Release of Gentamicin and Vancomycin from Preformed Spacers in Infected Total Hip Arthroplasties: Measurement of Concentrations and Inhibitory Activity in Patients’ Drainage Fluids and Serum

Gentamicin (G) and vancomycin (V) concentrations in drainage fluids obtained from patients during the first 24 hours after implantation of antibiotic-loaded polymethylmethacrylate (PMMA) spacers in two-stage revision of infected total hip arthroplasty were studied. The inhibitory activity of drainage fluids against different multiresistant clinical isolates was investigated as well. Seven hips were treated by implantation of industrial G-loaded spacers. Vancomycin was added by manually mixing with PMMA bone cement. Serum and drainage fluid samples were collected 1, 4, and 24 hours after spacer implantation. Antibiotics concentrations and drains bactericidal titer of combination were determined against multiresistant staphylococcal strains. The release of G and V from PMMA cement at the site of infection was prompt and effective. Serum levels were below the limit of detection. The local release kinetics of G and V from PMMA cement was similar, exerting a pronounced, combined inhibitory effect in the implant site. The inhibitory activity of drainage fluids showed substantial intersubject variability related to antibiotic concentrations and differed according to the pathogens tested. Gentamicin and vancomycin were released from temporary hip spacers at bactericidal concentrations, and their use in combination exerted strong inhibition against methicillin-resistant S. aureus and Coagulase Negative Staphylococci strains

Glycan analysis of human neutrophil granules implicates a maturation-dependent glycosylation machinery

Protein glycosylation is essential to trafficking and immune functions of human neutrophils. During granulopoiesis in the bone marrow, distinct neutrophil granules are successively formed. Distinct receptors and effector proteins, many of which are glycosylated, are targeted to each type of granule according to their time of expression, a process called "targeting by timing." Therefore, these granules are time capsules reflecting different times of maturation that can be used to understand the glycosylation process during granulopoiesis. Herein, neutrophil subcellular granules were fractionated by Percoll density gradient centrifugation, andN- andO-glycans present in each compartment were analyzed by LC-MS. We found abundant paucimannosidicN-glycans and lack ofO-glycans in the early-formed azurophil granules, whereas the later-formed specific and gelatinase granules and secretory vesicles contained complexN-andO-glycans with remarkably elongatedN-acetyllactosamine repeats with Lewis epitopes. Immunoblotting and histochemical analysis confirmed the expression of Lewis X and sialyl-Lewis X in the intracellular granules and on the cell surface, respectively. Many glycans identified are unique to neutrophils, and their complexity increased progressively from azurophil granules to specific granules and then to gelatinase granules, suggesting temporal changes in the glycosylation machinery indicative of "glycosylation by timing" during granulopoiesis. In summary, this comprehensive neutrophil granule glycome map, the first of its kind, highlights novel granule-specific glycosylation features and is a crucial first step toward a better understanding of the mechanisms regulating protein glycosylation during neutrophil granulopoiesis and a more detailed understanding of neutrophil biology and function

Comparative Analysis of PSA Density and an MRI-Based Predictive Model to Improve the Selection of Candidates for Prostate Biopsy

Clinically significant prostate cancer; Predictive model; Prostate-specific antigenCàncer de pròstata clínicament significatiu; Model predictiu; Antigen específic de la pròstataCáncer de próstata clínicamente significativo; Modelo predictivo; Antígeno específico de la próstataThis study is a head-to-head comparison between mPSAD and MRI-PMbdex. The MRI-PMbdex was created from 2432 men with suspected PCa; this cohort comprised the development and external validation cohorts of the Barcelona MRI predictive model. Pre-biopsy 3-Tesla multiparametric MRI (mpMRI) and 2 to 4-core transrectal ultrasound (TRUS)-guided biopsies for suspicious lesions and/or 12-core TRUS systematic biopsies were scheduled. Clinically significant PCa (csPCa), defined as Gleason-based Grade Group 2 or higher, was detected in 934 men (38.4%). The area under the curve was 0.893 (95% confidence interval [CI]: 0.880–0.906) for MRI-PMbdex and 0.764 (95% CI: 0.774–0.783) for mPSAD, with p < 0.001. MRI-PMbdex showed net benefit over biopsy in all men when the probability of csPCa was greater than 2%, while mPSAD did the same when the probability of csPCa was greater than 18%. Thresholds of 13.5% for MRI-PMbdex and 0.628 ng/mL2 for mPSAD had 95% sensitivity for csPCa and presented 51.1% specificity for MRI-PMbdex and 19.6% specificity for mPSAD, with p < 0.001. MRI-PMbdex exhibited net benefit over mPSAD in men with prostate imaging report and data system (PI-RADS) <4, while neither exhibited any benefit in men with PI-RADS 5. Hence, we can conclude that MRI-PMbdex is more accurate than mPSAD for the proper selection of candidates for prostate biopsy among men with suspected PCa, with the exception of men with a PI-RAD S 5 score, for whom neither tool exhibited clinical guidance to determine the need for biopsy.This research was funded by Instituto de Salut Carlos III (ESP), grant number PI20/01666

The current recommendation for the management of isolated high-grade prostatic intraepithelial neoplasia

Altres ajuts: Acord transformatiu CRUE-CSICObjective: To analyse the current predictive value of isolated high-grade prostatic intraepithelial neoplasia (HGPIN) for clinically significant prostate cancer (csPCa) detection in repeat biopsies. Patients and Methods: A cohort of 293 men with isolated HGPIN detected in previous biopsies performed without multiparametric magnetic resonance imaging (mpMRI), and who underwent repeat biopsy within 1 to 3 years, was analysed. Pre-repeat biopsy mpMRI and guided biopsies to suspicious lesions (Prostate Imaging - Reporting and Data System [PI-RADS] ≥3) and/or and systematic biopsies were performed. Persistent prostate cancer (PCa) suspicion, defined as sustained serum prostatespecific antigen level >4 ng/mL and/or abnormal digital rectal examination, was present in 248 men (84.6%), and was absent in 45 men (15.4%). A control group of 190 men who had no previous HGPIN, atypical small acinar proliferation or HGPIN with atypia who were scheduled to undergo repeat biopsy due to persistent PCa suspicion were also analysed. csPCa was defined as tumours of Grade Group ≥2.Results: In the subset of 45 men with isolated HGPIN, in whom PCa suspicion disappeared, only one csPCa (2.2%) and one insignificant PCa (iPCa) were detected. csPCa was detected in 34.7% of men with persistent PCa suspicion and previous HGPIN, and in 28.4% of those without previous HGPIN (P =0.180). iPCa was detected in 12.1% and 6.3%, respectively (P =0.039). Logistic regression analysis showed that the risk of csPCa detection was not predicted by previous HGPIN: odds ratio (OR) 1.369 (95% confidence interval [CI] 0.894-2.095; P =0.149); however, previous HGPIN increased the risk of iPCa detection: OR 2.043 (95% CI 1.016-4.109; P =0.006). Conclusion: The risk of csPCa in men with isolated HGPIN, in whom PCa suspicion disappears, is extremely low. Moreover, in those men in whom PCa suspicion persists, the risk of csPCa is not influenced by the previous finding of HGPIN. However, previous HGPIN increases the risk of iPCa detection. Therefore, repeat prostate biopsy should not be recommended solely because of a previous HGPIN

ESTILO DE VIDA ATIVO E INDICADORES DA SAÚDE E QUALIDADE DE VIDA EM IDOSOS

Lifestyle is composed of changeable behaviors, which is characterized as a set of habits, routines and choices that are positive and negative experienced by people throughout life. Objective: To highlight the active lifestyle as an indicator of health and quality of life in the elderly. Methods: This is an integrative literature review, carried out in the following databases: Virtual Health Library (VHL), Scientific Electronic Library Online (SciELO) and Google Scholar, using the following specific descriptors that are related to or part of the focus of the construct, such as: "lifestyle", "level of physical activity", "lifestyle and level of physical activity", "lifestyle in the elderly", "level of physical activity in the elderly" and "physical exercise and lifestyle in the elderly" were used for this purpose only original scientific articles published in Brazil in the last 10 years. The data were organized according to the similarity of the theme in question and gathered in chronological order. Results: Out of a total of 30 publications found, 06 articles met the proposed objectives. In the studies analyzed, it was identified that elderly people who maintain an active lifestyle have higher quality of life indexes. Considerations: Finally, physical exercise contributes in a favorable and significant way, thus favoring a healthier and safer aging. It is possible to improve the quality of life of the elderly, so that they can live more independently and healthily, preventing the diseases that occur during the aging process.Introducción: El estilo de vida está compuesto por conductas cambiantes, que se caracteriza como un conjunto de hábitos, rutinas y elecciones que son positivas y negativas experimentadas por las personas a lo largo de la vida. Objetivo: Destacar el estilo de vida activo como indicador de salud y calidad de vida en el adulto mayor. Métodos: Se trata de una revisión integradora de la literatura, realizada en las siguientes bases de datos: Biblioteca Virtual en Salud (BVS), Scientific Electronic Library Online (SciELO) y Google Scholar, utilizando los siguientes descriptores específicos que se relacionan o forman parte del enfoque del constructo, tales como: "estilo de vida", "nivel de actividad física", "estilo de vida y nivel de actividad física",  "estilo de vida en el anciano", "nivel de actividad física en el anciano" y "ejercicio físico y estilo de vida en el anciano" fueron utilizados para este propósito, solo artículos científicos originales publicados en Brasil en los últimos 10 años. Resultados: De un total de 30 publicaciones encontradas, 06 artículos cumplieron con los objetivos propuestos. En los estudios analizados se identificó que las personas mayores que mantienen un estilo de vida activo tienen mayores índices de calidad de vida. Consideraciones: Por último, el ejercicio físico contribuye de forma favorable y significativa, favoreciendo así un envejecimiento más saludable y seguro.   O estilo de vida é composto de comportamentos alteráveis, que se caracteriza como um conjunto de costumes, rotinas e escolhas sendo positivas e negativas vivenciadas pelas pessoas ao longo da vida. Objetivo: Destacar o estilo de vida ativo como indicador da saúde e qualidade de vida em idosos. Métodos: Trata-se de uma revisão bibliográfica do tipo integrativa, realizadas nas bases de dados: Biblioteca Virtual em Saúde (BVS), Scientific Eletronic Library Online (SciELO) e Google acadêmico, utilizando os seguintes descritores específicos que se relacionam ou fazem parte do foco do constructo como: “estilo de vida”, “nível de atividade física”, “estilo de vida e nível de atividade física”, “estilo de vida em idosos”, “nível de atividade física em idosos” e “exercício físico e estilo de vida em idosos” para tanto foram utilizados somente artigos científicos originais publicados no Brasil nos últimos 10 anos. Os dados foram organizados de acordo com a similaridade da temática em questão  e reunidos em ordem cronológica. Resultados: De um total de 30 publicações encontradas, 06artigos atenderam aos objetivos propostos. Nos estudos analisados foi identificado que idosos que mantêm um estilo de vida ativo têm maiores índices de qualidade de vida. Considerações: Por fim, os exercícios físicos contribuem de maneira favorável e significativa, favorecendo assim, um envelhecimento mais saudável e seguro. É possível melhorar a qualidade de vida dos idosos, a fim de que, possam viver com mais independência e saúde, prevenindo as doenças que ocorrem durante o processo de envelhecimento.  O estilo de vida é composto de comportamentos alteráveis, que se caracteriza como um conjunto de costumes, rotinas e escolhas sendo positivas e negativas vivenciadas pelas pessoas ao longo da vida. Objetivo: Destacar o estilo de vida ativo como indicador da saúde e qualidade de vida em idosos. Métodos: Trata-se de uma revisão bibliográfica do tipo integrativa, realizadas nas bases de dados: Biblioteca Virtual em Saúde (BVS), Scientific Eletronic Library Online (SciELO) e Google acadêmico, utilizando os seguintes descritores específicos que se relacionam ou fazem parte do foco do constructo como: “estilo de vida”, “nível de atividade física”, “estilo de vida e nível de atividade física”, “estilo de vida em idosos”, “nível de atividade física em idosos” e “exercício físico e estilo de vida em idosos” para tanto foram utilizados somente artigos científicos originais publicados no Brasil nos últimos 10 anos. Os dados foram organizados de acordo com a similaridade da temática em questão  e reunidos em ordem cronológica. Resultados: De um total de 30 publicações encontradas, 06artigos atenderam aos objetivos propostos. Nos estudos analisados foi identificado que idosos que mantêm um estilo de vida ativo têm maiores índices de qualidade de vida. Considerações: Por fim, os exercícios físicos contribuem de maneira favorável e significativa, favorecendo assim, um envelhecimento mais saudável e seguro. É possível melhorar a qualidade de vida dos idosos, a fim de que, possam viver com mais independência e saúde, prevenindo as doenças que ocorrem durante o processo de envelhecimento.

Simultaneous treatment with statins and aspirin reduces the risk of prostate cancer detection and tumorigenic properties in prostate cancer cell lines

Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467-0.812), ). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068-3.155), ) or the combination of both drugs (OR: 3.059 (95% CI: 1.894-4.939), ) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence

Who with suspected prostate cancer can benefit from Proclarix after multiparametric magnetic resonance imaging?

Cathepsin D; Magnetic resonance imaging; ProclarixCatepsina D; Imatges per ressonància magnètica; ProclarixCatepsina D; Imágenes por resonancia magnética; ProclarixProclarix is a new blood-based test to assess the likelihood of clinically significant prostate cancer (csPCa) defined as >2 grade group. In this study, we analyzed whether Proclarix and PSA density (PSAD) could improve the selection of candidates for prostate biopsy after multiparametric magnetic resonance imaging (mpMRI). Proclarix and PSAD were assessed in 567 consecutive men with suspected PCa in whom pre-biopsy 3 Tesla mpMRI, scoring with Prostate Imaging-Report and Data System (PI-RADS) v.2, and guided and/or systematic biopsies were performed. Proclarix and PSAD thresholds having csPCa sensitivity over 90% were found at 10% and 0.07 ng/(mL*cm3), respectively. Among 100 men with negative mpMRI (PI-RADS <3), csPCa was detected in 6 cases, which would have been undetected if systematic biopsies were avoided. However, Proclarix suggested performing a biopsy on 70% of men with negative mpMRI. In contrast, PSAD only detected 50% of csPCa and required 71% of prostate biopsies. In 169 men with PI-RADS 3, Proclarix avoided 21.3% of prostate biopsies and detected all 25 cases of csPCa, while PSAD avoided 26.3% of biopsies, but missed 16% of csPCa. In 190 men with PI-RADS 4 and 108 with PI-RADS 5, Proclarix avoided 12.1% and 5.6% of prostate biopsies, but missed 4.8% and 1% of csPCa, respectively. PSAD avoided 18.4% and 9.3% of biopsies, but missed 11.4% and 4.2% csPCa, respectively. We conclude that Proclarix outperformed PSAD in the selection of candidates for prostate biopsy, especially in men with PI-RADS <3.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Instituto de Salud Carlos III, (grant number PI20/01666)