Background Clown intervention has been shown to enhance emotional and behavioral processes, but few studies have comprehensively examined the effectiveness of this practice using biomarkers. Objective The aim of this study was to evaluate the effect of a clown intervention on the levels of psychological stress and cancer-related fatigue in pediatric patients with cancer undergoing chemotherapy. Methods Sixteen patients who met all criteria from a pediatric oncology inpatient unit in a Brazilian comprehensive cancer care hospital participated in this quasi-experimental study. Eight saliva samples were collected, comprising 4 at baseline and 4 after clown intervention (+1, +4, +9, and +13 hours after awakening). Salivary cortisol and α-amylase levels were determined using high-sensitivity enzyme-linked immunosorbent assay kits. Stress and fatigue were measured by the Child Stress Scale-ESI and the PedsQL Multidimensional Fatigue Scale, respectively. Relationships among stress, fatigue, and biomarker levels were investigated using nonparametric statistics. Results In comparison with baseline measurements, the total psychological stress and fatigue levels improved after the clown intervention at the collection time point +4 hours (P = .003 and P = .04, respectively). Salivary cortisol showed a significant decrease after clown intervention at the collection time points +1, +9, and +13 hours (P < .05); however, α-amylase levels remained unchanged. Conclusion These findings provide preliminary evidence that clown intervention merits further study as a way to reduce stress and fatigue in pediatric cancer inpatients, and that self-report and biomarker measures are feasible to collect in this patient group. Implications for Practice Clown intervention as a nonpharmacological intervention may improve stress and fatigue levels in pediatric inpatients with cancer undergoing chemotherapy.

Background: Pediatric cancer patients experience different psychological processes during hospitalization that may regulate the immune response and affect recovery and response to cancer treatment. In this study, we aimed to examine the feasibility of longitudinal testing of psychophysiological parameters of stress and fatigue in pediatric osteosarcoma patients hospitalized for chemotherapy submitted to clown intervention; and to investigate whether changes in the levels of biomarkers are associated with psychological stress and fatigue levels in these patients after the clown intervention. Methods: A pretest-posttest quasi-experimental pilot study was conducted at the pediatric oncology inpatient unit in a comprehensive cancer care center in Brazil including children and adolescents with osteosarcoma hospitalized for chemotherapy. Eight saliva samples were collected, comprising 4 at baseline (pre-intervention) and 4 after the clown intervention (+1, +4, +9, and +13 hours post-awakening). Salivary cortisol, α-amylase (sAA), cytokines, and matrix metalloproteinase-9 (MMP-9) levels were determined using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Stress and fatigue were measured by Child Stress Scale–ESI and PedsQL Multidimensional Fatigue Scale respectively. Bivariate association analysis between stress and fatigue scores and biomarker levels were investigated using nonparametric statistics. Effect sizes were calculated for each outcome variable. Results: Six pediatric osteosarcoma patients were enrolled with no missing data. No significant effects sizes were observed for psychophysiological outcomes. Effect sizes ranged from 0.54 (cortisol) to 0 (interleukin-1β [IL-1β]). Decreasing overall trends were observed for cortisol levels for all 6 pediatric osteosarcoma patients over time. In addition, a similar pattern of tumor necrosis factor–α (TNF-α) levels over time was found for all 6 patients. Patients with metastatic osteosarcoma showed a linear trend for a decrease in MMP-9 levels between 1 and 9 hours after the clown intervention and restoration to basal levels after 13 hours. Conclusions: The results of this pilot study suggest that it is feasible longitudinally measure psychophysiological outcomes in the pediatric osteosarcoma inpatients for chemotherapy. Clown intervention merits further study as a way to reduce stress as well as fatigue, since that the stress and cytokines measurements are feasible based on our work.

COVID-19 is still placing a heavy health and financial burden worldwide. Impairments in patient screening and risk management play a fundamental role on how governments and authorities are directing resources, planning reopening, as well as sanitary countermeasures, especially in regions where poverty is a major component in the equation. An efficient diagnostic method must be highly accurate, while having a cost-effective profile. We combined a machine learning-based algorithm with instrumental analysis using mass spectrometry to create an expeditious platform that discriminate COVID-19 in plasma samples within minutes, while also providing tools for risk assessment, to assist healthcare professionals in patient management and decision-making. A cohort of 728 patients (369 confirmed COVID-19 and 359 controls) was enrolled from three Brazilian epicentres (Sao Paulo capital, Sao Paulo countryside and Manaus) in the months of April, May, June and July 2020. We were able to elect and identify 21 molecules that are related to the disease's pathophysiology and 26 features to patient's health-related outcomes. With specificity >97% and sensitivity >83% from blinded data, this screening approach is understood as a tool with great potential for real-world application.

e16004 Background: The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom Bacillus Calmette-Guerin (BCG) has failed or is contraindicated are recently increasing due to the development of new drugs. In this scenario, a new perspective is represented by OncoTherad immunomodulator. OncoTherad is a nanostructured inorganic phosphate complex associated to glycosidic protein, developed by University of Campinas/ Brazil, which exhibits antitumor properties. This study detailed and characterized the therapeutic effects of OncoTherad based on activation of Toll-Like Receptors (TLRs) signaling pathways and regulation of receptor activator of nuclear factor kβ (RANK)/RANK ligand (RANKL) cytokine system in an animal model of NMIBC, as well as, compared these effects with BCG treatment. Methods: Fisher 344 female rats were submitted to NMIBC induction with N-methyl-N-nitrosourea (MNU). MNU treated animals were further divided into 3 groups (10 animals per group): the NMIBC group received 0.30 mL of saline solution; the NMIBC-BCG group received of 2 mg/mL of BCG; the NMIBC-OncoTherad group received 20 mg/Kg dose of OncoTherad. All animals were treated intravesically every other week for 6 weeks. Results: Our results demonstrated that OncoTherad intravesical immunotherapy led to distinct activation of TLRs 2 and 4-mediated innate immune system, resulting in increased interferons signaling pathway, which was more effective (80.0%) in the NMIBC treatment, when compared to BCG treatment (20.0%). Interferon signaling pathway activation induced by OncoTherad led to increase of iNOS expression, resulting in apoptosis and histopathological recovery. Also, OncoTherad immunotherapy decreased RANK/RANKL expression, resulting in reduced regulatory T (Treg) cells. Conclusions: The decreased of RANK/RANKL expression by OncoTherad was fundamental to up-regulation interferon signaling pathway and in suppresion of abnormal cell proliferation. Thus, OncoTherad immunotherapy could be considered an important therapeutic strategy for NMIBC, as well as, opens a new perspective for treatment of BCG-refractory or relapsed patients.

To define whether the association of male lower urinary tract symptoms (LUTS) and metabolic syndrome (MS) is real or simply an epiphenomenon, 490 male adults (mean age 58 ± 9 years) underwent International Prostate Symptom Score (IPSS), physical and prostate digital examinations, blood analysis, and urinary tract transabdominal ultrasound with prostate volume measurement. Mild, moderate, and severe LUTS were found in 350 (71.4%), 116 (23.7%), and 24 (4.9%) patients, respectively. MS was present in 198 (40.4%) patients, representing 37.4% (131 of 350) of those with mild LUTS, 46.5% (54 of 116) of those with moderate, and 54.1% (13 of 24) of those with severe. The odds ratio of MS having moderate or severe LUTS was 2.1. MS was more common in older age, higher body mass index, and larger prostate size. Moderate and severe LUTS were more frequent in older age, lower levels of high density cholesterol, and higher blood pressure. Older age and body mass index had significant relative risk for lower urinary tract symptoms and only age remained independent factor for LUTS on multivariate analysis. Our results suggest that the association of male LUTS, prostate volume, and MS might be coincidental and related to older age.

One in every four men under routine urological evaluation who considered themselves healthy present moderate and severe LUTS. Modifiable behavioral (education, sexual frequency, and ejaculation) and health-related (blood pressure and HDL cholesterol) targets were identified for future interventional studies and potential preventive actions and patient counseling.

e17048 Background: Standard treatment for high-grade non-muscle-invasive bladder cancer (HGNMIBC) is transurethral resection of the bladder tumor followed by intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. Up to 40% of patients with HGNMIBC will fail intravesical BCG therapy. A promising therapeutic perspective is represented by OncoTherad immunotherapy. OncoTherad is a nanostructured inorganic phosphate complex associated to glycosidic protein developed by University of Campinas/Brazil that exhibits antitumor properties. The aims of this study were to evaluate the efficacy and safety of OncoTherad immunotherapy for BCG-refractory or relapsed HGNMIBC. Methods: We conducted a prospective, single-center (Municipal Hospital of Paulinia, São Paulo, Brazil), single-arm phase I/ II study of OncoTherad immunotherapy in 29 (18 male, 11 female) patients with BCG-unresponsive HGNMIBC (≥ 1 previous course of BCG intravesical therapy). The schedule was initiated with weekly intravesical (120 mg/mL) and intramuscular (25 mg/mL) OncoTherad treatment for 6 weeks, followed by one every other week application for 3 months and, one monthly application until the end of the treatment (24 months). Follow-up was performed with systematic mapping biopsies of the bladder, cystoscopy and ultrasound. The primary endpoint was pathological complete response (pCR) and recurrence-free survival (RFS). The recurrence was defined as histology proven tumor recurrence (any grade) and monitored at 3-month intervals. Secondary endpoints were time to disease recurrence and safety response. Results: The median age of the 29 patients was 64 years (range 34-94). At baseline pTis, pTaG2-3, pT1G2-3 occurred in 10%, 59% and 31% of patients respectively. OncoTherad treatment showed pCR rates (95% CI) of 100% at 3, 6 and 9 months, 89,6% (26/29) at 12 months and, 89,6% (26/29) at 24 months. A 24-months RFS rate in all patients was 79,3%. Also, the median time to disease recurrence for patients was 459 days (15,3 months; 95% CI) at 24-months follow-up. 95% of adverse events were Grade 1 or 2. The most commonly reported treatment-related adverse events were dysuria (51,7%), cystitis (34,5%), pruritus (44,8%), rash (27,6%), arthralgia (27,6%) and fatigue (27,6%). Conclusions: In conclusion, OncoTherad seems a safe and effective treatment option for BCG-unresponsive HGNMIBC patients and may provide benefit for preventing tumor recurrence. Clinical trial information: RBR-6swqd2.

This study characterizes the clinical and morphofunctional effects of a 5α-reductase inhibitor on steroid hormone receptors in normal human prostate tissue, as potential mediators of the clinical effects of dutasteride. This work was a prospective, double-blind, and randomized study that evaluated 49 men aged between 45 and 70 years, with no alterations in a digital rectal examination and prostate-specific antigen measurements between 2.5 and 4.0 ng/mL. These patients underwent prostate biopsy guided by transretal ultrasound with prostate neoplasia being ruled out, and the patients were divided into two groups, with one group receiving dutasteride (n = 25) and one group receiving a placebo (n = 24). The patients were clinically assessed each quarter, and at the end of 12 months they underwent new laboratory tests, prostate rebiopsy, and histopathological, immunohistochemical and clinical analyses. The estrogen receptor-beta (ERβ) and androgen receptor immunoreactivities were higher, and the proliferation/apoptotic ratio was significantly lower with predominance of the apoptotic process, followed by a significant reduction in the prostate volume and the total serum prostate-specific antigen levels in the dutasteride group when compared with the placebo group, with a clear supremacy of ERβ. There were no significant variations in the serum estrogen and testosterone levels, in the body mass index, or in the ERα immunoreactivities in the dutasteride and placebo groups. The results demonstrated the importance of the ERβ pathway in the activation mechanisms of apoptosis, exerting a protective effect in the normal prostate, indicating that this receptor might be an important mediator of the clinical effects of dutasteride.