Vascular thrombosis is one of the major postoperative complications of free flap microvascular breast reconstruction operations. It is associated with higher morbidity, higher cost, increased length of hospital stay, and potentially flap loss. Our purpose is to evaluate the rate of this complication and whether patient characteristics play a role. Using the Nationwide Inpatient Sample (NIS) database, we examined the clinical data of patients who underwent free flap breast reconstruction between 2009 and 2010 in the United States. Multivariate and univariate regression analyses were performed to identify independent risk factors of flap thrombosis. A total of 15,211 patients underwent free flap breast reconstruction surgery (immediate reconstruction: 43%). The most common flap was the free deep inferior epigastric perforator (DIEP) flap (53.6%), followed by free transverse rectus abdominis myocutaneous (TRAM) flap (43.1%), free superficial inferior epigastric artery (SIEA) flap (2%), and free gluteal artery perforator (GAP) flap (1.3%). The overall rate of flap thrombosis was 2.4 %, with the highest rate seen in the SIEA group (11.4%) and the lowest in the TRAM group (1.7%). Peripheral vascular disease (adjusted odds ration [AOR] 10.61), SIEA flap (AOR, 4.76) and delayed reconstruction (AOR, 1.42) were found to be statistically significant risk factors for flap thrombosis. Other comorbidities were not linked. While the overall rate of flap thrombosis in free flap breast reconstruction was relatively low (2.4%), Plastic Surgeons should be aware that patients with peripheral vascular disease and those undergoing free SIEA flap are at higher risk of flap thrombosis and they should closely monitor flaps to increase the chance for early salvage.

Therapeutic, level IV.

Genetic variants within the fibrinogen Aa-chain encoding the aC-region commonly result in hypodysfibrinogenemia in patients. However, the (patho)physiological consequences and underlying mechanisms of such mutations remain undefined. Here, we generated Fga270 mice carrying a premature termination codon within the Fga gene at residue 271. The Fga270 mutation was compatible with Mendelian inheritance for offspring of heterozygous crosses. Adult Fga270/270 mice were hypofibrinogenemic with ~10% plasma fibrinogen levels relative to FgaWT/WTmice, linked to 90% reduction in hepatic Fga mRNA due to nonsense-mediated decay of the mutant mRNA. Fga270/270 mice had preserved hemostatic potential in vitro and in vivo in models of tail bleeding and laser-induced saphenous vein injury, while Fga-/- mice had continuous bleeding. Platelets from FgaWT/WTandFga270/270 mice displayed comparable initial aggregation following ADP stimulation, but Fga270/270 platelets quickly disaggregated. Despite ~10% plasma fibrinogen, the fibrinogen level in Fga270/270 platelets was ~30% of FgaWT/WT platelets with a compensatory increase in fibronectin. Notably, Fga270/270 mice showed complete protection from thrombosis in the inferior vena cava stasis model. In a model of Staphylococcus aureus peritonitis, Fga270/270 mice supported local, fibrinogen-mediated bacterial clearance and host survival comparable to FgaWT/WT, unlike Fga-/- mice. Decreasing the normal fibrinogen levels to ~10% with siRNA in mice also provided significant protection from venous thrombosis without compromising hemostatic potential and antimicrobial function. These findings both reveal novel molecular mechanisms underpinning fibrinogen aC-region truncation mutations and highlight the concept that selective fibrinogen reduction may be efficacious for limiting thrombosis while preserving hemostatic and immune protective functions.

The type VI secretion system (T6SS) is widely distributed in diverse bacterial species and habitats where it is required for interbacterial competition and interactions with eukaryotic cells. Previous work described the role of a T6SS in the beneficial symbiont, Vibrio fischeri, during colonization of the light organ of Euprymna scolopes squid. However, the prevalence and diversity of T6SSs found within the distinct symbiotic structures of this model host have not yet been determined. Here, we analyzed 73 genomes of isolates from squid light organs and accessory nidamental glands (ANGs) and 178 reference genomes. We found that the majority of these bacterial symbionts encode diverse T6SSs from four distinct classes, and most share homology with T6SSs from more distantly related species, including pathogens of animals and humans. These findings indicate that T6SSs with shared evolutionary histories can be integrated into the cellular systems of host-associated bacteria with different effects on host health. Furthermore, we found that one T6SS in V. fischeri is located within a genomic island with high genomic plasticity. Five distinct genomic island genotypes were identified, suggesting this region encodes diverse functional potential that natural selection can act on. Finally, analysis of newly described T6SSs in roseobacter clade ANG isolates revealed a novel predicted protein that appears to be a fusion of the TssB-TssC sheath components. This work underscores the importance of studying T6SSs in diverse organisms and natural habitats to better understand how T6SSs promote the propagation of bacterial populations and impact host health.