Traumatic Brain Injury in Patients With Frontal Sinus Fractures.

Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force that may lead to short or long-term impairment. Traumatic brain injury has been reported in up to 83% of craniofacial fractures involving the frontal sinus. However, the risk factors for TBI at presentation and persistent neurological sequelae in patients with frontal sinus fractures remain largely unstudied. The authors aim to evaluate the prevalence and risk factors associated with TBI on presentation and neurological sequelae in these patients. The authors retrospectively reviewed patients who presented with traumatic frontal sinus fractures in 2019. The authors' primary outcome was the prevalence of concomitant TBI on presentation, which authors defined as any patient with neurological symptoms/signs on presentation and/or patients with a Glasgow Coma Scale <15 with no acute drug or alcohol intoxication or history of dementia or other neurocognitive disorder. The authors' secondary outcome was the incidence of neurological sequelae after 1 month of injury. Bivariate analysis and multivariate logistic regression were performed. A total of 56 patients with frontal sinus fractures were included. Their median (interquartile range) age was 47 (31-59) years, and the median (interquartile range) follow-up was 7.3 (1.3-76.5) weeks. The majority were males [n = 48 (85.7%)] and non-Hispanic whites [n = 35 (62.5%)]. Fall was the most common mechanism of injury [n = 15 (26.8%)]. Of the 56 patients, 46 (82.1%) had concomitant TBI on presentation. All patients who had combined anterior and posterior table frontal sinus fractures [n = 37 (66.1%)] had TBI on presentation. These patients had 13 times the odds of concomitant TBI on presentation [adjusted odds ratio (95% CI): 12.7 (2.3-69.0)] as compared with patients with isolated anterior or posterior table fractures. Of 34 patients who were followed up more than 1 month after injury, 24 patients (70.6%) had persistent neurological sequelae, most commonly headache [n = 16 (28.6%)]. Patients who had concomitant orbital roof fractures had 32 times the odds of neurological sequelae after 1 month of injury [adjusted odds ratio (95% CI): 32 (2.4->100)]. Emergency physicians and referring providers should maintain a high degree of suspicion of TBI in patients with frontal sinus fractures. Head computed tomography at presentation and close neurological follow-up are recommended for patients with frontal sinus fracture with combined anterior and posterior table fractures, as well as those with concomitant orbital roof fractures.

Quadrivalent meningococcal tetanus toxoid-conjugate booster vaccination in adolescents and adults: phase III randomized study.

BACKGROUND: The immunogenicity and safety of a booster dose of tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT), alone or co-administered with MenB vaccine, were assessed in healthy 13-25-year olds who received MenACYW-TT or a CRM-conjugate vaccine (MCV4-CRM) 3-6 years earlier. METHODS: This phase IIIb open-label trial (NCT04084769) evaluated MenACYW-TT-primed participants, randomized to receive MenACYW-TT alone or with a MenB vaccine, and MCV4-CRM-primed participants who received MenACYW-TT alone. Functional antibodies against serogroups A, C, W and Y were measured using human complement serum bactericidal antibody assay (hSBA). The primary endpoint was vaccine seroresponse (post-vaccination titers ≥1:16 if pre-vaccination titers <1:8; or a ≥4-fold increase if pre-vaccination titers ≥1:8) 30 days post booster. Safety was evaluated throughout the study. RESULTS: The persistence of the immune response following primary vaccination with MenACYW-TT was demonstrated. Seroresponse after MenACYW-TT booster was high regardless of priming vaccine (serogroup A: 94.8% vs 93.2%; C: 97.1% vs 98.9%; W: 97.7% vs 98.9%; and Y; 98.9% vs 100% for MenACWY-TT-primed and MCV4-CRM-primed groups, respectively). Co-administration with MenB vaccines did not affect MenACWY-TT immunogenicity. No vaccine-related serious adverse events were reported. CONCLUSIONS: MenACYW-TT booster induced robust immunogenicity against all serogroups, regardless of the primary vaccine received, and had an acceptable safety profile. IMPACT: A booster dose of MenACYW-TT induces robust immune responses in children and adolescents primed with MenACYW-TT or another MCV4 (MCV4-DT or MCV4-CRM), respectively. Here, we demonstrate that MenACYW-TT booster 3-6 years after primary vaccination induced robust immunogenicity against all serogroups, regardless of the priming vaccine (MenACWY-TT or MCV4-CRM), and was well tolerated. Persistence of the immune response following previous primary vaccination with MenACYW-TT was demonstrated. MenACYW-TT booster with MenB vaccine co-administration did not affect MenACWY-TT immunogenicity and was well tolerated. These findings will facilitate the provision of broader protection against IMD particularly in higher-risk groups such as adolescents.

Craniofacial Fellowship Applicant Perceptions of Virtual Interviews.

INTRODUCTION: The 2021 interview cycle for craniofacial fellowship applicants was the first to be held virtually due to the coronavirus disease 2019 pandemic. Here, we detail the craniofacial fellowship applicant perceptions and experience on the virtual interview process. MATERIALS AND METHODS: An institutional review board-approved 35-question survey study on the perception of the virtual interview process among craniofacial fellowship applicants was conducted. Surveys were distributed to individuals who had applied through the match, overseen by the American Society of Craniofacial Surgeons (ASCFS). RESULTS: Ten surveys were fully completed with a corresponding response rate of 48%. The average number of interviews completed was 12.7±7.7 and 50% of applicants interviewed at >1 program in a single day. Overall, 90% of respondents preferred in-person interviews before the interview season, however, only 10% preferred the in-person format afterwards. Preference for a virtual-only format increased from 10% to 70%. Applicants cited cost (100%), ease of scheduling (90%), and ability to participate in more interviews (70%) as the primary strengths of the virtual platform; none reported difficulties with self-advocacy. After the interview cycle, 90% stated they would recommend virtual interviews. CONCLUSIONS: The greatest strengths of virtual interviews were the ability to participate in more interviews, the ease of scheduling, and the cost benefits. Most applicants reported the same or increased ability for self-advocacy with virtual interviews. Following the index interview cycle for 2021, the majority of fellowship applicants now appear to prefer a virtual-only or hybrid format and would recommend virtual interviews in the future.

Impact of Host Flexibility on Selectivity in a Supramolecular Host-Catalyzed Enantioselective aza-Darzens Reaction.

A highly enantioselective aza-Darzens reaction (up to 99% ee) catalyzed by an enantiopure supramolecular host has been discovered. To understand the role of host structure on reaction outcome, nine new gallium(III)-based enantiopure supramolecular assemblies were prepared via substitution of the external chiral amide. Despite the distal nature of the substitution in these catalysts, changes in enantioselectivity (61 to 90% ee) in the aziridine product were observed. The enantioselectivities were correlated to the flexibility of the supramolecular host scaffold as measured by the kinetics of exchange of a model cationic guest. This correlation led to the development of a best-in-class catalyst by substituting the gallium(III)-based host with one based on indium(III), which generated the most flexible and selective catalyst.

Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study.

BACKGROUND: The MenACYW-TT conjugate vaccine is approved for prevention of invasive meningococcal disease (IMD) as a single dose in individuals ≥2 years of age in the United States and ≥12 months in EU and some other countries. This Phase II study evaluated the safety and immunogenicity of this vaccine and of concomitant pediatric vaccines in infants/toddlers (6 weeks-15 months of age). METHODS: Five schedules of the MenACYW-TT conjugate vaccine were evaluated in the United States: 2, 4, 6, and 12 months; 2, 4, 6, and 15 months; 2, 4, and 12 months; 6 and 12 months; and 12 months alone. Routine pediatric vaccines (DTaP-IPV/Hib, PCV7/PCV13, MMR, and varicella) were administered per approved schedules. Proportions of participants with serum bactericidal antibodyassay with human complement (hSBA) titers ≥1:4 and ≥1:8, SBA with baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128, and immune responses against concomitant vaccines were determined. RESULTS: Tenderness and irritability were the most frequent solicited injection site and systemic reactions. Similar proportions of participants achieved an hSBA titer ≥1:8 for all four serogroups regardless of whether 2 or 3 doses were administered in the first year of life. Following a second-year dose, 91-100% of participants achieved the threshold for all 4 serogroups in all schedules regardless of the number of doses in the first year of life. Similar responses were seen with rSBA. Immunogenicity and safety profile of concomitant vaccines was similar whether the MenACYW-TT conjugate vaccine was administered or not. CONCLUSION: MenACYW-TT conjugate vaccine administered with pediatric vaccines is safe and immunogenic regardless of the schedule and does not affect the immunogenicity or safety of the concomitant vaccines. CLINICAL TRIAL REGISTRY: NCT01049035.

Syntheses of Amorfrutins and Derivatives via Tandem Diels-Alder and Anionic Cascade Approaches.

We describe two complementary approaches based on a convergent [4+2] logic toward the synthesis of amorfrutins, cannabinoids, and related plant metabolites. An anionic cascade cyclization employing ß-methoxycrotonates and ß-chloro-α,ß-unsaturated esters yielded amorfrutins in four linear steps and demonstrated utility of ß-alkoxycrotonate-derived nucleophiles as functional equivalents of ß-ketoester-derived dianions. Analogously, tandem Diels-Alder/retro-Diels-Alder cycloaddition of dimedone-derived bis(trimethylsiloxy)-dienes and α,ß-alkynyl ester dienophiles provided facile access to resorcinol precursors of amorfrutins and cannabinoids, avoiding late-stage installation of prenyl or geranyl moieties as in previous approaches.

An Untargeted Approach for Revealing Electrophilic Metabolites.

Reactive electrophilic intermediates such as coenzyme A esters play central roles in metabolism but are difficult to detect with conventional strategies. Here, we introduce hydroxylamine-based stable isotope labeling to convert reactive electrophilic intermediates into stable derivatives that are easily detectable via LC-MS. In the model system Caenorhabditis elegans, parallel treatment with 14NH2OH and 15NH2OH revealed >1000 labeled metabolites, e.g., derived from peptide, fatty acid, and ascaroside pheromone biosyntheses. Results from NH2OH treatment of a pheromone biosynthesis mutant, acox-1.1, suggested upregulation of thioesterase activity, which was confirmed by gene expression analysis. The upregulated thioesterase contributes to the biosynthesis of a specific subset of ascarosides, determining the balance of dispersal and attractive signals. These results demonstrate the utility of NH2OH labeling for investigating complex biosynthetic networks. Initial results with Aspergillus and human cell lines indicate applicability toward uncovering reactive metabolomes in diverse living systems.

Immunogenicity, safety and inter-lot consistency of a meningococcal conjugate vaccine (MenACYW-TT) in adolescents and adults: A Phase III randomized study.

BACKGROUND: MenACYW-TT is an investigational quadrivalent (serogroups A, C, W and Y) meningococcal conjugate vaccine that is being developed for protection against invasive meningococcal disease. METHODS: In this Phase 3, blinded, randomized study, 3344 meningococcal vaccine-naïve 10-55-year-olds were randomized (3:3:3:2) to receive one of three lots of MenACYW-TT or licensed quadrivalent meningococcal conjugate vaccine, MCV4-DT (NCT02842853). Antibody titers were assessed by human and rabbit complement serum bactericidal antibody assays. The co-primary objectives were to demonstrate lot-to-lot consistency of MenACYW-TT by the between-lot geometric mean titer ratios (GMTR) at Day 30, and non-inferiority of Day 30 vaccine seroresponses (titers ≥ 1:16 if pre-vaccination titers < 1:8, or ≥ 4-fold increase if pre-vaccination titers ≥ 1:8) with MenACYW-TT vs MCV4-DT. Further objectives included safety and immunogenicity. RESULTS: Lot consistency was demonstrated for all three lots, with GMTRs ranging from 0.87 to 1.1. The proportion of participants achieving seroresponse in the MenACYW-TT group (data pooled from the 3 lots) was non-inferior to MCV4-DT (A: 74% vs 55%; C: 89% vs 48%; W: 80% vs 61%; Y: 91% vs 73%, respectively). MenACYW-TT and MCV4-DT had similar safety profiles; no safety concerns were identified. CONCLUSIONS: The study met both co-primary endpoints, demonstrating lot-to-lot consistency and non-inferiority of MenACYW-TT vs MCV4-DT in adolescents and adults.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adults 56 years of age and older: a Phase II randomized study.

MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for the prevention of invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y in individuals aged 6 weeks and above. This Phase II, randomized, open-label, multicenter, exploratory study assessed the safety and immunogenicity of MenACYW-TT compared with a quadrivalent meningococcal polysaccharide vaccine (MPSV4) in 301 healthy adults aged ≥56 y in the US (NCT01732627). Participants were randomized 2:1 to receive MenACYW-TT or MPSV4. Serum bactericidal assays using human (hSBA) or baby rabbit (rSBA) complement were used to measure functional antibodies against meningococcal serogroups A, C, W, and Y at baseline and 30 d post-vaccination. Safety data were collected up to 30 d post-vaccination. Proportions of study participants with hSBA titers ≥1:8 against serogroups A, C, W, and Y were increased at Day 30 compared with baseline in both vaccine groups. The proportions of participants with hSBA titers ≥1:8 after MenACYW-TT vaccination were comparable to those after MPSV4 vaccination for serogroups A and C (A: 93.8% vs. 85.1%; C: 74.9% vs. 62.8%) and distinctly higher than after MPSV4 for serogroups W and Y (W: 79.5% vs. 60.6%; Y: 80.5% vs. 59.6%). Proportions of participants with rSBA titers ≥1:8 were comparable between vaccine groups for all four serogroups. The reactogenicity profiles of both vaccines were similar. Most unsolicited adverse events (AEs) were of Grade 1 or Grade 2 intensity, and no serious AEs were reported. The MenACYW-TT conjugate vaccine was well tolerated and immunogenic in adults aged ≥56 y.

Immunogenicity and safety of a booster dose of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adolescents and adults: a Phase III randomized study.

The quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) was assessed as a booster in this Phase III trial (NCT02752906). Quadrivalent meningococcal conjugate vaccine (MCV4)-primed individuals aged ≥15 y (n = 810) were randomized 1:1 to receive a single booster dose of MenACYW-TT (n = 403) or a licensed MCV4 (Menactra®; MCV4-DT [n = 407]). Serum bactericidal antibody assay with human complement (hSBA) was used to measure functional antibodies against serogroups A, C, W, and Y at baseline and Day 30 post-vaccination. Proportions of participants achieving seroresponse (post-vaccination titer ≥1:16 for those with baseline titer <1:8 or ≥4-fold increase in post-vaccination titer for those with baseline titer ≥1:8) were determined. Safety data were collected for 180 d post-vaccination. Non-inferiority of the immune response was demonstrated for MenACYW-TT compared with MCV4-DT based on the proportion of participants achieving hSBA vaccine seroresponse for each of the meningococcal serogroups at Day 30. Moreover, ≥99% of participants in both study groups had hSBA titers ≥1:8 for the four meningococcal serogroups at Day 30. Reactogenicity profiles were comparable between groups. These Phase III data in adolescents and adults show that MenACYW-TT boosts the immune response in those primed with MCV4 vaccines 4-10 y previously, irrespective of whether MCV4-DT or MCV4-CRM was used for priming.

A Phase II, randomized, immunogenicity and safety study of a quadrivalent meningococcal conjugate vaccine, MenACYW-TT, in healthy adolescents in the United States.

BACKGROUND: MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for use in individuals ≥6 weeks of age. We evaluated the safety and immunogenicity of MenACYW-TT when compared to a licensed quadrivalent conjugate meningococcal vaccine (Menveo®; MCV4-CRM; GlaxoSmithKline, Italy), and when co-administered with tetanus, diphtheria, acellular pertussis (Tdap) and human papilloma virus (HPV4) vaccines in healthy meningococcal vaccine-naïve adolescents (10-17 years old) in the United States of America. METHODS: In this pivotal Phase II, open-label, multicenter study, 1715 participants were randomized to receive MenACYW-TT, MCV4-CRM, MenACYW-TT co-administered with Tdap and HPV4, or Tdap and HPV4 vaccines alone (NCT02199691). The primary objective was to evaluate whether antibody responses to MenACYW-TT antigens were non-inferior to antibody responses after MCV4-CRM administration. Meningococcal antibody titers were determined using human complement serum bactericidal assay (hSBA) with titers measured at baseline, and 30 days post vaccination (D30). A vaccine seroresponse was defined as baseline titers <1:8 with post-vaccination titers ≥1:8 or baseline titers ≥1:8 with a ≥4-fold increase at post-vaccination. Safety data were collected up to six months post-vaccination. RESULTS: Non-inferiority was demonstrated for MenACYW-TT vs MCV4-CRM (primary endpoint), and for MenACYW-TT co-administered with Tdap and HPV4 vs MenACYW-TT alone (secondary endpoint). The vaccine seroresponse rate was higher with MenACYW-TT than with MCV4-CRM, for each serogroup: A: 75.6% vs 66.4%; C: 97.2% vs 72.6%; W: 86.2% vs 66.6%; Y: 97.0% vs 80.8%. The safety profiles of MenACYW-TT, MCV4-CRM, and Tdap and HPV4 vaccines, administered with or without MenACYW-TT, were comparable. There were no vaccine-related serious adverse events. CONCLUSIONS: The MenACYW-TT vaccine was well tolerated and generated an immune response that was non-inferior to the licensed MCV4-CRM vaccine. Immunogenicity and safety profiles were comparable when MenACYW-TT was administered with or without Tdap and HPV4 vaccines in meningococcal vaccine-naïve adolescents.

The superficial and deep inferior epigastric artery composite perforator flap for breast reconstruction: A case report.

The superficial inferior epigastric artery (SIEA) flap and the deep inferior epigastric perforator (DIEP) flap have been increasingly adopted for breast reconstruction; however, each have its own set of advantages and disadvantages. In the select subset of patients that cannot tolerate minimal abdominal fasciotomy that occurs with DIEP harvest and do not have adequate pedicle length that often occurs after SIEA harvest, we suggest another option for abdominally-based free flap breast reconstruction. Here, we describe the formation of a composite perforator based on the pedicle of the retro-rectus deep inferior epigastric vessels and the superficial inferior epigastric vessels, known as a superficial and deep inferior epigastric artery (SADIE) flap, which allows for a more compatible anastomotic size match than the SIEA and elongation of the vascular pedicle with minimal dissection of the anterior rectus fascia. Our patient is a 36 year-old female (BMI = 24) with a history of breast cancer who subsequently underwent skin-sparing mastectomy with tissue expander, chemotherapy, and eventual superior and deep inferior epigastric artery (SADIE) composite flap. The patient had an uncomplicated postoperative course at 6-month follow-up with excellent cosmesis. This modification in surgical technique has not been previously described in the literature and represents a suitable option for those desiring breast reconstruction, but have short pedicle length at harvest and cannot tolerate abdominal fasciotomy.

Intraoperative Techniques for the Plastic Surgeon to Improve Pain Control in Breast Surgery.

In recent years, there has been a growing emphasis placed on reducing length of hospital stay and health costs associated with breast surgery. Adequate pain control is an essential component of enhanced recovery after surgery. Postoperative pain management strategies include use of narcotic analgesia, non-narcotic analgesia, and local anesthetics. However, these forms of pain control have relatively brief durations of action and multiple-associated side effects. Intraoperative regional blocks have been effectively utilized in other areas of surgery but have been understudied in breast surgery. The aim of this article was to review various intraoperative techniques for regional anesthesia and local pain control in breast surgery and to highlight areas of future technique development.

External auditory canal stenting with nonlatex glove and Gelfoam.

External auditory canal stenosis, although uncommon, is a condition that is sometimes encountered by otolaryngologists. This condition has been shown to result from inflammatory changes that may be incited by many different causes. Various methods of stenting the canal open postoperatively have been described. We describe a readily accessible and inexpensive method of stenting the canal open postoperatively. The technique presented has been used effectively in all age groups at our institution, in cases ranging from trauma to postmastoidectomy procedures.