ABSTRACT
Perioperative stress and inflammatory signaling can invigorate pro-metastatic molecular processes in patients' tumors, potentially worsening long-term survival. Yet, it is unknown whether pre-operative psychotherapeutic interventions can attenuate such effects. Herein, three weeks before surgery, forty women diagnosed with stage I-III invasive ductal/lobular breast carcinoma were randomized to a 6-week one-on-one psychological intervention (6 meetings with a medical psychologist and bi-weekly phone calls) versus standard nursing-staff-attention. The intervention protocol was individually tailored based on evaluation of patients' emotional, cognitive, physiological, and behavioral stress response-patterns, and also included psychoeducation regarding medical treatments and recruitment of social support. Resected primary tumors were subjected to whole-genome RNA sequencing and bioinformatic analyses, assessing a priori hypothesized cancer-relevant molecular signatures. Self-report questionnaires (BSI-18, Hope-18, MSPSS, and a stress-scale) were collected three (T1) and one (T2) week before surgery, a day before (T3) and after (T4) surgery, and three weeks (T5) and 3-months (T6) following surgery. The intervention reduced distress (GSI), depression, and somatization scores (BSI-18: p < 0.01, p < 0.05, p < 0.05; T5 vs. T1). Additionally, tumors from treated patients (vs. controls) showed: (i) decreased activity of transcription control pathways involved in adrenergic and glucocorticoid signaling (CREB, GR) (p < 0.001), pro-inflammatory signaling (NFkB) (p < 0.01), and pro-malignant signaling (ETS1, STAT and GATA families) (p < 0.001, p < 0.01, p < 0.005); (ii) increased M1 macrophage polarization (p < 0.05), and CD4+ T cell activity (p < 0.01); and an unexpected increase in epithelial-to-mesenchymal-transition (EMT) signature (p < 0.005). This is the first randomized controlled trial to show beneficial effects of a psychological perioperative intervention on tumor pro-metastatic molecular biomarkers.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/surgery , Psychosocial Intervention , Biomarkers , Adrenergic Agents , CognitionABSTRACT
Stress-induced ß2-adrenergic receptor (ß2AR) activation in B cells increases IgG secretion; however, the impact of this activation on antibody affinity and the underlying mechanisms remains unclear. In the current study, we demonstrate that stress in mice following ovalbumin (OVA) or SARS-CoV-2 RBD immunization significantly increases both serum and surface-expressed IgG binding to the immunogen, while concurrently reducing surface IgG expression and B cell clonal expansion. These effects were abolished by pharmacological ß2AR blocking or when the experiments were conducted in ß2AR -/- mice. In the second part of our study, we used single B cell sorting to characterize the monoclonal antibodies (mAbs) generated following ß2AR activation in cultured RBD-stimulated B cells from convalescent SARS-CoV-2 donors. Ex vivo ß2AR activation increased the affinities of the produced anti-RBD mAbs by 100-fold compared to mAbs produced by the same donor control cultures. Consistent with the mouse experiments, ß2AR activation reduced both surface IgG levels and the frequency of expanded clones. mRNA sequencing revealed a ß2AR-dependent upregulation of the PI3K pathway and B cell receptor (BCR) signaling through AKT phosphorylation, as well as an increased B cell motility. Overall, our study demonstrates that stress-mediated ß2AR activation drives changes in B cells associated with BCR activation and higher affinity antibodies.
Subject(s)
Adrenergic Agents , COVID-19 , Mice , Animals , Phosphatidylinositol 3-Kinases , SARS-CoV-2/metabolism , Receptors, Adrenergic, beta-2/metabolism , Immunoglobulin GABSTRACT
Cancer-related cognitive impairment (CRCI) is commonly reported post-chemotherapy in adults with solid tumours. Hodgkin lymphoma (HL) mostly affects young adults. Data regarding CRCI in HL survivors (HLS) are scarce. The current study aimed to objectively assess CRCI incidence and characteristics in HLS. HLS, who completed first-line (chemotherapy ± radiation) therapy and remained in complete remission for 6 months to 5 years from therapy end, were evaluated. Age- and education-matched healthy individuals served as controls (n = 14). Test results were compared to population norms and healthy controls. Study participants completed self-reported questionnaires evaluating fatigue, depression, anxiety, quality of life and cognitive function. Subjects underwent neurocognitive evaluation, assessing processing speed, memory, attention, executive functions and intelligence domains. The present study included 51 HLS with a median age of 28 years, mean education of 14·5 ± 2·5 years. Complaints related to cognitive deterioration and fatigue were significantly more severe and frequent in HLS compared to healthy controls. Objective neurocognitive evaluation demonstrated that 30% of HLS were impaired in ≥2 cognitive domains. In conclusion, the present study demonstrates that fatigue and cognitive impairment, predominantly in executive functions and memory, constitute frequent and alarming findings in HLS. These adverse effects can persist and exert an impact on all aspects of life.
Subject(s)
Cognitive Dysfunction/etiology , Hodgkin Disease/complications , Survivors/psychology , Adult , Case-Control Studies , Executive Function , Fatigue , Female , Humans , Incidence , Male , Memory , Quality of Life , Surveys and QuestionnairesABSTRACT
The COVID-19 pandemic emphasized the pivotal role of the social environment, prompting a surge in research on its impact on well-being and health. This article aims to examine the link between the social environment, the immune system, and health outcomes, with a particular focus on positive aspects like social support and prosocial behaviors that are under-explored. Different aspects of the social environment are examined: the negative effects of loneliness and adverse social conditions, contrasted with the benefits of social support and prosocial behaviors. While the mechanisms behind negative effects are partially studied, those driving the positive effects remain elusive. Understanding the mechanisms of lack of social connection and their effects will allow us to explore the benefits of social connections and whether they can reverse the adverse outcomes. Potential psychoneuroimmunology mechanisms are proposed, highlighting the promotion of a 'safe' state by the vagus nerve, oxytocin circuits, and the additional contribution of the reward pathways. This article reviews the need to bridge knowledge gaps, urging further research to study the causal effects of positive social interactions on immune response and health outcomes to raise clinical awareness and interventions. Such interventions may include integrating lonely individuals with prosocial activities, thereby improving their physical and mental health. There is growing potential to harness the power of social connections for the betterment of individual health and society as a whole.
ABSTRACT
The outset of the COVID-19 pandemic was characterized by prolonged periods of chronic stress and social isolation. While studies have investigated the changes to well-being (WB) during this period, the impact of the social environment on long-term physical and mental health requires further study. This study aimed to assess the factors influencing WB and health outcomes, with the hypothesis that a positive social environment would play a significant immediate and long-term role in improving WB and preventing the effects of anxiety associated with the pandemic. At time point 1 (April 2020), an Israeli sample of 206 participants (84% female, mean age 31.5) responded to traditional questionnaires assessing mental health and social support. Factors affecting WB were assessed within subjects during the first COVID-19 lockdown for 6 weeks using a daily survey (Beiwe phone application). A year later, in May 2021, at time point 2, the initial questionnaires were readministered to a subset of the same participants (N = 94). We found that anxiety during the first lockdown adversely affected WB and predicted health and WB deterioration a year later. In contrast, a high quality of social relationships was associated with better short- and long-term WB, and mitigated the adverse effects of anxiety. Daily activities, including physical activity, meditation, and romantic relations, were also positively associated with WB during the first lockdown but did not have long-term effects. In summary, our study underscores the enduring health advantages of a positive social environment, particularly during stressful periods. These results have implications for health policymakers: programs which support individuals with high anxiety and low support, by integrating them into community-based interventions, promise to enhance well-being (WB) and health, as well as to fortify the community as a whole.
Subject(s)
COVID-19 , Humans , Female , Adult , Male , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Pandemics , Anxiety/epidemiology , Anxiety DisordersABSTRACT
Hoarding Disorder (HD) is under recognised and under-treated. Though HD develops by early adulthood, patients present only later in life, resulting in research based largely on samples of predominantly older females. Whilst formerly associated with Obsessive-Compulsive Disorder (OCD), it is now recognised that individuals with HD often have inattention symptoms reminiscent of Attention Deficit/Hyperactivity Disorder (ADHD). Here, we investigated HD in adults with ADHD. Patients in an ADHD clinic (n = 88) reported on ADHD, HD and OCD-related symptoms, and compared with age, gender and education matched controls (n = 90). Findings were assessed independently in an online UK sample to verify replication using a dimensional approach (n = 220). Clinically significant hoarding symptoms were found in â¼20% versus 2% of ADHD and control groups, respectively, with those with hoarding being on average in their thirties and with approximately half being male. Greater hoarding severity was noted even in the remaining patients compared with controls (d = 0.89). Inattention was the only significant statistical predictor of hoarding severity in patients. Similarly, inattention, alongside depression and anxiety were the greatest predictors of hoarding in the independent sample where 3.2% identified as having clinically significant hoarding. Patients with ADHD had a high frequency of hoarding symptoms, which were specifically linked to inattention. HD should be routinely assessed in individuals with ADHD, as they do not typically disclose associated difficulties, despite these potentially leading to impaired everyday functioning. Research in HD should also investigate adults with ADHD, who are younger and with a greater prevalence of males than typical HD samples.
ABSTRACT
BACKGROUND: Under the 'Choosing Wisely' (CW) framework, professional organisations internationally have advocated limiting imaging for asymptomatic patients following curative cancer therapy, based on limited value and high cost. F18-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) was widely adopted locally for surveillance lymphoma imaging after 2004. OBJECTIVES: Prior to ratification of a local CW recommendation to limit surveillance imaging in lymphoma, we aimed to assess: (A) performance characteristics of surveillance FDG-PET/CT; (B) rates, clinical consequences and costs of false positives (FP); and (C) patients and professionals' attitudes towards overuse. METHODS: Mixed methods (quantitative and qualitative) study. We analysed surveillance FDG-PET/CT results of two patient cohorts (n1=215 Hodgkin lymphoma and non-Hodgkin lymphoma; n2=203 Hodgkin lymphoma only). FPs were defined by negative biopsy or clinical follow-up. We held focus group discussions and in-depth interviews eliciting attitudes of 26 patients and 11 clinicians, respectively. RESULTS: FPs were observed in 25.1% (95% CI 20.5 to 30.5) per scan-cohort 1, and 41.7% (95% CI 37.9 to 45.6) per patient-cohort 2, engendering frequent additional testing. Specific characteristics and location of findings altered the FP rate. The estimated cost per relapse detected was $50 000 (cohort 2). Patients sought reassurance via surveillance imaging, which they considered highly accurate, yet stressful. Aware of radiation risks, they were largely unconcerned about consequences of FPs. Confidence in the treating physicians was an important factor in patients' acceptance of forgoing imaging. Clinicians, frequently under patient pressure to order imaging, generally believed that it did not affect prognosis (with important exceptions), welcomed professional guidelines, but rejected regulatory restrictions on its use. CONCLUSION: Acceptance of CW recommendations to limit overuse may be enhanced by quantitative data on consequences and costs of surveillance imaging, supplemented by qualitative data on patient and physician attitudes.
Subject(s)
Hodgkin Disease , Positron Emission Tomography Computed Tomography , Fluorodeoxyglucose F18 , Hodgkin Disease/diagnostic imaging , Humans , Positron-Emission Tomography , Radiopharmaceuticals , Retrospective StudiesABSTRACT
Hodgkin lymphoma (HL) is common in young adults and considered curable in most patients. Young HL survivors (HLS) are at risk of long-term adverse effects. Our study aimed to assess various fatigue and quality of life (QoL) complaints, and their correlations with treatment. Self-reported questionnaires assessing fatigue (MFI-20) and QoL-related issues (EORTC-QOL-C-30) were used to examine HLS aged 18-65 who completed first-line chemotherapy ± radiotherapy (RT) and were in complete remission for at least six months post-therapy. The cohort included 120 HLS (median age 32 years), assessed between 6 months and 15 years post-treatment. About 28% presented with severe fatigue and severely reduced QoL. Higher fatigue levels were associated with four cycles of the ABVD + RT. Young HLS experience high levels of persistent physical fatigue, emotional distress, and cognitive decline that are insufficiently investigated. Assessment of these complaints is essential and further investigation may provide tailored solutions for a better QoL for HLS.