Immediate versus delayed breast reconstruction: Long-term follow-up on health-related quality of life and satisfaction with breasts.

INTRODUCTION: Health-related quality of life (HRQL) can be improved by breast reconstruction following mastectomy. The optimal timing of the reconstruction remains unclear. METHODS: A cross-sectional study on 338 women who had undergone immediate or delayed breast reconstruction between 08/2017 and 07/2019 was performed. The postoperative HRQL was assessed using the BREAST-Q Reconstruction Module and the 36-Item Short Form Survey (SF-36). Regression analysis was performed for group-wise comparison. RESULTS: A total of 146 (43%) patients participated. Seventy-seven patients (53%) had undergone immediate, and 69 patients (47%) had delayed reconstruction. The median age was 55 years (interquartile ratio [IQR] 50-62) for the Immeda group te, and 60 years (IQR 54-65) for the delayed reconstruction group. The median follow-up time was 2.3 years (IQR 1.8-2.9). No difference between the groups was detected in satisfaction with breasts (median 61, IQR 53-71 vs. 62, IQR 46-71, p = 0.62), physical well-being of the chest (median 100, IQR 80-100 vs. 100, IQR 80-100, p = 0.95) or psychosocial well-being (median 69, IQR 54-83 vs. 62, IQR 54-74, p = 0.19). No difference was detected in the SF-36 domains either. CONCLUSIONS: The timing of the breast reconstruction does not affect the postoperative HRQL. Patients with both immediate and delayed breast reconstruction reported high satisfaction with the breast and psychosocial well-being.

Truncating NFKB1 variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis.

In monogenic autoinflammatory diseases, mutations in genes regulating innate immune responses often lead to uncontrolled activation of inflammasome pathways or the type I interferon (IFN-I) response. We describe a mechanism of autoinflammation potentially predisposing patients to life-threatening necrotizing soft tissue inflammation. Six unrelated families are identified in which affected members present with necrotizing fasciitis or severe soft tissue inflammations. Exome sequencing reveals truncating monoallelic loss-of-function variants of nuclear factor κ light-chain enhancer of activated B cells (NFKB1) in affected patients. In patients' macrophages and in NFKB1-variant-bearing THP-1 cells, activation increases both interleukin (IL)-1ß secretion and IFN-I signaling. Truncation of NF-κB1 impairs autophagy, accompanied by the accumulation of reactive oxygen species and reduced degradation of inflammasome receptor nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3), and Toll/IL-1 receptor domain-containing adaptor protein inducing IFN-ß (TRIF), thus leading to combined excessive inflammasome and IFN-I activity. Many of the patients respond to anti-inflammatory treatment, and targeting IL-1ß and/or IFN-I signaling could represent a therapeutic approach for these patients.