Comparison of hormonal receptor expression and HER2 status between circulating tumor cells and breast cancer metastases

OBJECTIVES: Breast cancer (BC) is the most common neoplasm in women. Biopsy of metastatic lesions is recommended to confirm estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status as there are discrepancies in these patterns between primary tumors and metastases in up to 40% of the cases. Circulating tumor cells (CTCs) are related to BC outcomes and could potentially be an alternative to the invasive procedures of metastasis rebiopsy. ISET(R) technology is not currently employed to detect CTCs in patients with BC. Emerging data support that the characterization of CTC protein expression can refine its prognostic value. Transforming growth factor (TGF)-B plays a role in BC progression and invasiveness. Thus, in this study, we aimed to compare ER, PR, and HER2 expression in primary tumors, CTCs, and metastases and evaluate TGF-B type 1 receptor (TGF-B RI) expression in CTCs as prognostic factor for progression free survival (PFS) and overall survival (OS). METHODS: This prospective study was conducted at the A.C. Camargo Cancer Center, Brazil. Blood samples were processed in ISET(R) (Isolation by SizE of Tumors, Rarecells, France) before computed tomography–guided biopsy of suspected metastatic lesions. Protein expression levels in CTCs were compared to those in primary tumors/ metastases (medical records). RESULTS: Of the 39 patients initially included, 27 underwent both biopsies of metastases and blood collection and were considered for analysis. The concordance rates for ER, PR, and HER2 expression between primary tumors and metastases were high. No loss of HER2 expression at any metastasis site and retention of the same pattern of protein expression in all triple-negative (TN) tumors (92.5%, 81.5% and 96.2% respectively) (p<0.0001) was observed. When metastases/CTCs were classified as TN/non–TN, CTCs showed high specificity (93%), accuracy (84.2%), and negative predictive value (88%). The median OS of patients without TGF-B RI expression in CTCs was 42.6 versus 20.8 months for TGF-B RI expression-positive ones (p>0.05). CONCLUSION: The role of CTCs detected by ISET has not yet been established in BC. Here, we suggest that this methodology may be useful to evaluate metastasis in non–TN cases as well as TGF-B RI expression in CTCs, which may impact patient survival. Due to sample limitations, future studies must focus on specific BC subtypes and an expansion of the cohort

Changes in attachment dimensions during the treatment of acute post-traumatic stress disorder in sexually assaulted Brazilian women

Introduction: Attachment patterns are established during early childhood; however, extreme experiences throughout life may change this structure, either toward attachment security or insecurity. We analyzed changes in attachment dimensions in women with acute post-traumatic stress disorder (PTSD) following sexual assault, that were randomized to a 14-week treatment with either the medication sertraline or Interpersonal Psychotherapy. Methods: Seventy-four adult women who presented significant reduction in PTSD symptoms across the trial responded to the Revised Adult Attachment Scale at baseline, on week 8 of treatment, and at the end of the trial, on week 14. We fitted a generalized linear model to explain the attachment anxiety and avoidance scores at baseline. A generalized linear mixed model investigated how attachment dimensions changed over time. Socioeconomic data, treatment type, history of childhood trauma, and PTSD severity over the 14-week period were the considered covariates. Results: At baseline, attachment anxiety was associated with a history of early trauma. Attachment anxiety remained stable during the follow-up. Attachment avoidance, on the other hand, significantly increased from baseline to week 14. Higher avoidance was observed in patients with higher total PTSD scores and on the cluster of hyperarousal symptoms. Races other than White (black, mixed-race, or Asian) and younger age were associated with higher attachment avoidance. Discussion: Contrary to our expectations, attachment avoidance increased during follow-up, indicating changes in the interpersonal realm beyond the symptoms of PTSD

Validation of the Brazilian-Portuguese version of the Clinician Administered Post Traumatic Stress Disorder Scale-5

Objectives: The aim of this study was to validate CAPS-5 for the Brazilian-Portuguese language on a sample of 128 individuals from two centers (from the cities of São Paulo and Porto Alegre) who have been recently exposed to a traumatic event. Methods: We performed a reliability analysis between interviewers (with a subset of 32 individuals), an internal consistency analysis, and a confirmatory factorial analysis for the validation study. Results: The inter-rater reliability of the total PTSD symptom severity score was high [intraclass correlation coefficient =0.994, 95% CI (0.987–0.997), p < 0.001]. Cohen’s Kappa for individual items ranged between 0.759 and 1. Cronbach’s alpha coefficients indicated high internal consistency for the CAPS-5 full scale (α = 0.826) and an acceptable level of internal consistency for the four symptom clusters. The confirmatory factorial analysis for the 20-item original CAPS-5 did not fit the data well. A 15-item model with better results was then established by excluding the following CAPS-5 items: dissociative amnesia, recklessness, distorted cognitions, irritability, and hypervigilance. Conclusion: Despite the limitation of the predominance of female victims, and the high number of sexually assaulted women in our sample, the model with only 15 items provided a good fit to the data with high internal consistency (α = 0.835)

Small renal masses in Latin-American population : Characteristics and prognostic factors for survival, recurrence and metastasis - A multi-institutional study from LARCG database

To evaluate demographic, clinical and pathological characteristics of small renal masses (SRM) (≤ 4 cm) in a Latin-American population provided by LARCG (Latin-American Renal Cancer Group) and analyze predictors of survival, recurrence and metastasis. A multi-institutional retrospective cohort study of 1523 patients submitted to surgical treatment for non-metastatic SRM from 1979 to 2016. Comparisons between radical (RN) or partial nephrectomy (PN) and young or elderly patients were performed. Kaplan-Meier curves and log-rank tests estimated 10-year overall survival. Predictors of local recurrence or metastasis were analyzed by a multivariable logistic regression model. PN and RN were performed in 897 (66%) and 461 (34%) patients. A proportional increase of PN cases from 48.5% (1979-2009) to 75% (after 2009) was evidenced. Stratifying by age, elderly patients (≥ 65 years) had better 10-year OS rates when submitted to PN (83.5%), than RN (54.5%), p = 0.044. This disparity was not evidenced in younger patients. On multivariable model, bilaterality, extracapsular extension and ASA (American Society of Anesthesiologists) classification ≥3 were predictors of local recurrence. We did not identify significant predictors for distant metastasis in our series. PN is performed in Latin-America in a similar proportion to developed areas and it has been increasing in the last years. Even in elderly individuals, if good functional status, sufficiently fit to surgery, and favorable tumor characteristics, they should be encouraged to perform PN. Intending to an earlier diagnosis of recurrence or distant metastasis, SRM cases with unfavorable characteristics should have a more rigorous follow-up routine

Modelos de sobrevivência com fração de cura usando um termo de fragilidade e tempo de vida Weibull modificada generalizada

In survival analysis, some studies are characterized by having a significant fraction of units that will never suffer the event of interest, even if accompanied by a long period of time. For the analysis of long-term data, we approach the standard mixture model by Berkson & Gage, where we assume the generalized modified Weibull distribution for the lifetime of individuals at risk. This model includes several classes of models as special cases, allowing its use to discriminate models. The standard mixture model implicitly assume that those individuals experiencing the event of interest possess homogeneous risk. Alternatively, we consider the standard mixture model with a frailty term in order to quantify the unobservable heterogeneity among individuals. This model is characterized by the inclusion of a unobservable random variable, which represents information that can not or have not been observed. We assume multiplicative frailty with a gamma distribution. For the lifetime of individuals at risk, we assume the Weibull distribution, obtaining the frailty Weibull standard mixture model. For both models, we realized simulation studies with the purpose of analyzing the frequentists properties of estimation procedures. Applications to real data set showed the applicability of the proposed models in which parameter estimates were determined using the approaches of maximum likelihood and Bayesian.Em análise de sobrevivência determinados estudos caracterizam-se por apresentar uma fração significativa de unidades que nunca apresentarão o evento de interesse, mesmo se acompanhados por um longo período de tempo. Para a análise de dados com longa duração, abordamos o modelo de mistura padrão de Berkson & Gage supondo que os tempos de vida dos indivíduos em risco seguem distribuição Weibull modificada generalizada. Este modelo engloba diversas classes de modelos como casos particulares, propiciando o uso deste para discriminar modelos. O modelo abordado assume implicitamente que todos os indivíduos que falharam possuem risco homogêneo. Alternativamente, consideramos o modelo de mistura padrão com um termo de fragilidade com o objetivo de quantificar a heterogeneidade não observável entre os indivíduos. Este modelo é caracterizado pela inclusão de uma variável aleatória não observável, que representa as informações que não podem ou que não foram observadas. Assumimos que a fragilidade atua de forma multiplicativa com distribuição gama. Para os tempos de vida dos indivíduos em risco consideramos a distribuição Weibull, obtendo o modelo de mistura padrão Weibull com fragilidade. Para os dois modelos realizamos estudos de simulação com o objetivo de analisar as propriedades frequentistas dos processos de estimação. Aplicações a conjunto de dados reais mostraram a aplicabilidade dos modelos propostos, em que a estimação dos parâmetros foram determinadas através das abordagens de máxima verossimilhança e Bayesiana

Opinião de médicos brasileiros sobre o tratamento da COVID-19

Objetivo: Investigar a opinião de médicos brasileiros sobre o tratamento precoce da COVID-19 com hidroxicloroquina/cloroquina e azitromicina em pacientes com suspeita clínica e sobre o tratamento com corticoterapia na fase inflamatória da doença. Métodos: Trata-se de uma pesquisa de opinião, com amostragem por conveniência, com médicos atuantes no Brasil. A coleta dos dados ocorreu no período de 26 de maio a 8 de junho de 2020 (13 dias), por meio de um formulário Google, disponibilizado publicamente nas redes sociais e aplicativos de comunicação. Realizou-se uma análise descritiva dos dados, teste de independência, teste T Student e modelo de regressão logística com análise multivariada. Resultados: A pesquisa contou com 1.020 médicos participantes, com média de 21,9 anos de formado. 72,4% dos participantes apresentaram-se a favor do tratamento precoce com hidroxicloroquina/cloroquina e azitromicina e 89,7% dos médicos apresentaram-se favoráveis ao uso da corticoterapia para o tratamento da fase inflamatória da COVID-19. Constatou-se também que participantes com maior idade, com residência médica, atuantes nas regiões Nordeste e Norte possuíam mais chances de serem favoráveis aos tratamentos. Por outro lado, profissionais especialistas em medicina intensiva, infectologia e pneumologia, além de atuantes nas unidades de terapia intensiva, mostraram-se mais desfavoráveis. Conclusão: A maioria dos médicos investigados nesta pesquisa de opinião mostrou-se a favor do tratamento precoce apresentado e do uso da corticoterapia no tratamento da COVID-19. Já os especialistas em medicina intensiva, infectologia e pneumologia e profissionais atuantes nas Unidades de Terapia Intensiva mostraram-se mais desfavoráveis

A Modified Cure Rate Model Based on a Piecewise Distribution with Application to Lobular Carcinoma Data

A novel cure rate model is introduced by considering, for the number of concurrent causes, the modified power series distribution and, for the time to event, the recently proposed power piecewise exponential distribution. This model includes a wide variety of cure rate models, such as binomial, Poisson, negative binomial, Haight, Borel, logarithmic, and restricted generalized Poisson. Some characteristics of the model are examined, and the estimation of parameters is performed using the Expectation–Maximization algorithm. A simulation study is presented to evaluate the performance of the estimators in finite samples. Finally, an application in a real medical dataset from a population-based study of incident cases of lobular carcinoma diagnosed in the state of São Paulo, Brazil, illustrates the advantages of the proposed model compared to other common cure rate models in the literature, particularly regarding the underestimation of the cure rate in other proposals and the improved precision in estimating the cure rate of our proposal