC by 10% without detriment, even after enrolling patients at an a priori greater risk of BCs than were the RCT patients.

Undetectable PSA after radical prostatectomy is more likely in low burden N+ prostate cancer patients when an extended lymph node dissection is performed. / Frecuencia de PSA indetectable en pacientes con cáncer de próstata N+ baja carga tras prostatectomía radical y linfadenectomía ampliada.

OBJECTIVES: To analyze the likelihood of undetectable PSA (< 0.01 ng/mL) after extended (ePLND) versus standard pelvic lymph-nodes dissection (sPLND) in pN+ patients. MATERIALS AND METHODS: The institutional prospectively maintained Prostate Cancer Database was queried for patients who underwent radical prostatectomy with PLND and were found with 3or less lymph-nodal metastases between 2007 and 2017. The extension of the PLND was defined according to the number of lymph-nodes (LN) removed. Patients in the 75th or higher percentile of lymph-nodes removed were considered as the ePLND group; patients in the 25th or lower percentile in the sPLND group. Groups were compared in clinical and pathological variables. Student T-test was used for comparing continuous variables; chi-square test was used for categorical variables. Multivariable logistic regression assessed the probability of undetectable PSA at 3rd month postoperatively. Kaplan-Meier method estimated the probability of biochemical recurrence. Differences between the groups were compared by Log-rank test. RESULTS: 1478 patients were treated within the time span considered. 95 with 1 to 3 lymph-nodal metastases were extracted. After accounting for inclusion criteria, 23 patients with a median of 11 LN removed were included in the sPLND group (25th percentile); 23 patients with > 27 LN were included in ePLND group (75th percentile). Surgical time was longer for ePLND. Sixteen patients (69.6%) who underwent ePLND had undetectable PSA postoperatively. At multivariable analysis, the probability of undetectable PSA at 3rd month was higher in patients who received an ePLND (HR=5.18; IC 95%=1.16-23.11; P=.03). CONCLUSIONS: ePLND is more likely to predict undetectable PSA at third month after radical prostatectomy, irrespective of disease characteristics.

Distinct magnetic field dependence of Néel skyrmion sizes in ultrathin nanodots.

We investigate the dependence of the Néel skyrmion size and stability on perpendicular magnetic field in ultrathin circular magnetic dots with out-of-plane anisotropy and interfacial Dzyaloshinskii-Moriya exchange interaction. Our results show the existence of two distinct dependencies of the skyrmion radius on the applied field and dot size. In the case of skyrmions stable at zero field, their radius strongly increases with the field applied parallel to the skyrmion core until skyrmion reaches the metastability region and this dependence slows down. More common metastable skyrmions demonstrate a weaker increase of their size as a function of the field until some critical field value at which these skyrmions drastically increase in size showing a hysteretic behavior with coexistence of small and large radius skyrmions and small energy barriers between them. The first case is also characterized by a strong dependence of the skyrmion radius on the dot diameter, while in the second case this dependence is very weak.

Cognitive function in patients on androgen suppression: A prospective, multicentric study. / Función cognitiva en pacientes tratados con supresión androgénica: estudio prospectivo y multicéntrico.

OBJECTIVE: To assess the effect of androgen deprivation therapy (ADT) on cognitive performance (CP) in patients with prostate cancer (PCa) after 6 months of treatment with luteinizing hormone-releasing hormone (LHRH) analogues. MATERIAL AND METHODS: Prospective, observational, multicentre, open-label study of patients diagnosed with nonmetastatic or asymptomatic metastatic PCa scheduled to receive LHRH analogues for≥6 months. We assessed four CP domains at baseline and after 6 months of ADT: 1) Working memory: Wechsler Adult Intelligence Scale III (WAIS III) Digit Span Subtest (WAIS III-Digit); 2) Visual memory: ad hoc visual memory test; 3) Visuospatial ability: Judgement of Line Orientation (JLO) and Mental Rotation of Three-Dimensional Objects (3D-Rotation); and 4) Nonverbal analytical reasoning: WAIS III Matrix Reasoning Test (WAIS III-MRT). Changes outside the baseline 95% confidence intervals were considered significant. RESULTS: A total of 308 patients completed the study. Of these, 245 (79.6%) experienced no statistically significant changes on any test and 63 patients (20.4%) experienced significant changes in ≥1 test. Of these, most presented a change in only one test, distributed evenly between improvements (58 patients; 18.8%) and worsening (56 patients; 18.2%). For individual tests, most patients (87.8% to 91.8%) had no change from baseline; however, the significant changes (improvement vs. deterioration, respectively) were as follows: WAIS III-Digit (6.3% vs. 5.9%); visual memory (5.3% vs. 5.7%); JLO (5.3% vs. 4.5%); 3D-Rotation (4.1% vs. 4.1%); and WAIS III-MRT (4.8% vs. 5.8%). CONCLUSIONS: CP in patients with PCa does not appear to be adversely affected by 6 months of LHRH analogue administration.

Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital. / Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico.

OBJECTIVES: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. MATERIAL AND METHODS: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. RESULTS: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. CONCLUSIONS: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase.

Methodology of a systematic review. / Metodología de una revisión sistemática.

CONTEXT: The objective of evidence-based medicine is to employ the best scientific information available to apply to clinical practice. Understanding and interpreting the scientific evidence involves understanding the available levels of evidence, where systematic reviews and meta-analyses of clinical trials are at the top of the levels-of-evidence pyramid. ACQUISITION OF EVIDENCE: The review process should be well developed and planned to reduce biases and eliminate irrelevant and low-quality studies. The steps for implementing a systematic review include (i) correctly formulating the clinical question to answer (PICO), (ii) developing a protocol (inclusion and exclusion criteria), (iii) performing a detailed and broad literature search and (iv) screening the abstracts of the studies identified in the search and subsequently of the selected complete texts (PRISMA). SYNTHESIS OF THE EVIDENCE: Once the studies have been selected, we need to (v) extract the necessary data into a form designed in the protocol to summarise the included studies, (vi) assess the biases of each study, identifying the quality of the available evidence, and (vii) develop tables and text that synthesise the evidence. CONCLUSIONS: A systematic review involves a critical and reproducible summary of the results of the available publications on a particular topic or clinical question. To improve scientific writing, the methodology is shown in a structured manner to implement a systematic review.

Trocar site hernia after laparoscopic ventral hernia repair.

BACKGROUND: The incidence of trocar site hernia (TSH) after laparoscopic ventral hernia repair (LVHR) is reported to be low. The present study investigates the associated risk factors, with a view to preventing this complication. METHODS: A retrospective study was made of the incidence of TSH in a personal series of LVHR, recording anthropometric and clinical data on the patients. Risk factors were assessed by bivariate and multivariate analyses. The patients were subjected to clinical and telephone follow-up. RESULTS: In a series of 27 LVHR, the incidence of TSH was 22% (6 patients). The use of meshes larger than 10 x 15 cm for LVHR was the only TSH risk factor to reach statistical significance. Female gender and diabetes showed a higher incidence in the TSH group. CONCLUSIONS: The use of large meshes may be a risk factor for TSH. We believe this to be due to dilatation of the trocar orifice during introduction of the mesh, and also to postoperative retraction of the mesh.