Personalized cardiovascular risk assessment in Rheumatoid Arthritis patients using circulating molecular profiles and their modulation by TNFi, IL6Ri, and JAKinibs.

BACKGROUND & OBJECTIVES: This study aimed to: 1) analyze the inflammatory profile of Rheumatoid Arthritis (RA) patients, identifying clinical phenotypes associated with cardiovascular (CV) risk; 2) evaluate biologic and targeted-synthetic disease-modifying antirheumatic drugs (b-DMARDs and ts-DMARDs': TNFi, IL6Ri, JAKinibs) effects; and 3) characterize molecular mechanisms in immune-cell activation and endothelial dysfunction. PATIENTS & METHODS: A total of 387 RA patients and 45 healthy donors were recruited, forming three cohorts: i) 208 RA patients with established disease but without previous CV events; ii) RA-CVD: 96 RA patients with CV events, and iii) 83 RA patients treated with b-DMARDs/ts-DMARDs for 6 months. Serum inflammatory profiles (cytokines/chemokines/growth factors) and NETosis/oxidative stress-linked biomolecules were evaluated. Mechanistic in vitro studies were performed on monocytes, neutrophils and endothelial cells (EC). RESULTS: In the first RA-cohort, unsupervised clustering unveiled three distinct groups: cluster 3 (C3) displayed the highest inflammatory profile, significant CV-risk score, and greater atheroma plaques prevalence. In contrast, cluster 1 (C1) exhibited the lowest inflammatory profile and CV risk score, while cluster 2 (C2) displayed an intermediate phenotype. Notably, 2nd cohort RA-CVD patients mirrored C3's inflammation. Treatment with b-DMARDs or ts-DMARDs effectively reduced disease-activity scores (DAS28) and restored normal biomolecules levels, controlling CV risk. In vitro, serum from C3-RA or RA-CVD patients increased neutrophils activity and CV-related protein levels in cultured monocytes and EC, which were partially prevented by pre-incubation with TNFi, IL6Ri, and JAKinibs. CONCLUSIONS: Overall, analyzing circulating molecular profiles in RA patients holds potential for personalized clinical management, addressing CV risk and assisting healthcare professionals in tailoring treatment, ultimately improving outcomes.

Sentinel Lymph Node Biopsy in Prostate Cancer: An Overview of Diagnostic Performance, Oncological Outcomes, Safety, and Feasibility.

Sentinel node biopsy (SNB) for prostate cancer (PCa) represents an innovative technique aimed at improving nodal staging accuracy. The routinary adoption of this procedure in patients undergoing radical prostatectomy (RP) might be crucial to identify candidates who could effectively benefit from extensive pelvic lymph nodal dissection (ePLND). Despite some promising results, SNB for PCa is still considered experimental due to the lack of solid evidence and procedural standardization. In this regard, our narrative review aimed to analyze the most recent literature in this field, providing an overview of both the diagnostic accuracy measures and the oncological outcomes of SNB.

Free-indocyanine green-guided pelvic lymph node dissection during radical prostatectomy.

INTRODUCTION AND OBJECTIVES: Extended Pelvic Lymph Node Dissection (ePLND) remains the most accurate technique for the detection of occult lymph node metastases (LNMs) in prostate cancer (CaP) patients. Here we aim to examine whether free-Indocyanine Green (F-ICG) could accurately assess the pathological nodal (pN) status in CaP patients during real-time lymphangiography as a potential replacement for ePLND. MATERIALS AND METHODS: 219 consecutive patients undergoing F-ICG-guided PLND, ePLND and radical prostatectomy (RP) for clinical-localized CaPwere included in this prospective single-center study. The pathological outcomes of F-ICG-guided PLND were compared to confirmatory ePLND. Parameters of a binary diagnostic test for the proper classification of the pN status of patients ('per-patient' analysis) and for the probability of detecting all the metastatic LNs ('per-node' analysis) were calculated. Outcome measures were prevalence, accuracy (Acc), sensitivity (Se), negative predictive value (NPV), and likelihood ratio of a negative F-ICG-guided PLND test result [LR(-)]. RESULTS: F-ICG-guided PLND successfully visualized LNs in all procedures with no adverse events. The overall per-patient F-ICG staging Acc was 97.7%, Se was 91.4%, with a NPV of 97.0%, and LR(-) of 8.6%. At the overall per-node level, 4,780 LNs were removed and 1,535 (32.1%) were fluorescent in vivo. F-ICG-guided PLND identified LNMs with a Se of 63.4%. CONCLUSIONS: This study confirms that F-ICG-guided lymphangiography correctly staged almost 98% of patients. The high per-patient NPV suggested that avoiding ePLND is safe for most patients when F-ICG stained nodes were pN0. Thus, more conservative approaches might minimise perioperative morbidity during LNMs diagnosis in selected patients.

New imaging technologies for robotic kidney cancer surgery.

Objective: Kidney cancers account for approximately 2% of all newly diagnosed cancer in 2020. Among the primary treatment options for kidney cancer, urologist may choose between radical or partial nephrectomy, or ablative therapies. Nowadays, robotic-assisted partial nephrectomy (RAPN) for the management of renal cancers has gained popularity, up to being considered the gold standard. However, RAPN is a challenging procedure with a steep learning curve. Methods: In this narrative review, different imaging technologies used to guide and aid RAPN are discussed. Results: Three-dimensional visualization technology has been extensively discussed in RAPN, showing its value in enhancing robotic-surgery training, patient counseling, surgical planning, and intraoperative guidance. Intraoperative imaging technologies such as intracorporeal ultrasound, near-infrared fluorescent imaging, and intraoperative pathological examination can also be used to improve the outcomes following RAPN. Finally, artificial intelligence may play a role in the field of RAPN soon. Conclusion: RAPN is a complex surgery; however, many imaging technologies may play an important role in facilitating it.

New Ultra-minimally Invasive Surgical Treatment for Benign Prostatic Hyperplasia: A Systematic Review and Analysis of Comparative Outcomes.

CONTEXT: Benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) is diagnosed in up to 80% of men during their lifetime. Several novel ultra-minimally invasive surgical treatments (uMISTs) for BPH/benign prostatic obstruction (BPO) have become available over the past 5 yr. OBJECTIVE: To evaluate the perioperative and functional outcomes of recently introduced uMISTs for BPH/BPO, including Urolift, Rezum, temporary implantable nitinol device, prostatic artery embolization (PAE), and intraprostatic injection. EVIDENCE ACQUISITION: A systematic literature search was conducted in December 2020 using Medline (via PubMed), Embase (via Ovid), Scopus, and Web of Science (registered on PROSPERO as CRD42021225014). The search strategy used PICO criteria and article selection was conducted in accordance with the PRISMA guidelines. The risk of bias and the quality of the articles included were assessed. A dedicated data extraction form was used to collect the data of interest. Pooled and cumulative analyses were performed to compare perioperative and functional outcomes between study groups. A random-effects model using the DerSimonian and Laird method was used to evaluate heterogeneity. Stata version 15.0 software was used for all statistical analyses. EVIDENCE SYNTHESIS: The initial electronic search identified 3978 papers, of which 48 ultimately met the inclusion criteria and were included in the analysis. Pooled analysis revealed a uMIST benefit in terms of International Prostate Symptom Score (IPSS; -9.81 points, 95% confidence interval [CI] -11.37 to -8.25 at 1 mo; -13.13 points, 95% CI -14.98 to -11.64 at 12 mo), maximum flow rate (from +3.66 ml/s, 95% CI 2.8-4.5 to +4.14 ml/s, 95% CI 0.72-7.56 at 12 mo), and postvoid residual volume (-10.10 ml, 95% CI -27.90 to 7.71 at 12 mo). No negative impact was observed on scores for the International Index of Erectile Function-5, Male Sexual Health Questionnaire-Ejaculatory Dysfunction bother and function scales (overall postintervention change in pooled median score of 1.88, 95% CI 1.34-2.42 at the start of follow-up; and 1.04, 95% CI 0.28-1.8 after 1 yr), or the IPSS-Quality of Life questionnaire. CONCLUSIONS: Novel uMISTs can yield fast and effective relief of LUTS without affecting patient quality of life. Only Rezum, UroLift, and PAE had a minimal impact on patients' sexual function with respect to baseline, especially regarding preservation of ejaculation. PATIENT SUMMARY: We reviewed outcomes for recently introduced ultra-minimally invasive surgical treatments for patients with lower urinary tract symptoms caused by benign prostate enlargement or obstruction. The evidence suggests that these novel techniques are beneficial in terms of controlling symptoms while preserving sexual function. TAKE HOME MESSAGE: Novel ultra-minimally invasive treatments can yield fast and effective relief of lower urinary tract symptoms without affecting a patient's quality of life.

Integrative Clinical, Molecular, and Computational Analysis Identify Novel Biomarkers and Differential Profiles of Anti-TNF Response in Rheumatoid Arthritis.

Background: This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients. Methods: A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions. Results: Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort. Conclusions: Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, the reestablishment of the altered oxidative status, the reduction of NETosis, and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.

Indocyanine green guidance improves the efficiency of extended pelvic lymph node dissection during laparoscopic radical prostatectomy.

OBJECTIVES: To evaluate whether indocyanine green guidance can improve the quality of extended pelvic lymph node dissection in patients undergoing radical prostatectomy. METHODS: A total of 214 patients underwent laparoscopic radical prostatectomy with indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection. These patients (group A) were matched 1:1 for clinical risk groups according to the National Comprehensive Cancer Network classification with patients who underwent the same procedure without fluorescence guidance (group B). Biochemical recurrence was defined as two consecutive prostate-specific antigen rises of at least 0.2 ng/mL. The Kaplan-Meier method and Cox regression models were used to identify predictors of biochemical recurrence. RESULTS: The median number of retrieved nodes was significantly higher in group A (22 vs 14, P < 0.001). The rate of lymph node metastases was higher in group A (65.9% vs 34.1%, P = 0.01). Increasing the yield of lymph node dissection was independently and negatively correlated with the biochemical recurrence risk in both overall and pN-positive patients (hazard ratio 0.97, P = 0.03; and hazard ratio 0.95, P = 0.02). The 5-year biochemical recurrence-free survival rates were (75.8% vs 65.9, P = 0.09) and (54.1% vs 24.9%, P = 0.023) for group A and group B in the overall cohort and pN-positive cohort, respectively. CONCLUSION: Indocyanine green-guided lymph node dissection plus extended pelvic lymph node dissection improves identification of lymphatic drainage, resulting in a higher number of lymph nodes and retrieved lymph node metastases, and allowing a more accurate local staging and a prolonged biochemical recurrence-free survival.

Autonomous robots: a new reality in healthcare? A project by European Association of Urology-Young Academic Urologist group.

PURPOSE OF REVIEW: Artificial intelligence appears as a potential revolution in the general process of medical training, disease diagnosis and treatment. A novel disruptive technology of the 21st century will be 'learner' robots from artificial intelligence systems able to use all the combination of the available knowledge in medical repositories to give the best standard of care. RECENT FINDINGS: The autonomy level of robots depends on three factors: the complexity of the task; the environment in which the robot operates, and the required level of human-robot interaction. Autonomous robots in healthcare may be classified in delivery, nurse, and surgical robots. The increasing capability of robots to perform independent actions and complex tasks raises responsibility and accountability issues in a wide variety of application domains. Ethical analyses of these issues are underway and are mostly oriented toward the development of ethical policies requiring a law frame on robotic autonomous behaviors. SUMMARY: Autonomous robots have the potential to improve current medical practice offering a more secure, reliable, and reproducible medicine. Many advancements are required for these new technologies to be fully integrated. Furthermore, the ethical implications of these technologies are yet to be evaluated.

Evaluation of Fluorescent Confocal Microscopy for Intraoperative Analysis of Prostate Biopsy Cores.

BACKGROUND: Diagnosis of prostate cancer is based on histopathological evaluation, which is time-consuming. Fluorescent confocal microscopy (FCM) is a novel technique that allows rapid tissue analysis. OBJECTIVE: To determine if FCM could be used for real-time diagnosis of prostate cancer and evaluate concordance with traditional analysis. DESIGN, SETTING, AND PARTICIPANTS: From January 2019 to March 2020, 182 magnetic resonance imaging-targeted prostate biopsy cores from 57 consecutive biopsy-naïve men with suspected prostate cancer were taken. These were intraoperatively stained with acridine orange for analysis using FCM (VivaScope; MAVIG, Munich, Germany) and subsequently sent for traditional haematoxylin-eosin histopathological (HEH) examination. Two expert uropathologists analysed the FCM and HEH cores blinded to the counterpart results in a single institution. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Agreement between FCM and HEH analysis in terms of the presence of cancer was analysed at biopsy core and region of interest (ROI) levels, considering HEH as the reference test. RESULTS AND LIMITATIONS: FCM allowed intraoperative assessment of prostate biopsy cores with strong histopathological evaluation agreement: Cohen's κ for agreement was 0.81 at the biopsy core level and 0.69 for the ROI level. Positive predictive values (85% and 83.78%) and negative predictive values (95.1% and 85.71%) were high at the biopsy core and ROI levels. These initial results are encouraging, but given the single-centre and preliminary nature of the study, further confirmation is required. CONCLUSIONS: FCM allowed rapid evaluation of prostate biopsy cores. This technique is feasible and achieves rapid closure with a reliable diagnosis, parallel to the gold standard analysis. Initial results are promising but further studies are needed to validate and define the role of this technique. PATIENT SUMMARY: A novel microscopic technique reduces the time needed to obtain a prostate cancer diagnosis by speeding up biopsy processing. Although the initial results are promising; this development needs to be confirmed in further studies.

Prediction of significant prostate cancer in biopsy-naïve men: Validation of a novel risk model combining MRI and clinical parameters and comparison to an ERSPC risk calculator and PI-RADS.

BACKGROUND: Risk models (RM) need external validation to assess their value beyond the setting in which they were developed. We validated a RM combining mpMRI and clinical parameters for the probability of harboring significant prostate cancer (sPC, Gleason Score ≥ 3+4) for biopsy-naïve men. MATERIAL AND METHODS: The original RM was based on data of 670 biopsy-naïve men from Heidelberg University Hospital who underwent mpMRI with PI-RADS scoring prior to MRI/TRUS-fusion biopsy 2012-2015. Validity was tested by a consecutive cohort of biopsy-naïve men from Heidelberg (n = 160) and externally by a cohort of 133 men from University College London Hospital (UCLH). Assessment of validity was performed at fusion-biopsy by calibration plots, receiver operating characteristics curve and decision curve analyses. The RM`s performance was compared to ERSPC-RC3, ERSPC-RC3+PI-RADSv1.0 and PI-RADSv1.0 alone. RESULTS: SPC was detected in 76 men (48%) at Heidelberg and 38 men (29%) at UCLH. The areas under the curve (AUC) were 0.86 for the RM in both cohorts. For ERSPC-RC3+PI-RADSv1.0 the AUC was 0.84 in Heidelberg and 0.82 at UCLH, for ERSPC-RC3 0.76 at Heidelberg and 0.77 at UCLH and for PI-RADSv1.0 0.79 in Heidelberg and 0.82 at UCLH. Calibration curves suggest that prevalence of sPC needs to be adjusted to local circumstances, as the RM overestimated the risk of harboring sPC in the UCLH cohort. After prevalence-adjustment with respect to the prevalence underlying ERSPC-RC3 to ensure a generalizable comparison, not only between the Heidelberg and die UCLH subgroup, the RM`s Net benefit was superior over the ERSPC`s and the mpMRI`s for threshold probabilities above 0.1 in both cohorts. CONCLUSIONS: The RM discriminated well between men with and without sPC at initial MRI-targeted biopsy but overestimated the sPC-risk at UCLH. Taking prevalence into account, the model demonstrated benefit compared with clinical risk calculators and PI-RADSv1.0 in making the decision to biopsy men at suspicion of PC. However, prevalence differences must be taken into account when using or validating the presented risk model.

Role of MRI in planning radical prostatectomy: what is the added value?

INTRODUCTION: The goal of radical prostatectomy is to eradicate oncological disease while achieving the best possible functional outcomes. In this regard, nerve sparing offers a greater chance of recovering potency after surgery. Accurately locating prostate cancer foci is instrumental for identifying good candidates for this approach whilst maintaining safe oncological margins. In addition to this, the length of membranous urethra is an independent predictor of time to, and extent of, continence recovery. The introduction of Mp-MRI allows visualising malignant tissue within the prostate gland, which could lead to image-directed surgery planning as with other solid-organ cancers such as kidney, pancreas, breast or testes. METHODS: A narrative review of the available literature was performed. RESULTS: Mp-MRI demonstrated moderate sensitivity and high specificity to detect extra-capsular extension, seminal vesicle involvement or T3 stage. Measurements of membranous urethral length have shown to be useful in predicting probability of achieving continence after surgery. Furthermore, image-guided surgery has shown to be accurate to determine surgical planes to safely preserve neurovascular bundles. CONCLUSION: The use of Mp-MRI for pre-surgical planning introduces a new scenario where the previously homogeneous radical prostatectomy can be tailored to suit patient and tumour features. This has the potential to improve functional outcomes whilst not compromising on surgical margins. Moreover, the introduction of Mp-MRI increases the ability to predict functional outcomes after surgery and allows for a more accurate local staging. This in turn provides more information to both patients and clinicians in the decision-making process regarding treatment.

Current concepts in oligometastatic prostate cancer: Is there a role for radical prostatectomy?

INTRODUCTION: Prostate cancer is the most common solid organ malignancy in men. Despite the implementation of PSA screening, the incidence of metastatic prostate cancer in Spain is still around 4%. In this clinical scenario, systemic treatment is the gold standard. Cytoreductive surgery is a standard approach for some solid organ metastatic tumours. Recently there isinterest in exploring the clinical benefit of local treatment (LT) to the primary site in oligometastatic prostate cancer. MATERIALS AND METHODS: Review of the relevant literature to evaluate the benefit of local treatment (LT) in metastatic prostate cancer. RESULTS: Local treatment of the primary tumour has demonstrated oncological and symptomatic benefit in other malignancies. Multimodal therapies have demonstrated oncological and symptomatic benefit in locally advanced prostate cancer. Furthermore, surgery has been shown to reduce symptomatic progression in metastatic prostate cancer. CONCLUSION: The role of surgery to the primary site or metastasis directed treatment is currently being investigated, in the context of oligometastatic prostate cancer. Retrospective data provide a rationale for ongoing randomized controlled trials in this area. New imaging modalities might have a great impact in this conceptual change. Further data is still needed to recommend this approach as a standard of care.

INTRODUCCIÓN: El cáncer de próstata es el tumor maligno más frecuente en varones. A pesar de la implementación del cribado con PSA, la incidenciade cáncer de próstata metastásico en España está en torno al 4%. En este escenario clínico, el tratamiento sistémico es el patrón de referencia. La cirugía citoreductora es un abordaje estándar para algunos tumores metastásicos de órganos sólidos. Recientemente, hay interés en explorar los beneficios clínicos del tratamiento local (TL) en el sitio primario en el cáncer de próstataoligometastásico.MATERIAL Y MÉTODOS: Revisión de la literatura relevante para evaluar el beneficio del tratamiento local en el cáncer de próstata metastásico.RESULTADOS: El tratamiento local del tumor primario ha demostrado beneficios oncológicos y sintomáticos en otros tumores malignos. Los tratamientos multimodales han demostrado beneficios en cáncer de próstata localmente avanzado. Además, la cirugía se ha demostrado que reduce la progresión sintomática en el cáncer de próstata metastásico.CONCLUSIONES: El papel de la cirugía del sitio primario o tratamiento dirigido a las metastasis está actualmente siendo investigado en el contexto del cáncer depróstata oligometastásico. Los datos retrospectivos dan una justificación para los ensayos clínicos aleatorizados en marcha en esta área. Las nuevas modalidades de imagen podrían tener un gran impacto en este cambio conceptual. Todavía son necesarios más datos para recomendar este abordaje como un tratamiento estándar.

New standards in prostate biopsy.

OBJECTIVES: Prostate cancer diagnosis is undergoing a significant change in recent years. The concern about prostate cancer overtreatment as well astechnological developments that allow for better visualization of prostate cancer lesions are the main drivers for this change. METHODS: This was a narrative review of the literature on prostate cancer diagnosis. RESULTS: The diagnostic pathway of prostate cancer based on PSA screening and systematic TRUS has remained unaltered for many years. This is not free of errorand many men with insignificant prostate cancer will be diagnosed. Secondly, men with significant prostate cancer will be missed. Moreover, TRUS approach is associated with a non-negligible rate of sepsis. With the introduction of prostate multiparametric MRI, it seems that we are moving towards a less invasive method of triaging men for prostate biopsy and adopting a biopsy technique which aims to target specific areas within the prostate rather than randomly sampling it. There are a number of other imaging modalities that have attracted attention such as Elastography, histoscanning and contrast enhanced ultrasound. A targeted-only biopsy approach is a feasible option for prostate cancer diagnosis that can improve significant cancer detection and reduce insignificant cancer detection when compared to TRUS biopsy. CONCLUSION: The introduction of multiparametric prostate MRI has the potential to change the way that we diagnose men with prostate cancer.

OBJETIVOS: El diagnóstico del cáncer de próstata está sufriendo un cambio significativo en los años recientes. La preocupación por el sobretratamientoasí cómo los desarrollos tecnológicos que permiten una mejor visualización de las lesiones del cáncer de próstata son los impulsores principales de este cambio.MÉTODOS: Hacemos una revisión narrativa de la literatura sobre el diagnóstico de cáncer de próstata. RESULTADOS: La vía diagnóstica del cáncer de próstata basada en cribado con PSA y biopsia transrectal ecodirigida ha permanecido inalterada durante muchosaños. Esto no está libre de error y se diagnostican muchos varones con cáncer de próstata insignificante. En segundo lugar, se pierden varones con cáncer de próstata significativo. Además, el abordaje con ecografía transrectal se asocia con una tasa no despreciable de sepsis. Con la introducción de la RMN multiparamétrica, parece que nos estamos moviendo hacia un métodomenos invasivo de triaje de varones para biopsia prostática y a adoptar una técnica de biopsia que busque dirigirse a áreas específicas dentro de la próstata más que un muestreo al azar. Hay un número de técnicas de imagen diferentes que han atraído la atención tales como elastografía, histoescaner y ecografía con contraste. En comparación con la biopsia transrectal, un abordaje de biopsia dirigida solo es una opción factible para el diagnóstico de cáncer de próstata que puede mejorar significativamente la detección de cáncer y disminuir la detección de cáncer insignificante. CONCLUSION: La introducción de la RMN multiparamétrica de próstata tiene el potencial de cambiar la forma en que diagnosticamos a los varones con cáncerde próstata.

Prostate cancer treated with irreversible electroporation: MRI-based volumetric analysis and oncological outcome.

BACKGROUND: To assess multiparametric magnetic resonance imaging (mpMRI) characteristics in prostate cancer (PCa) before and after irreversible electroporation (IRE) and to investigate their correlation with the presence of post-operative recurrence of PCa. METHODS: MpMRI was performed in 30 men with PCa prior to treatment, after 10 days and at 6 months. An additional scan at 1 year was available for 18 men. Two radiologists assessed retrospectively the following parameters by planimetry: tumour volume, necrotic volume (early post-treatment scan) and residual fibrosis. Residual tumour/recurrence were defined as a suspicious area within the treatment field scored ≥ 4 on a 1-to-5 scale. Oncological outcome was also assessed. RESULTS: The median follow-up of the entire study was 16 months. Six men were undertreated and showed mpMRI recurrence after 6 months. At 1-year, three additional men had recurrence. Overall, four of these 9 men (44%) were retreated. The other five men did not receive any further treatment. Median time to re-treatment was 15 months. Median pre-treatment lesion volume was 0.65 cc, 0.66 cc and 0.43 cc on the different mpMRI sequences (T2-weighted, diffusion-weighted and dynamic contrast enhanced imaging). Median necrotic volume was 10.77 cc. Median overall residual fibrosis volumes were 0.84 cc and 0.95 cc at 6-month and 1-year mpMRI. Pre-treatment, necrotic and residual fibrosis volumes were significantly different (p < 0.001). Pre-treatment tumour volumes on diffusion-weighted imaging and necrotic volumes were correlated (r = 0.18; p = 0.02). CONCLUSIONS: MpMRI is able to visualise the IRE ablation effects in men with PCa. MpMRI-derived parameters - such as tumour, necrotic and fibrosis volumes - can be measured and are potentially useful for assessing efficacy in the medium term, as with other ablative techniques.

Recommendations for the use of parenteral methotrexate in rheumatic diseases. / Recomendaciones sobre el uso de metrotexato parenteral en enfermedades reumáticas.

OBJECTIVE: To develop recommendations for the use of parenteral methotrexate (MTX) in rheumatic diseases, mainly rheumatoid arthritis, based on best evidence and experience. METHODS: A group of 21 experts on parenteral MTX use was selected. The coordinator formulated 13 questions about parenteral MTX (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (involving Medline, EMBASE and the Cochrane Library). Three different reviewers selected the articles. Evidence tables were created. Abstracts from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) were evaluated. Based on this evidence, the coordinator proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Center for Evidence-Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). RESULTS: Most of the evidence involved rheumatoid arthritis. A total of 13 preliminary recommendations on the use of parenteral MTX were proposed; 11 of them were accepted. Two of the 13 were not voted and are commented on in the main text. CONCLUSIONS: The manuscript aims to solve frequent questions and help in decision-making strategies when treating patients with parenteral MTX.

Incidence, associated factors and clinical impact of severe infections in a large, multicentric cohort of patients with systemic lupus erythematosus.

OBJECTIVES: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS: A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ≥1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (≥10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS: Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect.

Analysis of Duplicated Multiple-Samples Rank Data Using the Mack-Skillings Test.

Appropriate analysis for duplicated multiple-samples rank data is needed. This study compared analysis of duplicated rank preference data using the Friedman versus Mack-Skillings tests. Panelists (n = 125) ranked twice 2 orange juice sets: different-samples set (100%, 70%, vs. 40% juice) and similar-samples set (100%, 95%, vs. 90%). These 2 sample sets were designed to get contrasting differences in preference. For each sample set, rank sum data were obtained from (1) averaged rank data of each panelist from the 2 replications (n = 125), (2) rank data of all panelists from each of the 2 separate replications (n = 125 each), (3) jointed rank data of all panelists from the 2 replications (n = 125), and (4) rank data of all panelists pooled from the 2 replications (n = 250); rank data (1), (2), and (4) were separately analyzed by the Friedman test, although those from (3) by the Mack-Skillings test. The effect of sample sizes (n = 10 to 125) was evaluated. For the similar-samples set, higher variations in rank data from the 2 replications were observed; therefore, results of the main effects were more inconsistent among methods and sample sizes. Regardless of analysis methods, the larger the sample size, the higher the χ(2) value, the lower the P-value (testing H0 : all samples are not different). Analyzing rank data (2) separately by replication yielded inconsistent conclusions across sample sizes, hence this method is not recommended. The Mack-Skillings test was more sensitive than the Friedman test. Furthermore, it takes into account within-panelist variations and is more appropriate for analyzing duplicated rank data.

[Penile necrosis as clinical presentation of systemic Calciphylaxis: Report of two cases and bibliographic review]. / Necrosis peneana como síntoma dubut de calcifilaxis sistémica análisis de 2 casos y revisión de la literatura.

OBJECTIVE: Calciphylaxis is a potentially lethal syndrome reported mainly in patients with ESRD on hemodialysis. Etiopathogenesis remains unclear and there is much controversy regarding optimal diagnostic and therapeutic approach. Penile necrosis as a disease presentation is extremely rare. We report two clinical cases treated in our center and perform an evidence review. METHODS: Clinical data was obtained from both patients and an evidence review was performed on PubMed under the criteria "penile necrosis" and "Calciphylaxis". RESULTS: Both patients underwent partial penectomy due to severe penile necrosis. After surgery both patients received treatment with sodium thiosulfate (STS) 20mg in every hemodialysis session. Both patients showed stabilization of necrotic lesions. DISCUSSION: The same way that biopsying the ischemic lesions produced by Calciphylaxis is discussed and even misadvised, the role of aggressive surgery as first line therapy might be uncertain specially with the raising of new specific drugs such as sodium thiosulfate (STS) that have shown efficacy stopping disease progression.