Rationale: It is now well established that immune responses can take place outside of primary and secondary lymphoid organs. We previously described the presence of tertiary lymphoid structures (TLS) in patients with non-small cell lung cancer (NSCLC) characterized by clusters of mature dendritic cells (DCs) and T cells surrounded by B-cell follicles. We demonstrated that the density of these mature DCs was associated with favorable clinical outcome. Objectives: To study the role of follicular B cells in TLS and the potential link with a local humoral immune response in patients with NSCLC. Methods: The cellular composition of TLS was investigated by immunohistochemistry. Characterization of B-cell subsets was performed by flow cytometry. A retrospective study was conducted in two independent cohorts of patients. Antibody specificity was analyzed by ELISA. Measurements and Main Results: Consistent with TLS organization, all stages of B-cell differentiation were detectable in most tumors. Germinal center somatic hypermutation and class switch recombination machineries were activated, associated with the generation of plasma cells. Approximately half of the patients showed antibody reactivity against up to 7 out of the 33 tumor antigens tested. A high density of follicular B cells correlated with long-term survival, both in patients with early-stage NSCLC and with advanced-stage NSCLC treated with chemotherapy. The combination of follicular B cell and mature DC densities allowed the identification of patients with the best clinical outcome. Conclusions: B-cell density represents a new prognostic biomarker for NSCLC patient survival, and makes the link between TLS and a protective B cell-mediated immunity.

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Severe osteoporotic fractures (hip, proximal humerus, pelvic, vertebral and multiple rib fractures) carry an increased risk of mortality. This retrospective cohort study in the French national healthcare database aimed to estimate refracture and mortality rates after severe osteoporotic fractures at different sites, and to identify mortality‐related variables. A total of 356,895 patients hospitalized for severe osteoporotic fracture between 2009 and 2014 inclusive were analyzed. The cohort was followed for 2 to 8 years up to the study end or until the patient died. Data were extracted on subsequent hospitalizations, refracture events, treatments, comorbidities of interest and survival. Time to refracture and survival were described using Kaplan‐Meier analysis by site of fracture and overall. Mortality risk factors were identified using a Cox model. Hip fractures accounted for 60.4% of the sample (N = 215,672). In the 12 months following fracture, 58,220 patients (16.7%) received a specific osteoporosis treatment, of whom 21,228 were previously treatment‐naïve. The 12‐month refracture rate was 6.3% (95% confidence interval [CI], 6.2%–6.3%), ranging from 4.0% (95% CI, 3.7%–4.3%) for multiple rib fractures to 7.8% (95% CI, 7.5%–8.1%) for pelvic fractures. Twelve‐month all‐cause mortality was 12.8% (95% CI, 12.7%–12.9%), ranging from 5.0% (95% CI, 4.7%–5.2%) for vertebral fractures to 16.6% (95% CI, 16.4%–16.7%) for hip fractures. Osteoporosis‐related mortality risk factors included fracture site, previous osteoporotic fracture (hazard ratio 1.21; 95% CI, 1.18–1.23), hip refracture (1.74; 95% CI, 1.71–1.77), and no prior osteoporosis treatment (1.24; 95% CI, 1.22–1.26). Comorbid cancer (3.15; 95% CI, 3.09–3.21) and liver disease (2.54; 95% CI, 2.40–2.68) were also strongly associated with mortality. In conclusion, severe osteoporotic fractures, including certain non‐hip nonvertebral fractures, carry a high burden in terms of mortality and refracture risk. However, most patients received no anti‐osteoporotic treatment. The findings emphasize the importance of better management of patients with severe fractures, and of developing effective strategies to reduce fracture risk in patients with osteoporosis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Non-persistence (treatment discontinuation or switch) with vitamin K antagonists was lower than with rivaroxaban and dabigatran in French primary care; however, non-persistence with the newest drug, apixaban, was similar to vitamin K antagonists. Larger studies with longer follow-up are needed to support these findings. This study is registered on ClinicalTrials.gov (NCT02488421).

The time spent with a temperature below 38.4 °C was independently associated with patient's outcome and explained 73% of the effect of the randomization on the day 14 mortality. Heart rate lowering was not a mediator of mortality.