Harnessing Brazilian biodiversity database: identification of flavonoids as potential inhibitors of SARS-CoV-2 main protease using computational approaches and all-atom molecular dynamics simulation.

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the etiological agent responsible for the global outbreak of COVID-19 (Coronavirus Disease 2019). The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a vital role in mediating viral replication and transcription. In this study, a comprehensive computational approach was employed to investigate the binding affinity, selectivity, and stability of natural product candidates as potential new antivirals acting on the viral polyprotein processing mediated by SARS-CoV-2 Mpro. A library of 288 flavonoids extracted from Brazilian biodiversity was screened to select potential Mpro inhibitors. An initial filter based on Lipinski's rule of five was applied, and 204 compounds that did not violate any of the Lipinski rules were selected. The compounds were then docked into the active site of Mpro using the GOLD program, and the poses were subsequently re-scored using MM-GBSA (Molecular Mechanics Generalized Born Surface Area) binding free energy calculations performed by AmberTools23. The top five flavonoids with the best MM-GBSA binding free energy values were selected for analysis of their interactions with the active site residues of the protein. Next, we conducted a toxicity and drug-likeness analysis, and non-toxic compounds were subjected to molecular dynamics simulation and free energy calculation using the MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method. It was observed that the five selected flavonoids had lower MM-GBSA binding free energy with Mpro than the co-crystal ligand. Furthermore, these compounds also formed hydrogen bonds with two important residues, Cys145 and Glu166, in the active site of Mpro. Two compounds that passed the drug-likeness filter showed stable conformations during the molecular dynamics simulations. Among these, NuBBE_867 exhibited the best MM-PBSA binding free energy value compared to the crystallographic inhibitor. Therefore, this study suggests that NuBBE_867 could be a potential inhibitor against the main protease of SARS-CoV-2 and may be further examined to confirm our results.

Glyphosate hormesis induced by treatment via seed stimulates the growth and biomass accumulation in soybean seedlings.

Glyphosate hormesis, identified as a potential means to enhance crop yields, encounters practical constraints because it is typically assessed through foliar applications. The expression and extend of hormesis in this approach are influenced by unpredictable environmental conditions, highlighting the need to explore alternative glyphosate application methods, such as seed treatment. This study aimed to assess glyphosate hormesis on growth rates and biomass accumulation in seedlings soybean cultivars. Two dose-response experiments [doses from 0 to 2880 g acid equivalent (ae) ha-1], one via foliar and one via seed, were conducted on three soybean cultivars [one non-glyphosate-resistant (NGR) and two glyphosate-resistant (GR, one RR and one RR2)]. In a subsequent experiment, three safe glyphosate doses (0, 90 and 180 g ae ha-1) applied via seed were evaluated on four soybean cultivars (two RR and two RR2). For foliar applications, the range of glyphosate doses increasing growth rates and dry biomass by 12-28 % were 5.6-45 g ae ha-1 for the NGR cultivar, of 45-720 g ae ha-1 for RR and of 11.25-180 g ae ha-1 for RR2. In the seed treatment, biomass increases of 16-60 % occurred at 45-180 g ae ha-1 for the NGR and RR cultivars, and 90-360 g ae ha-1 for RR2. Glyphosate doses of 90 and 180 g ae ha-1, applied via seeds, provided greater growth and biomass accumulation for the RR and RR2 soybean cultivars. Both foliar and seed applications of glyphosate increased growth and biomass accumulation in soybean cultivars, with seed treatments showing greater and more consistent enhancements. These findings propose practical and viable alternative for harnessing glyphosate hormesis to facilitate the early development of soybeans and potentially enhance crop yield.

A history under construction: Manguinhos-Maré in the present time. / Uma história em construção: Manguinhos-Maré no tempo presente.

The two first decades of the twenty-first century were representative of the contemporary history of the Oswaldo Cruz Foundation (Fundação Oswaldo Cruz) and demonstrated its active role in the national health scenario. This article discusses the spatial transformations that took place in the territory occupied by the foundation from the year 2000 onward. The transformations in the use of this territory and it's institutional policy within the national context are described, along with the social demands that have impacted the institution, namely large-scale urban transformations and pandemics. This research uses the premises of the history of the present to investigate the changes that took place on the Manguinhos-Maré campus and in the discourse of the institutions involved in managing and planning these changes through analysis of institutional reports, digital mapping, and aerial images.

As duas primeiras décadas do século XXI foram representativas para a história contemporânea da Fundação Oswaldo Cruz e demonstraram seu protagonismo no cenário nacional da saúde. O artigo apresenta transformações espaciais ocorridas no território ocupado pela instituição a partir de 2000. Relacionam-se as transformações no uso dos territórios com sua política institucional no contexto nacional e são ressaltadas as demandas sociais que impactaram a instituição ­ transformações urbanas de grande porte e pandemias. O trabalho averigua, sob os pressupostos da história do tempo presente, as mudanças ocorridas no campus Manguinhos-Maré e no discurso de sujeitos institucionais gestores e projetistas. Para isso, conjuga análise dos relatórios institucionais, da base digital cartográfica e de imagens aéreas.

Exploring Natural Alkaloids from Brazilian Biodiversity as Potential Inhibitors of the Aedes aegypti Juvenile Hormone Enzyme: A Computational Approach for Vector Mosquito Control.

This study explores the potential inhibitory activity of alkaloids, a class of natural compounds isolated from Brazilian biodiversity, against the mJHBP enzyme of the Aedes aegypti mosquito. This mosquito is a significant vector of diseases such as dengue, zika, and chikungunya. The interactions between the ligands and the enzyme at the molecular level were evaluated using computational techniques such as molecular docking, molecular dynamics (MD), and molecular mechanics with generalized Born surface area (MMGBSA) free energy calculation. The findings suggest that these compounds exhibit a high binding affinity with the enzyme, as confirmed by the binding free energies obtained in the simulation. Furthermore, the specific enzyme residues that contribute the most to the stability of the complex with the compounds were identified: specifically, Tyr33, Trp53, Tyr64, and Tyr129. Notably, Tyr129 residues were previously identified as crucial in the enzyme inhibition process. This observation underscores the significance of the research findings and the potential of the evaluated compounds as natural insecticides against Aedes aegypti mosquitoes. These results could stimulate the development of new vector control agents that are more efficient and environmentally friendly.

Applications of Artificial Intelligence and Radiomics in Molecular Hybrid Imaging and Theragnostics for Neuro-Endocrine Neoplasms (NENs).

Nuclear medicine has acquired a crucial role in the management of patients with neuroendocrine neoplasms (NENs) by improving the accuracy of diagnosis and staging as well as their risk stratification and personalized therapies, including radioligand therapies (RLT). Artificial intelligence (AI) and radiomics can enable physicians to further improve the overall efficiency and accuracy of the use of these tools in both diagnostic and therapeutic settings by improving the prediction of the tumor grade, differential diagnosis from other malignancies, assessment of tumor behavior and aggressiveness, and prediction of treatment response. This systematic review aims to describe the state-of-the-art AI and radiomics applications in the molecular imaging of NENs.

Hormetic Effect of Glyphosate on the Morphology, Physiology and Metabolism of Coffee Plants.

Glyphosate is a nonselective herbicide of systemic action that inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthase, thus compromising amino acid production and consequently the growth and development of susceptible plants. The objective of this study was to evaluate the hormetic effect of glyphosate on the morphology, physiology, and biochemistry of coffee plants. Coffee seedlings (Coffea arabica cv Catuaí Vermelho IAC-144) were transplanted into pots filled with a mixture of soil and substrate and subjected to ten doses of glyphosate: 0, 11.25, 22.5, 45, 90, 180, 360, 720, 1440, and 2880 g acid equivalent (ae) ha-1. Evaluations were performed using the morphological, physiological, and biochemical variables. Data analysis for the confirmation of hormesis occurred with the application of mathematical models. The hormetic effect of glyphosate on coffee plant morphology was determined by the variables plant height, number of leaves, leaf area, and leaf, stem, and total dry mass. Doses from 14.5 to 30 g ae ha-1 caused the highest stimulation. In the physiological analyses, the highest stimulation was observed upon CO2 assimilation, transpiration, stomatal conductance, carboxylation efficiency, intrinsic water use efficiency, electron transport rate, and photochemical efficiency of photosystem II at doses ranging from 4.4 to 55 g ae ha-1. The biochemical analyses revealed significant increases in the concentrations of quinic acid, salicylic acid, caffeic acid, and coumaric acid, with maximum stimulation at doses between 3 and 140 g ae ha-1. Thus, the application of low doses of glyphosate has positive effects on the morphology, physiology, and biochemistry of coffee plants.

Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa).

A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. In the temperature range of 255-290 °C, the energy involved in the BG degradation process was approximately 17 J/g. DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition.

Quantum evaluation and therapeutic activity of (E)-N-(4-methoxyphenyl)-2-(4-(3-oxo-3-phenylprop-1-en-1-yl) phenoxy)acetamide and its modified derivatives against EGFR and VEGFR-2 in the treatment of triple-negative cancer via in silico approach.

The most dangerous subtype of breast cancer, triple-negative breast cancer (TNBC), accounts for 25% of all breast cancer-related deaths and 15% of all breast cancer cases. TNBC is distinguished by the lack of immunohistochemical expression of HER2, progesterone receptors, or oestrogen receptors. Although it has been reported that upregulation of EGFR and VEGFR-2 is associated with TNBC progression, no proven effective targeted therapy exists at this time. We used structural bioinformatics methods, including density functional theory, molecular docking, molecular dynamic simulation, pharmacokinetic and drug-likeness models, to identify promising EGFR/VEGFR-2 inhibitors from N-(4-methoxyphenyl)-2-[4-(3-oxo-3-phenylprop-1-en-1-yl) phenoxy] acetamide and six of its modified derivatives in light of the lack of effective targets inhibitor Version 14 of Spartan software was used to analyse density functional theory. The Schrodinger software suite 2018's Maestro interface was used for the molecular docking analysis, and the admetSAR and swissADME servers were used for drug-likeness and absorption, distribution, metabolism, excretion, and toxicity. All of the compounds showed strong electronic characteristics. Additionally, all of the tested compounds met the ADMET and drug-likeness requirements without a single instance of Lipinski's rule of five violations. Additionally, the molecules' levels of affinity for the target proteins varied. The highest binding affinities were demonstrated by the MOLb-VEGFR-2 complex (- 9.925 kcal/mol) and the MOLg-EGFR complex (- 5.032 kcal/mol). The interaction of the molecules in the domain of the EGFR and VEGFR-2 receptors was also better understood through molecular dynamic simulation of the complex.

The role of the antioxidant system and the photosynthetic behavior of paraquat-resistant Conyza sumatrensis in Brazil.

Greenhouse experiments were carried out aiming to characterize-morphologically and biochemically-resistant and susceptible plants of C. sumatrensis. Two experiments were carried out to evaluate the behavior of morphological variables such as leaf area, height, and dry biomass weight, without application of paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride). Other experiments were conducted with two rates of paraquat application (0 and 800 g a.i ha-1); physiological variables were assessed at 2, 4, and 24 h after application (HAA), and plants were collected at 4 HAA for biochemical analyses of antioxidant enzymes and cell membrane peroxidation level. Without herbicide application, paraquat-resistant populations had higher dry biomass, leaf area, liquid photosynthetic rate, carboxylation efficiency, and stomatal conductance. The recovery of the photosynthetic apparatus by resistant plants after paraquat application is rapid (16 HAA) and, in general, presents physiological improvements in terms of photosynthetic rate and carboxylation efficiency. After paraquat treatment, the antioxidant system enzymes of resistant plants showed increased activity and decreased membrane peroxidation, indicating that these enzymes play an important role in the resistance mechanism of these plants.

Uma história em construção: Manguinhos-Maré no tempo presente / A history under construction: Manguinhos-Maré in the present time

Resumo As duas primeiras décadas do século XXI foram representativas para a história contemporânea da Fundação Oswaldo Cruz e demonstraram seu protagonismo no cenário nacional da saúde. O artigo apresenta transformações espaciais ocorridas no território ocupado pela instituição a partir de 2000. Relacionam-se as transformações no uso dos territórios com sua política institucional no contexto nacional e são ressaltadas as demandas sociais que impactaram a instituição - transformações urbanas de grande porte e pandemias. O trabalho averigua, sob os pressupostos da história do tempo presente, as mudanças ocorridas no campus Manguinhos-Maré e no discurso de sujeitos institucionais gestores e projetistas. Para isso, conjuga análise dos relatórios institucionais, da base digital cartográfica e de imagens aéreas.

Abstract The two first decades of the twenty-first century were representative of the contemporary history of the Oswaldo Cruz Foundation (Fundação Oswaldo Cruz) and demonstrated its active role in the national health scenario. This article discusses the spatial transformations that took place in the territory occupied by the foundation from the year 2000 onward. The transformations in the use of this territory and it's institutional policy within the national context are described, along with the social demands that have impacted the institution, namely large-scale urban transformations and pandemics. This research uses the premises of the history of the present to investigate the changes that took place on the Manguinhos-Maré campus and in the discourse of the institutions involved in managing and planning these changes through analysis of institutional reports, digital mapping, and aerial images.

Dynamics of 2,4-D and Dicamba Applied to Corn Straw and Their Residual Action in Weeds.

2,4-D and dicamba are used in the postemergence management of eudicotyledonous weeds in different crops, most of which are grown under no-tillage systems. Due to the application methods for these products, their dynamics in straw and their residual action in soil have rarely been explored. Thus, the objective of this study was to evaluate the dynamics of 2,4-D and dicamba that have been applied to corn straw and to verify their relationship with residual control action in weeds. In the dynamics experiments, the herbicides were applied to 5 t ha-1 of straw, and rainfall simulations were performed with variable amounts and at different periods after application to evaluate herbicide movement in the straw. In the residual action experiments, the species Digitaria insularis, Conyza spp., Bidens pilosa, Amaranthus hybridus, Euphorbia heterophylla, and Eleusine indica were sown in trays, and 2,4-D and dicamba were applied directly to the soil, to the soil with the subsequent addition of the straw, and to the straw; all of these applications were followed by a simulation of 10 mm of rain. The physical effect of the straw and the efficacy of the herbicides in terms of pre-emergence control of the weed species were evaluated. The leaching of 2,4-D and dicamba from the corn straw increased with a higher volume of rainfall, and the longer the drought period was, the lower the final amount of herbicide that leached. The presence of the corn straw on the soil exerted a physical control effect on Conyza spp.; significantly reduced the infestation of D. insularis, B. pilosa, A. hybridus, and E. indica; and broadened the control spectrum of 2,4-D and dicamba, assisting in its residual action and ensuring high levels of control of the evaluated weeds. In the absence of the straw, 2,4-D effectively controlled the pre-emergence of D. insularis, Conyza spp., and A. hybridus, and dicamba effectively controlled D. insularis, Conyza spp., B. pilosa, A. hybridus, E. heterophylla, and E. indica.

An In Silico Investigation to Explore Anti-Cancer Potential of Foeniculum vulgare Mill. Phytoconstituents for the Management of Human Breast Cancer.

Breast cancer is one of the most prevalent cancers in the world. Traditionally, medicinal plants have been used to cure various types of diseases and disorders. Based on a literature survey, the current study was undertaken to explore the anticancer potential of Foeniculum vulgare Mill. phytoconstituents against breast cancer target protein (PDB ID: 6CHZ) by the molecular docking technique. Molecular docking was done using Autodock/vina software. Toxicity was predicted by the Protox II server and drug likeness was predicted by Molinspiration. 100 ns MD simulation of the best protein-ligand complexes were done using the Amber 18 tool. The present molecular docking investigation has revealed that among the 40 selected phytoconstituents of F. vulgare, α-pinene and D-limonene showed best binding energy (-6 and -5.9 kcal/mol respectively) with the breast cancer target. α-Pinene and D-limonene followed all the parameters of toxicity, and 100 ns MD simulations of α-pinene and D-limonene complexes with 6CHZ were found to be stable. α-Pinene and D-limonene can be used as new therapeutic agents to cure breast cancer.

A Computational Approach Applied to the Study of Potential Allosteric Inhibitors Protease NS2B/NS3 from Dengue Virus.

Dengue virus (DENV) is a danger to more than 400 million people in the world, and there is no specific treatment. Thus, there is an urgent need to develop an effective method to combat this pathology. NS2B/NS3 protease is an important biological target due it being necessary for viral replication and the fact that it promotes the spread of the infection. Thus, this study aimed to design DENV NS2B/NS3pro allosteric inhibitors from a matrix compound. The search was conducted using the Swiss Similarity tool. The compounds were subjected to molecular docking calculations, molecular dynamics simulations (MD) and free energy calculations. The molecular docking results showed that two compounds, ZINC000001680989 and ZINC000001679427, were promising and performed important hydrogen interactions with the Asn152, Leu149 and Ala164 residues, showing the same interactions obtained in the literature. In the MD, the results indicated that five residues, Lys74, Leu76, Asn152, Leu149 and Ala166, contribute to the stability of the ligand at the allosteric site for all of the simulated systems. Hydrophobic, electrostatic and van der Waals interactions had significant effects on binding affinity. Physicochemical properties, lipophilicity, water solubility, pharmacokinetics, druglikeness and medicinal chemistry were evaluated for four compounds that were more promising, showed negative indices for the potential penetration of the Blood Brain Barrier and expressed high human intestinal absorption, indicating a low risk of central nervous system depression or drowsiness as the the side effects. The compound ZINC000006694490 exhibited an alert with a plausible level of toxicity for the purine base chemical moiety, indicating hepatotoxicity and chromosome damage in vivo in mouse, rat and human organisms. All of the compounds selected in this study showed a synthetic accessibility (SA) score lower than 4, suggesting the ease of new syntheses. The results corroborate with other studies in the literature, and the computational approach used here can contribute to the discovery of new and potent anti-dengue agents.

Prognostic Value of the BIO-Ra Score in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223 after the European Medicines Agency Restricted Use: Secondary Investigations of the Multicentric BIO-Ra Study.

The multicentric retrospective BIO-Ra study combined inflammatory indices from peripheral blood and clinical factors in a composite prognostic score for metastatic castration-resistant prostate cancer patients receiving Radium-223 (Ra-223). In the present study, we evaluated (i) the prognostic power of the BIO-Ra score in the framework of the restricted use of Ra-223 promoted by the European Medicines Agency in 2018; (ii) the treatment completion prediction of the BIO-Ra score. Four hundred ninety-four patients from the BIO-Ra cohort were divided into three risk classes according to the BIO-Ra score to predict the treatment completion rate (p < 0.001 among all the three groups). Patients receiving Ra-223 after restriction (89/494) were at later stages of the disease compared with the pre-restriction cohort (405/494), as a higher percentage of BIO-Ra high-risk classes (46.1% vs. 34.6%) and lower median Overall survival (12.4 vs. 23.7 months, p < 0.001) was observed. Despite this clinically relevant difference, BIO-Ra classes still predicted divergent treatment completion rates in the post-restriction subgroup (72%, 52.2%, and 46.3% of patients belonging to low-, intermediate-, and high-risk classes, respectively). Although the restricted use has increased patients at higher risk with unfavourable outcome after Ra-223 treatment, the BIO-Ra score maintains its prognostic value.

Biological maturation influences selection process in youth elite soccer players.

This study examined the influence of birth date, salivary testosterone [sT] concentration, sexual maturity status, and general strength on the selection process of an elite Brazilian soccer club during a 12-month period, which was a 2nd phase of a 24-month selection process. The stature, body mass, sT, sexual maturity status [Tanner scale], and hand grip strength were assessed for 143 players during 2 weeks. From these 143 players, 100 players were dismissed [DIS] and 43 players were selected to integrate the club's under-14 squad. Following 1-year training period, the under-14 team was assembled with 9 players designated as starters [STA], and then, comparisons were conducted taking into account a group of non-starters (selected; SEL = 34 players) and STA (n = 09). The DIS, SEL, STA players, and reference population, were compared for birth distribution. A greater proportion of players was born in the first trimester in the STA [75.0%], SEL [57.1%] and DIS [50.0%] groups compared to the reference population [25.8%]. One-way ANOVA showed a higher sT for STA group [516.0 ± 129.9 pmol·L-1], compared to SEL [415.5 ± 117.9 pmol·L-1] and DIS groups [390.9 ± 84.9 pmol·L-1; p = 0.003), and Kruskall-Wallis test showed a higher gonadal development for STA compared to DIS [p = 0.001]. The current findings suggest a strong influence of birth date and biological maturation on young soccer players selection process. Soccer coaches should consider these influences when making decisions about player selection of elite youth players.

Phytoconstituents of traditional Himalayan Herbs as potential inhibitors of Human Papillomavirus (HPV-18) for cervical cancer treatment: An In silico Approach.

Human papillomavirus (HPV) induced cervical cancer is becoming a major cause of mortality in women. The present research aimed to identify the natural inhibitors of HPV-18 E1 protein (1R9W) from Himalayan herbs with lesser toxicity and higher potency. In this study, one hundred nineteen phytoconstituents of twenty important traditional medicinal plants of Northwest Himalayas were selected for molecular docking with the target protein 1R9W of HPV-18 E1 Molecular docking was performed by AutoDock vina software. ADME/T screening of the bioactive phytoconstituents was done by SwissADME, admetSAR, and Protox II. A couple of best protein-ligand complexes were selected for 100 ns MD simulation. Molecular docking results revealed that among all the selected phytoconstituents only thirty-five phytoconstituents showed the binding affinity similar or more than the standard anti-cancer drugs viz. imiquimod (-6.1 kJ/mol) and podofilox (-6.9 kJ/mol). Among all the selected thirty-five phytoconstituents, eriodictyol-7-glucuronide, stigmasterol, clicoemodin and thalirugidine showed the best interactions with a docking score of -9.1, -8.7, -8.4, and -8.4 kJ/mol. Based on the ADME screening, only two phytoconstituents namely stigmasterol and clicoemodin selected as the best inhibitor of HPV protein. MD simulation study also revealed that stigmasterol and clicoemodin were stable inside the binding pocket of 1R9W, Stigmasterol and clicoemodin can be used as a potential investigational drug to cure HPV infections.

Radium-223 in mCPRC patients: a large real-life Italian multicenter study.

BACKGROUND: Radium-223 is a targeted alpha-particles therapy approved for the treatment of mCRPC patients with symptomatic bone metastases. To our knowledge we account for the largest cohort of mCRPC patients subjected to Radium-223 treatment in our country. We aim to describe in a real-life setting the largest cohort of mCRPC patients treated with Radium-223 ever taken into consideration. METHODS: Four hundred and thirty consecutive mCRPC patients were enrolled. Clinical data have been collected at baseline and at the end of the Radium-223 treatment. Furthermore, the overall survival(OS) of our population has been provided. RESULTS: One hundred fifty-seven patients (36.5%) were still alive at the time of data analysis. A mean number of 4.95±1.6 cycles of Radium-223 was reached by our cohort. 265 patients (61.6%) completed the whole six cycles regimen. The mean follow-up period from the first cycle of Radium-223 to the date of the analysis was 12.7 months. The analysis of patients Annual Incidence Rate (AIR) in relation to the number of Radium-223 cycles received depicting a clear advantage for those patients who completed the whole six administrations planned, with an AIR (AIR=0.32) of much lesser value compared to those that have performed five cycles (AIR =0.98). 165 patients (38.4%) dropped out of treatment for death or disease progression. CONCLUSIONS: This study offers a cross-section of the clinical performance of Radium-223 treatment in a real-world context, confirming on a large scale the effectiveness of Radium-223 in improving the OS and quality of life, along with the preservation of an excellent safety profile.

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study).

PURPOSE: To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2). PATIENTS AND METHODS: Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score. RESULTS: Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1). CONCLUSIONS: The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs.