Inequities in the Impacts of Hurricanes and Other Extreme Weather Events for Cancer Survivors.

In this minireview, we examine the impacts of hurricanes and other extreme weather events on cancer survivors, focusing on structural and social determinants of health. We briefly explore influences on biological, psychosocial, and behavioral outcomes and discuss risk and resilience factors in cancer survivorship during and after hurricanes. Our goal is to inform future directions for research that can identify areas in which we can most efficiently improve cancer outcomes and inform changes in health systems, clinical practice, and public health policies. This timely minireview provides researchers and clinicians with an overview of challenges and opportunities for improving disaster preparedness and response for cancer survivors.

The relationship of lifetime history of depression on the ovarian tumor immune microenvironment.

BACKGROUND: Depression is associated with a higher ovarian cancer risk. Prior work suggests that depression can lead to systemic immune suppression, which could potentially alter the anti-tumor immune response. METHODS: We evaluated the association of pre-diagnosis depression with features of the anti-tumor immune response, including T and B cells and immunoglobulins, among women with ovarian tumor tissue collected in three studies, the Nurses' Health Study (NHS; n = 237), NHSII (n = 137) and New England Case-Control Study (NECC; n = 215). Women reporting depressive symptoms above a clinically relevant cut-point, antidepressant use, or physician diagnosis of depression at any time prior to diagnosis of ovarian cancer were considered to have pre-diagnosis depression. Multiplex immunofluorescence was performed on tumor tissue microarrays to measure immune cell infiltration. In pooled analyses, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the positivity of tumor immune cells using a beta-binomial model comparing those with and without depression. We used Bonferroni corrections to adjust for multiple comparisons. RESULTS: We observed no statistically significant association between depression status and any immune markers at the Bonferroni corrected p-value of 0.0045; however, several immune markers were significant at a nominal p-value of 0.05. Specifically, there were increased odds of having recently activated cytotoxic (CD3+CD8+CD69+) and exhausted-like T cells (CD3+Lag3+) in tumors of women with vs. without depression (OR = 1.36, 95 %CI = 1.09-1.69 and OR = 1.24, 95 %CI = 1.01-1.53, respectively). Associations were comparable when considering high grade serous tumors only (comparable ORs = 1.33, 95 %CI = 1.05-1.69 and OR = 1.25, 95 %CI = 0.99-1.58, respectively). There were decreased odds of having tumor infiltrating plasma cells (CD138+) in women with vs. without depression (OR = 0.54, 95 %CI = 0.33-0.90), which was similar among high grade serous carcinomas, although not statistically significant. Depression was also related to decreased odds of having naïve and memory B cells (CD20+: OR = 0.54, 95 %CI = 0.30-0.98) and increased odds of IgG (OR = 1.22, 95 %CI = 0.97-1.53) in high grade serous carcinomas. CONCLUSION: Our results provide suggestive evidence that depression may influence ovarian cancer outcomes through changes in the tumor immune microenvironment, including increasing T cell activation and exhaustion and reducing antibody-producing B cells. Further studies with clinical measures of depression and larger samples are needed to confirm these results.

Stress hormones are associated with inflammatory cytokines and attenuation of T-cell function in the ascites from patients with high grade serous ovarian cancer.

Mounting evidence suggests that chronic stress and subsequent distress can promote ovarian cancer progression. These altered psychological states have been linked to sustained release of stress hormones, activation of the ß-adrenergic receptors in ovarian cancer cells, and induction of pro-tumoral signaling pathways. In addition, data suggest that chronic stress promotes an inflammatory landscape highlighted by increased infiltration of tumor-associated macrophages into the ovarian tumor microenvironment (TME). In ovarian cancer, ascites is a unique TME comprised of tumor, and immune cells, which secrete pro-tumoral cytokines and chemokines that modulate tumor-associated immunity. However, our knowledge about how stress hormones impact the ascites TME remains limited. We hypothesized that the ascites harbors measurable levels of stress hormones, and accumulation of these in the ascites generates a pro-tumorigenic, inflammatory, and immunosuppressive TME. We evaluated ascites samples from 49 patients with high grade serous ovarian cancer (HGSOC) and quantified cortisol and stress hormones metabolites, metanephrine (MN), and normetanephrine (NMN) in all samples. We also measured 38 individual cytokines in the ascites, including several pro-inflammatory cytokines, such as IL-6, which were positively correlated to MN or NMN levels of those samples. Conversely, we found cortisol levels were negatively correlated to several pro-inflammatory cytokines. As T-cells are integral to the TME and our analyses identified cytokines in the ascites known to modulate T-cell function, we characterized ascites-derived T-cells and assessed the impact of stress hormones on the T-cell phenotype. Our data show an altered CD4+/CD8+ T-cell ratio and a heterogeneous expression of exhaustion markers in T-cells from the ascites, while ascites-derived CD8+ T-cells exposed to epinephrine had decreased co-expression CD38 and Granzyme B. To extend these findings to animal models, we subjected ovarian cancer-bearing mice to daily restraint stress, which resulted in increased tumor growth in two models. Congruent with our human analyses, we detected corticosterone, MN, and NMN in the ascites from tumor-bearing mice, and these stress hormones correlated with several inflammatory cytokines. Moreover, daily restraint stress leads to increased CD4+PD-1+/CD8+PD-1+ T-cell ratio in the ovarian tumor microenvironment. Overall, these data highlight a role of stress hormones in the ascites TME as a driver of tumor-associated inflammation, T-cell suppression, and disease progression.

Racial and Ethnic Disparities in Cancer Care During the COVID-19 Pandemic.

Importance: The full effect of the COVID-19 pandemic on cancer care disparities, particularly by race and ethnicity, remains unknown. Objectives: To assess whether the race and ethnicity of patients with cancer was associated with disparities in cancer treatment delays, adverse social and economic effects, and concerns during the COVID-19 pandemic and to evaluate trusted sources of COVID-19 information by race and ethnicity. Design, Setting, and Participants: This national survey study of US adults with cancer compared treatment delays, adverse social and economic effects, concerns, and trusted sources of COVID-19 information by race and ethnicity from September 1, 2020, to January 12, 2021. Exposures: The COVID-19 pandemic. Main Outcomes and Measures: The primary outcome was delay in cancer treatment by race and ethnicity. Secondary outcomes were duration of delay, adverse social and economic effects, concerns, and trusted sources of COVID-19 information. Results: Of 1639 invited respondents, 1240 participated (75.7% response rate) from 50 US states, the District of Columbia, and 5 US territories (744 female respondents [60.0%]; median age, 60 years [range, 24-92 years]; 266 African American or Black [hereafter referred to as Black] respondents [21.5%]; 186 Asian respondents [15.0%]; 232 Hispanic or Latinx [hereafter referred to as Latinx] respondents [18.7%]; 29 American Indian or Alaska Native, Native Hawaiian, or multiple races [hereafter referred to as other] respondents [2.3%]; and 527 White respondents [42.5%]). Compared with White respondents, Black respondents (odds ratio [OR], 6.13 [95% CI, 3.50-10.74]) and Latinx respondents (OR, 2.77 [95% CI, 1.49-5.14]) had greater odds of involuntary treatment delays, and Black respondents had greater odds of treatment delays greater than 4 weeks (OR, 3.13 [95% CI, 1.11-8.81]). Compared with White respondents, Black respondents (OR, 4.32 [95% CI, 2.65-7.04]) and Latinx respondents (OR, 6.13 [95% CI, 3.57-10.53]) had greater odds of food insecurity and concerns regarding food security (Black respondents: OR, 2.02 [95% CI, 1.34-3.04]; Latinx respondents: OR, 2.94 [95% CI, [1.86-4.66]), financial stability (Black respondents: OR, 3.56 [95% CI, 1.79-7.08]; Latinx respondents: OR, 4.29 [95% CI, 1.98-9.29]), and affordability of cancer treatment (Black respondents: OR, 4.27 [95% CI, 2.20-8.28]; Latinx respondents: OR, 2.81 [95% CI, 1.48-5.36]). Trusted sources of COVID-19 information varied significantly by race and ethnicity. Conclusions and Relevance: In this survey of US adults with cancer, the COVID-19 pandemic was associated with treatment delay disparities and adverse social and economic effects among Black and Latinx adults. Partnering with trusted sources may be an opportunity to overcome such disparities.

Rheumatoid Arthritis, Statin Indication and Lipid Goals: Analysis According to Different Recommendations.

BACKGROUND: Different strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis (RA). OBJECTIVES: (1) To estimate the cardiovascular risk by different strategies in RA patients, analyzing which proportion of patients would be candidates to receive statin therapy; (2) to identify how many patients meet the recommended lipid goals. METHODS: A cross-sectional study was performed from a secondary database. The QRISK-3 score, the Framingham score (adjusted for a multiplying factor×1.5), the ASCVD calculator and the SCORE calculator were estimated. The indications for statin therapy according to NICE, Argentine Consensus, ACC/AHA, and new European guidelines were analyzed. The recommended LDL-C goals were analyzed. RESULTS: A total of 420 patients were included. In total, 24.7% and 48.7% of patients in primary and secondary prevention were receiving statins, respectively. Only 19.4% of patients with cardiovascular history received high intensity statins. Applying the ACC/AHA guidelines (based on ASCVD score), the Argentine Consensuses (based on adjusted Framingham score), the NICE guidelines (based on QRISK-3) and European recommendations (based on SCORE), 26.9%, 26.5%, 41.1% and 18.2% of the population were eligible for statin therapy, respectively. Following the new European recommendations, 50.0%, 46.2% and 15.9% of the patients with low-moderate, high or very high risk achieved the suggested lipid goals. CONCLUSION: Applying four strategies for lipid management in our population, the cardiovascular risk stratification and the indication for statins were different. A significant gap was observed when comparing the expected and observed statin indication, with few patients achieving the LDL-C goals.

Rheumatoid Arthritis, Statin Indication and Lipid Goals: Analysis According to Different Recommendations / Artritis reumatoide, indicación de estatinas y objetivos lipídicos: Análisis según diferentes recomendaciones

Background: Different strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis (RA).Objectives(1) To estimate the cardiovascular risk by different strategies in RA patients, analyzing which proportion of patients would be candidates to receive statin therapy; (2) to identify how many patients meet the recommended lipid goals. Methods: A cross-sectional study was performed from a secondary database. The QRISK-3 score, the Framingham score (adjusted for a multiplying factor×1.5), the ASCVD calculator and the SCORE calculator were estimated. The indications for statin therapy according to NICE, Argentine Consensus, ACC/AHA, and new European guidelines were analyzed. The recommended LDL-C goals were analyzed. Results: A total of 420 patients were included. In total, 24.7% and 48.7% of patients in primary and secondary prevention were receiving statins, respectively. Only 19.4% of patients with cardiovascular history received high intensity statins. Applying the ACC/AHA guidelines (based on ASCVD score), the Argentine Consensuses (based on adjusted Framingham score), the NICE guidelines (based on QRISK-3) and European recommendations (based on SCORE), 26.9%, 26.5%, 41.1% and 18.2% of the population were eligible for statin therapy, respectively. Following the new European recommendations, 50.0%, 46.2% and 15.9% of the patients with low-moderate, high or very high risk achieved the suggested lipid goals. Conclusion: Applying four strategies for lipid management in our population, the cardiovascular risk stratification and the indication for statins were different. A significant gap was observed when comparing the expected and observed statin indication, with few patients achieving the LDL-C goals.(AU)

Antecedentes: Se han propuesto diferentes estrategias para el manejo del riesgo cardiovascular en pacientes con artritis reumatoide (AR).Objetivos(1) estimar el riesgo cardiovascular mediante diferentes estrategias en pacientes con AR, analizando qué proporción de pacientes deberían recibir estatinas; (2) identificar cuántos pacientes alcanzaron los objetivos lipídicos recomendados. Métodos: Estudio de corte transversal. Se estimaron los puntajes QRISK-3, Framingham (ajustado por un factor multiplicador × 1,5), ASCVD y SCORE. Se analizaron las indicaciones de estatinas, según las guías NICE, el Consenso Argentino, las guías ACC/AHA 2018 y las nuevas directrices europeas. Se analizaron los objetivos de C-LDL. Resultados: Se incluyeron 420 pacientes; 24,7 y 48,7% de los pacientes en prevención primaria y secundaria recibían estatinas, respectivamente. El 19,4% de los pacientes con antecedentes cardiovasculares recibían estatinas de alta intensidad. Aplicando las guías ACC/AHA (basadas en el puntaje ASCVD), el Consenso Argentino (basado en el puntaje ajustado de Framingham), las pautas NICE (basadas en el QRISK-3) y las recomendaciones europeas (basadas en el SCORE), 26,9, 26,5, 41,1 y el 18,2% de la población eran elegibles para el tratamiento con estatinas, respectivamente. Siguiendo las nuevas recomendaciones europeas, 50, 46,2 y 15,9% de los pacientes con riesgo bajo-moderado, alto o muy alto lograron los objetivos lipídicos recomendados. Conclusión: Aplicando varias estrategias para el manejo de los lípidos en nuestra población, la estratificación del riesgo cardiovascular y la indicación de estatinas fueron diferentes. Se observó una brecha significativa entre la indicación de estatinas esperada y observada, logrando los objetivos de C-LDL muy pocos pacientes.(AU)

Impact of Seismic Activity on Access to Health Care in Hispanic/Latino Cancer Patients from Puerto Rico.

On 7 January 2020, the southern region of Puerto Rico was struck by a 6.4 magnitude earthquake, followed by continual seismic activity. Our team performed secondary analyses to explore the relationship between exposure to seismic activity, protection (support) received, and barriers to health care access for cancer patients. Methods: The research team collected data from the database of a longitudinal case-control cohort parent study concerning the impact of Hurricane Maria in Puerto Rican cancer patients. The participants from the parent study were recruited in community clinics. The extracted data was collected from 51 cancer patients who completed the parent study's interviews from January−July 2020 (seismic activity period). Barriers to health care were assessed using the Barrier to Care Questionaries (BCQ), which is composed of five subscales: skills, marginalization, knowledge and beliefs expectations, and pragmatics. Exposure to seismic activity and protection was assessed using their respective subscales from the Scale of Psychosocial Impact of Disasters. Results: The results showed a significant relationship between exposure to seismic activity and barriers to health care (p < 0.001) and its five subscales (p < 0.01). These results shed light on potential access to care barriers that could hinder cancer patient treatment in the event of a natural disaster.

Brief Report: Hispanic Patients' Trajectory of Cancer Symptom Burden, Depression, Anxiety, and Quality of Life.

Background: Anxiety and depression symptoms are known to increase cancer symptom burden, yet little is known about the longitudinal integrations of these among Hispanic/Latinx patients. The goal of this study was to explore the trajectory and longitudinal interactions among anxiety and depression, cancer symptom burden, and health-related quality of life in Hispanic/Latinx cancer patients undergoing chemotherapy. METHODS: Baseline behavioral assessments were performed before starting chemotherapy. Follow-up behavioral assessments were performed at 3, 6, and 9 months after starting chemotherapy. Descriptive statistics, chi-square tests, Fisher's exact tests, and Mann-Whitney tests explored associations among outcome variables. Adjusted multilevel mixed-effects linear regression models were also used to evaluate the association between HADS scores, follow-up visits, FACT-G scale, MDASI scale, and sociodemographic variables. RESULTS: Increased cancer symptom burden was significantly related to changes in anxiety symptoms' scores (adjusted ß^ = 0.11 [95% CI: 0.02, 0.19]. Increased quality of life was significantly associated with decreased depression and anxiety symptoms (adjusted ß^ = -0.33; 95% CI: -0.47, -0.18, and 0.38 adjusted ß^= -0.38; 95% CI: -0.55, -0.20, respectively). CONCLUSIONS: Findings highlight the need to conduct periodic mental health screenings among cancer patients initiating cancer treatment.

E2F3 drives the epithelial-to-mesenchymal transition, cell invasion, and metastasis in breast cancer.

E2F3 is a transcription factor that may initiate tumorigenesis if overexpressed. Previously, we demonstrated that E2F3 mRNA is overexpressed in breast cancer and that E2F3 overexpression results in centrosome amplification and unregulated mitosis, which can promote aneuploidy and chromosome instability to initiate and sustain tumors. Further, we demonstrated that E2F3 leads to overexpression of the mitotic regulator Shugoshin-1, which until recently had unknown roles in cancer. This study aims to evaluate the roles of E2F3 and Shugoshin-1 in breast cancer metastatic potential. Here we demonstrated that E2F3 and Shugoshin-1 silencing leads to reduced cell invasion and migration in two mesenchymal triple-negative breast cancer (TNBC) cell lines (MDA-MB-231 and Hs578t). Moreover, E2F3 and Shugoshin-1 modulate the expression of epithelial-to-mesenchymal transition-associated genes such as Snail, E-Cadherin, and multiple matrix metalloproteinases. Furthermore, E2F3 depletion leads to reductions in tumor growth and metastasis in NOD-scid Gamma mice. Results from this study suggest a key role for E2F3 and a novel role for Shugoshin-1 in metastatic progression. These results can further help in the improvement of TNBC targeted therapies by interfering with pathways that intersect with the E2F3 and Shugoshin-1 signaling pathways.

A Biopsychosocial Approach to Grief, Depression, and the Role of Emotional Regulation.

According to the field of affective neuroscience, grief has been identified as one of the seven primary emotions necessary for human survival. However, maladaptive grief could cause significant impairment in an individual's life, leading to psychopathologies such as major depressive disorder. Research on grief has shifted to a biopsychosocial approach, leaving behind outdated models-such as the Kübler-Ross theory-that have shown poor consistency. The field of psychoneuroimmunology has identified adverse life events such as social loss as being associated with major depressive disorder, and inflammatory processes in chronic health conditions. Likewise, scientists in the field of affective neuroscience have theorized that prolonged and sustained activation of the grief neurological pathway can cause a cascade of neurotransmitters that inhibits the reward-seeking system, causing symptoms of depression. The objective of this review is to highlight findings on the grief process using a biopsychosocial approach to explore grief's impact on psychopathophysiology.

Effects of long-term norepinephrine treatment on normal immortalized ovarian and fallopian tube cells.

Sustained adrenergic stimulation by norepinephrine (NE) contributes to ovarian carcinoma metastasis and impairment of chemotherapy response. Although the effect of sustained NE stimulation in cancer progression is well established, less is known about its role in cancer initiation. To determine the extent to which stress hormones influence ovarian cancer initiation, we conducted a long-term (> 3 months; > 40 population doublings) experiment in which normal immortalized fallopian tube secretory (iFTSEC283) and ovarian surface epithelial (iOSE11) cell lines and their isogenic pairs containing a p53 mutation (iFTSEC283p53R175H; iOSE11p53R175H), were continuously exposed to NE (100 nM, 1 µM, 10 µM). Fallopian tube cells displayed a p53-independent increase in proliferation and colony-forming ability in response to NE, while ovarian surface epithelial cells displayed a p53-independent decrease in both assays. Fallopian tube cells with mutant p53 showed a mild loss of chromosomes and TP53 status was also a defining factor in transcriptional response of fallopian tube cells to long-term NE treatment.

Depression, Anxiety, and Social Environmental Adversity as Potential Modulators of the Immune Tumor Microenvironment in Breast Cancer Patients.

Background: Mounting data suggest that exposure to chronic stress is associated with worse breast cancer outcomes. This study aimed to explore the impact of social environmental adversity (SEA, e.g., child abuse, crime, sexual, and physical violence), depressive symptomatology, and anxiety on immune cell infiltration into the breast tumor microenvironment. Methods: Participants (n = 33) completed a series of surveys assessing depression and anxiety symptoms, adverse childhood events (ACE), and trauma history. Tumor-associated macrophages (CD68+), B cells (CD19+), and T cells (CD3+) were identified by immunohistochemical analyses of formalin-fixed paraffin-embedded tumor samples and quantified. Spearman rank tests were used to explore the relationships between the variables studied. Results: Exposure to SEA was high (ACE = 72%, exposure to crime = 47%, and exposure to physical/sexual assault = 73%) among participants. Moreover, 30% reported a comorbid history of depression and ACE; 39% reported one or more traumatic events, and clinically significant depression symptomatology, while 21% reported trauma history and significant anxiety symptomatology. Increased tumor-infiltrating B cells were significantly correlated with exposure to crime, anxiety symptoms, and exposure to an ACE. The ACE plus anxiety group presented the highest infiltration of B cells, T cells, and macrophages. Conclusion: These findings support a role for SEA, anxiety symptoms, and depression as potential modulators of the immune tumor microenvironment in breast cancer.

Rheumatoid Arthritis, Statin Indication and Lipid Goals: Analysis According to Different Recommendations.

BACKGROUND: Different strategies have been proposed for the cardiovascular risk management of patients with rheumatoid arthritis (RA). OBJECTIVES: (1) To estimate the cardiovascular risk by different strategies in RA patients, analyzing which proportion of patients would be candidates to receive statin therapy; (2) to identify how many patients meet the recommended lipid goals. METHODS: A cross-sectional study was performed from a secondary database. The QRISK-3 score, the Framingham score (adjusted for a multiplying factor×1.5), the ASCVD calculator and the SCORE calculator were estimated. The indications for statin therapy according to NICE, Argentine Consensus, ACC/AHA, and new European guidelines were analyzed. The recommended LDL-C goals were analyzed. RESULTS: A total of 420 patients were included. In total, 24.7% and 48.7% of patients in primary and secondary prevention were receiving statins, respectively. Only 19.4% of patients with cardiovascular history received high intensity statins. Applying the ACC/AHA guidelines (based on ASCVD score), the Argentine Consensuses (based on adjusted Framingham score), the NICE guidelines (based on QRISK-3) and European recommendations (based on SCORE), 26.9%, 26.5%, 41.1% and 18.2% of the population were eligible for statin therapy, respectively. Following the new European recommendations, 50.0%, 46.2% and 15.9% of the patients with low-moderate, high or very high risk achieved the suggested lipid goals. CONCLUSION: Applying four strategies for lipid management in our population, the cardiovascular risk stratification and the indication for statins were different. A significant gap was observed when comparing the expected and observed statin indication, with few patients achieving the LDL-C goals.

Zoledronic Acid Abrogates Restraint Stress-Induced Macrophage Infiltration, PDGF-AA Expression, and Ovarian Cancer Growth.

Multiple studies suggest that chronic stress accelerates the growth of existing tumors by activating the sympathetic nervous system. Data suggest that sustained adrenergic signaling can induce tumor growth, secretion of pro-inflammatory cytokines, and macrophage infiltration. Our goal was to study the role of adrenergic-stimulated macrophages in ovarian cancer biology. Cytokine arrays were used to assess the effect of adrenergic stimulation in pro-tumoral cytokine networks. An orthotopic model of ovarian cancer was used to assess the in vivo effect of daily restraint stress on tumor growth and adrenergic-induced macrophages. Cytokine analyses showed that adrenergic stimulation modulated pro-inflammatory cytokine secretion in a SKOV3ip1 ovarian cancer cell/U937 macrophage co-culture system. Among these, platelet-derived growth factor AA (PDGF-AA), epithelial cell-derived neutrophil-activating peptide (ENA-78), Angiogenin, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5), Lipocalin-2, macrophage migration inhibitory factor (MIF), and transferrin receptor (TfR) were upregulated. Enriched biological processes included cytokine-mediated signaling pathways and positive regulation of cell proliferation. In addition, daily restraint stress increased ovarian cancer growth, infiltration of CD68+ macrophages, and expression of PDGF-AA in orthotopic models of ovarian cancer (SKOV3ip1 and HeyT30), while zoledronic acid, a macrophage-depleting agent, abrogated this effect. Furthermore, in ovarian cancer patients, high PDGFA expression correlated with worse outcomes. Here, it is shown that the adrenergic regulation of macrophages and PDGFA might play a role in ovarian cancer progression.