Prevalence of muscle atrophy in pediatric patients during ICU hospitalization.

To evaluate the muscle thickness and prevalence of muscle atrophy of the biceps brachii/brachialis (BB) and quadriceps femoris (QF) in critically ill children using ultrasound (US). The prospective longitudinal study was conducted in the pediatric intensive care unit (PICU) of a tertiary hospital in southern Brazil with children and adolescents of both sexes, aged 1 month to 12 years, on invasive mechanical ventilation for 24 h. US measurements were taken up to 24 h after admission, 72 h after, and weekly until discharge from the PICU. One hundred one patients were selected, of whom 97 underwent two evaluations, 68 three evaluations, and 26 four ultrasound evaluations. The median age was 6 months, with 63 (62.4%) < 1 year old. The most prevalent clinical diagnosis was respiratory diseases (70.3%). There was a reduction in BB thickness from 1 to 2 weeks (- 0.10 cm, p = 0.009) and in QF from 24 h to 2 weeks (- 0.20 cm, p = 0.013) and 72 h to 2 weeks (- 0.18 cm, p = 0.045). The prevalence of muscle atrophy (decrease > 10% in thickness) was 41.2% in at least one muscle group between 24 and 72 h, 39.7% between 24 h and 1 week, and 59.3% between 24 h and 2 weeks. The US allows the evaluation of BB and QF muscle thickness in critically ill children, and monitoring muscles during PICU hospitalization is important. The prevalence of muscle atrophy was 30.8% in the biceps brachii and 46.2% in the quadriceps femoris at the end of 2 weeks of PICU hospitalization, regardless of age and diagnosis. What is Known: • Ultrasound has emerged as a promising method, being a clinically valuable tool for bedside muscle monitoring in critical patients. • Using the ultrasound to measure the muscle thickness in adults has demonstrated good sensitivity for detecting muscle atrophy. However, this method has only been previously validated in few studies with small sample of pediatric patients. What is New: • Using the ultrasound, we observed that critically ill children experienced a loss of muscle thickness and muscle atrophy, especially during the second week of intubation. • The significant prevalence of muscle atrophy at the end of PICU hospitalization highlights the importance of ultrasound in identifying muscle loss.

Two-Stage Framework for Faster Semantic Segmentation.

Semantic segmentation consists of classifying each pixel according to a set of classes. Conventional models spend as much effort classifying easy-to-segment pixels as they do classifying hard-to-segment pixels. This is inefficient, especially when deploying to situations with computational constraints. In this work, we propose a framework wherein the model first produces a rough segmentation of the image, and then patches of the image estimated as hard to segment are refined. The framework is evaluated in four datasets (autonomous driving and biomedical), across four state-of-the-art architectures. Our method accelerates inference time by four, with additional gains for training time, at the cost of some output quality.

Identification of CD114 Membrane Receptors as a Molecular Target in Medulloblastomas.

Medulloblastomas are the most common solid tumors in children, accounting for 8-30% of pediatric brain cancers. It is a high-grade tumor with aggressive behavior and a typically b poor prognosis. Its treatment includes surgery, chemotherapy, and radiotherapy, and presents high morbidity. Significant clinical, genetic, and prognostic differences exist between its four molecular subgroups: WNT, SHH, Group 3, and Group 4. Many studies seek to develop new chemotherapeutic agents for medulloblastomas through the identification of genes whose expressions are new molecular targets for drugs, such as membrane receptors associated with cell replication. This study aimed to assess the association of CD114 expression with mortality in patients with medulloblastoma. Databases from the Medulloblastoma Advanced Genomics International Consortium (MAGIC) were analyzed, focusing on the expression of the CD114 membrane receptor in different molecular types and its possible association with mortality. Our findings showed different CD114 expressions between Group 3 and other molecular groups, as well as between the molecular subtypes SHH γ and Group 3 α and Group 3 ß. There was no statistically significant difference between the other groups and subtypes. Regarding mortality, this study did not find statistical significance in the association between low and high CD114 expressions and mortality. Medulloblastoma is a heterogeneous disease with many subtype variations of its genetic and intracellular signaling pathways. Similarly to this study, which could not demonstrate different CD114 membrane receptor expression patterns between groups, others who sought to associate CD114 expression with mortality in other types of cancer failed to establish a direct association. Since many indications point to the relation of this gene with cancer stem cells (CSCs), it may be part of a more extensive cellular signaling pathway with an eventual association with tumor recurrence. This study found no direct relationship between CD114 expression and mortality in patients with medulloblastoma. Further studies are needed on the intracellular signaling pathways associated with this receptor and its gene (the CSF3R).

Antifungal and antibiofilm activities of the essential oil of leaves from Lippia gracilis Schauer against phytopathogenic fungi.

AIMS: This study aimed to evaluate the antifungal and antibiofilm effects of essential oil (EO) from leaves of Lippia gracilis and its major constituents, thymol and carvacrol, against phytopathogenic fungi. METHODS AND RESULTS: The leaves of L. gracilis were hydrodistilled to obtain the EO and the chemical composition was determined by GC/MS analysis. The antifungal activity of EO of L. gracilis was evaluated on the vegetative and mycelial growth of Colletotrichum gloeosporioides, Colletotrichum lindemuthianum, Fusarium oxysporum and Fusarium solani. In addition, the ability of the oil to inhibit fungal biofilm formation was assessed by total biomass quantification using crystal violet staining, analysis of metabolic activity, and scanning electron microscopy (SEM). Moreover the antifungal and antibiofilm activities of the monoterpenes, thymol and carvacrol, present in EO of L. gracilis were evaluated against F. oxysporum. The analysis of the chemical composition of EO extracted from L. gracilis, revealed the presence of monoterpenes (94·13%), which included carvacrol (48·57%) and thymol (7·78%), and 4 sesquiterpenes (3·74%). In general, EO showed significant antifungal activity and inhibited the formation of fungal biofilms. Furthermore, thymol and carvacrol showed significant antifungal and antibiofilm activities against F. oxysporum. SEM images showed structural changes in fungal morphology upon treatment with EO of L. gracilis. CONCLUSION: The results presented in this study showed promising antifungal and antibiofilm effects of EO of L. gracilis and its major components, carvacrol and thymol. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings indicate that the EO extracted from L. gracilis, and the monoterpenes, carvacrol and thymol have a great potential as antifungal and antibiofilm agents. Furthermore, this is the first report of the antibiofilm activity of the EO of L. gracilis and its major components against phytopathogenic fungi.

Association of the HLA-B27 antigen and the CTLA4 gene CT60/rs3087243 polymorphism with ankylosing spondylitis in Algerian population: A case-control study.

Ankylosing spondylitis (AS) is a complex inflammatory disease that represents a major health problem both in Algeria and worldwide. Several lines of evidence support that genetic risk factors play a role in AS etiology and the CTLA4 gene has attracted a considerable attention. In this study, we were interested in evaluating the HLA-B27 frequency and in exploring the CTLA4 gene in a sample of the North African population. The dataset of the current study is composed of 81 patients with AS and 123 healthy controls. All samples were genotyped by TaqMan® allelic discrimination assay. The genetic risk of the HLA-B27 specificity and the CTLA4/CT60 polymorphism were assessed by odds ratios (OR) with 95% confidence intervals (CI). High spondylitis risk was detected for HLA-B27 allele (OR= 14.62, p = 10-6 ) in addition to a significant association of the CT60*G allele (OR= 1.89, p = .002). After gender and age stratifications, the association of the CT60*G allele was still significant in females sample (OR= 2.10, p = .001) and when age up to 30 years (OR = 2.21, p = .008). Interestingly, the CT60*G allele revealed an increased spondylitis risk in the B27 negative group (OR= 2.81, p = .006). The present work showed in West Algerian population that the HLA-B27 antigen and the variation in the CTLA4 3'UTR region played an important role in the ankylosing spondylitis susceptibility. The heterogeneity of this disease is deduced by genetic difference found between B27+ and B27- groups.

VAV1 regulates experimental autoimmune arthritis and is associated with anti-CCP negative rheumatoid arthritis.

Rheumatoid arthritis (RA) patients can be stratified into two subgroups defined by the presence or absence of antibodies against citrullinated circular peptides (anti-CCP) with most of the genetic association found in anti-CCP positive RA. Here we addressed the role of VAV1, previously associated to multiple sclerosis (MS), in the pathogenesis of RA in experimental models and in a genetic association study. Experimental arthritis triggered by pristane or collagen type II was induced in DA rats and in the DA.BN-R25 congenic line that carries a polymorphism in Vav1. Difference in arthritis severity was observed only after immunization with pristane. In a case-control study, 34 SNPs from VAV1 locus were analyzed by Immunochip genotyping in 11475 RA patients (7573 anti-CCP positive and 3902 negative) and 15,870 controls in six cohorts of European Caucasians. A combination of the previous MS-associated haplotype and two additional SNPs was associated with anti-CCP negative RA (alleles G-G-A-A of rs682626-rs2546133-rs2617822-rs12979659, OR=1.13, P=1.27 × 10-5). The same markers also contributed to activity of RA at baseline with the strongest association in the anti-CCP negative group for the rs682626-rs12979659 G-A haplotype (ß=-0.283, P=0.0048). Our study suggests a role for VAV1 and T-cell signaling in the pathology of anti-CCP-negative RA.

Antibacterial activity of a novel antimicrobial peptide [W7]KR12-KAEK derived from KR-12 against Streptococcus mutans planktonic cells and biofilms.

The aims of this study were to describe the synthesis of a novel synthetic peptide based on the primary structure of the KR-12 peptide and to evaluate its antimicrobial and anti-biofilm activities against Streptococcus mutans. The antimicrobial effect of KR-12 and [W7]KR12-KAEK was assessed by determining the minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations. The evaluation of anti-biofilm activity was assessed through total biomass quantification, colony forming unit counting and scanning electron microscopy. [W7]KR12-KAEK showed MIC and MBC values ranging from 31.25 to 7.8 and 62.5 to 15.6 µg ml-1, respectively. Furthermore, [W7]KR12-KAEK significantly reduced biofilm biomass (50-100%). Regarding cell viability, [W7]KR12-KAEK showed reductions in the number of CFUs at concentrations ranging from 62.5 to 7.8 µg ml-1 and 500 to 62.5 µg ml-1 with respect to biofilm formation and preformed biofilms, respectively. SEM micrographs of S. mutans treated with [W7]KR12-KAEK suggested damage to the bacterial surface. [W7]KR12-KAEK is demonstrated to be an antimicrobial agent to control microbial biofilms.

Emissions from the combustion of eucalypt and pine chips in a fluidized bed reactor.

Interest in renewable energy sources has increased in recent years due to environmental concerns about global warming and air pollution, reduced costs and improved efficiency of technologies. Under the European Union (EU) energy directive, biomass is a suitable renewable source. The aim of this study was to experimentally quantify and characterize the emission of particulate matter (PM2.5) resulting from the combustion of two biomass fuels (chipped residual biomass from pine and eucalypt), in a pilot-scale bubbling fluidized bed (BFB) combustor under distinct operating conditions. The variables evaluated were the stoichiometry and, in the case of eucalypt, the leaching of the fuel. The CO and PM2.5 emission factors were lower when the stoichiometry used in the experiments was higher (0.33±0.1 g CO/kg and 16.8±1.0 mg PM2.5/kg, dry gases). The treatment of the fuel by leaching before its combustion has shown to promote higher PM2.5 emissions (55.2±2.5 mg/kg, as burned). Organic and elemental carbon represented 3.1 to 30 wt.% of the particle mass, while carbonate (CO3(2-)) accounted for between 2.3 and 8.5 wt.%. The particulate mass was mainly composed of inorganic matter (71% to 86% of the PM2.5 mass). Compared to residential stoves, BFB combustion generated very high mass fractions of inorganic elements. Chloride was the water soluble ion in higher concentration in the PM2.5 emitted by the combustion of eucalypt, while calcium was the dominant water soluble ion in the case of pine.

Relationship between SNPs and expression level for candidate genes in rheumatoid arthritis.

OBJECTIVES: The study of polymorphisms of genes differentially expressed may lead to the identification of putative causal genetic variants in multifactorial diseases such as rheumatoid arthritis (RA). Based on preceding transcriptomic results, we genotyped 10 single nucleotide polymorphisms (SNPs) belonging to six genes (S100A8, RNASE2, PGLYRP1, RUNX3, IL2RB, and LY96) showing the highest fold change (> 1.9) when level of expression was compared between RA patients and controls. These SNPs were then analysed to evaluate their role in RA. METHOD: The relationship between gene expression and genotypes of SNPs was first investigated by Kruskal-Wallis and Mann-Whitney tests in RA patients and controls. The genetic association of these SNPs with RA were then analysed using family-based association tests in trio families. RESULTS: We found that RNASE2 gene expression was related to rs2013109 genotypes in 14 RA patients (p = 0.030). The association study in a discovery sample of 200 French trio families revealed a significant association with RA for one SNP, PGLYRP1-rs2041992 (p = 0.019); this association was stronger in trios where RA patients carried the HLA-DRB1 shared epitope (SE) (p = 0.003). However, this association was not found in a replication sample of 240 European trio families (p = 0.6). CONCLUSIONS: Family-based association tests did not reveal an association between RA and any SNP of the candidate genes tested. However, RNASE2 gene expression was differentially expressed in RA patients considering a sequence polymorphism. This result led us to highlight the potential disease-specific regulation for this candidate gene in RA.

Management of infusion-related reactions in cancer therapy: strategies and challenges.

Several anticancer therapies have the potential to cause infusion-related reactions (IRRs) in the form of adverse events that typically occur within minutes to hours after drug infusion. IRRs can range in severity from mild to severe anaphylaxis-like reactions. Careful monitoring at infusion initiation, prompt recognition, and appropriate clinical assessment of the IRR and its severity, followed by immediate management, are required to ensure patient safety and optimal outcomes. Lack of standardization in the prevention, management, and reporting of IRRs across cancer-treating institutions represents not only a quality and safety gap but also a disparity in cancer care. The present article, supported by recently published data, was developed to standardize these procedures across institutions and provide a useful tool for health care providers in clinical practice to recognize early signs and symptoms of an IRR and promptly and appropriately manage the event.

Unresectable stage III non-small cell lung cancer: Insights from a Portuguese expert panel.

INTRODUCTION: The management of unresectable stage III non-small cell lung cancer (NSCLC) is clinically challenging and there is no current consensus on optimal strategies. Herein, a panel of Portuguese experts aims to present practical recommendations for the global management of unresectable stage III NSCLC patients. METHODS: A group of Portuguese lung cancer experts debated aspects related to the diagnosis, staging and treatment of unresectable stage III NSCLC in light of current evidence. Recent breakthroughs in immunotherapy as part of a standard therapeutic approach were also discussed. This review exposes the major conclusions obtained. RESULTS: Practical recommendations for the management of unresectable stage III NSCLC were proposed, aiming to improve the pathways of diagnosis and treatment in the Portuguese healthcare system. Clinical heterogeneity of patients with stage III NSCLC hinders the development of single standardised algorithm where all fit. CONCLUSIONS: A timely diagnosis and a proper staging contribute to the best management of each patient, optimizing treatment tolerance and effectiveness. The expert panel considered chemoradiotherapy as the preferable approach when surgery is not possible. Management of adverse events and immunotherapy as a consolidation therapy are also essential steps for a successful strategy.

Lung cancer screening in Brazil: recommendations from the Brazilian Society of Thoracic Surgery, Brazilian Thoracic Association, and Brazilian College of Radiology and Diagnostic Imaging.

Although lung cancer (LC) is one of the most common and lethal tumors, only 15% of patients are diagnosed at an early stage. Smoking is still responsible for more than 85% of cases. Lung cancer screening (LCS) with low-dose CT (LDCT) reduces LC-related mortality by 20%, and that reduction reaches 38% when LCS by LDCT is combined with smoking cessation. In the last decade, a number of countries have adopted population-based LCS as a public health recommendation. Albeit still incipient, discussion on this topic in Brazil is becoming increasingly broad and necessary. With the aim of increasing knowledge and stimulating debate on LCS, the Brazilian Society of Thoracic Surgery, the Brazilian Thoracic Association, and the Brazilian College of Radiology and Diagnostic Imaging convened a panel of experts to prepare recommendations for LCS in Brazil. The recommendations presented here were based on a narrative review of the literature, with an emphasis on large population-based studies, systematic reviews, and the recommendations of international guidelines, and were developed after extensive discussion by the panel of experts. The following topics were reviewed: reasons for screening; general considerations about smoking; epidemiology of LC; eligibility criteria; incidental findings; granulomatous lesions; probabilistic models; minimum requirements for LDCT; volumetric acquisition; risks of screening; minimum structure and role of the multidisciplinary team; practice according to the Lung CT Screening Reporting and Data System; costs versus benefits of screening; and future perspectives for LCS.

Cytotoxicity and expression of genes involved in the cellular stress response and apoptosis in mammalian fibroblast exposed to cotton cellulose nanofibers.

Cellulose nanofibers (CNF) have mechanical properties that make them very attractive for applications in the construction of polymeric matrices, drug delivery and tissue engineering. However, little is known about their impact on mammalian cells. The objective of this study was to evaluate the cytotoxicity of CNF and their effect on gene expression of fibroblasts cultured in vitro. The morphology of CNF was analyzed by transmission electron microscopy and the surface charge by Zeta potential. Cell viability was analyzed by flow cytometry assay and gene expression of biomarkers focused on cell stress response such as Heat shock protein 70.1 (HSP70.1) and Peroxiredoxin 1 (PRDX1) and apoptosis as B-cell leukemia (BCL-2) and BCL-2 associated X protein (BAX) by RT-PCR assay. Low concentrations of CNF (0.02-100 µg ml(-1)) did not cause cell death; however, at concentrations above 200 µg ml(-1), the nanofibers significantly decreased cell viability (86.41 ± 5.37%). The exposure to high concentrations of CNF (2000 and 5000 µg ml(-1)) resulted in increased HSP70.1, PRDX1 and BAX gene expression. The current study concludes that, under the conditions tested, high concentrations (2000 and 5000 µg ml(-1)) of CNF cause decreased cell viability and affect the expression of stress- and apoptosis-associated molecular markers.

Inhibition of initial adhesion of oral bacteria through a lectin from Bauhinia variegata L. var. variegata expressed in Escherichia coli.

AIMS: The aim of the present work was to study the in vitro effect of native and recombinant Bauhinia variegata var. variegata lectins in inhibiting early adhesion of Streptococcus mutans, Streptococcus sanguis and Streptococcus sobrinus to experimentally acquired pellicle. METHODS AND RESULTS: Native lectin from B. variegata (BVL) was purified by affinity chromatography of extract of seeds. The recombinant lectin (rBVL-I) was expressed in E. coli strain BL21 (DE3) from a genomic clone encoding the mature B. variegata lectin gene using the vector pAE-bvlI. Recombinant protein deposited in inclusion bodies was solubilized and subsequently purified by affinity chromatography. The rBVL-I was compared to BVL for agglutination of erythrocytes and initial adherence of oral bacteria on a saliva-coated surface. The results revealed that rBVL-I acts similarly to BVL for agglutination of erythrocytes. Both lectins showed adhesion inhibition effect on Step. sanguis, Step. mutans and Step. sobrinus. CONCLUSION: We report, for the first time, the inhibition of early adhesion of oral bacteria by a recombinant lectin. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results support the proposed biotechnological application of lectins in a strategy to reduce development of dental caries by inhibiting the initial adhesion and biofilm formation.

Production of oocytes of Nile tilapia (Oreochromis niloticus) for in vitro fertilization via hormonal treatments.

Only a few studies have described hormonal treatments for induction of synchronicity and gamete collection in Nile tilapia (Oreochromis niloticus), both important for assortative matings in breeding programmes and essential for polyploidy technologies. In this study, we compared the effectiveness of carp pituitary extract (CPE), Nile tilapia pituitary extract (TPE), human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) protocols on the induction of spawning and egg production in Nile tilapia. Among the hormonal treatments analysed, only hCG was effective for producing viable gametes for in vitro fertilization. To verify the viability of this hormonal treatment, hCG was tested using different doses (1000, 2000, 3000, 4000 and 5000 IU/kg) in a large number of females (208 animals) from two Nile tilapia lines. The results indicated that hCG doses between 1000 and 5000 IU/kg could be used to induce final oocyte maturation in Nile tilapia with collection of stripped oocytes. This is the first study to report differential reproductive responses to hormonal treatment between tilapia lines: line 1 was more efficient at producing eggs and post-hatching larvae after hCG induction than line 2. In conclusion, we demonstrated that the hCG protocol may be applied on a large scale to induce final oocyte maturation in Nile tilapia. The development of a protocol for in vitro fertilization in Nile tilapia may aid in breeding programmes and biotechnological assays for the development of genetically modified lines of Nile tilapia.

Reliability of ultrasound in the assessment of muscle thickness in critically ill children.

INTRODUCTION: Ultrasound has been used to quantify and qualify muscle morphology in critically ill children and can detect changes in muscle thickness. The aim of this study was to assess the reliability of ultrasound measurement of muscle thickness in critically ill children and to compare the assessments made by an expert with those made by inexperienced sonographers. MATERIAL AND METHODS: Cross-sectional observational study conducted in the paediatric intensive care unit of a tertiary care university hospital in Brazil. The sample included patients aged 1 month to 12 years who received invasive mechanical ventilation for at least 24 h. Ultrasound images of the biceps brachii/brachialis and quadriceps femoris were obtained by one experienced sonographer and several inexperienced sonographers. We assessed intrarater and inter-rater reliability by means of the intraclass correlation coefficient (ICC) and Bland-Altman plot analysis. RESULTS: Muscle thickness was measured in 10 children with a mean age of 15.5 months. The mean thickness of the assessed muscles as 1.14 cm for the biceps brachii/brachialis (standard deviation [SD], 0.27) and 1.85 cm for the quadriceps femoris (SD, 0.61). The intrarater and inter-rater reliability were good for all sonographers (ICC > 0.81). The differences were small, there was no significant bias in the Bland-Altman plots and all measurements were within the limits of agreement, except for 1 measurement of biceps and quadriceps. CONCLUSION: Sonography can be used in critically ill children to accurately assess changes in muscle thickness, even by different evaluators. More studies are needed to establish a standardised approach to the use of ultrasound for monitoring muscle loss in order to incorporate it in clinical practice.

End-of-life care in Brazilian Pediatric Intensive Care Units.

OBJECTIVE: Most deaths in Pediatric Intensive Care Units involve forgoing life-sustaining treatment. Such deaths required carefully planned end-of-life care built on compassion and focused on palliative care measures. This study aims to assess topics related to the end of life care in Brazilian pediatric intensive care units from the perspective of a multidisciplinary team. METHOD: The authors used a tested questionnaire, utilizing Likert-style and open-ended questions. After ethics committee approval, it was sent by email from September to November/2019 to three Pediatric Intensive Care Units in the South and Southeast of Brazil. One unit was exclusively dedicated to oncology patients; the others were mixed units. RESULTS: From 144 surveys collected (23% response rate) 136 were analyzed, with 35% physicians, 30% nurses, 21% nurse technicians, and 14% physiotherapists responding. Overall, only 12% reported enough end-of-life care training and 40% reported never having had any, albeit this was not associated with the physician's confidence in forgoing life-sustaining treatment. Furthermore, 60% of physicians and 46% of other professionals were more comfortable with non-escalation than withdrawing therapies, even if this could prolong suffering. All physicians were uncomfortable with palliative extubation; 15% of all professionals have witnessed it. The oncologic team uniquely felt that "resistance from the teams of specialists" was the main barrier to end-of-life care implementation. CONCLUSION: Most professionals felt unprepared to forego life-sustaining treatment. Even for terminally ill patients, withholding is preferred over the withdrawal of treatment. Socio-cultural barriers and the lack of adequate training may be contributing to insecurity in the care of terminally ill patients, diverging from practices in other countries.

"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.