The Facial Artery Perforator Flap.

BACKGROUND: Reconstruction of facial melanoma defects can be challenging. Large defects of the midface, cheek, and nasolabial fold are often reconstructed using a cervicofacial flap which requires significant flap elevation and undermining. Surgeons are often hesitant to commit to such a large reconstruction without definitive pathologic evidence of negative margins. However, local perforator flaps may be used as an alternative to large flaps with less dissection and donor site morbidity and may also allow for more facile re-advancement in the event of a positive margin on final pathology. The goal of this study is to evaluate a perforator flap based on the facial artery to determine if it is a safe and cosmetically favorable option to immediately repair oncologic-related defects on the cheek and midface. METHODS: A retrospective review of all melanoma cases performed by the senior author between January 2016 and December 2021 was conducted. Patients who underwent reconstruction using a facial artery perforator flap were included. RESULTS: Sixteen patients were included in our cohort. The average age was 67.3 years and 53% (n=8) were female. Fourteen patients had the primary defect located on the cheek, 1 from the nasolabial fold, and 1 from the distal nasal sidewall. All patients received immediate reconstruction. Excisional margins ranged from 0.5 to 2 cm. Two patients had positive margins following pathology results with one undergoing treatment with imiquimod and the other opting for re-excision. No complications involving the defect or donor site were reported after an average follow-up time of 113.8 days. CONCLUSION: The facial artery perforator flap is a safe and cosmetically favorable option to immediately repair oncologic-related defects on the cheek and midface.

Sociodemographic Disparities in Access to Cleft Rhinoplasty.

Various sociodemographic factors affect patient access to care. This study aims to assess how factors such as government-funded insurance and socioeconomic status impact the ability of adolescents with cleft lip-associated nasal deformities to access secondary rhinoplasty procedures. Patients older than 13 years old with a history of cleft lip/palate were identified in the National Inpatient Sample database from 2010 to 2012. Those who received a secondary rhinoplasty were identified using the International Classification of Diseases, Ninth Revision (ICD-9) procedural codes. A multivariate logistic regression model with post hoc analyses was performed to analyze if insurance status, socioeconomic status, and hospital-level variables impacted the likelihood of undergoing rhinoplasty. Of the 874 patients with a cleft lip/palate history, 154 (17.6%) underwent a secondary rhinoplasty. After controlling for various patient-level and hospital-level variables, living in a higher income quartile (based on zip code of residence) was an independent predictor of receiving a secondary cleft rhinoplasty (odds ratio=1.946, P =0.024). Patients had lower odds of receiving a cleft rhinoplasty if care occurred in a private, nonprofit hospital compared with a government-owned hospital (odds ratio=0.506, P =0.030). Income status plays a significant role in cleft rhinoplasty access, with patients from lower income households less likely to receive a secondary cleft rhinoplasty. Hospital-specific factors such as geographic region, bed size, urbanization, and teaching status may also create barriers for patients and their families in accessing surgical care for cleft lip nasal deformities.

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.

Disparities in Access to Cranial Remodeling Orthosis for Deformational Plagiocephaly.

OBJECTIVE: Moderate to severe cases of deformational plagiocephaly (DP) may be treated with cranial remolding orthoses (CRO). This study investigated the socioeconomic disparities in access to care for CRO for DP correction. DESIGN: This was a retrospective review of medical records from a single CRO company in Connecticut from 2014 to 2020. METHODS: Demographic variables were collected from all patients. Univariable logistic regressions were used to identify differences for presenting age at consultation, whether CRO was pursued, and length of CRO treatment by insurance payor and household income quartile. RESULTS: Of the 5620 patients identified, 4100 (73.0%) received CRO, with 674 (12.0%) receiving a second helmet. Of those receiving CRO, 1536 (37.5%) had Medicaid insurance while 2558 (62.4%) were commercially insured. Patients on Medicaid were 1.30 times more likely to have delayed presentation (P = .017), while patients from the lowest income quartile were 1.26 1.50 (P < .001) and 1.58 (P < .001) times more likely to have a delayed presentation relative to those in the highest and second-highest income quartiles, respectively. Patients in the highest and second-highest income quartiles were also 1.55 (P < .001) and 1.45 (P < .001) more likely, respectively, to receive CRO after consultation than those from the lowest income quartile. CONCLUSIONS: Lower income and Medicaid-insured patients had delayed presentation for CRO consultation. Those from the lowest income quartile were more likely to never receive CRO than those from wealthier backgrounds. Low socioeconomic status and Medicaid insurance, which can have more restrictive coverage policies for CRO, may result in the delayed treatment of DP.

Oncolytic virus treatment differentially affects the CD56dim and CD56bright NK cell subsets in vivo and regulates a spectrum of human NK cell activity.

Natural killer (NK) cells protect against intracellular infection and cancer. These properties are exploited in oncolytic virus (OV) therapy, where antiviral responses enhance anti-tumour immunity. We have analysed the mechanism by which reovirus, an oncolytic dsRNA virus, modulates human NK cell activity. Reovirus activates NK cells in a type I interferon (IFN-I) dependent manner, inducing STAT1 and STAT4 signalling in both CD56dim and CD56bright NK cell subsets. Gene expression profiling revealed the dominance of IFN-I responses and identified induction of genes associated with NK cell cytotoxicity and cell cycle progression, with distinct responses in the CD56dim and CD56bright subsets. However, reovirus treatment inhibited IL-15 induced NK cell proliferation in an IFN-I dependent manner and was associated with reduced AKT signalling. In vivo, human CD56dim and CD56bright NK cells responded with similar kinetics to reovirus treatment, but CD56bright NK cells were transiently lost from the peripheral circulation at the peak of the IFN-I response, suggestive of their redistribution to secondary lymphoid tissue. Coupled with the direct, OV-mediated killing of tumour cells, the activation of both CD56dim and CD56bright NK cells by antiviral pathways induces a spectrum of activity that includes the NK cell-mediated killing of tumour cells and modulation of adaptive responses via the trafficking of IFN-γ expressing CD56bright NK cells to lymph nodes.

Disparities in Craniosynostosis Outcomes by Race and Insurance Status.

ABSTRACT: Disparities in access to care for surgical intervention in craniosynostosis have been suggested as a cause in discrepancies between the surgical approach and consequently perioperative outcomes following surgery. This work aimed to investigate the influence of race, insurance status, and the presence of craniosynostosis-related conditions on the short-term outcomes after the surgical management of craniosynostosis. Using the National Inpatient Sample database for the years 2010 to 2012, sociodemographic predictors for 30-day postoperative complication rates and requirements for blood transfusion in craniosynostosis surgeries were identified. Medicaid patients were significantly more likely to experience complications (P = 0.013) and higher rates of blood transfusions (P = 0.011). Compared to those without any complications, patients who experienced postoperative complications and blood transfusions were older (191.5 versus 181.7 days old, P < 0.001), had a greater number of chronic diseases (P < 0.001), and had a longer average length of stay (P < 0.001). On multivariable regression, Medicaid patients were 1.7 times more likely to experience any postoperative complication compared to privately insured patients. White patients also experienced a 0.741 times lower likelihood of requiring a blood transfusion. At the hospital level, receiving surgery at government-operated hospitals was found to be a protective factor for postoperative complications compared to for-profit private (P = 0.016) and nonprofit private (P = 0.028). Healthcare providers and policy makers should be cognizant of these sociodemographic disparities and their potential causes to ensure equitable treatment for all patients regardless of insurance status and racial/ethnic background.

The Opportunity Cost of Resident Involvement in Adult Craniofacial Surgery: An Analysis of Relative Value Units.

PURPOSE: Within the academic surgical setting resident involvement may confer longer operative times. The increasing pressures to maximize clinical productivity and decreasing reimbursement rates, however, may conflict with these principles. This study calculates the opportunity cost of resident involvement in craniofacial surgery. METHODS: Retrospective analysis was conducted with patients who underwent craniofacial procedures from the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2012. Patients were selected based on relevant Current Procedural Terminology codes for craniofacial pathologies (ie, trauma, head and neck reconstruction, orthognathic surgery, and facial reanimation). Variables included patient demographics, operative time, and presence or absence of resident trainee. Average relative value units were calculated to determine the opportunity cost of resident involvement for each craniofacial procedure. RESULTS: In total, 2096 patients were identified through the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2012. Resident involvement was associated with a statistically significant higher operative time (P < 0.001) for facial reanimation, facial trauma, orthognathic surgery, and head and neck reconstruction. The opportunity costs per case associated with resident involvement were the highest for head and neck reconstruction ($1468.04), followed by orthognathic surgery ($1247.03), facial trauma ($533.03), and facial reanimation ($358.32). Resident involvement was associated with higher rate of complications for head and neck reconstruction (P < 0.043). CONCLUSIONS: Resident involvement is associated with longer operative times, higher complications, and higher re-operations, compared to attending exclusive surgical care. Future studies may consider how reimbursements should align incentives to promote resident education and training.

A Preliminary Management Algorithm for Velopharyngeal Insufficiency in Cleft-Orthognathic Patients.

PURPOSE: Patients born with a cleft palate often suffer from velopharyngeal insufficiency (VPI) due to the soft palate musculature's abnormal structure. Surgical correction of the palate at a young age can hinder maxillary growth, requiring surgical correction of the maxillomandibular discrepancy at skeletal maturity. Orthognathic surgery can then cause or further exacerbate VPi in these patients. The purpose of this paper is to assess cleft-orthog-nathic patients under the lens of persistent or newly-developed VPi, to understand outcomes and generate a targeted management algorithm. METHODS: A retrospective study was performed inspecting cleft-orthognathic patients presenting to a single surgeon. Patients with sufficient follow-up were placed into predefined algorithmic cohorts by their VPi development pattern in relation to orthognathic surgery. They were further stratified into groups by level of adherence to our algorithm to evaluate VPi outcomes. Demographic factors, risk factors, and outcomes were compared between groups via Welch t test and Fisher exact test. RESULTS: Fifty-one patients were examined, including 16 with VPI. Velopharyngeal insufficiency fully resolved amongst all algorithmically adherent patients and remained in nonadherent patients ( P  < 0.001). CONCLUSIONS: Our targeted algorithm may improve symptoms and the management of VPI in cleft-orthognathic patients. Multi-centered studies with larger sample sizes and prospective studies are encouraged to validate our proposed treatment algorithm further.

Postoperative Edema Resolution Post-Orthognathic Triple Jaw Surgery: A Three-Dimensional Volumetric Analysis.

PURPOSE: The final result following orthognathic surgery may be hidden for months due to postoperative swelling. However, no substantial evidence supports this time estimate. Our study aims to three-dimensionally quantify volumetric changes in facial edema following triple-jaw surgery. MATERIALS AND METHODS: This was a retrospective, three-dimensional (3D) study of patients who underwent primary orthognathic triple jaw surgery (Le Fort I, Bilateral Sagittal Split Osteotomy (BSSO), and osseous genioplasty) by the senior author (DMS). Vectra 3D Software (Canfield, Fairfield, NJ) was used to assess and quantify volumetric changes between serial 3D photos. An inverse line of best-fit was plotted to assess reduction in postoperative facial edema. The effects of gender, age, body mass index, and tranexamic acid administration on swelling resolution were analyzed through mixed linear model analysis. RESULTS: A total of 46 patients (198 images) met the study criteria. The equation for the inverse function line of best fit was y = -13.14ln (x) + 39.54 (P < 0.01). On average, 60% of the swelling resolved in 1 month, 84% after 6 months, and nearly 93% after 12 months. There were no significant differences in the rate of swelling resolution when accounting for age, gender, body mass index, or tranexamic acid administration. CONCLUSIONS: Most facial edema resolved during the first month following triple jaw surgery, with significant reduction in swelling between 6 and 12 months postoperatively. After 1 year, approximately 10% of the initial edema remained.

Which Maturation Indicator is Most Accurate in Predicting Cessation of Facial Growth? A Systematic Review of the Literature.

PURPOSE: The determination of facial growth maturity is crucial before surgical intervention in pediatric patients. To the author's knowledge, there are several indicators of skeletal maturity, but there remains a lack of consensus regarding their application when determining surgical timing. The purpose of this study was to determine the most accurate skeletal maturity indicator in predicting facial growth maturation. MATERIALS AND METHODS: A systematic review was done to determine the most predictive indicator for facial growth maturity. We hypothesized that menses' onset was the most predictive of these maturity indicators. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic search of MEDLINE, Cochrane, Embase, Scopus databases, and Google Scholar, was done in October 2020 to identify citations related to maturity indicators assessing craniofacial growth. The quality of evidence was determined using the Joanna Briggs Institute Critical Appraisal Checklist for Cohort Studies. RESULTS: Of the 13,289 articles screened, 1 retrospective and 1 prospective study met inclusion criteria. No articles were identified that provided evidence for our hypothesis. Based on the 2 included studies, it was concluded that a handwrist x-ray was more predictive of facial growth cessation (compared to other skeletal maturity indicators). CONCLUSIONS: Based on the literature, handwrist radiography serves as the most predictive method in determining the facial growth maturity. The paucity of articles within this investigation highlights the need for greater research efforts to investigate the predictability of indicators to evaluate facial growth maturation. PROSPERO REGISTRATION NUMBER: CRD42020207388.

Non-Surgical Correction of Congenital Ear Anomalies: A Critical Assessment of Caretaker Burdens and Aesthetic Outcomes.

INTRODUCTION: Congenital ear anomalies result from cartilage and skin compression in utero. They can be corrected in infancy before the cartilage hardens and loses its malleability. Caretaker burden of ear molding and its impact on esthetic outcomes has not been studied. METHODS: Demographic and procedural variables were retrospectively collected for infants who underwent ear molding. Parents were surveyed regarding their experience, caretaker burden, and esthetic outcome. Outside physicians were provided with pre- and post-treatment photographs and asked to rate outcomes. A Likert scale was developed for responses and converted to a numeric score from 1 to 5 with 5 as the most desirable. RESULTS: Seventy-four patients comprising 121 ears were included. Mean age at treatment was 20.1 ± 21.4 days with treatment duration of 21.1 ± 7.7 days. Parental participation in the survey was 70.1%. Questions that queried parents' experiences revealed a "very positive" experience with minor burden related to bathing and cleaning (Mean Likert Score 4.1, Range 1-5). Favorable parent-reported outcomes were obtained regarding anticipated social distress (4.28, 1-5), satisfaction with results (4.27, 1-5), and perception of final appearance (4.18, 1-5). Physician assessments of esthetic outcomes were slightly lower, but favorable between "somewhat effective" and "very effective" (3.46, 1-5). Earlier treatment trended favorably, but did not reach significance. Ear malformations had higher parent-reported satisfaction than ear deformations (4.75 ± 0.46 vs 4.21 ± 1.25, p = 0.025). CONCLUSION: Despite the additional obligation for new parents, infant ear molding is rated low in terms of caretaker burden. Esthetic outcomes are excellent as assessed by parents and physicians. However, caretakers reported higher esthetic outcomes than physician evaluations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Characteristics and physiological basis of falls in ventricular outputs after immediate cord clamping at delivery in preterm fetal lambs.

KEY POINTS: Controversy exists about the physiological mechanism(s) underlying decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, the four major determinants of ventricular output (afterload, preload, heart rate and contractility) were measured concurrently in fetal lambs at 15 s intervals over a 2 min period after cord clamping and before ventilation following delivery. After cord clamping, right (but not left) ventricular output fell by 20% in the initial 30 s, due to increased afterload associated with higher arterial blood pressures, but both outputs then halved over 45 s, due to a falling heart rate and deteriorating ventricular contractility accompanying rapid declines in arterial oxygenation to asphyxial levels. Ventricular outputs subsequently plateaued from 75 to 120 s, associated with rebound rises in ventricular contractility accompanying asphyxia-induced surges in circulating catecholamines. These findings provide a physiological basis for the clinical recommendation that effective ventilation should occur within 60 s after immediate cord clamping. ABSTRACT: Controversy exists about the physiological mechanism(s) underlying large decreases in cardiac output after immediate clamping of the umbilical cord at birth. To define these mechanisms, anaesthetized preterm fetal lambs (127(1)d, n = 12) were instrumented with flow probes and catheters in major central arteries, and a left ventricular (LV) micromanometer-conductance catheter. Following immediate cord clamping at delivery, haemodynamics, LV and right ventricular (RV) outputs, and LV contractility were measured at 15 s intervals during a 2 min non-ventilatory period, with aortic blood gases and circulating catecholamine (noradrenaline and adrenaline) concentrations measured at 30 s intervals. After cord clamping, (1) RV (but not LV) output fell by 20% in the initial 30 s, due to a reduced stroke volume associated with increased arterial blood pressures, (2) both outputs then halved over the next 45 s, associated with falls in heart rate, arterial blood pressures and ventricular contractility accompanying a rapid decline in arterial oxygenation to asphyxial levels, (3) reduced outputs subsequently plateaued from 75 to 120 s, associated with rebound rises in blood pressures and ventricular contractility accompanying exponential surges in circulating catecholamines. These findings are consistent with a time-dependent decline of ventricular outputs after immediate cord clamping, which comprised (1) an initial, minor fall in RV output related to altered loading conditions, (2) ensuing large decreases in both LV and RV outputs related to the combination of bradycardia and ventricular dysfunction during emergence of an asphyxial state, and (3) subsequent stabilization of reduced LV and RV outputs during ongoing asphyxia, supported by cardiovascular stimulatory effects of marked sympathoadrenal activation.

Deficiency of Prebiotic Fiber and Insufficient Signaling Through Gut Metabolite-Sensing Receptors Leads to Cardiovascular Disease.

BACKGROUND: High blood pressure (BP) continues to be a major, poorly controlled but modifiable risk factor for cardiovascular death. Among key Western lifestyle factors, a diet poor in fiber is associated with prevalence of high BP. The impact of lack of prebiotic fiber and the associated mechanisms that lead to higher BP are unknown. Here we show that lack of prebiotic dietary fiber leads to the development of a hypertensinogenic gut microbiota, hypertension and its complications, and demonstrate a role for G-protein coupled-receptors (GPCRs) that sense gut metabolites. METHODS: One hundred seventy-nine mice including C57BL/6J, gnotobiotic C57BL/6J, and knockout strains for GPR41, GPR43, GPR109A, and GPR43/109A were included. C57BL/6J mice were implanted with minipumps containing saline or a slow-pressor dose of angiotensin II (0.25 mg·kg-1·d-1). Mice were fed diets lacking prebiotic fiber with or without addition of gut metabolites called short-chain fatty acids ([SCFA)] produced during fermentation of prebiotic fiber in the large intestine), or high prebiotic fiber diets. Cardiac histology and function, BP, sodium and potassium excretion, gut microbiome, flow cytometry, catecholamines and methylation-wide changes were determined. RESULTS: Lack of prebiotic fiber predisposed mice to hypertension in the presence of a mild hypertensive stimulus, with resultant pathological cardiac remodeling. Transfer of a hypertensinogenic microbiota to gnotobiotic mice recapitulated the prebiotic-deprived hypertensive phenotype, including cardiac manifestations. Reintroduction of SCFAs to fiber-depleted mice had protective effects on the development of hypertension, cardiac hypertrophy, and fibrosis. The cardioprotective effect of SCFAs were mediated via the cognate SCFA receptors GPR43/GPR109A, and modulated L-3,4-dihydroxyphenylalanine levels and the abundance of T regulatory cells regulated by DNA methylation. CONCLUSIONS: The detrimental effects of low fiber Westernized diets may underlie hypertension, through deficient SCFA production and GPR43/109A signaling. Maintaining a healthy, SCFA-producing microbiota is important for cardiovascular health.

The 3D reconstructed skin micronucleus assay: considerations for optimal protocol design.

Implementation of the seventh amendment to the EU Cosmetics Directive has driven much research into suitable in vitro alternative assays to support satisfactory risk assessments. One such assay is the reconstructed skin micronucleus (RSMN) assay. First reported in 2006, further development occurred and a standard protocol was published in 2011. To evaluate and optimise the assay at Covance Laboratories, we tested nine chemicals [4-nitrophenol (4-NP), cyclohexanone (CH), 2-ethyl-1,3-hexanediol (2-EHD), methyl methansulfonate (MMS), mitomycin C (MMC), ethyl nitrosourea (ENU), benzo[a]pyrene (BaP), cyclophosphamide (CPA) and vinblastine (VIN)] using the EpiDerm™ 3D skin model (MatTek Corporation®, IVLSL, Bratislava, Slovakia) and compared the data using the standard 48-h treatment regimen and also an emerging 72-h treatment protocol. The EpiDerm™ tissue has reportedly some metabolic capacity but data using 48-h treatments has provided mixed results. Our investigations demonstrate that the two chemicals requiring metabolic activation (BaP and CPA) were negative following the 48-h protocol but were clearly positive following 72-h treatment. Furthermore, Replication Index (RI) data showed higher RI values in vehicle control treatments (indicating increased cell division) across the treatment set following 72-h treatments. A general greater magnitude of micronucleus (MN) induction was also observed following test chemical treatment. These data suggest that the 72-h treatment protocol is more suitable as a standard approach for the detection of clastogenic, aneugenic and metabolically activated chemicals in the RSMN assay. For further assay optimisation, we compare the statistical power of scoring cells from duplicate or triplicate cultures per treatment concentration and provide recommendations.

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.

The Pregnancy and EARly Life study (PEARL) - a longitudinal study to understand how gut microbes contribute to maintaining health during pregnancy and early life.

BACKGROUND: The early life period represents the first step in establishing a beneficial microbial ecosystem, which in turn affects both short and longer-term health. Changes during pregnancy influence the neonatal microbiome; through transmission of maternal microbes during childbirth, and beyond, through nutritional programming. However, in-depth exploration of longitudinal maternal-infant cohorts, with sampling of multiple body sites, complemented by clinical and nutritional metadata, and use of cutting-edge experimental systems are limited. The PEARL study will increase our knowledge of; how microbes (including viruses/phages, bacteria, fungi and archaea) change in composition and functional capacity during pregnancy; transmission pathways from mother to infant; the impact of various factors on microbial communities across pregnancy and early life (e.g. diet), and how these microbes interact with other microbes and modulate host processes, including links to disease onset. METHODS: PEARL is a longitudinal observational prospective study of 250 pregnant women and their newborns, with stool and blood samples, questionnaires and routine clinical data collected during pregnancy, labour, birth and up to 24 months post birth. Metagenomic sequencing of samples will be used to define microbiome profiles, and allow for genus, species and strain-level taxonomic identification and corresponding functional analysis. A subset of samples will be analysed for host (immune/metabolite) molecules to identify factors that alter the host gut environment. Culturing will be used to identify new strains of health-promoting bacteria, and potential pathogens. Various in vitro and in vivo experiments will probe underlying mechanisms governing microbe-microbe and microbe-host interactions. DISCUSSION: Longitudinal studies, like PEARL, are critical if we are to define biomarkers, determine mechanisms underlying microbiome profiles in health and disease, and develop new diet- and microbe-based therapies to be tested in future studies and clinical trials. TRIAL REGISTRATION: This study is registered in the ClinicalTrials.gov Database with ID: NCT03916874 .

Balancing need and risk, supply and demand: Developing a tool to prioritize naloxone distribution.

Background: Opioid overdose deaths continue to rise nationally. The demand for naloxone, the opioid overdose antidote, is outpacing the supply. With increasing naloxone requests, tools to prioritize distribution are critical to ensure available supplies will reach those at highest risk of overdose. Methods: We developed a standardized "Naloxone Request Form" (NRF) and corresponding weighted prioritization algorithm to serve as decisional aid to better enable grant staff to prioritize naloxone distribution in a data-driven manner. The algorithm computed raw priority scores for each agency, which were then separated into the predetermined quintiles. Historical naloxone distribution decisions were compared with agencies' prioritization quintile. Results: Results demonstrated that the NRF and corresponding algorithm was successful at prioritizing agencies based on potential impact. Although, overall, naloxone was distributed more heavily to the agencies deemed highest priority, our algorithm identified significant shortcomings of the "first come, first served" method of distribution we had initially deployed. Conclusions: This work has laid the foundation to use this tool prospectively to allow for data-driven decision-making for naloxone distribution. Our tool is flexible and can be customized to best fit the needs of a variety of programs and locations to ensure the distribution of limited supplies of naloxone have the greatest impact.

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.

Facial Dysmorphology in Saethre-Chotzen Syndrome.

PURPOSE: Classic features of Saethre-Chotzen syndrome (SCS) described in the literature include a prominent nasal bridge, eyelid ptosis, telorbitism, maxillary hypoplasia, and mandibular prognathism. The purpose of this study was to evaluate objectively the bony features of SCS. METHODS: Preoperative computer tomography scans of 15 SCS patients, 23 normal controls, 13 bicoronal nonsyndromic, and 7 unicoronal nonsyndromic craniosynostosis patients were included for analysis. Unaffected controls and nonsyndromic patients were age- and sex-matched to SCS patients. Morphometric cephalometrics were analyzed using three-dimensional computer tomography reconstructions. Mann-Whitney U were used to compare facial measurements between SCS and normal and nonsyndromic craniosynostosis controls. RESULTS: Telorbitism was present in bicoronal SCS patients only (P = 0.04) but absent in the unicoronal and bicoronal/metopic cohorts. The angle of the nasal bone relative to the sella was not different between SCS and controls (P = 0.536), although the angle of the nasal bone relative to the forehead was decreased in SCS by 15.5° (P < 0.001). Saethre-Chotzen syndrome had a 2.6° maxillary retrusion relative to controls (P = 0.03). In addition, SCS patients aged 4 to 7 months had a wider (39.34 versus 35.04, P = 0.017) and anteroposteriorly foreshortened (32.12 versus 35.06, P = 0.039) maxilla. There was no difference in mandibular prognathism among SCS patients as measured by the sella-nasion-B point angle compared to controls (P = 0.705). CONCLUSIONS: Despite classic descriptions, on morphometric analysis SCS patients did not demonstrate consistency across all suture subtypes in terms of telorbitism, a broad nasal bridge, or mandibular prognathism. Rather, SCS subtypes of SCS based on suture pathology more closely resemble nonsyndromic patients.

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.