Free flap reconstruction following head and neck trauma.

BACKGROUND: Free flap (FF) reconstruction of traumatic injuries to the head and neck is uncommon. METHODS: Multi-institutional retrospective case series of patients undergoing FF reconstruction for a traumatic injury (n = 103). RESULTS: Majority were gunshot wounds (GSW; 85%, n = 88) and motor vehicle accidents (11%, n = 11). Majority underwent osseous reconstruction (82%, n = 84). FF failures (9%, n = 9/103) occurred in GSW patients (100%, n = 9/9) and when multiple subsites were injured (89%, n = 8/9). Preoperative antibiotics correlated with lower rates of a neck washouts (4% vs. 19%) (p = 0.01) and 30-day readmissions (4% vs. 17%) (p = 0.02). CONCLUSIONS: All FF failures occurred in the setting of a GSW and the majority involved multiple subsites. Preoperative antibiotics correlated with lower rates of postoperative washout procedures and 30-day readmission.

Lateral nasal wall extension of the nasoseptal flap for skull-base and medial orbital wall defects.

BACKGROUND: Sinonasal and skull-base tumors that previously required open resection can often be completely resected via an endonasal approach. The nasoseptal flap (NSF) is the workhorse vascularized tissue flap for the endoscopic reconstruction of large skull-base defects from tumor resections. The objective of the current article is to describe a novel modification of the NSF for simultaneous reconstruction of skull-base and medial orbital wall defects. METHODS: An extension of the standard NSF to include mucosa of the lateral nasal wall was developed for closure of simultaneous skull-base and medial orbital wall defects. Outcomes including successful cerebrospinal fluid (CSF) leak closure, orbital edema, and postoperative cosmesis are reported. Eyelid edema was characterized according to the Surgeon Periorbital Rating of Edema and Ecchymosis (SPREE) scale. RESULTS: Three patients underwent reconstruction using the modified NSF (average age 75 years). The average defect size of the skull base was 3.6 ± 0.1 cm by 2.3 ± 0.2 cm. The average defect size of the medial orbit was 2.7 ± 0.1 cm by 2.6 ± 0.1 cm. All defects were successfully covered intraoperatively using the lateral nasal wall extension of the NSF. Two patients developed mild eyelid edema, whereas 1 individual had no noticeable swelling (SPREE classification 2, 2, and 1). All patients were successfully sealed at last clinical follow up (average 28 weeks). CONCLUSION: The modification of the NSF described here provides excellent coverage for reconstruction of large anterior skull-base defects and simultaneous medial orbital wall defects.

Resveratrol and ivacaftor are additive G551D CFTR-channel potentiators: therapeutic implications for cystic fibrosis sinus disease.

BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in defective Cl- transport and cause chronic bacterial infections in the upper and lower airways of cystic fibrosis (CF) patients. Ivacaftor is a CFTR potentiator that improves Cl- transport in CF patients with at least 1 copy of the G551D mutation. Resveratrol is also a potent CFTR potentiator that increases determinants of mucociliary transport. The objective of this study is to determine whether resveratrol and ivacaftor improve Cl- secretion in G551D CFTR over either agent alone. METHODS: Fisher rat thyroid cells (FRT) transfected with G551D CFTR and human sinonasal epithelial cells (HSNE) containing the CFTR G551D mutation were subjected to pharmacologic manipulation of transepithelial ion transport in Ussing chambers. Activity was further evaluated using whole-cell patch clamp methods in G551D FRT cells. RESULTS: In G551D FRT cells, resveratrol (100 µM) and ivacaftor (10 µM) significantly increased Cl- transport (change in short-circuit current, δISC = µA/cm2 ) compared with single-agent and dimethylsulfoxide vehicle controls (resveratrol + ivacaftor 4.97 ± 0.57 vs ivacaftor 0.74 ± 0.12 vs resveratrol 2.96 ± 0.52 vs control 0.74 ± 0.12; p < 0.001). Maximal Cl- secretion (20 µM forskolin) was also significantly enhanced (p < 0.0001). Activity was confirmed in G551D HSNE (resveratrol + ivacaftor 4.48 ± 0.39 vs ivacaftor 1.05 ± 0.11 vs. resveratrol 0.84 ± 0.3 vs control, 0.0 ± 0.02; p < 0.001), and whole-cell patch clamp analysis in G551D FRT cells (resveratrol + ivacaftor -2535 ± 179.3 pA vs ivacaftor -1408.9 ± 101.3 pA vs resveratrol; -766.2 ± 71.2 pA; p < 0.0001). CONCLUSION: Additive improvement in G551D CFTR-mediated Cl- secretion suggests that resveratrol could enhance ivacaftor therapy in these patients and improve CF-related rhinosinusitis.

l-Methionine anti-biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor.

BACKGROUND: Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l-Methionine is an amino acid with reported biofilm-inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co-treatment with ivacaftor and l-methionine can reduce the formation of Pseudomonas aeruginosa biofilms. METHODS: P aeruginosa (PAO-1 strain) biofilms were studied in the presence of l-methionine and/or ivacaftor. For static biofilm assays, PAO-1 was cultured in a 48-well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter-Glo™ assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs. RESULTS: l-Methionine (0.5 µM) significantly reduced PAO-1 biofilm mass (32.4 ± 18.0%; n = 4; p < 0.001) compared with controls. Low doses of ivacaftor alone (4, 8, and 12 µg/mL) had no effect on biofilm formation. When combined with ivacaftor (4 µg/mL), a synergistic anti-biofilm effect was noted at 0.05 µM and 0.5 µM of l-methionine (two-way analysis of variane, p = 0.0415) compared with corresponding concentrations of l-methionine alone. CONCLUSION: Ivacaftor enhanced the anti-biofilm activity of l-methionine against the PAO-1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l-methionine combinations for P aeruginosa sinusitis are planned.