A series of naphthyridinol analogs of α-tocopherol (α-TOH, right) with varying sidechain substitution was synthesized to determine how systematic changes in the lipophilicity of these potent antioxidants impact their radical-trapping activities in lipid bilayers, regenerability by water-soluble reductants, and binding to human tocopherol transport protein (TTP). The activities of the naphthyridinols were assayed in phosphatidylcholine unilamellar liposomes using a recently developed high-throughput assay that employs a boron dipyrromethene conjugate of α-TOH (H(2)B-PMHC) that undergoes fluorescence enhancement upon oxidation. The naphthyridinols afforded a dose-dependent protection of H(2)B-PMHC consistent with unprecedented peroxyl radical-trapping activity in lipid bilayers. While sidechain length and/or branching had no effect on their apparent reactivity, it dramatically impacted reaction stoichiometry, with more lipophilic compounds trapping two peroxyl radicals and more hydrophilic compounds trapping significantly less than one. It is suggested that the less lipophilic compounds autoxidize rapidly in the aqueous phase and that preferential partitioning of the more lipophilic compounds to the bilayer protects them from autoxidation. The cooperativity of a lipophilic naphthyridinol with water-soluble reducing agents was also studied in liposomes using H(2)B-PMHC and revealed superior regenerability by each of ascorbate, N-acetylcysteine, and urate when compared to α-TOH. Binding assays with human TTP, a key determinant of the bioavailability of the tocopherols, reveal that the naphthyiridinols can be very good ligands for the protein. In fact, naphthyridinols with sidechains of eight or more carbons had affinities for TTP which were similar to, and in one case 10-fold better than, α-TOH.

Background: Epidural nerve blocks (EA) have been widely used in abdominal and thoracic surgery as an adjunct to general anesthesia (GA). The role for EA in microsurgical free flap breast reconstruction remains unclear with concerns regarding its impact on flap survival and operating room efficiency. The purpose of this study was to examine the effectiveness of epidural blocks in patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction. Methods: A retrospective analysis of patients undergoing DIEP breast reconstruction under GA alone was compared with those receiving EA/GA. Electronic records were analyzed for patient demographics, intraoperative data, and postoperative outcomes. The primary outcome was 48-hour narcotic usage and secondary outcomes were intraoperative vasopressor consumption, surgical delay, and safety profile. Results: Sixty-one patients underwent DIEP reconstruction, 46 (75%) underwent EA/GA and 15 (25%) underwent GA alone. Epidural blocks were associated with a significant delay in operating room start time (67.8 min versus 45.6 min; P = 0.0004.) Patients in the EA/GA group also had a significant increase in vasopressor use (n = 38 versus n = 8; P = 0.037); however, there was no difference in flap complication rate [1 (2%) versus 2 (13%); P = 0.15]. Postoperatively, patients who received an epidural block had a reduced average pain score (1.1 versus 2.2; P = 0.0235), but there was no difference in 48-hour narcotic usage. Conclusions: Although epidural blocks reduce postoperative pain following DIEP flap breast reconstruction, they increase intraoperative vasopressor use and delay the start time of the case. Further studies are required to elucidate whether the benefits of improved pain control outweigh the potential risk for increased surgical complications and increased health care costs.

Background: Cranioplasty is a critical intervention to restore the calvarium using autologous or alloplastic materials with singlestage composite scalp and calvarial reconstruction reserved for complex cases. This study aims to identify 30-day outcomes in scalp and calvarial reconstruction using the American College of Surgeons National Surgical Quality Improvement Program database. Methods: The authors conducted a retrospective analysis of the 2010 to 2018 American College of Surgeons National Surgical Quality Improvement Program database. Adult patients who underwent cranioplasty were identified using current procedural terminology coding and included by exposure type (autologous, alloplastic, composite, or other). Subjects with missing exposure or outcome data were excluded. Primary outcome was 30-day reoperation, whereas secondary outcomes were 30-day unplanned readmission and transfusion. Univariate analysis was completed to assess differences in demographics, comorbidities, and postoperative complications. Multivariable logistic regression was used to control for confounders. Results: In total, 1719 patients underwent cranioplasty (mean age 54.7 ± 15.3 years, 43.5% male), including 169(9.8%) autologous, 1303(75.8%) alloplastic, 32(1.9%) composite, and 215(12.5%) other procedures. Cranioplasty procedures were associated with 30-day complication and mortality rate of 16.5% and 2.4%, respectively. Composite cranioplasty was associated with decreased 30-day reoperation (adjusted odds ratios 0.11, 95% confidence interval 0.014-0.94, P = 0.044). There was no statistically significant difference in readmission between cranioplasty groups. Alloplastic cranioplasty was associated with decreased odds of postoperative transfusion (adjusted odds ratios 0.47, 95% confidence interval 0.27â 0.84, P= 0.01). Conclusions: Cranioplasty is an increasingly common procedure. Alloplastic cranioplasty is associated with decreased 30-day transfusion requirement, whereas single-stage composite reconstruction is a viable option and associated with decreased 30-day reoperation with no difference in readmission.

Background An important risk inherent to both alloplastic and autologous immediate breast reconstruction (IBR) is the higher incidence of postoperative complications and delays to adjuvant therapy. The main objective of this retrospective cohort study was to identify risk factors for locoregional recurrence after breast cancer mastectomy and IBR. Methods A 6‐year retrospective study of breast cancer patients treated with mastectomy only (MO) or mastectomy and IBR (MIBR) was conducted from January 2013 to May 2019. The outcomes of interest included delay in adjuvant chemoradiotherapy, postoperative complications, and locoregional recurrence. Cox regression survival was used to estimate the risk of locoregional recurrence and time to adjuvant therapy. Results Of 1832 patients reviewed, 720 (38%) were included. The cohort consisted of 443 (62%) MO and 277 (38%) MIBR [140 (51%) direct‐to‐implant (MIBRi1), 96(35%) tissue expander to implant (MIBRi2), and 41(15%) autologous flap (MIBRf)]. MIBR had more delays to adjuvant therapy compared to MO [113 (70%) vs. 72 (80%) months, p = 0.022]. Kaplan‐Meier analysis showed that MIBRi2 had significantly shorter DFS compared to MO [MIBRi2: 39.2 (15.6) vs MO: 41.7 (19.6) months, log‐rank p‐value = 0.01]. Cox regression indicated that MIBRi2 was associated with a 3.26‐higher risk of locoregional recurrence compared to MO [HR: 3.26; 95% CI: 1.56, 9.24]. Conclusions Cox regression showed MIBRi2 was significantly associated with increased risk of locoregional recurrence compared to MO. Neither delays nor postoperative complications were identified as significant risk factors for locoregional recurrence risk.