ABSTRACT
In surgical pathology departments, reflex first-line techniques (RFLTs) are aimed at reducing workloads and addressing recent shortages of medical personnel. However, the impacts thereof on economic and diagnostic factors have been poorly addressed. Also, in the era of global warming, environmental considerations are crucial. This study assessed the economic and diagnostic efficacies of routine pathological RFLT and the quality of care and sustainability. Ten RFLTs of the Bordeaux University Hospital pathology department (six special stains, one cytology technique, and three immunohistochemical tests) were studied. First, a retrospective economic analysis evaluated the average cost of these RFLTs per slide and per year. Second, diagnostic relevance was prospectively surveyed. Third, the effects of changes made were analyzed over 2 years. The ten RFLTs were associated with average annual costs of 46,708. Diagnostic relevance analysis indicated that most stains were unnecessary; only 17% were requested as second-line techniques. Elimination of 7/10 tests afforded annual cost savings of 22,522 and reduced the workload by 5568 tests/year, without compromising the workflow or diagnostic quality. Seven of ten RFLTs could be eliminated without compromising diagnostic quality or the workflow. This afforded not only financial benefits but also positive social and environmental impacts. We offer valuable insights into appropriate practices in surgical pathology laboratories. Collaboration between the medical and technical teams was crucial; other healthcare sectors would also benefit from our approach.
ABSTRACT
Acquired mutations in the UBA1 gene were recently identified in patients with severe adult-onset auto-inflammatory syndrome called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). However, the precise physiological and clinical impact of these mutations remains poorly defined. Here we study a unique prospective cohort of VEXAS patients. We show that monocytes from VEXAS are quantitatively and qualitatively impaired and display features of exhaustion with aberrant expression of chemokine receptors. In peripheral blood from VEXAS patients, we identify an increase in circulating levels of many proinflammatory cytokines, including IL-1ß and IL-18 which reflect inflammasome activation and markers of myeloid cells dysregulation. Gene expression analysis of whole blood confirms these findings and also reveals a significant enrichment of TNF-α and NFκB signaling pathways that can mediate cell death and inflammation. This study suggests that the control of the nflammasome activation and inflammatory cell death could be therapeutic targets in VEXAS syndrome.