BackgroundHomeostatic turnover of the extracellular matrix conditions the structure and function of the healthy lung. In lung transplantation, long-term management remains limited by chronic lung allograft dysfunction, an umbrella term used for a heterogeneous entity ultimately associated with pathological airway and/or parenchyma remodeling.ObjectiveThis study assessed whether the local cross-talk between the pulmonary microbiota and host cells is a key determinant in the control of lower airway remodeling posttransplantation.MethodsMicrobiota DNA and host total RNA were isolated from 189 bronchoalveolar lavages obtained from 116 patients post lung transplantation. Expression of a set of 11 genes encoding either matrix components or factors involved in matrix synthesis or degradation (anabolic and catabolic remodeling, respectively) was quantified by real-time quantitative PCR. Microbiota composition was characterized using 16S ribosomal RNA gene sequencing and culture.ResultsWe identified 4 host gene expression profiles, among which catabolic remodeling, associated with high expression of metallopeptidase-7, -9, and -12, diverged from anabolic remodeling linked to maximal thrombospondin and platelet-derived growth factor D expression. While catabolic remodeling aligned with a microbiota dominated by proinflammatory bacteria (eg, Staphylococcus, Pseudomonas, and Corynebacterium), anabolic remodeling was linked to typical members of the healthy steady state (eg, Prevotella, Streptococcus, and Veillonella). Mechanistic assays provided direct evidence that these bacteria can impact host macrophage-fibroblast activation and matrix deposition.ConclusionsHost-microbes interplay potentially determines remodeling activities in the transplanted lung, highlighting new therapeutic opportunities to ultimately improve long-term lung transplant outcome.

Objective: To evaluate the clinical course of and risk factors for arterial thrombotic events in adult inpatients with coronavirus disease 2019 . Methods: All consecutive adult patients admitted for COVID-19 infection in a referral center in France and discharged from the hospital between April 1 and April 30, 2020, were included. All arterial thrombotic events that occurred through discharge were considered for analysis. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic medical records with use of a standardized data collection form. Results: Overall, 531 COVID-19þ patients were analyzed. Among them, 30 (5.6%) experienced arterial thrombotic events. Arterial thrombotic events in the setting of COVID-19 infection happened at a median of 11 (5-20) days after the first symptoms of infection; occurred in high-risk patients according to traditional cardiovascular risk factors; had an atypical pattern, such as thrombosis of the aorta, upper limb, or renal arteries or cerebral microvasculopathy in 7 (23.3%) cases; and were associated with an in-hospital mortality rate of 40%. Arterial thrombotic events increased the risk of death by 3-fold in COVID-19þ patients (hazard ratio, 2.96; 95% CI, 1.4 to 4.7; P¼.002). A subdistribution survival hazard model showed that a concentration of D-dimer above 1250 ng/mL increased the risk of arterial thrombotic events in COVID-19þ patients by more than 7 (subdistribution hazard ratio, 7.68; 95% CI, 2.9 to 20.6; P<.001). Conclusion:A dramatically high rate of in-hospital death was observed in patients who suffered arterial thrombotic events in the setting of COVID-19 infection. A D-dimer level above 1250 ng/mL at entry may identify COVID-19þ patients at risk for arterial thrombotic events.

Cefiderocol is a novel siderophore cephalosporin, which has proven in vitro activity against carbapenem-resistant (CR) Gram-negative pathogens and stability towards all carbapenemases. The aim of this study was to describe the first cases of prescriptions and the efficacy of cefiderocol for compassionate use in the 2 months following its access in France. We performed a national retrospective study of all patients who received at least one dose of cefiderocol from 2 November 2018 to 5 November 2019. We collected clinical characteristics and outcome through a standard questionnaire. Bacterial isolates from 12 patients were centralized and analyzed in the French National Reference Center for Antimicrobial Resistance, and sequenced using Illumina technology. Finally, 13 patients from 7 French university hospitals were included in the study. The main type of infection treated by cefiderocol was respiratory tract infections (RTI, n = 10). The targeted bacteria were Pseudomonas aeruginosa (n = 12), including carbapenemase-producing P. aeruginosa (n = 9), Acinetobacter baumannii (n = 2), Klebsiella pneumoniae (n = 1), and Enterobacter hormaechei (n = 1). Overall, of the 12 patients whose samples were analyzed, 5 P. aeruginosa strains were not susceptible to cefiderocol (4 categorized as resistant and 1 as intermediate) according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. If considering susceptible strains, the cure rate was 6/7, while being 0/5 among not-susceptible strains. This study underlines the necessity to test strains in adequate conditions.