Clinico-pathologic factors and survival of patients with breast cancer diagnosed with de novo brain metastasis: a national cancer database analysis.

PURPOSE: Patients with Breast Cancer (BC) with Brain Metastasis (BCBM) have poor survival outcomes. We aimed to explore the clinico-pathologic and therapeutic factors predicting the survival in patients with de novo BCBM using the National Cancer Database (NCDB). PATIENTS AND METHODS: The NCDB was queried for patients with BC between 2010 and 2020. Survival analysis with Kaplan-Meier curves and log rank tests were used to find median overall survival (OS) in months (95% CI) across the different variables. A multivariate cox regression model was computed to identify significant predictors of survival. RESULTS: Out of n = 2,610,598 patients, n = 9005 (0.34%) had de novo BCBM. A trend of decreasing OS was observed with increasing age, Charlson-Deyo score (CDS), and number of extracranial metastatic sites. The highest median OS was observed in the Triple Positive and the lowest OS in the Triple Negative subgroup. Based on treatment regimen, combination of systemic therapy and local therapy achieved the highest OS. A positive trend in OS was observed in the BC subgroup analysis with targeted therapy demonstrating a survival benefit when added to systemic therapy. The multivariate cox regression model showed that age, race, ethnicity, insurance, median income, facility type, CDS, BC subtype, metastatic location sites, and treatment combinations received were significantly associated with risk of death. Receiving only local treatment for BM without systemic therapy more than doubled the risk of death compared to combining it with systemic therapy. CONCLUSIONS: This analysis suggests that treatment of systemic disease is the major factor influencing survival in patients with BCBM. Moreover, targeted therapy with anti-HER2 increased survival when added to systemic therapy explaining the highest median OS noted in the Triple Positive subgroup.

"You matter": patients perceptions and disparities about cancer care and telehealth during and after COVID-19 pandemic.

PURPOSE: Disparities in cancer care have been exacerbated by the COVID-19 pandemic. The aim of this study is to establish how telehealth mitigated the effect of COVID-19 on the healthcare sector and to identify potential disparities in perception and experience with telehealth in cancer care during and after the pandemic. METHODS: We identified individuals with an established cancer diagnosis who received treatment at a comprehensive academic cancer center with a diverse patient population between 2019 and 2021, during the COVID-19 pandemic. Participants were asked to complete a self-administrated survey intended to collect patient-reported outcomes on socioeconomic and mental health challenges incurred during the pandemic as well as participants' experience with telehealth. The assessment was adapted from a 21-question-based survey applied for mental health. Descriptive statistics were used to summarize participant characteristics and the response to the survey items. Multivariable logistic regression was performed to assess and analyze the contributing factors to the survey responses. RESULTS: A total of N = 136 participants were included in this analysis. The majority of participants (60.6%) reported increased anxiety, stress, or experience of distress as a direct result of COVID-19. However, among 54.1% of survey responders participated in a telehealth appointment and 84.4% agreed it was an easy and effective experience. CONCLUSION: Elderly, male, and black participants reported the worst impact related to the pandemic. The majority of patients had a positive experience with telehealth. The results of the study suggest that telehealth services can serve as a tool for patients with cancer during and beyond active treatment to access supportive services.

Predictors of mortality in hospitalised patients with COVID-19: a 1-year case-control study.

BACKGROUND: A paucity of predictive models assessing risk factors for COVID-19 mortality that extend beyond age and gender in Latino population is evident in the current academic literature. OBJECTIVES: To determine the associated factors with mortality, in addition to age and sex during the first year of the pandemic. DESIGN: A case-control study with retrospective revision of clinical and paraclinical variables by systematic revision of clinical records was conducted. Multiple imputations by chained equation were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalisation. No intervention was performed. SETTING: High-complexity centre above 2640 m above sea level (masl) in Colombia. PARTICIPANTS: A population sample of 564 patients admitted to the hospital with confirmed COVID-19 by PCR. Deceased patients (n=282) and a control group (n=282), matched by age, sex and month of admission, were included. MAIN OUTCOME MEASURE: Mortality during hospitalisation. MAIN RESULTS: After the imputation of datasets, CART analysis estimated 11 clinical profiles based on respiratory distress, haemoglobin, lactate dehydrogenase, partial pressure of oxygen to inspired partial pressure of oxygen ratio, chronic kidney disease, ferritin, creatinine and leucocytes on admission. The accuracy model for prediction was 80.4% (95% CI 71.8% to 87.3%), with an area under the curve of 78.8% (95% CI 69.63% to 87.93%). CONCLUSIONS: This study discloses new interactions between clinical and paraclinical features beyond age and sex influencing mortality in COVID-19 patients. Furthermore, the predictive model could offer new clues for the personalised management of this condition in clinical settings.

Molecular mimicry and autoimmunity in the time of COVID-19.

Infectious diseases are commonly implicated as potential initiators of autoimmune diseases (ADs) and represent the most commonly known factor in the development of autoimmunity in susceptible individuals. Epidemiological data and animal studies on multiple ADs suggest that molecular mimicry is one of the likely mechanisms for the loss of peripheral tolerance and the development of clinical disease. Besides molecular mimicry, other mechanisms such as defects in central tolerance, nonspecific bystander activation, epitope-determinant spreading, and/or constant antigenic stimuli, may also contribute for breach of tolerance and to the development of ADs. Linear peptide homology is not the only mechanism by which molecular mimicry is established. Peptide modeling (i.e., 3D structure), molecular docking analyses, and affinity estimation for HLAs are emerging as critical strategies when studying the links of molecular mimicry in the development of autoimmunity. In the current pandemic, several reports have confirmed an influence of SARS-CoV-2 on subsequent autoimmunity. Bioinformatic and experimental evidence support the potential role of molecular mimicry. Peptide dimensional analysis requires more research and will be increasingly important for designing and distributing vaccines and better understanding the role of environmental factors related to autoimmunity.

Antivinculin Antibodies in Systemic Sclerosis: Associations With Slow Gastric Transit and Extraintestinal Clinical Phenotype.

OBJECTIVE: The gastrointestinal (GI) tract is commonly affected in systemic sclerosis (SSc). A positive association between antivinculin antibody levels and GI symptom severity is reported in SSc. We sought to examine whether antivinculin antibodies associate with measures of GI dysmotility and extraintestinal clinical phenotype in SSc. METHODS: A total of 88 well-characterized patients with SSc and GI disease were assayed for antivinculin antibodies by enzyme-linked immunosorbent assay. Whole-gut scintigraphy, GI symptom scores, and clinical features of SSc were compared between patients with and without antibodies. RESULTS: Twenty of 88 (23%) patients had antivinculin antibodies, which were more prevalent in patients with slow gastric transit (35% versus 22%). In the univariate analyses, patients who were positive for antivinculin antibodies were more likely to have limited cutaneous disease (odds ratio [OR] 9.60 [95% confidence interval (95% CI) 1.19, 77.23]) and thyroid disease (OR 4.09 [95% CI 1.27, 13.21]). Such patients were also less likely to have lung involvement based on a Medsger Severity Score of ≥2 (OR 0.25 [95% CI 0.07, 0.92]). Higher levels of antivinculin autoantibodies were associated with less gastric emptying (ß coefficient -3.41 [95% CI -6.72, -0.09]). The association between antivinculin antibodies and each of these clinical features remained significant in the multivariable model. In particular, the presence of antivinculin antibodies (ß coefficient -6.20 [95% CI -12.33, -0.063]) and higher levels of antivinculin antibodies (ß coefficient -3.64 [95% CI -7.05, -0.23]) were each significantly associated with slower gastric transit. CONCLUSION: Antivinculin antibodies associate with slower gastric transit in SSc and may provide insight into GI complications of SSc.

Is post-COVID syndrome an autoimmune disease?

INTRODUCTION: Post-COVID syndrome (PCS) is recognized as a new entity in the context of SARS-CoV-2 infection. Though its pathogenesis is not completely understood, persistent inflammation from acute illness and the development of autoimmunity play a critical role in its development. AREAS COVERED: The mechanisms involved in the emergence of PCS, their similarities with post-viral and post-care syndromes, its inclusion in the spectrum of autoimmunity and possible targets for its treatment. EXPERT OPINION: An autoimmune phenomenon plays a major role in most causative theories explaining PCS. There is a need for both PCS definition and classification criteria (including severity scores). Longitudinal and controlled studies are necessary to better understand this new entity, and to find what additional factors participate into its development. With the high prevalence of COVID-19 cases worldwide, together with the current evidence on latent autoimmunity in PCS, we may observe an increase of autoimmune diseases (ADs) in the coming years. Vaccination's effect on the development of PCS and ADs will also receive attention in the future. Health and social care services need to develop a new framework to deal with PCS.

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta-analysis.

BACKGROUND: Thyroid autoimmunity is the most frequent condition involved in polyautoimmunity (PolyA). However, the frequency of latent and overt PolyA in patients with autoimmune thyroid disease (AITD) as the index condition is unknown. Therefore, the purpose of this study was to determine the prevalence of these types of PolyA in patients with AITD as the index condition. METHODS: This study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Searches through MEDLINE, Embase and LILACS were done to find articles in Spanish and English. Relevant vocabulary terms and key terms related to AITD and other autoimmune diseases were used. Two investigators independently screened the eligible studies, extracted data and assessed the quality and risk of bias. Fixed and random effect models were used accordingly. Cluster analysis was used to determine similarities among diseases in the articles included (based on Jaccard index). RESULTS: A total of 56 articles fulfilled the inclusion criteria. Of these, 25 were case-controls, 17 were cohorts, and 14 were cross-sectional studies. These studies included a total of 47 509 patients. Female was the predominant gender and included 38 950 patients (81.23%, 95% CI: 80.85-81.60). Graves' disease (GD) was the most common type of thyroid autoimmunity (69.16%, 95% CI: 68.23-70.07). Globally, overt PolyA was found in 13.46% of the patients with AITD. This type of PolyA was represented mainly by type 1 diabetes and autoimmune gastritis. Latent PolyA was presented in 17.45% of the patients, and anti-proinsulin, anti-parietal cells and dsDNA antibodies were the most common. HT had the highest frequency of overt PolyA in Europe (15.60%, 95% CI: 14.72-16.53), whereas latent PolyA was most common in patients with GD in Asia (21.03%, 95% CI: 17.76-24.71). Overt and latent PolyA were associated with gastrointestinal and endocrinological ADs in most of cases and clustered with rheumatological, dermatological and neurological ADs. CONCLUSIONS: Latent and overt PolyA are common in patients with AITD. These results provide insightful information for early diagnosis and management of concurrent ADs in patients with AITD. Aggregation of ADs in different clusters may help to define different phenotypes associated with thyroid autoimmunity that are critically relevant in clinical settings.

Development of an Intracellular Screen for New Compounds Able To Inhibit Mycobacterium tuberculosis Growth in Human Macrophages.

Here we describe the development and validation of an intracellular high-throughput screening assay for finding new antituberculosis compounds active in human macrophages. The assay consists of a luciferase-based primary identification assay, followed by a green fluorescent protein-based secondary profiling assay. Standard tuberculosis drugs and 158 previously recognized active antimycobacterial compounds were used to evaluate assay robustness. Data show that the assay developed is a short and valuable tool for the discovery of new antimycobacterial compounds.

Violencia en el hogar / Domestic violence

La violencia de los hogares urbanos, asociada en primer lugar con los estratos de pobreza, tendría una relación directamente proporcional entre pobreza y violencia al interior de la familia. Es probable que formas más sutiles de manifestación de la violencia se den en los estratos medios y altos, pero hay una clara correlación entre el uso de la violencia física y la pobreza; una clarísima correlación de hogares de alto riesgo, no solamente de violencia física sino de abuso sexual y de abandono en los hogares. El país no se ha dado suficiente cuenta del papel tan grande que ha dejado de cumplir el varón en la sociedad colombiana. Colombia es uno de los países que estadísticamente tiene mayor número de hogares con mujeres jefes de hogar. La ausencia del varón como padre conduce a una presencia del hombre como marido o como compañero temporal que termina necesariamente en violencia contra los menores de edad. Esto además se asocia con factores clarísimos de ignorancia en la mujer, dado el bajo nivel de ingresos de ésta y, sobre todo, en un entorno que toca lo psicológico, que es el problema de la autoestima en esa mujer