Association of Continuous Intraoperative Vasopressor Use With Reoperation Rates in Head and Neck Free-Flap Reconstruction.

Importance: Continuous vasopressor use in free-flap reconstruction is a point of contention among microvascular surgeons despite data demonstrating safety. Objective: To investigate the association between continuous vasopressor use and the incidence of reoperation in the early postoperative period. Design, Setting, and Participants: In this cohort study, a retrospective medical record review was conducted of patients who underwent head and neck free-flap reconstructions between May 1, 2014, and October 31, 2019, in an academic tertiary care center. All patients undergoing free-flap reconstruction for head and neck defects were included. Exposures: Continuous intraoperative vasopressors. Main Outcomes and Measures: Patient medical records were queried for demographic variables; intraoperative use of vasopressors; vasopressor type, duration, and infusion rate; reoperation within the first 5 postoperative days; and reason for reoperation. Results: Four hundred forty-nine consecutive free-flap reconstructions were performed on 426 patients. The mean age was 62 years (IQR, 55.7-71.1); 293 patients were men (65.3%), 380 were White (84.6%), 55 were Black (12.2%), and 14 were of other race or ethnicity (3.1%). A total of 174 patients received a continuous vasopressor during their reconstruction. Twenty-three reoperations occurred within 5 days postoperatively, 8 of which included vasopressors during initial intervention. Vasopressor type had no association with reoperation (4.5% vs 5.5% [8/174 vs 15/275, respectively] for patients who received vasopressors vs those who did not) (dobutamine odds ratio [OR], 1.02 [95% CI, 0.21-2.91]; dopamine OR, 1.48 [95% CI, 0.33-4.26]). No difference was seen in the duration (dobutamine OR, 1.50 [95% CI, 0.78-2.90]; dopamine OR, 0.87 [95% CI, 0.59-1.28]) or infusion rate (dobutamine OR, 1.50 [95% CI, 0.99-1.02]; dopamine OR, 1.00 [95% CI, 0.99-1.01]) of vasopressors between patients who underwent reoperation and those who did not. Analysis after the exclusion of reasons for reoperation that did not represent possible microvascular anastomosis failure (eg, Doppler malfunction, donor site complications) showed no increased propensity for reoperation (OR, 1.18; 95% CI, 0.27-3.9). Conclusions and Relevance: In this cohort study, use of vasopressors for extensive periods intraoperatively during free-tissue transfer appeared to have no association with the rate of reoperation within 5 days of intervention, regardless of agent used, simultaneous use of agents, type of free-flap operation performed, or reason for reoperation. This study adds to the body of literature supporting the judicious use of vasopressors in patients requiring intraoperative pharmacological pressure support during free-flap reconstruction.

Production of 10-methyl branched fatty acids in yeast.

BACKGROUND: Despite the environmental value of biobased lubricants, they account for less than 2% of global lubricant use due to poor thermo-oxidative stability arising from the presence of unsaturated double bonds. Methyl branched fatty acids (BFAs), particularly those with branching near the acyl-chain mid-point, are a high-performance alternative to existing vegetable oils because of their low melting temperature and full saturation. RESULTS: We cloned and characterized two pathways to produce 10-methyl BFAs isolated from actinomycetes and γ-proteobacteria. In the two-step bfa pathway of actinomycetes, BfaB methylates Δ9 unsaturated fatty acids to form 10-methylene BFAs, and subsequently, BfaA reduces the double bond to produce a fully saturated 10-methyl branched fatty acid. A BfaA-B fusion enzyme increased the conversion efficiency of 10-methyl BFAs. The ten-methyl palmitate production (tmp) pathway of γ-proteobacteria produces a 10-methylene intermediate, but the TmpA putative reductase was not active in E. coli or yeast. Comparison of BfaB and TmpB activities revealed a range of substrate specificities from C14-C20 fatty acids unsaturated at the Δ9, Δ10 or Δ11 position. We demonstrated efficient production of 10-methylene and 10-methyl BFAs in S. cerevisiae by secretion of free fatty acids and in Y. lipolytica as triacylglycerides, which accumulated to levels more than 35% of total cellular fatty acids. CONCLUSIONS: We report here the characterization of a set of enzymes that can produce position-specific methylene and methyl branched fatty acids. Yeast expression of bfa enzymes can provide a platform for the large-scale production of branched fatty acids suitable for industrial and consumer applications.

Pectointercostal Fascial Block Catheters for Thoracic Injuries: A Case Series.

Providing analgesia for patients with anterior rib and sternum fracture has been addressed from various types of modalities. Regional anesthesia via epidurals or peripheral nerve blocks, opiates, and other forms of multimodal pain regimens have been used. However, in the polytraumatic injury patient, positioning for an epidural may be problematic, and a predominantly opiate-based treatment plan may compromise respiratory status. In this case series, we describe the pectointercostal fascial block as another tool to treat patients with anterior rib and sternal fracture with polytraumatic injuries. All 3 of the block's successes were evident by improvement in the respiratory status of each patient.

High-oleate yeast oil without polyunsaturated fatty acids.

BACKGROUND: Oleate-enriched triacylglycerides are well-suited for lubricant applications that require high oxidative stability. Fatty acid carbon chain length and degree of desaturation are key determinants of triacylglyceride properties and the ability to manipulate fatty acid composition in living organisms is critical to developing a source of bio-based oil tailored to meet specific application requirements. RESULTS: We sought to engineer the oleaginous yeast Yarrowia lipolytica for production of high-oleate triacylglyceride oil. We studied the effect of deletions and overexpressions in the fatty acid and triacylglyceride synthesis pathways to identify modifications that increase oleate levels. Oleic acid accumulation in triacylglycerides was promoted by exchanging the native ∆9 fatty acid desaturase and glycerol-3-phosphate acyltransferase with heterologous enzymes, as well as deletion of the Δ12 fatty acid desaturase and expression of a fatty acid elongase. By combining these engineering steps, we eliminated polyunsaturated fatty acids and created a Y. lipolytica strain that accumulates triglycerides with > 90% oleate content. CONCLUSIONS: High-oleate content and lack of polyunsaturates distinguish this triacylglyceride oil from plant and algal derived oils. Its composition renders the oil suitable for applications that require high oxidative stability and further demonstrates the potential of Y. lipolytica as a producer of tailored lipid profiles.

Engineering of a high lipid producing Yarrowia lipolytica strain.

BACKGROUND: Microbial lipids are produced by many oleaginous organisms including the well-characterized yeast Yarrowia lipolytica, which can be engineered for increased lipid yield by up-regulation of the lipid biosynthetic pathway and down-regulation or deletion of competing pathways. RESULTS: We describe a strain engineering strategy centered on diacylglycerol acyltransferase (DGA) gene overexpression that applied combinatorial screening of overexpression and deletion genetic targets to construct a high lipid producing yeast biocatalyst. The resulting strain, NS432, combines overexpression of a heterologous DGA1 enzyme from Rhodosporidium toruloides, a heterlogous DGA2 enzyme from Claviceps purpurea, and deletion of the native TGL3 lipase regulator. These three genetic modifications, selected for their effect on lipid production, enabled a 77 % lipid content and 0.21 g lipid per g glucose yield in batch fermentation. In fed-batch glucose fermentation NS432 produced 85 g/L lipid at a productivity of 0.73 g/L/h. CONCLUSIONS: The yields, productivities, and titers reported in this study may further support the applied goal of cost-effective, large -scale microbial lipid production for use as biofuels and biochemicals.