Dorsal Augmentation With the Dorsal Extension Spreader Graft.

Spreader grafts traditionally are used to improve airflow through opening the internal nasal valve, as well as enhance the cosmetic appearance of the nose. The graft's versatility proves useful in surgical correction of several nasal profiles by enhancing dorsal aesthetic lines and by maintenance of the nasal pyramid at midline. The authors describe a modified spreader graft that adds an additional benefit of dorsal augmentation in patients with underprojected or saddle noses. This technique utilizes harvested septal cartilage and fixation of the graft that extends beyond the septal and upper lateral cartilage dorsal border to improve nasal dorsum height. Patients who received this operative technique by the senior author were identified and their operative courses and surgical outcomes were analyzed. Case examples are provided to illustrate indications and outcomes. This grafting technique allows for improved functionality, defined dorsal aesthetic lines, changes in nasal width, and a more balanced profile in patients with underprojected noses.

Decreasing Inpatient Opioid Use Following Orthognathic Surgery.

PURPOSE: Strategies to decrease postoperative opioid use are important for mitigating the immediate and long-term risks associated with their use. We aimed to investigate the impact of perioperative various factors on inpatient opioid needs for patients undergoing orthognathic surgery. METHODS: This was a retrospective cohort study of all patients who underwent orthognathic surgery performed by the senior author from 2012 to 2018. Patients were grouped into intravenous (IV) acetaminophen and no-IV acetaminophen cohorts. Opioid medications received by patients during hospital stay were converted to mean morphine equivalents (MME) for comparison. Additional factors that influenced opioid consumption, such as transexamic acid (TXA) and postoperative nausea and vomiting (PONV), were identified using univariate analysis. Factors found to have statistical significance were added to a multivariate linear regression model. RESULTS: 319 patients were included. Those who received IV acetaminophen had lower rates of total opioid use (57.3 versus 74.8 MME; P = 0.002) and postoperative opioid use (24.0 versus 37.7 MME; P < 0.001). Perioperative prothrombotic agents, such as TXA, were associated with lower total and postoperative MME (P = 0.005, P = 0.002). Multivariate regression analysis showed that increased PONV resulted in increased postoperative opioid use, whereas perioperative acetaminophen lowered total and postoperative quantities. CONCLUSIONS: Perioperative IV acetaminophen is an effective method for decreasing inpatient opioid analgesia after orthognathic surgery. Intravenous TXA and PONV control may provide additional benefit to decreasing inpatient opioid consumption. More research as to the mechanisms and ideal clinical applications for both IV acetaminophen and TXA are warranted.

Racial Disparities in the Surgical Management of Benign Craniomaxillofacial Bone Lesions.

PURPOSE: Racial disparities can influence surgical care in the United States. The purpose of this study was to determine if race and ethnicity were independent risk factors for adverse 30-day outcomes after surgical management of benign craniomaxillofacial bone tumors. METHODS: This was a retrospective cohort study from 2012 to 2018 National Surgical Quality Improvement Program databases. Patients undergoing surgical removal of craniomaxillofacial benign lesions based on Current Procedural Terminology and International Classification of Diseases codes were included. Patients who had unrelated concurrent surgeries, or malignant, skull-based or soft tissue lesions were excluded. Primary outcomes were surgical complications and hospital length of stay (LOS). Univariate analyses were used with race as the independent variable to identify predictors of primary outcomes. Statistically significant factors were added to a multivariable logistic regression model. RESULTS: This study included 372 patients. Postoperative complications were highest among Black patients, who had a 4-fold increase in minor complications (P = 0.023) and over a 6-fold increase in major complications (P = 0.008) compared to White patients. Black patients also had a mean increase of 2.3 days in LOS compared to White patients (P < 0.001). The multivariate regression model showed higher rates of major complications and longer LOS for Black patients (P = 0.003, P = 0.006, respectively). CONCLUSIONS: Even when controlling for other variables, Black race was an independent risk factor for major complications and increased LOS. Further research should seek to identify the root cause of these findings in order to ensure safe and equitable surgery for all patients, regardless of race or ethnicity.

Development and validation of a rapid liquid chromatography/tandem mass spectrometry method to quantitate gabapentin and buprenorphine in human serum.

RATIONALE: Gabapentin has shown initial promise as an opioid-sparing medication in pain patients as well as a treatment for opioid withdrawal and liquid chriomatography/tandem mass spectrometry (LC/MS/MS) is often used for clinical monitoring. Despite reports of validated tandem mass spectrometric methods for the determination of gabapentin and buprenorphine, mechanisms for the collision-induced fragmentation have not been adequetely described. METHODS: A rapid analytical method has been developed to determine gabapentinoid, gabapentin, and the partial opioid agonist, buprenorphine, in 20 µL of human serum using LC/MS/MS with a chromatographic run time of 2 min. A simplified sample cleanup procedure using methanol precipitation of serum proteins/lipids followed by evaporation and reconstitution in mobile phase was demonstrated. Gabapentin and buprenorphine were detected following positive ion electrospray ionization using multiple-reaction monitoring. The internal standard approach was used for quantitation with labeled gabapentin-D10 and buprenorphine-D4 serving as internal standards. Using organic reaction principals and stable isotope labels, collision-induced fragmentation mechanisms for both gabapentin and buprenorphine are proposed. The method was validated according to the FDA Guidance for Industry - Bioanalytical Method Validation. RESULTS: Accuracy was demonstrated by error values ≤15% for buprenorphine and ≤6% for gabapentin. The inter-day precision was ≤4.88% and 15.59% for gabapentin and buprenorphine and the intra-day precision was ≤5.20% and 11.65% for gabapentin and buprenorphine. The lower limit of quantitation corresponded to 10 ng/mL for gabapentin and 1 ng/mL for buprenorphine in serum. Recoveries were 104 ± 2.55% and 85 ± 2.03% for gabapentin and buprenorphine, respectively. CONCLUSIONS: Concentrations of gabapentin and buprenorphine were determined for five authentic human serum samples to further validate the utility of the method and applicable to therapeutic drug monitoring beyond its use as a drug screening assay. Furthermore, new mechanisms for the collision-induced dissociation of gabapentin and buprenorphine have been proposed.

Discovery of Novel Reductive Elimination Pathway for 10-Hydroxywarfarin.

Coumadin (R/S-warfarin) anticoagulant therapy is highly efficacious in preventing the formation of blood clots; however, significant inter-individual variations in response risks over or under dosing resulting in adverse bleeding events or ineffective therapy, respectively. Levels of pharmacologically active forms of the drug and metabolites depend on a diversity of metabolic pathways. Cytochromes P450 play a major role in oxidizing R- and S-warfarin to 6-, 7-, 8-, 10-, and 4'-hydroxywarfarin, and warfarin alcohols form through a minor metabolic pathway involving reduction at the C11 position. We hypothesized that due to structural similarities with warfarin, hydroxywarfarins undergo reduction, possibly impacting their pharmacological activity and elimination. We modeled reduction reactions and carried out experimental steady-state reactions with human liver cytosol for conversion of rac-6-, 7-, 8-, 4'-hydroxywarfarin and 10-hydroxywarfarin isomers to the corresponding alcohols. The modeling correctly predicted the more efficient reduction of 10-hydroxywarfarin over warfarin but not the order of the remaining hydroxywarfarins. Experimental studies did not indicate any clear trends in the reduction for rac-hydroxywarfarins or 10-hydroxywarfarin into alcohol 1 and 2. The collective findings indicated the location of the hydroxyl group significantly impacted reduction selectivity among the hydroxywarfarins, as well as the specificity for the resulting metabolites. Based on studies with R- and S-7-hydroxywarfarin, we predicted that all hydroxywarfarin reductions are enantioselective toward R substrates and enantiospecific for S alcohol metabolites. CBR1 and to a lesser extent AKR1C3 reductases are responsible for those reactions. Due to the inefficiency of reactions, only reduction of 10-hydroxywarfarin is likely to be important in clearance of the metabolite. This pathway for 10-hydroxywarfarin may have clinical relevance as well given its anticoagulant activity and capacity to inhibit S-warfarin metabolism.

In Situ Inner Lumen Attachment of Heparin to Poly(ether sulfone) Hollow Fiber Membranes Used for Microdialysis Sampling.

An in situ chemical surface modification method to attach heparin to the inner lumen of a single hollow fiber poly(ether sulfone) (PES) membrane incorporated into a commercial microdialysis sampling device is described. The immobilization process uses gentle, room-temperature conditions with the enzyme laccase (E.C. 1.10.3.2) and 4-hydroxybenzoic acid (4HBA). The resulting functionalized inner membrane surface with a carboxylic acid functional groups allowed for (1-ethyl-3-(3-(dimethylamino)propyl) carbodimide)/ N-hydroxysuccinimide) EDC/NHS chemistry to attach heparin to the membrane surface. X-ray photoelectron spectroscopy measurements suggested successful attachment of 4HBA polymers and heparin onto the PES membrane. The microdialysis extraction efficiency after membrane surface modification was measured with model compounds fluorescein isothiocyanate (FITC)-labeled dextrans and lysozyme and the cytokines acidic fibroblast growth factor (aFGF) and CXCL1 (KC/GRO). This work demonstrates an in situ method to modify commercially available PES hollow fiber microdialysis membranes with amine or carboxylic acid functional groups.

Managing plant population spread: prediction and analysis using a simple model.

Models can be used to direct the management of population spread for the control of invasives or to encourage species of conservation value. Analytical models are attractive because of their theoretical basis and limited data requirements, but there is concern that their simplicity may limit their practical utility. We address the applied use of simple models in a study of a declining annual herb, Rhinanthus minor. We parameterized a population-spread model using field data on demography and dispersal for four management systems: grazed only (GR), hay-cut once (H1), hay-cut twice (H2), and hay-cut with autumn grazing (HG). Within a replicated experiment we measured spread rates of introduced R. minor populations over eight years. The modeled and measured spread rates were very similar in terms of both patterns of management effects and absolute values, so that in both cases HG > H2, H1 > GR. The treatments affected both dispersal and demography (establishment and survival) and so we used decomposition approaches to analyze the major causes of differences in population spread. Increased dispersal under hay-cutting was more important than demographic changes and accounted for approximately 70% of the differences in spread rate between the hay-cut and grazed-only treatments. Furthermore, management effects on the tail of the dispersal curve were by far the most critical in governing spread. This study suggests that simple models can be used to inform practical conservation management, and we demonstrate straightforward uses of our model to predict the impacts of different management strategies. While simple models can give accurate projections, we emphasize that they must be parameterized with high-quality data gathered at the appropriate spatial scale.