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.

Antibiotic prophylaxis in clean and clean-contaminated plastic surgery: A critical review.

Antibiotic prophylaxis is frequently used in plastic surgery procedures, despite the generally low rates of infection and few guidelines on the practice. The increasing prevalence of bacterial resistance to antibiotics calls for a reduction in unnecessary antibiotic use. The aim of this review was to create an updated summary of the available data on the effectiveness of antibiotic prophylaxis in reducing the postoperative infection in clean and clean-contaminated plastic surgery. A systematic literature search was performed on the databases Medline, Web of Science, and Scopus, limited to articles published January 2000 onward. Randomized controlled trials (RCTs) were included in the primary review, whereas older RCTs and other studies were sought if 2 or fewer relevant RCTs were identified. Overall, 28 relevant RCTs, 2 nonrandomized trials, and 15 cohort studies were identified. Although the number of studies for each type of surgery is limited, the data suggest that prophylactic systemic antibiotic may be unnecessary in noncontaminated facial plastic surgery, reduction mammaplasty, and breast augmentation. In addition, no benefit is apparent from extending the antibiotic prophylaxis over 24 h in rhinoplasty, aerodigestive tract reconstruction, and breast reconstruction. No studies assessing the necessity of antibiotic prophylaxis in abdominoplasty, lipotransfer, soft tissue tumor surgery, or gender affirmation surgery were identified. In conclusion, limited data are available on the effectiveness of antibiotic prophylaxis in clean and clean-contaminated plastic surgery. More studies on this topic are needed before strong recommendations can be made on the use of antibiotics in this setting.