Religious transformations in the Middle Ages: towards a new archaeological agenda

The study of religious change in Europe between the collapse of the Roman Empire and the Reformation forms one of the cornerstones of medieval archaeology but has been riven by period, denominational and geographical divisions. This paper lays the groundwork for a fundamental rethink of archaeological approaches to medieval religions, by adopting a holistic framework that places Christian, pagan, Islamic and Jewish case studies of religious transformation in a long-term, comparative perspective. Focused around the analytical themes of ‘hybridity and resilience’ and ‘tempo and trajectories’, our approach shifts attention away from the singularities of national narratives of religious conversion towards a deeper understanding of how religious beliefs, practices and identity were renegotiated by medieval people in their daily lives

Neurobiol Aging

GRN mutations are frequent causes of familial frontotemporal degeneration. Although there is no clear consensual threshold, plasma progranulin levels represent an efficient biomarker for predicting GRN mutations when decreased. We evaluated plasma levels to determine whether it could also predict age at onset, clinical phenotype, or disease progression in 160 GRN carriers. Importantly, progranulin levels were influenced by gender, with lower levels in male than in female patients in our study. Although we found no correlation with age at onset or with clinical phenotype, we confirmed that decreased level predicts GRN mutations, even in presymptomatic carriers more than four decades before disease onset. We also provided first evidence for the stability of levels throughout longitudinal trajectory in carriers, over a 4-year time span. Finally, we confirmed that progranulin levels constitute a reliable, cost-effective marker, suitable as a screening tool in patients with familial frontotemporal degeneration, and more broadly in patients without family history or with atypical presentations who are less likely to be referred for molecular diagnosis

Different Clinical Contexts of Use of Blood Neurofilament Light Chain Protein in the Spectrum of Neurodegenerative Diseases

One of the most pressing challenges in the clinical research of neurodegenerative diseases (NDDs) is the validation and standardization of pathophysiological biomarkers for different contexts of use (CoUs), such as early detection, diagnosis, prognosis, and prediction of treatment response. Neurofilament light chain (NFL) concentration is a particularly promising candidate, an indicator of axonal degeneration, which can be analyzed in peripheral blood with advanced ultrasensitive methods. Serum/plasma NFL concentration is closely correlated with cerebrospinal fluid NFL and directly reflects neurodegeneration within the central nervous system. Here, we provide an update on the feasible CoU of blood NFL in NDDs and translate recent findings to potentially valuable clinical practice applications. As NFL is not a disease-specific biomarker, however, blood NFL is an easily accessible biomarker with promising different clinical applications for several NDDs: (1) early detection and diagnosis (i.e., amyotrophic lateral sclerosis, Creutzfeldt–Jakob disease, atypical parkinsonisms, sporadic late-onset ataxias), (2) prognosis (Huntington’s disease and Parkinson’s disease), and (3) prediction of time to symptom onset (presymptomatic mutation carriers in genetic Alzheimer’s disease and spinocerebellar ataxia type 3)

Le lipomodelage du sein dans un contexte cancérologique : mise au point à partir d’une revue de littérature actualisée et des référentiels nationaux et internationaux

National audienc

50P Early breast cancer in women aged 35 years or younger: A French population-based case control-matched analysis

International audienceBackgroundThere is a scarcity of data exploring prognostic factors in young patients with breast cancer (BC), and the independent negative impact of age by itself is still debated. We aimed to assess shared and intrinsic prognostic factors in a large cohort of patients aged 35 years or younger, compared to a control group aged from 36 to 50.MethodsPatients ≤50 years old were retrospectively identified from a large cohort of 23 134 early BC patients who underwent primary surgery in 18 academic centers between 1990 and 2014. Multivariate Cox analysis aiming to identify factors associated with disease-free and overall survival (DFS and OS) were built for the total cohort, and then for the ≤35 years cohort only. To further assess the independent impact of age on DFS and OS, 1 to 3 case control analysis was performed by matching ≤35 and 36 to 50 according to histology, grade, tumor size, lymphovascular invasion (LVI), nodal status, endocrine receptors (ER), endocrine therapy (ET) and chemotherapy (CT).ResultsOn 6 481 patients included, 556 were aged ≤35 years, and 5 925 from 36 to 50. Compared to the 36-50 group, age ≤35 was significantly associated with larger tumors, higher grade, ER negativity, macroscopic lymph node involvement, LVI, and higher rates of mastectomy and chemotherapy use. In multivariate analysis, age ≤35 was associated with worse DFS (HR 1.59, 95% CI 1.35-1.88; p<0.001), and OS (HR 1.32, 95% CI 1.06-1.64; p=0.014), as were high grade, large tumor size, LVI, macroscopic lymph node involvement, ER negativity, and absence of ET or CT. Adverse prognostic impact of age ≤35 was maintained in the case control-matched analysis for DFS (HR 1.56, 95%CI 1.28-1.91, p<0.001), and OS (HR 1.33, 95%CI 1.02-1.73, p=0.032). When considering patients ≤35 for multivariate analysis, only ER, tumor size, lymph node involvement and LVI remained statistically significantly associated with OS and DFS.ConclusionsAn age ≤35 years is associated with less favorable features at BC diagnosis, and more aggressive treatment strategies. Our results support the poor prognosis value of young age, which independently persisted when adjusting for other prognostic factors and treatments, as well as in the control-matched analysis

Lack of prognostic impact of sentinel node micro-metastases in endocrine receptor-positive early breast cancer: results from a large multicenter cohort☆

International audienceBackground: Prognostic impact of lymph node micro-metastases (pN1mi) has been discordantly reported in the literature. The need to clarify this point for decision-making regarding adjuvant therapy, particularly for patients with endocrine receptor (ER)-positive status and HER2-negative tumors, is further reinforced by the generalization of gene expression signatures using pN status in their recommendation algorithm.Patients and methods: We retrospectively analyzed 13 773 patients treated for ER-positive breast cancer in 13 French cancer centers from 1999 to 2014. Five categories of axillary lymph node (LN) status were defined: negative LN (pN0i-), isolated tumor cells [pN0(i+)], pN1mi, and pN1 divided into single (pN1 = 1) and multiple (pN1 > 1) macro-metastases (>2 mm). The effect of LN micro-metastases on outcomes was investigated both in the entire cohort of patients and in clinically relevant subgroups according to tumor subtypes. Propensity-score-based matching was used to balance differences in known prognostic variables associated with pN status.Results: As determined by sentinel LN biopsy, 9427 patients were pN0 (68.4%), 546 pN0(i+) (4.0%), 1446 pN1mi (10.5%) and 2354 pN1 with macro-metastases (17.1%). With a median follow-up of 61.25 months, pN1 status, but not pN1mi, significantly impacted overall survival (OS), disease-free survival (DFS), metastasis-free survival (MFS), and breast-cancer-specific survival. In the subgroup of patients with known tumor subtype, pN1 = 1, as pN1 > 1, but not pN1mi, had a significant prognostic impact on OS. DFS and MFS were only impacted by pN1 > 1. Similar results were observed in the subgroup of patients with luminal A-like tumors (n = 7101). In the matched population analysis, pN1macro, but not pN1mi, had a statistically significant negative impact on MFS and OS.Conclusion: LN micro-metastases have no detectable prognostic impact and should not be considered as a determining factor in indicating adjuvant chemotherapy. The evaluation of the risk of recurrence using second-generation signatures should be calculated considering micro-metastases as pN0

Lung transplantation for COVID-19-associated acute respiratory distress syndrome: The first French patient

International audienc