Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance

[EN] Background: Prostate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present. In spite of the improvement with multiparametric MRI, the low reproducibility of its reading undermines the specificity of the method. Recent development of prostatespecific radiotracers has grown the interest on using positron emission tomography (PET) scanners for this purpose, but technological improvements are still required (current scanners have resolutions in the range of 4¿5 mm). Results: The main goal of this work is to improve state-of-the-art PCa imaging and diagnosis. We have focused our efforts on the design of a novel prostate-dedicated PET scanner, named ProsPET. This system has small scanner dimensions defined by a ring of just 41 cm inner diameter. In this work, we report the design, implementation, and evaluation (both through simulations and real data) of the ProsPET scanner. We have been able to achieve < 2 mm resolution in reconstructed images and high sensitivity. In addition, we have included a comparison with the Philips Gemini-TF scanner, which is used for routine imaging of PCa patients. The ProsPET exhibits better contrast, especially for rod sizes as small as 4.5 mm in diameter. Finally, we also show the first reconstructed image of a PCa patient acquired with the ProsPET. Conclusions: We have designed and built a prostate specific PET system, with a small footprint and improved spatial resolution when compared to conventional whole-body PET scanners. The gamma ray impact within each detector block includes accurate DOI determination, correcting for the parallax error. The potential role of combined organdedicated prostate-specific membrane antigen (PSMA) PET and ultrasound devices, as a prebiopsy diagnostic tool, could be used to guide sampling of the most aggressive sites in the prostate.The work presented in this article has been partially funded by a research grant from the regional government of the Comunitat Valenciana (Spain), co-funded by the European Union ERDF funds (European Regional Development Fund) of the Comunitat Valenciana 2014-2020, with reference IDIFEDER/2018/032 (High-Performance Algorithms for the Modelling, Simulation and early Detection of diseases in Personalized Medicine). This project has also received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the EU Grant 603002 under the FP7 program and by the Spanish Ministerio de Economia, Industria y Competitividad under Grant e and through PROSPET (DTS15/00152) funded by the Ministerio de Economia y Competitividad.Cañizares-Ledo, G.; Gonzalez-Montoro, A.; Freire, M.; Lamprou, E.; Barrio, J.; Sánchez Martínez, F.; Benlloch Baviera, JM.... (2020). Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance. EJNMMI Physics. 7(1):1-17. https://doi.org/10.1186/s40658-020-00305-yS11771GLOBOCAN 2018. http://www.gco.iarc.fr/today/ datasources-methods. Accessed 26 Dec 2019.Ferlay J, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN. Int J Cancer. 2012;2015:136–E359.Rawla P. Epidemiology of prostate cancer. 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Precise Modeling of the Exoplanet Host Star and CoRoT Main Target HD 52265

This paper presents a detailed and precise study of the characteristics of the Exoplanet Host Star and CoRoT main target HD 52265, as derived from asteroseismic studies. The results are compared with previous estimates, with a comprehensive summary and discussion. The basic method is similar to that previously used by the Toulouse group for solar-type stars. Models are computed with various initial chemical compositions and the computed p-mode frequencies are compared with the observed ones. All models include atomic diffusion and the importance of radiative accelerations is discussed. Several tests are used, including the usual frequency combinations and the fits of the \'echelle diagrams. The possible surface effects are introduced and discussed. Automatic codes are also used to find the best model for this star (SEEK, AMP) and their results are compared with that obtained with the detailed method. We find precise results for the mass, radius and age of this star, as well as its effective temperature and luminosity. We also give an estimate of the initial helium abundance. These results are important for the characterization of the star-planet system.Comment: 9 pages, 6 figures, 7 tables, to be published in Astronomy and Astrophysic

Time-Expanded F-OTDR based on binary sequences

In this paper, the capabilities of time-expanded phase-sensitive optical time-domain reflectometry (TE F-OTDR) using binary sequences are demonstrated. We present a highly flexible and integrable TE F-OTDR approach that allows a customized distributed optical fiber sensor (range, spatial resolution, and acoustic sampling) by simply changing the length of the binary sequence and the reference clock frequencies of the binary sequence generators. The here presented architecture eliminates the need for the cumbersome arbitrary signal generators used to date to create the dual-comb spectra for interrogating the fiber. In this approach, the use of large binary sequences allows us to obtain dual combs in a simple and cost-effective way. Spatial resolution of ~1 cm is achieved, attaining ~15, 000 independent measurements points along the interrogated fiber, with a capability of sensing ~30, 000 measurements points

Major Adverse Cardiovascular Events in Coronary Type 2 Diabetic Patients: Identification of Associated Factors Using Electronic Health Records and Natural Language Processing

Diabetes mellitus; Natural language processing; Risk factorsDiabetis mellitus; Processament del llenguatge natural; Factors de riscDiabetes mellitus; Procesamiento del lenguaje natural; Factores de riesgoPatients with Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are at high risk of developing major adverse cardiovascular events (MACE). This is a multicenter, retrospective, and observational study performed in Spain aimed to characterize these patients in a real-world setting. Unstructured data from the Electronic Health Records were extracted by EHRead®, a technology based on Natural Language Processing and machine learning. The association between new MACE and the variables of interest were investigated by univariable and multivariable analyses. From a source population of 2,184,662 patients, we identified 4072 adults diagnosed with T2DM and CAD (62.2% male, mean age 70 ± 11). The main comorbidities observed included arterial hypertension, hyperlipidemia, and obesity, with metformin and statins being the treatments most frequently prescribed. MACE development was associated with multivessel (Hazard Ratio (HR) = 2.49) and single coronary vessel disease (HR = 1.71), transient ischemic attack (HR = 2.01), heart failure (HR = 1.32), insulin treatment (HR = 1.40), and percutaneous coronary intervention (PCI) (HR = 2.27), whilst statins (HR = 0.73) were associated with a lower risk of MACE occurrence. In conclusion, we found six risk factors associated with the development of MACE which were related with cardiovascular diseases and T2DM severity, and treatment with statins was identified as a protective factor for new MACE in this study.This study was funded by AstraZeneca Spain (Externally Sponsored Scientific Research, ESR-18-13815) and sponsored by the Spanish Society of Cardiology

Single layer centrifugation (SLC) for bacterial removal with Porcicoll positively modifies chromatin structure in boar spermatozoa

The storage of boar semen samples at 17 degrees C for artificial insemination (AI) doses enables the proliferation of the bacteria, making antibiotics necessary. This can contribute to the development of antimicrobial resistance (AMR). This study tested bacterial presence and sperm chromatin structure after using a low-density colloid (Porcicoll) as an antibiotic alternative to eliminate bacteria. Ejaculates (8 boars, 3 ejac-ulates each) were split as control and low-density colloid centrifugation (single layer centrifugation, SLC, 20%, and 30% Porcicoll) into 500 ml tubes. Analyses were carried out at days 0, 3, and 7 (17 degrees C) for microbial presence and sperm chromatin structure analysis: %DFI (DNA fragmentation) and %HDS (chromatin immaturity), monobromobimane (mBBr; free thiols and disulfide bridges), and chromomycin A3 (CMA3; chromatin compaction). Besides comparing bacterial presence (7 species identified) and chromatin variables between treatments, the associations between these sets of variables were described by canonical correlation analysis (CCA). Results showed a significant decrease of some bacteria or a complete removal after SLC (especially for P30). SLC also caused a decrease of %HDS and an increase of disulfide bridges and low and medium mBBr populations, suggesting the removal of immature sperm (poor chromatin compaction). CCA showed an association pattern compatible with the degradation of sperm chromatin parameters with bacterial contamination, especially Enterobacteria, P. aeuriginosa, and K. variicola. In conclusion, bacterial contamination affects sperm chromatin beyond DNA fragmentation; SLC with low-density colloid not only removes bacteria from boar semen, but also chromatin structure is enhanced after selection.(c) 2023 Published by Elsevier Inc

Amyloid-β reduces the expression of neuronal FAIM-L, thereby shifting the inflammatory response mediated by TNFα from neuronal protection to death

The brains of patients with Alzheimer’s disease (AD) present elevated levels of tumor necrosis factor-α (TNFα), a cytokine that has a dual function in neuronal cells. On one hand, TNFα can activate neuronal apoptosis, and on the other hand, it can protect these cells against amyloid-β (Aβ) toxicity. Given the dual behavior of this molecule, there is some controversy regarding its contribution to the pathogenesis of AD. Here we examined the relevance of the long form of Fas apoptotic inhibitory molecule (FAIM) protein, FAIM-L, in regulating the dual function of TNFα. We detected that FAIM-L was reduced in the hippocampi of patients with AD. We also observed that the entorhinal and hippocampal cortex of a mouse model of AD (PS1M146LxAPP751sl) showed a reduction in this protein before the onset of neurodegeneration. Notably, cultured neurons treated with the cortical soluble fractions of these animals showed a decrease in endogenous FAIM-L, an effect that is mimicked by the treatment with Aβ-derived diffusible ligands (ADDLs). The reduction in the expression of FAIM-L is associated with the progression of the neurodegeneration by changing the inflammatory response mediated by TNFα in neurons. In this sense, we also demonstrate that the protection afforded by TNFα against Aβ toxicity ceases when endogenous FAIM-L is reduced by short hairpin RNA (shRNA) or by treatment with ADDLs. All together, these results support the notion that levels of FAIM-L contribute to determine the protective or deleterious effect of TNFα in neuronal cells

Impact of the COVID-19 Pandemic on a Cancer Fast-Track Programme

Introduction: The COVID-19 pandemic has disrupted many aspects of clinical practice in oncology, particularly regarding early cancer diagnosis, sparking public health concerns that possible delays could increase the proportion of patients diagnosed at advanced stages. In 2009, a cancer fast-track program (CFP) was implemented at the Clinico-Malvarrosa Health Department in Valencia, Spain with the aim of shortening waiting times between suspected cancer symptoms, diagnosis and therapy initiation. Objectives: The study aimed to explore the effects of the COVID-19 pandemic on our cancer diagnosis fast-track program. Methods: The program workflow (patients included and time periods) was analysed from the beginning of the state of alarm on March 16th, 2020 until March 15th, 2021. Data was compared with data from the same period of time from the year before (2019). Results: During the pandemic year, 975 suspected cancer cases were submitted to the CFP. The number of submissions only decreased during times of highest COVID-19 incidence and stricter lockdown, and overall, referrals were slightly higher than in the previous 2 years. Cancer diagnosis was confirmed in 197 (24.1%) cases, among which 33% were urological, 23% breast, 16% gastrointestinal and 9% lung cancer. The median time from referral to specialist appointment was 13 days and diagnosis was reached at a median of 18 days. In confirmed cancer cases, treatment was started at around 30 days from time of diagnosis. In total, 61% of cancer disease was detected at early stage, 20% at locally advanced stage, and 19% at advanced stage, displaying time frames and case proportions similar to pre-pandemic years. Conclusions: Our program has been able to maintain normal flow and efficacy despite the challenges of the current pandemic, and has proven a reliable tool to help primary care physicians referring suspected cancer patients.S

Changes in health sciences students' perception of obstetric violence after an educational intervention

Background Obstetric violence is a type of gender-based violence that is presented structurally. This type of violence has physical and psychological consequences for both the women who experience it and health professionals. The World Health Organization adds that health professionals need training to ensure that pregnant women are treated with compassion and dignity. Objectives The objective of the study was to evaluate health sciences students' perception of obstetric violence and to identify possible changes after an educational intervention. Design A pre-post quasi-experimental study was carried out between January and June 2019. Settings and participants Students of medicine and nursing from Jaume I University (Universitat Jaume I) (Spain). Methods An ad hoc scale comprising 33 items was designed to measure the students' perceptions. In addition, sociodemographic and control variables were collected. Descriptive analyses of the sample and the scale were carried out, and a bivariate analysis was performed. Results Of the students surveyed, 89.7% were women, and the majority was nursing students. Of the 33 items, 28 (84.84%) showed statistically significant changes in the pre-post-intervention measurement. Twenty-five of the 33 items (75.75%) showed a relationship with the sociodemographic variables of gender, field, course and ever having been pregnant. Conclusion This study shows the change in health sciences students' perceptions of obstetric violence after an educational intervention. In addition, the normalization of this type of violence was observed with the progression of training and with personal obstetric experience.Background Obstetric violence is a type of gender-based violence that is presented structurally. This type of violence has physical and psychological consequences for both the women who experience it and health professionals. The World Health Organization adds that health professionals need training to ensure that pregnant women are treated with compassion and dignity

Network meta‐analysis of post‐exposure prophylaxis randomized clinical trials

Objectives: We performed a network meta‐analysis of PEP randomized clinical trials to evaluate the best regimen. / Methods: After MEDLINE/Pubmed search, studies were included if: (1) were randomized, (2) comparing at least 2 PEP three‐drug regimens and, (3) reported completion rates or discontinuation at 28 days. Five studies with 1105 PEP initiations were included and compared ritonavir‐boosted lopinavir (LPV/r) vs. atazanavir (ATV) (one study), cobicistat‐boosted elvitegravir (EVG/c) (one study), raltegravir (RAL) (one study) or maraviroc (MVC) (two studies). We estimated the probability of each treatment of being the best based on the evaluation of five outcomes: PEP non‐completion at day 28, PEP discontinuation due to adverse events, PEP switching due to any cause, lost to follow‐up and adverse events. / Results: Participants were mostly men who have sex with men (n = 832, 75%) with non‐occupational exposure to HIV (89.86%). Four‐hundred fifty‐four (41%) participants failed to complete their PEP course for any reason. The Odds Ratio (OR) for PEP non‐completion at day 28 in each antiretroviral compared to LPV/r was: ATV 0.95 (95% CI 0.58–1.56; EVG/c: OR 0.65 95% CI 0.30–1.37; RAL: OR 0.68 95% CI 0.41–1.13; and MVC: OR 0.69 95% CI 0.47–1.01. In addition, the rankogram showed that EVG/c had the highest probability of being the best treatment for the lowest rates in PEP non‐completion at day 28, switching, lost to follow‐up or adverse events and MVC for PEP discontinuations due to adverse events. / Conclusions: Our study shows the advantages of integrase inhibitors when used as PEP, particularly EVG as a Single‐Tablet Regimen

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms