In view of the potential gravity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection for patients with cancer, epidemiological data are vital to assess virus circulation among patients and staff of cancer centres. We performed a prospective study to investigate seroprevalence of SARS-CoV-2 antibodies among staff and patients with cancer at a large cancer centre, at the end of the period of first national lockdown in France and to determine factors associated with the risk of SARS-CoV-2 infection.After the first lockdown, all medical and non-medical staff, as well as all patients attending the medical oncology department were invited to undergo serological testing for SARS-CoV-2 between 11 May and 30 June 2020. All participants were also invited to complete a questionnaire collecting data about their living and working conditions, and for patients, medical management during lockdown.A total of 1,674 subjects (663 staff members, 1011 patients) were included. Seroprevalence was low in both staff (1.8%) and patients (1.7%), despite more features of high risk for severe forms among patients. None of the risk factors tested in our analysis (working or living conditions, comorbidities, management characteristics during lockdown) was found to be statistically associated with seroprevalence in either staff or patients. There was no significant difference in the proportion of symptomatic and asymptomatic subjects between staff and patients. Only fever, loss of smell, and loss of taste were significantly more frequent among seropositive patients, in both staff and patients.We report very low seroprevalence of antibodies against SARS-CoV-2 in the staff (caregiving and non-caregiving) and patients of a large cancer care centre in which strict hygiene, personal protection, and social distancing measures were implemented.
ABSTRACT Exosomes are nanovesicles released by all cells that can be found in the blood. A key point for their use as potential biomarkers in cancer is to differentiate tumour‐derived exosomes from other circulating nanovesicles. Heat shock protein‐70 (HSP70) has been shown to be abundantly expressed by cancer cells and to be associated with bad prognosis. We previously showed that exosomes derived from cancer cells carried HSP70 in the membrane while those from non‐cancerous cells did not. In this work, we opened a prospective clinical pilot study including breast and lung cancer patients to determine whether it was possible to detect and quantify HSP70 exosomes in the blood of patients with solid cancers. We found that circulating exosomal HSP70 levels, but not soluble HSP70, reflected HSP70 content within the tumour biopsies. Circulating HSP70 exosomes increased in metastatic patients compared to non‐metastatic patients or healthy volunteers. Further, we demonstrated that HSP70‐exosome levels correlated with the disease status and, when compared with circulating tumour cells, were more sensitive tumour dissemination predictors. Finally, our case studies indicated that HSP70‐exosome levels inversely correlated with response to the therapy and that, therefore, monitoring changes in circulating exosomal HSP70 might be useful to predict tumour response and clinical outcome.
Objectives The aims of this study are (1) to characterize factors influencing self-management behaviors and quality of life in adolescent and young adult (AYA) patients with childhood-onset systemic lupus erythematosus (cSLE) and (2) to identify barriers and facilitators of treatment adherence via focus groups. Methods AYAs with cSLE ages 12–24 years and primary caregivers of the adolescents participated in this study. Recruitment occurred during pediatric rheumatology clinic visits at a Midwestern children's hospital or the hospital's cSLE active clinic registry. Information about disease severity was obtained from patient health records. Pain and fatigue questionnaires were administered. Descriptive statistics were used to analyze data. Results Thirty-one AYA patients and caregivers participated in six focus groups. Ten major themes emerged from sessions; four were expressed both by the AYA and caregiver groups: knowledge deficits about cSLE, symptoms limiting daily function, specifically mood and cognition/learning, barriers and facilitators of adherence, and worry about the future. Themes unique to AYA participants included symptoms limiting daily functioning—pain/fatigue, self-care and management, impact on personal relationships, and health care provider communication/relationship. For caregiver groups unique themes included need for school advocacy, disruption of family schedule, and sense of normalcy for their adolescent. Conclusion AYAs with cSLE face a lifelong disease characterized by pervasive pain, fatigue, organ damage, isolation—social and/or physical—and psycho-socioeducational challenges. This study confirmed that continued psychosocial support, health information education, adherence interventions, and personalized treatment plans are necessary to increase self-management and autonomy in AYAs with cSLE.
Loss‑of‑function BRCA mutations are frequent in high‑grade serous ovarian carcinoma. BRCA1 and ‑2 mutations lead to homologous recombination (HR) deficiency. Poly(ADP‑ribose) polymerases (PARP) are enzymes involved in DNA repair. PARP inhibitors (PARPi) lead to DNA damage accumulation in cells deficient in HR. Olaparib (a PARPi) is currently used for the treatment of high‑grade serous ovarian carcinoma with germline or somatic BRCA mutations; however, numerous patients do not respond or eventually develop resistance to these agents. The TP53 gene encodes the p53 protein, which is often referred to as the 'guardian of the genome'. TP53 mutations at diagnosis are known to promote resistance to chemotherapy. In the present study, four cases of patients with BRCA‑mutated cancer treated with olaparib, who progressed following the PARPi treatment, are reported. Exome analyses were performed on a primary tumor biopsy at diagnosis, then on a progressing metastasis following olaparib treatment. Exome analyses following olaparib treatment identified de novo TP53 mutations, as well as increased frequencies of pre‑existing TP53 mutations compared with the primary tumor. In HCT116 TP53‑/‑ cells carrying BRCA2 pathogenic mutations, TP53 inactivating mutations were associated with lower sensitivity to olaparib in vitro. Thus, inactivating TP53 mutations may be associated to olaparib resistance in the presence of BRCA mutations. In conclusion, the present findings demonstrated resistance to PARPi with de novo TP53 mutations that may be clinically relevant. As TP53 mutations are easily detectable with targeted next‑generation sequencing panels, these may serve as surrogate markers for the onset of PARPi resistance in the context of routine patient management strategies.
