Causes of death in individuals with lifetime major depression: a comprehensive machine learning analysis from a community-based autopsy center.

BACKGROUND: Depression can be associated with increased mortality and morbidity, but no studies have investigated the specific causes of death based on autopsy reports. Autopsy studies can yield valuable and detailed information on pathological ailments or underreported conditions. This study aimed to compare autopsy-confirmed causes of death (CoD) between individuals diagnosed with major depressive disorder (MDD) and matched controls. We also analyzed subgroups within our MDD sample, including late-life depression and recurrent depression. We further investigated whether machine learning (ML) algorithms could distinguish MDD and each subgroup from controls based on their CoD. METHODS: We conducted a comprehensive analysis of CoD in individuals who died from nontraumatic causes. The diagnosis of lifetime MDD was ascertained based on the DSM-5 criteria using information from a structured interview with a knowledgeable informant. Eleven established ML algorithms were used to differentiate MDD individuals from controls by simultaneously analyzing different disease category groups to account for multiple tests. The McNemar test was further used to compare paired nominal data. RESULTS: The initial dataset included records of 1,102 individuals, among whom 232 (21.1%) had a lifetime diagnosis of MDD. Each MDD individual was strictly paired with a control non-psychiatric counterpart. In the MDD group, the most common CoD were circulatory (67.2%), respiratory (13.4%), digestive (6.0%), and cancer (5.6%). Despite employing a range of ML models, we could not find distinctive CoD patterns that could reliably distinguish individuals with MDD from individuals in the control group (average accuracy: 50.6%; accuracy range: 39-59%). These findings were consistent even when considering factors within the MDD group, such as late-life or recurrent MDD. When comparing groups with paired nominal tests, no differences were found for circulatory (p=0.450), respiratory (p=0.790), digestive (p=1.000), or cancer (p=0.855) CoD. CONCLUSIONS: Our analysis revealed that autopsy-confirmed CoD exhibited remarkable similarity between individuals with depression and their matched controls, underscoring the existing heterogeneity in the literature. Future research should prioritize more severe manifestations of depression and larger sample sizes, particularly in the context of CoD related to cancer.

Factors associated with decreased respiratory pressures in high-risk pregnant women / Fatores associados à diminuição das pressões respiratória em gestantes de alto risco

Introduction: The gestational period brings anatomical and physiological changes to women in several systems, especially the respiratory system. Objective: To determine whether there is an association between gestational age (GA), Diabetes, uterine fundal height (UFH), Body Mass Index (BMI), level of dyspnea, and physical activity with maximum respiratory and nasal pressures. Methods: Cross-sectional study that included 55 high-risk pregnant women in the 2nd and 3rd trimester of pregnancy at the Obstetrics Outpatient Clinic of the Hospital das Clínicas in Recife ­ PE, Brazil, personal, sociodemographic, anthropometric, clinical and Maximal Inspiratory Pressure (MIP) data were described and nasal inspiratory pressure (NIP), that, using regression and multivariate analysis, analyzed the influence of risk factors for high-risk pregnancy with NIP considering a p<0.005. Results: Among the pregnant women, according to the clinical variables, it was observed that 56.4% (n=31) had a gestational age above 28 weeks, 27.3% (n=15) diabetes, 25.5% (n=14) asthma, 43.6% (n=24) Gestational Hypertension, 56.4% (n=31) obesity, 85.5% (n=47) complaints of dyspnea 38.1% (n=21) mild to severe dyspnea and 65.5% (n=36) vigorous physical activity. Low MIP (76.76 cmH2O) and NIP (68.62 cmH2O) values were found for age. An association was observed between an increase in UFH and a decrease of 0.8 cmH2O in NIP, regardless of gestational age. Conclusion: High-risk pregnant women in the second and third trimester of pregnancy have decreased NIP and MIP with a negative association of UFH with NIP regardless of gestational age.

Introdução: O período gestacional traz para a mulher alterações anatômicas e fisiológicas, em diversos sistemas, principalmente no sistema respiratório. Objetivo: Determinar se há associação da idade gestacional (IG), Diabetes, altura de fundo de útero (AFU), Índice de Massa Corpórea (IMC), nível de dispneia e atividade física com as pressões respiratória máxima e nasal. Método: Estudo transversal que incluiu 55 gestantes de alto risco no 2º e 3º trimestre de gestação do Ambulatório de Obstetrícia do Hospital das Clínicas de Recife ­ PE, foi descrito os dados pessoais, sociodemográficos, antropométricos, clínicos e das Pressão Inspiratória Máxima (PImáx) e pressão inspiratória nasal (PIN), que, por meio da regressão e da análise multivariada analisou a influência dos fatores de risco para gestação de alto risco com a PIN considerando um p<0,005. Resultados: Dentre as gestantes, segundo as variáveis clínicas, observou-se que 56,4% (n=31) apresentaram idade gestacional acima de 28 semanas, 27,3% (n=15) diabetes, 25,5% (n=14) asma, 43,6% (n=24) Hipertensão Arterial Sistêmica Gestacional (HASG), 56,4% (n=31) obesidade, 85,5% (n=47) queixas de dispneia 38,1% (n=21) dispneia de um pouco forte a forte e 65,5% (n=36) atividade física vigorosa. Foram encontrados valores baixos de PImáx (76,76 cmH2O) e PIN (68,62 cmH2O) para a idade. Foi observada uma associação do aumento da AFU com a diminuição de 0,8 cmH2O da PIN, independentemente da idade gestacional. Conclusão: As gestantes de alto risco no segundo e terceiro trimestre gestacional apresentam PIN e PImáx diminuídas com uma associação negativa da AFU com a PIN independentemente da idade gestacional.

Tratamento reabilitador com prótese obturadora em paciente acometido por maxilectomia parcial: relato de caso / Rehabilitative treatment with obturator prosthesis in a patient suffering from partial maxillectomy: case report

Introdução: O tratamento de tumores malignos ou benignos, podem resultar em procedimentos cirúrgicos, como a maxilectomia parcial ou total, gerando comunicação bucosinusal nos pacientes. Uma forma de resolver estas alterações maxilofaciais é através do tratamento reabilitador com próteses obturadoras a fim de restabelecer a função mastigatória, estética, fonética e psicológica. Objetivo: o objetivo deste trabalho foi relatar o caso clínico de um paciente oncológico que foi reabilitado com prótese obturadora devido à maxilectomia por neoplasia maligna de seio maxilar. Relato de caso: Paciente de 62 anos, sexo masculino, procurou atendimento odontológico no Centro de Oncologia Bucal da Universidade Estadual Paulista "Júlio de Mesquita Filho" (UNESP) de Araçatuba ­ SP após a realização de uma maxilectomia parcial com comunicação bucosinusal e foi encaminhado para o Curso de Especialização em Prótese Dentária da Faculdade de Odontologia ­ Unesp/Araçatuba-SP para a reabilitação. Foi proposto, primeiramente a realização da prótese obturadora para fechar a comunicação bucosinusal e uma prótese total inferior para o arco antagonista e, posteriormente, a realização de uma prótese facial. Conclusão: O tratamento reabilitador com próteses obturadoras possui um bom resultado estético e funcional, favorecendo uma melhor função mastigatória e fonética, e melhorando consideravelmente a condição psicológica que é muito afetada nos pacientes submetidos a maxilectomia total ou parcial, sendo necessário uma boa interação com toda a equipe multiprofissional envolvida para que haja um melhor tratamento integrado para a reabilitação e melhora da qualidade de vida(AU)

Introduction: The treatment of malignant or benign tumors can result in surgical procedures, such as partial or total maxillectomy, generating oral communication in patients. One way to resolve these maxillofacial changes is through rehabilitative treatment with obturator prostheses in order to reestablish masticatory, aesthetic, phonetic and psychological function. Objective: the objective of this work was to report the clinical case of a cancer patient who was rehabilitated with an obturator prosthesis due to maxillectomy for malignant neoplasia of the maxillary sinus. Case report: A 62-year-old male patient sought dental care at the Oral Oncology Center of the Universidade Estadual Paulista "Júlio de Mesquita Filho" (UNESP) in Araçatuba ­ SP after undergoing a partial maxillectomy with oral cavity and was referred for the Specialization Course in Dental Prosthesis at the Faculty of Dentistry ­ Unesp/Araçatuba-SP for rehabilitation. It was proposed, firstly, to create an obturator prosthesis to close the bucosinusal communication and a total lower prosthesis for the antagonistic arch and, later, to create a facial prosthesis. Conclusion: Rehabilitative treatment with obturator prostheses has a good aesthetic and functional result, favoring better chewing and phonetic function, and considerably improving the psychological condition that is greatly affected in patients undergoing total or partial maxillectomy, requiring good interaction with the entire the multidisciplinary team involved so that there is better integrated treatment for rehabilitation and improved quality of life

The relationship of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate cortex of bipolar disorder subjects: A post-mortem study.

Increased levels of inflammation markers have been found in the peripheral tissue of individuals with bipolar disorder (BD), especially during mood episodes. Previous studies found distinctive inflammatory profiles across different brain regions, but potential associations with clinical symptoms are still lacking. This study aims to evaluate the association of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate of individuals with BD. Levels of IL-1ß, IL-6, IL-17A, cortisol, and C-reactive protein (CRP) were measured in the hippocampus and anterior cingulate of 14 BD individuals and their non-psychiatric controls. Neuropsychiatric symptoms present in the three months before death were assessed using the Neuropsychiatric Inventory (NPI). In the BD group, greater NPI scores were associated with higher IL-6 in the hippocampus (p = 0.011) and cingulate (p = 0.038) and higher IL-1ß (p = 0.039) in the hippocampus. After adjusting for age, sex and CDR, IL-1ß and IL-6 were still associated with higher NPI in the hippocampus. In correlation analysis considering both BD and their controls, moderate positive associations were found between NPI and IL-6 and cortisol in the hippocampus (p < 0.001 and p = 0.006) and cingulate (p = 0.024 and p = 0.016), IL-1ß (p < 0.001) and IL-17A in the hippocampus (p = 0.002). No difference in inflammatory markers was found according to type of psychotropic medication used. Hence, in individuals with BD, neuropsychiatric symptoms were differently associated with specific inflammatory cytokines and CRP in the hippocampus and cingulate. These results suggest that the neuroinflammatory changes occurring in BD may be more complex than previously expected and could be associated with clinical manifestations.

Current practice in intermediate risk differentiated thyroid cancer - a review.

Although the overall prognosis for differentiated thyroid cancer (DTC) is excellent, a subset of patients will experience disease recurrence or may not respond to standard treatments. In recent years, DTC management has become more personalized in order to enhance treatment efficacy and avoid unnecessary interventions.In this context, major guidelines recommend post-surgery staging to assess the risk of disease persistence, recurrence, and mortality. Consequently, risk stratification becomes pivotal in determining the necessity of postoperative adjuvant therapy, which may include radioiodine therapy (RIT), the degree of TSH suppression, additional imaging studies, and the frequency of follow-up.However, the intermediate risk of recurrence is a highly heterogeneous category that encompasses various risk criteria, often combined, resulting in varying degrees of aggressiveness and a recurrence risk ranging from 5 to 20%. Furthermore, there is not enough long-term prognosis data for these patients. Unlike low- and high-risk DTC, the available literature is contradictory, and there is no consensus regarding adjuvant therapy.We aim to provide an overview of intermediate-risk differentiated thyroid cancer, focusing on criteria to consider when deciding on adjuvant therapy in the current context of personalized approach, including molecular analysis to enhance the accuracy of patient management.

Saúde do Trabalhador: qual o papel do fonoaudiólogo? / Occupational Health: what is the role of the speech therapist? / Salud Laboral: ¿cuál es el papel del logopeda?

Introdução: A fonoaudiologia teve inserção na Saúde do trabalhador principalmente por práticas de cuidados relacionados a audição e voz. Para a oferta de um cuidado mais aderente às necessidades dos trabalhadores, é necessário que as práticas fonoaudiológicas se ampliem nesse campo, propondo ações de promoção em saúde e cuidados em distúrbios da comunicação relacionados ao trabalho, visando a atenção integral à saúde dos trabalhadores e, assim, desapegando-se das ações essencialmente assistenciais e reabilitadoras. Objetivo: O presente estudo se propõe a compreender a formação do Fonoaudiólogo em Saúde do Trabalhador. Método: Trata-se de um estudo quantitativo, aplicou-se questionário eletrônico aos Fonoaudiólogos que atuam em Centros de Referência em Saúde do Trabalhador (CERESTs) buscando descrever o perfil desses profissionais, sua relação com o trabalho e as práticas realizadas. Resultados: Foram alcançados 33 fonoaudiólogos que atuam em Centros de Referência em Saúde do Trabalhador (CERESTs) do país em 14 estados brasileiros. O estudo verificou um grupo de profissionais majoritariamente feminino, porém heterogêneo quanto ao ano de formação, faixa etária, ano de entrada no CEREST e tempo de serviço. Verificou-se que as cargas horárias semanais variam de seis a 44 horas e, ainda, que as fonoaudiólogas realizam além das ações de núcleo específicas, atividades coletivas internas, externas, intersetoriais e ações de vigilância. Conclusão: Foi possível caracterizar o perfil das fonoaudiólogas que atuam nos CERESTs, além de levantar as ações e atividades realizadas, contribuindo para o entendimento do atual estado da Saúde do Trabalhador na Fonoaudiologia e para a proposição de ampliação da atuação na área. (AU)

Introduction: Speech therapy has been inserted in Worker's Health mainly through care practices related to hearing and voice. It is necessary for speech therapy practices to expand in this field, proposing health promotion actions and care for work-related communication disorders, aiming at comprehensive care for workers' health, and thus detaching from essentially care and rehabilitative actions. Objective: The present study proposes to understand the formation of the Speech-Language Pathologist in Occupational Health. Method: This is a quantitative study, an electronic questionnaire was applied to Speech-Language Pathologists who work in Occupational Health Reference Centers (CERESTs) seeking to describe the profile of these professionals, their relationship with work and the practices performed. Results: The study reached 33 speech therapists working in Workers' Health Reference Centers (CERESTs) from 14 Brazilian states. The study found a group of mostly female professionals, but heterogeneous as to year of graduation, age, year of entry in CEREST and years of service, it was identified that the weekly workloads vary from six to 44 hours and also that speech therapists perform specific nucleus actions, but also internal and external collective activities, intersectional and vigilance actions. Conclusion: It was possible to characterize the profile of speech therapists who work in CERESTs, and also to identify the actions and activities performed, contributing to the understanding of the current state of Occupational Health in Speech Therapy and to the proposition of expanding work in the area. (AU)

Introducción: La logopedia se ha insertado en la Salud del Trabajador principalmente a través de prácticas asistenciales relacionadas con la audición y la voz. Es necesario que las prácticas fonoaudiológicas se expandan en este campo, proponiendo acciones de promoción de la salud y atención a los trastornos de la comunicación relacionados con el trabajo, visando la atención integral a la salud de los trabajadores, y despegándose así de acciones esencialmente asistenciales y rehabilitadoras. Objetivo: El presente estudio se propone comprender la formación del Fonoaudiólogo en Salud Ocupacional. Método: Se trata de un estudio cuantitativo, se aplicó un cuestionario electrónico a los fonoaudiólogos que actúan en los Centros de Referencia en Salud del Trabajo (CERESTs) buscando describir el perfil de estos profesionales, su relación con el trabajo y las prácticas realizadas. Resultados: Llegamos a 33 logopedas que trabajan en los Centros de Referencia de Salud de los Trabajadores (CEREST) de 14 estados brasileños. El estudio encontró un grupo de profesionales mayoritariamente femenino, pero heterogéneo en cuanto al año de graduación, la edad, el año de incorporación al CEREST y la antigüedad, las cargas de trabajo semanales que varían de seis a 44 horas y también que los logopedas realizan, además de las acciones básicas específicas, actividades colectivas internas y externas, acciones intersectoriales y de vigilancia. Conclusión: Fue posible caracterizar el perfil de las fonoaudiólogas que acuden a los CEREST, además de levantar las acciones y actividades realizadas contribuyendo así a la comprensión del estado actual de la Salud del Trabajador en la Fonoaudiología y a la propuesta de ampliación de la enseñanza en el área. (AU)

The elusive Luminal B breast cancer and the mysterious chemokines.

PURPOSE: Invasive ductal breast cancer (IDC) is heterogeneous. Staging and immunohistochemistry (IH) allow for effective therapy but are not yet ideal. Women with Luminal B tumors show an erratic response to treatment. This prospective study with 81 women with breast cancer aims to improve the prognostic stratification of Luminal B patients. METHODS: This is a prospective translational study with 81 women with infiltrating ductal carcinoma, grouped by TNM staging and immunohistochemistry, for survival analysis, and their correlations with the chemokines. Serum measurements of 13 chemokines were performed, including 7 CC chemokines [CCL2(MCP1), CCL3(MIP1α), CCL4(MIP1ß), CCL5(Rantes), CCL11(Eotaxin), CCL17(TARC), CCL20(MIP3α)], 6 CXC chemokines [CXCL1(GroAlpha), CXCL5(ENA78), CCXCL8(IL-8), CXCL9(MIG), CXCL10(IP10), CXCL11(ITAC)]. RESULTS: Overall survival was significantly dependent on tumor staging and subtypes by immunohistochemistry, with a median follow-up time the 32.87 months (3.67-65.63 months). There were age correlations with IP10/CXCL10 chemokines (r = 0.4360; p = 0.0079) and TARC/CCL17 (Spearman + 0.2648; p = 0.0360). An inverse correlation was found between body weight and the chemokines Rantes/CCL5 (r = - 0.3098; p = 0.0169) and Eotaxin/CCL11 (r = - 0.2575; p = 0.0470). Smokers had a higher concentration of MIP3α/CCL20 (Spearman + 0.3344; p = 0.0267). Luminal B subtype patients who expressed lower concentrations of ENA78/CXCL5 (≤ 254.83 pg/ml) (Log-Rank p = 0.016) and higher expression of MIP1ß/CCL4 (> 34.84 pg/ml) (Log-Rank p = 0.014) had a higher risk of metastases. CONCLUSION: Patients with Luminal B breast tumors can be better stratified by serum chemokine expression, suggesting that prognosis is dependent on biomarkers other than TNM and IH.

Analysis of the surgical approach in prostate cancer staging: results from the surveillance, epidemiology and end results program.

Surgery is not used as a criterion for staging prostate cancer, although there is evidence that the number of analyzed and affected lymph nodes have prognosis value. The aim of this study was to determine whether there are significant differences in staging criteria in patients who underwent prostatectomy compared to those who did not, and whether the number of affected and analyzed lymph nodes (LN) plays a prognostic role. In this retrospective study, a test cohort consisting of 404,210 newly diagnosed men with prostate cancer, between 2004 and 2010, was obtained from the 17 registries (Nov 2021 submission); a validation consisting of 147,719 newly diagnosed men with prostate cancer between 2004 and 2019 was obtained from the 8 registries (Nov 2021 submission). Prostate cancer-specific survival was analyzed by Kaplan-Meier curves, survival tables and Cox regression; overall survival was analyzed only to compare Harrell's C-index between different staging criteria. In initial analyses, it was observed that the prognostic value of lymph node metastasis changes according to the type of staging (clinical or pathological), which is linked to the surgical approach (prostatectomy). Compared with T4/N0/M0 patients, which are also classified as stage IVA, N1/M0 patients had a shorter [adjusted HR: 1.767 (1429-2184), p < 0.0005] and a longer [adjusted HR: 0.832 (0.740-0.935), p = 0.002] specific survival when submitted to prostatectomy or not, respectively. Analyzing separately the patients who were submitted to prostatectomy and those who were not, it was possible to obtain new LN metastasis classifications (N1: 1 + LN; N2: 2 + LNs; N3: > 2 + LNs). This new (pathological) classification of N allowed the reclassification of patients based on T and Gleason grade groups, mainly those with T3 and T4 disease. In the validation group, this new staging criterion was proven to be superior [specific survival C-index: 0.908 (0.906-0.911); overall survival C-index: 0.788 (0.786-0.791)] compared to that currently used by the AJCC [8th edition; specific survival C-index: 0.892 (0.889-0.895); overall survival C-index: 0.744 (0.741-0.747)]. In addition, an adequate number of dissected lymph nodes results in a 39% reduction in death risk [adjusted HR: 0.610 (0.498-0.747), p < 0.0005]. As main conclusion, the surgery has a major impact on prostate cancer staging, mainly modifying the effect of N on survival, and enabling the stratification of pathological N according to the number of affected LN. Such a factor, when considered as staging criteria, improves the prognosis classification.

Reprogramming of tumor-associated macrophages by polyaniline-coated iron oxide nanoparticles applied to treatment of breast cancer.

Breast cancer is the most commonly diagnosed type of cancer among the female population worldwide. It is a disease with a high incidence and geographic distribution that negatively impacts global public health and deleteriously affect the quality of life of cancer patients. Among the new approaches, cancer immunotherapy is the most promising trend in oncology by stimulating the host's own immune system to efficiently destroy cancer cells. Recent evidence has indicated that iron oxide nanoparticles can promote the reprograming of M2 into M1 macrophages with anti-tumor effects in the tumor microenvironment. Thus, the aim of the present work was to evaluate the ability of polyaniline-coated maghemite (Pani/γ-Fe2O3) nanoparticles to modulate human macrophages in 2D monolayers and 3D multicellular breast cancer models. It was observed that Pani/γ-Fe2O3 NPs re-educated IL-10-stimulated macrophages towards a pro-inflammatory profile, decreasing the proportion of CD163+ and increasing the CD86+ proportion in 2D models. NPs were successfully taken-up by macrophages presented in the 3D model and were also able to induce an increasing in their CD86+ proportion in triple MCTs model. Overall, our findings open new perspectives on the use of Pani/γ-Fe2O3 NPs as an immunomodulatory therapy for macrophage reprogramming towards an anti-tumor M1 phenotype, providing a new tool for breast cancer immunotherapies.

Peptide Microarrays for Flavivirus Diagnosis.

Flavivirus are the most alarming prevalent viruses worldwide due to its vast impact on public health. Most early symptoms of diseases caused by Flavivirus are similar among each other and to other febrile illnesses making the clinical differential diagnosis challenging. In addition, due to cross-reactivity and a relatively limited persistence of viral RNA in infected individuals, the current available diagnosis strategies fail to efficiently provide a differential viral identification. In this context, virus-specific tests are essential to improve patient care, as well as to facilitate disease surveillance and the effective control of transmission. Here, we describe the use of protein microarrays as an effective tool for screening peptides differentially recognized by anti-Yellow Fever virus antibodies induced by vaccination or by natural viral infection.

The role of T-cells in head and neck squamous cell carcinoma: From immunity to immunotherapy.

Head and neck squamous cell carcinoma (HNSCC) encompass a group of complex entities of tumours affecting the aerodigestive upper tract. The main risk factors are strongly related to tobacco and alcohol consumption, but also HPV infection is often associated. Surgery, radiotherapy and/or chemotherapy are the standard treatments, though the 5-year overall survival is less than 50%. The advances in genomics, molecular medicine, immunology, and nanotechnology have shed a light on tumour biology which helps clinical researchers to obtain more efficacious and less toxic therapies. Head and neck tumours possess different immune escape mechanisms including diminishing the immune response through modulating immune checkpoints, in addition to the recruitment and differentiation of suppressive immune cells. The insights into the HNSCC biology and its strong interaction with the tumour microenvironment highlights the role of immunomodulating agents. Recently, the knowledge of the immunological features of these tumours has paved the way for the discovery of effective biomarkers that allow a better selection of patients with odds of improving overall survival through immunotherapy. Specially biomarkers regarding immune checkpoint inhibitors antibodies, such as anti-PD-1/PD-L1 and anti-CTLA-4 in combination with standard therapy or as monotherapy. New immunotherapies to treat head and neck cancer carcinomas, such as CAR T cells and nanoparticles have been the center of attention and in this review, we discuss the necessity of finding targets for the T cell in the cancer cells to generate CAR T cells, but also the relevance of evaluating specificity and safety of those therapies.

The effect of delayed treatment in breast cancer patients: How much is too late? An experience of a single-center study effect of surgery delay in survival.

BACKGROUND AND OBJECTIVES: Proper treatment is critical for control and curative intent in breast cancer. Delays in receiving treatment can influence patients' prognoses. METHODS: Retrospective, observational, single-center study based on data from medical records of 747 patients with non-metastatic invasive ductal breast carcinoma (I-III) in the initial analysis, comprising 554 patients undergoing adjuvant and 193 neoadjuvant treatment. Kaplan-Meier, Cox regression and time-dependent Cox regression were performed to obtain the predictive value of time to surgery and time to first treatment. Immortal time bias was managed and only 721 patients were included in the multivariable analysis. RESULTS: During a median observation of 64.4 months, there were 140 death events and 177 disease progression events. Time to surgery (TTS) and time from completion of neoadjuvant chemotherapy to surgery (TNS) showed a significant impact on overall survival, associated with a 6% increased chance of death [HR: 1.06 (1.03-1.09), p < 0.001] and 4% [HR: 1.04 (1.00-1.09), p = 0.048] with a one-month increment, respectively. By multivariable analysis, continuous TTS had a different weight as a prognostic factor in stage IIIA/IIIB [adjusted HR: 1.249 (1.072-1.454), p = 0.004] compared to stage I/II [adjusted HR: 1.093 (1.048-1.141), p < 0.0005]. Likewise, TNS was significant after adjusting for other factors [adjusted HR: 1.092 (1.038-1.148), p = 0.001]. CONCLUSION: Delay in receiving surgery with curative intent impairs the survival of patients with breast cancer.

Epidermal growth factor receptor (EGFR) expression in the serum of patients with triple-negative breast carcinoma: prognostic value of this biomarker.

Background: Epidermal growth factor receptor (EGFR) overexpression has been considered a poor prognostic factor in breast cancer. Methodology: A prospective study of 206 women with breast cancer analysed by stages (I, II, III and IV) and by immunohistochemical subtype (Luminal A, Luminal B, HER2+ and triple-negative (TN)); 89 healthy controls with normal recent mammography were included. The EGFR measured in the serum (sEGFR) was detected by the Enzyme-Linked Immunosorbent Assay (ELISA) method (R&D Systems kit DY231) collected by blood before any treatment in patients. Kaplan-Meier method and Cox regression were carried out to obtain the prognostic value, considering significance if p < 0.05. Results: With a median follow-up of 36.6 months, 47 deaths occurred. Multivariable Cox regression showed difference of overall survival (OS) associated with sEGFR levels (sEGFR ≤ or > 47.8 ng/mL) in patients with TN cancers, but not of Luminal A, Luminal B or HER2+ subtypes; adjusted by stage, the death risk increased by approximately 415% [hazard ratio (HR): 5.149 (1.900-13.955), p = 0.001] for patients with sEGFR > 47.8 ng/mL compared to patients with a lower sEGFR value. There was no significant correlation of sEGFR with staging, histological tumour grade (G1/G2/G3), Ki67 (< or ≥14%) or body mass index. Conclusions: Increased sEGFR expression in patients with TN tumours is a significant predictor of lower OS and its quantification is inexpensive and straightforward.

Mapping and Validation of Peptides Differentially Recognized by Antibodies from the Serum of Yellow Fever Virus-Infected or 17DD-Vaccinated Patients.

Yellow Fever disease is caused by the Yellow Fever virus (YFV), an arbovirus from the Flaviviridae family. The re-emergence of Yellow Fever (YF) was facilitated by the increasing urbanization of sylvatic areas, the wide distribution of the mosquito vector, and the low percentage of people immunized in the Americas, which caused severe outbreaks in recent years, with a high mortality rate. Therefore, serological approaches capable of discerning antibodies generated from the wild-type (YFV-WT) strain between the vaccinal strain (YFV-17DD) could facilitate vaccine coverage surveillance, enabling the development of strategies to avoid new outbreaks. In this study, peptides were designed and subjected to microarray procedures with sera collected from individuals infected by WT-YFV and 17DD-YFV of YFV during the Brazilian outbreak of YFV in 2017/2018. From 222 screened peptides, around ten could potentially integrate serological approaches aiming to differentiate vaccinated individuals from naturally infected individuals. Among those peptides, one was synthesized and validated through ELISA.

A hierarchical approach to combine histological grade and immunohistochemical factors to identify high-risk luminal breast cancers.

Background: The luminal subtype accounts for ~70% of newly diagnosed breast cancer patients. Although it has a better prognosis, approximately 30% of them develop a late relapse. Identifying those patients is of interest to improve treatment decisions. Methods: A retrospective observational, single-centre study based on data from medical records of 572 non-metastatic (I-III) invasive ductal breast carcinoma patients, 448 with luminal tumours and 124 with triple-negative tumours. Kaplan-Meier, Cox regression and time-dependent Cox regression were carried out to obtain the prognosis value of risk factors. Results: During a median observation of 5.5 years, 105 distant metastasis events and 105 all-cause deaths were observed. In addition to known clinicopathological factors (i.e., age, tumour size and lymph node metastasis), the high semi-quantitative expression of both hormone receptors was associated with distant metastasis-free survival (DMFS) (adjusted hazard ratio (HaR): 0.524 (0.316-0.867), p = 0.012) and overall survival (OS) (adjusted HaR: 0.486 (0.286-0.827), p = 0.008). The stratified analysis made it possible to identify risk modification factors. Subsequent stratification by histological grade, Ki-67 and semi-quantitative PR expression or, mainly, the composite semi-quantitative expression of hormone receptors (cHR) enabled the identification of luminal breast cancer patients of adjuvant schema at higher risk for metastasis and death. However, initial analyses including patients of neoadjuvant therapy pointed to a path of subsequent stratification by cHR and histological grade, also enabling grouping of luminal breast cancer patients with similar prognosis for DMFS (cHR ≤ 4+ G2 or G3 versus triple-negative, adjusted HaR: 0.703 (0.415-1.189), p = 0.189) and OS (cHR ≤4+ G2 or G3 versus triple-negative, adjusted HaR: 0.662 (0.403-1.088), p = 0.104). Conclusion: The semi-quantitative expression of both cHR, Ki-67 proliferation index and histological grade can identify luminal breast cancer patients at greater risk of developing metastasis and death when combined in a hierarchical fashion, and could be useful for a better prognosis stratification in services from low- and middle-income countries.

Ethyl Acetate Fraction of Bixa orellana and Its Component Ellagic Acid Exert Antibacterial and Anti-Inflammatory Properties against Mycobacterium abscessus subsp. massiliense.

Mycobacterium abscessus subsp. massiliense (Mabs) causes chronic infections, which has led to the need for new antimycobacterial agents. In this study, we investigated the antimycobacterial and anti-inflammatory activities of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc). In silico analysis predicted that ElAc had low toxicity, was not mutagenic or carcinogenic, and had antimicrobial and anti-inflammatory activities. Apparently, ElAc can interact with COX2 and Dihydrofolate reductase (DHFR) enzymes, which could explain both activities. In vitro analysis showed that BoEA and ElAc exerted antimicrobial activity against Mabs (minimum inhibitory concentration of 1.56, 1.56 mg/mL and bactericidal concentration of 6.25, 3.12 mg/mL, respectively. Clarithromycin showed MIC and MBC of 1 and 6 µg/mL). Treatment with BoEA or ElAc increased survival of Tenebrio molitor larvae after lethal infection with Mabs and reduced carrageenan-induced paw edema in mice, around 40% of edema volume after the fourth hour, similarly to diclofenac. In conclusion, BoEA and ElAc exert antimicrobial effects against Mabs and have anti-inflammatory effects, making them potential sources of antimycobacterial drugs. The biological activities of ElAc may be due to its high binding affinities predicted for COX2 and DHFR enzymes.

Prognosis value of lymphovascular invasion in patients with invasive ductal breast carcinoma according to lymph node metastasis status.

Background: Tumour lymphovascular invasion is not routinely assessed in all pathology services, and whether reporting it quantitatively or qualitatively is the main factor associated with the loss of this prognostic event. This study aimed to analyse the prognostic value of qualitatively reported lymphovascular invasion in patients with invasive breast ductal carcinoma. Methods: This was a retrospective, single-center study, enrolling a total of 426 patients with invasive ductal carcinoma of the breast with a report of lymphovascular invasion, with a median follow-up of approximately 4.5 years. Kaplan-Meier and Cox regression was performed to obtain the predictive value of lymphovascular invasion. Propensity score matching was performed to reduce bias by standardising factors with significant differential distribution of lymphovascular invasion status. Results: Lymphovascular invasion was present in 197 (49.2%) patients. Multivariate Cox regression showed that lymphovascular invasion independently increases the risk of death by almost two times (adjusted hazard ratio (HR): 2.045 (1.226-3.406), p = 0.006) and the risk of distant metastasis by more than two times (adjusted HR: 2.373 (1.404-4.010), p = 0.001). Subgroup analysis after matching by propensity score in adjuvant-only patients showed that the lymphovascular invasion is a factor of increased death in N- patients (adjusted HR: 12.597 (1.624-97.728), p = 0.015) and of distant metastasis-free survival in N+ patients (adjusted HR: 4.862 (1.649-14.335), p = 0.004) and almost for N- patients (adjusted HR 7.905 (0.969-64.509), p = 0.004). Conclusion: The presence of lymphovascular invasion is a predictor of worse prognosis in patients with invasive ductal carcinoma of the breast, even with metastatic lymph node disease (N1-N3).

Efeito da estimulação auditiva rítmica associada à fisioterapia na mobilidade funcional de idosos sedentários: um ensaio clínico randomizado / Effect of rhythmic auditory stimulation associated with physiotherapy on the functional mobility of sedentary elderly: a randomized clinical trial

A Estimulação Auditiva Rítmica (EAR) tem despertado interesse pelos efeitos positivos durante o envelhecimento sobre os declínios da mobilidade. Objetivo: Avaliar os efeitos de um treinamento com estimulação auditiva rítmica associada à fisioterapia sobre mobilidade funcional em idosos sedentários. Métodos: Neste ensaio clínico randomizado, controlado, simples cego os idosos foram alocados em três grupos: controle (GC), estimulação auditiva rítmica associada à fisioterapia (EAR+FT) e fisioterapia (FT). Os grupos FT e EAR+FT foram submetidos a 12 sessões com o protocolo da fisioterapia (três vezes por semana, 40 min/sessão). Ao grupo EAR+FT eram acrescidos a estimulação auditiva rítmica com música (10-20 min/sessão), fornecidos pelo aplicativo ParkinSONS®. Para a análise dos dados, foi utilizada a ANOVA two-way com medidas repetidas para comparação entre os grupos e o tempo, com o post hoc de Tukey. O tamanho do efeito das intervenções também foi calculado. O nível de significância estabelecido foi de p<0.05. Resultados: Não foi encontrada diferença significativa entre os grupos. Na análise pareada, foi observado que o grupo EAR+FT apresentou resultados significativos e tamanho do efeito benéfico com aumento da velocidade (p= 0.0001), redução do tempo (p= 0.001) e do número de passos (p= 0.0007), redução nos valores do TUG (p= 0.0001), aumento do deslocamento no TAF (p= 0.0001), melhora dos escores no TUG-ABS (p= 0.003) e PAP (p= 0.0001). Conclusão: Verificou-se um efeito positivo do uso da EAR associada à fisioterapia sobre mobilidade funcional de idosos sedentários, repercutindo sobre os parâmetros espaços-temporais, o risco de quedas e a execução de atividades funcionais.

Rhythmic auditory stimulation (RAS) has aroused interest in the positive effects of aging on mobility declines. Objective: Evaluate the effects of training with rhythmic auditory stimulation associated with physiotherapy on functional mobility in sedentary elderly. Method: In this randomized, controlled, simple-blind clinical trial, the elderly were divided into three groups: control (CG), rhythmic auditory stimulation associated with physiotherapy (RAS+FT) and physiotherapy (FT). The FT and RAS+FT groups were submitted to 12 sessions with the physiotherapy protocol (three times a week, 40 min/session). Rhythmic auditory stimulation with music (10-20 min/session), provided by the ParkinSONS® app, was added to the RAS+FT group. For data analysis, two-way ANOVA with repeated measures was used for comparison between groups and time, with Tukey's post hoc. The effect size of interventions was also calculated. The level of significance established was p<0.05. Results: No significant differences were found between groups. In the paired analysis, it was observed that the RAS+FT group presented significant results and size of the beneficial effects with increased speed (p= 0.0001), reduction in time (p= 0.001), number of steps (p= 0.0007), reduction in TUG values (p= 0.0001), increase in displacement in TAF (p= 0.0001), improvement in scores in TUG-ABS (p= 0.003) and PAP (p= 0.0001). Conclusions: There was a positive effect of the use of RAS associated with physiotherapy on the functional mobility of sedentary elderly, reflecting on the spatiotemporal parameters, the risk of falls and the performance of functional activities.

Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.

BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).

The benefits of trastuzumab in the treatment of HER2+ breast cancer as a function of exposure time.

BACKGROUND: Breast cancer is a heterogeneous disease with overexpression of several receptors, such as human epidermal receptor 2 (HER2), which is a prognostic and predictive biomarker for treatment with the anti-HER2 monoclonal antibody trastuzumab. This study aimed to test the contribution of this regimen in patients with overexpression/amplification of HER2 for periods shorter than the 1-year treatment recommendation. METHODS: A retrospective single-centre study involving 155 patients with non-metastatic (stages I-III) invasive ductal HER2+ breast carcinoma, with a median follow-up of 48.9 months after completion of adjuvant therapy, except endocrine therapy. RESULTS: About 60% of patients received trastuzumab therapy for a median time of 365 days. Although the use of trastuzumab for a short period has provided some benefit, analyses of survival with a continuous dependent variable have revealed a minimum time for improved survival. In the multivariate analysis by Cox regression, trastuzumab use duration exceeding 9 weeks resulted in protection against distant metastasis (adjusted HR: 0.307 (0.139-0.678), p = 0.004), disease progression (adjusted hazard ratio (HR) 0.353 (0.175-0.714), p = 0.004) and death (adjusted HR: 0.267 (0.105-0.678), p = 0.005), being superior to multimodal systemic therapy with chemotherapy and to endocrine therapy without trastuzumab, but inferior to almost 1 year of administration of this monoclonal antibody, especially regarding overall survival (adjusted HR: 0.203 (0.069-0.596), p = 0.004). CONCLUSION: Despite showing some benefits, the protective effect derived from a suboptimal time of trastuzumab exposure is inferior to the standard course of 1 year.