Prostate cancer biomarkers: a practical review based on different clinical scenarios

Traditionally, diagnosis and staging of prostate cancer (PCa) have been based on prostate-specific antigen (PSA) level, digital rectal examination (DRE), and transrectal ultrasound (TRUS) guided prostate biopsy. Biomarkers have been introduced into clinical practice to reduce the overdiagnosis and overtreatment of low-grade PCa and increase the success of personalized therapies for high-grade and high-stage PCa. The purpose of this review was to describe available PCa biomarkers and examine their use in clinical practice. A nonsystematic literature review was performed using PubMed and Scopus to retrieve papers related to PCa biomarkers. In addition, we manually searched websites of major urological associations for PCa guidelines to evaluate available evidence and recommendations on the role of biomarkers and their potential contribution to PCa decision-making. In addition to PSA and its derivates, thirteen blood, urine, and tissue biomarkers are mentioned in various PCa guidelines. Retrospective studies have shown their utility in three main clinical scenarios: (1) deciding whether to perform a biopsy, (2) distinguishing patients who require active treatment from those who can benefit from active surveillance, and (3) defining a subset of high-risk PCa patients who can benefit from additional therapies after RP. Several validated PCa biomarkers have become commercially available in recent years. Guidelines now recommend offering these tests in situations in which the assay result, when considered in combination with routine clinical factors, is likely to affect management. However, the lack of direct comparisons and the unproven benefits, in terms of long-term survival and cost-effectiveness, prevent these biomarkers from being integrated into routine clinical use

A Gradient-Based Approach for Breast DCE-MRI Analysis

Breast cancer is the main cause of female malignancy worldwide. Effective early detection by imaging studies remains critical to decrease mortality rates, particularly in women at high risk for developing breast cancer. Breast Magnetic Resonance Imaging (MRI) is a common diagnostic tool in the management of breast diseases, especially for high-risk women. However, during this examination, both normal and abnormal breast tissues enhance after contrast material administration. Specifically, the normal breast tissue enhancement is known as background parenchymal enhancement: it may represent breast activity and depends on several factors, varying in degree and distribution in different patients as well as in the same patient over time. While a light degree of normal breast tissue enhancement generally causes no interpretative difficulties, a higher degree may cause difficulty to detect and classify breast lesions at Magnetic Resonance Imaging even for experienced radiologists. In this work, we intend to investigate the exploitation of some statistical measurements to automatically characterize the enhancement trend of the whole breast area in both normal and abnormal tissues independently from the presence of a background parenchymal enhancement thus to provide a diagnostic support tool for radiologists in the MRI analysis

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, Rezūm, 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 Rezūm, 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

Working Group on Biological Parameters (WGBIOP) 2021

The main objective of the Working Group on Biological Parameters (WGBIOP) is to review the status, issues, developments, and quality assurance of biological parameters used in assessment and management. WGBIOP (1) plans workshops, exchanges, and validation studies on a range of biological varia-bles to review the quality of information supplied for stock assessment and improve quality as-surance and training; (2) investigates data availability and develops documentation and methods to improve communication between data collectors and end-users; (3) delivers new and im-proved functionality for the SmartDots platform. Four otolith exchanges and two workshops were completed in 2020–2021 using SmartDots— eight further exchanges are ongoing. Proposed future exchanges and workshops were reviewed and approved. The development of the SmartDots platform proceeded with the inclusion of the maturity, eggs, atresia, fecundity, and larval identification modules into the software version. A live SmartDots tutorial for event coordinators was conducted. Work to further develop quality assurance guidelines—and review national applications of these—progressed. Age and maturity validation studies were reviewed and a new method for prioritizing future validation work was proposed. Progress with the Stock Identification Database (SID) was reviewed, and the potential for creating a WGBIOP library collection and active involvement of WGBIOP in updating FishBase.org data were evaluated. The importance of identifying and documenting links be-tween all relevant databases and document repositories was identified, and a task to address this was initiated. Work on improving the feedback loop between data collectors and stock assessors on the usage and quality of biological parameters in stock assessment continued. Moving forward, WGBIOP aims to continue collaboration with WGALES and WGSMART on the development of the SmartDots platform, encouraging cross-group sharing of skills and ex-perience to optimize results. WGBIOP aims to improve accessibility to its outputs through up-dates to SID and FishBase.org, and the potential creation of a WGBIOP library collection. WGBIOP hopes to improve two-way communication between data collectors and end-users around the quality and utility of biological parameters used in assessment. WGBIOP also aims to amalgamate all validation activities into one coherent workstream.ICE

Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract – possible synergistic and resistance mechanisms

Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin

De jure determinants of new firm formation: how the pillars of constitutions influence entrepreneurship

This paper provides empirical evidence supporting the view that constitutions are the primary and fundamental institutional determinant of entrepreneurship. It shows that some of the provisions contained in national constitutions are positively and significantly associated with a standard measure of entrepreneurial dynamics, namely the rate of new business density. Using for 115 countries a novel dataset containing the characteristics of the constitutions enacted in the world, applying an IV-GMM treatment to deal with the endogeneity of constitutional rules, and controlling for de facto variables, the paper finds that provisions about the right to conduct/establish a business, the right to strike, consumer protection, anti-corruption, and compulsory education promote higher rates of new firm formation. Contrasting results are instead obtained for provisions concerning protection of intellectual property rights

Transport-theoretical Description of Nuclear Reactions

In this review we first outline the basics of transport theory and its recent generalization to off-shell transport. We then present in some detail the main ingredients of any transport method using in particular the Giessen Boltzmann-Uehling-Uhlenbeck (GiBUU) implementation of this theory as an example. We discuss the potentials used, the ground state initialization and the collision term, including the in-medium modifications of the latter. The central part of this review covers applications of GiBUU to a wide class of reactions, starting from pion-induced reactions over proton and antiproton reactions on nuclei to heavy-ion collisions (up to about 30 AGeV). A major part concerns also the description of photon-, electron- and neutrino-induced reactions (in the energy range from a few 100 MeV to a few 100 GeV). For this wide class of reactions GiBUU gives an excellent description with the same physics input and the same code being used. We argue that GiBUU is an indispensable tool for any investigation of nuclear reactions in which final-state interactions play a role. Studies of pion-nucleus interactions, nuclear fragmentation, heavy ion reactions, hyper nucleus formation, hadronization, color transparency, electron-nucleus collisions and neutrino-nucleus interactions are all possible applications of GiBUU and are discussed in this article.Comment: 173 pages, review article. v2: Text-rearrangements in sects. 2 and 3 (as accepted for publication in Physics Reports

Brain death and postmortem organ donation: Report of a questionnaire from the CENTER-TBI study

Background: We aimed to investigate the extent of the agreement on practices around brain death and postmortem organ donation. Methods: Investigators from 67 Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study centers completed several questionnaires (response rate: 99%). Results: Regarding practices around brain death, we found agreement on the clinical evaluation (prerequisites and neurological assessment) for brain death determination (BDD) in 100% of the centers. However, ancillary tests were required for BDD in 64% of the centers. BDD for nondonor patients was deemed mandatory in 18% of the centers before withdrawing life-sustaining measures (LSM). Also, practices around postmortem organ donation varied. Organ donation after circulatory arrest was forbidden in 45% of the centers. When withdrawal of LSM was contemplated, in 67% of centers the patients with a ventricular drain in situ had this removed, either sometimes or all of the time. Conclusions: This study showed both agreement and some regional differences regarding practices around brain death and postmortem organ donation. We hope our results help quantify and understand potential differences, and provide impetus for current dialogs toward further harmonization of practices around brain death and postmortem organ donation

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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