Ten Year Follow-up After Face Transplantation - a Single Center Retrospective Cohort Study.

Face transplantation has emerged as reconstructive option for the most challenging facial deformities. A comprehensive analysis of functional outcomes, medical complications, incidence of malignancy, and chronic rejection in face transplantation recipients over an extended follow-up period has not yet been published leaving a notable gap in the literature. We retrospectively collected data of morbidity, rejection, vasculopathy, metabolic side effects, as well as functional outcome of sensory return, facial motor function, and speech from nine patients who underwent face transplantation at Brigham and Women´s Hospital (Boston, USA) between 2009 - 2020. The median follow-up was 120 months (54 - 154 months). Four grafts (40%) developed signs of clinical and histopathological chronic rejection without evidence of vasculopathy on computer tomography angiograms. Sensory return assessed with WEST-Monofilament showed an increase in six patients (66.7%) and facial expression analysis showed improvement throughout the whole cohort at their most recent follow up. Speech intelligibility was stable or increasing for five patients (55.6%). In conclusion, the long-term outcomes reveal promising results in terms of overall graft retention, and functional recovery. Metabolic, malignant, and infectious complications, as well as graft rejection episodes are expected to occur in this population, and some may be related to patient's age and lifestyle.

Sports participation after craniosynostosis repair: the critical role of post-operative guidance in parental decision-making.

PURPOSE: Despite previous research supporting patient safety in sports after craniosynostosis surgery, parental anxiety remains high. This study sought to evaluate the role of healthcare providers in guiding patients and families through the decision-making process. METHODS: Parents of children with repaired craniosynostosis were asked to assess sports involvement and parental decision-making in children ages 6 and older. Questions were framed primarily on 5-point Likert scales. Sport categorizations were made in accordance with the American Academy of Pediatrics. Chi-squared, linear regression, and Pearson correlation tests were used to analyze associations between the questions. RESULTS: Forty-three complete parental responses were recorded. Mean ages at surgery and time of sports entry were 7.93 ± 4.73 months and 4.76 ± 2.14 years, respectively. Eighty-two percent of patients participated in a contact sport. Discussions with the primary surgeon were more impactful on parental decisions about sports participation than those with other healthcare providers (4.04 ± 1.20 vs. 2.69 ± 1.32). Furthermore, children whose parents consulted with the primary surgeon began participating in sports at a younger age (4.0 ± 1.0 vs. 5.8 ± 2.7 years, p = 0.034). The mean comfort level with contact sports (2.8 ± 1.4) was lower than that with limited-contact (3.8 ± 1.1, p = 0.0001) or non-contact (4.4 ± 1.3, p < 0.0001) sports. CONCLUSION: This study underscores the critical role that healthcare professionals, primarily surgeons, have in guiding families through the decision-making process regarding their children's participation in contact sports.

Update on long-term mental health outcomes in eight face transplant recipients from a single center.

OBJECTIVE: Face transplantation is a groundbreaking and complex surgical intervention offering profound physical and psychological benefits to patients with severe facial disfigurements. This report provides an update on the long-term psychosocial outcome of eight face transplant recipients. METHOD: All transplant recipients were initially transplanted at Brigham and Women´s Hospital (Boston, USA) between 2011 and 2020 and seen as outpatient patients at Yale New Haven Hospital (New Haven, USA). A mixed-methods approach was used to assess the psychological and social well-being of these patients. The Short-Form 12, Brief-COPE, EQ-VAS and CES-D were administered between October 2022 and October 2023. RESULTS: Older age of face transplant recipients was significantly and positively associated with better mental health and increased use of both emotional and instrumental support (Brief-COPE). The initial enhancement in patients' self-reported quality of life, as assessed by the EQVAS, declined on the EQ-VAS score at the last follow-up. Similarly, an increase in depression score was observed (CES-D score) up through the last follow-up assessment. Both of the latter results, however, did not reach statistical significance. CONCLUSIONS: These results underscore the importance of ongoing psychological support throughout the long-term journey of recovery for face transplant recipients. These findings emphasize the need for a comprehensive, patient-centered approach that also addresses the complex psychological dimensions and contributes to our understanding of the mental health dynamics involved in face transplantation, stressing the need for guidelines and continued research in this evolving field.

Surgical Management of Breast Capsular Contracture-A Multi-institutional Data Analysis of Risk Factors for Early Complications.

BACKGROUND: Capsular contracture (CC) is a common complication following implant-based breast surgery, often requiring surgical intervention. Yet, little is known about risk factors and outcomes following CC surgery. METHODS: We reviewed the American College of Surgeons National Surgical Quality Improvement Program database (2008-2021) to identify female patients diagnosed with CC and treated surgically. Outcomes of interest included the incidence of surgical and medical complications at 30-days, reoperations, and readmissions. Confounder-adjusted multivariable analyses were performed to establish risk factors. RESULTS: 5,057 patients with CC were identified (mean age: 55 ± 12 years and mean body mass index [BMI]: 26 ± 6 kg/m2). While 2,841 (65%) women underwent capsulectomy, capsulotomy was performed in 742 patients (15%). Implant removal and replacement were recorded in 1,160 (23%) and 315 (6.2%) cases, respectively. 319 (6.3%) patients experienced postoperative complications, with 155 (3.1%) reoperations and 99 (2.0%) readmissions. While surgical adverse events were recorded in 139 (2.7%) cases, 86 (1.7%) medical complications occurred during the 30 day follow-up. In multivariate analyses, increased BMI (OR: 1.04; p = 0.009), preoperative diagnosis of hypertension (OR: 1.48; p = 0.004), and inpatient setting (OR: 4.15; p < 0.001) were identified as risk factors of complication occurrence. CONCLUSION: Based on 14 years of multi-institutional data, we calculated a net 30 day complication rate of 6.3% after the surgical treatment of CC. We identified higher BMI, hypertension, and inpatient setting as independent risk factors of postoperative complications. Plastic surgeons may wish to integrate these findings into their perioperative workflows, thus optimizing patient counseling and determining candidates' eligibility for CC surgery. LEVEL OF EVIDENCE III: 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 .

Using the SCAR-Q to Evaluate Morbidity of Scars in Craniosynostosis Repair.

OBJECTIVE: While previous literature has investigated the psychosocial impact and aesthetic satisfaction associated with post-operative scarring for certain pediatric craniofacial conditions, the impact of the scar burden resulting from craniosynostosis surgery has not been adequately studied. PARTICIPANTS: SCAR-Q was shared with patients ages 8 and older. Thirty-two complete patient responses were recorded. INTERVENTIONS: SCAR-Q is a PROM that consists of three independent scales - appearance, symptoms, and psychosocial impact - associated with a scar. MAIN OUTCOME MEASURES: Mann-Whitney U, linear regression, and Pearson correlation tests were used to evaluate associations between the scales, in addition to patient characteristics such as sex and suture involvement. RESULTS: Mean ages at time of surgery and survey completion were 9.65 ± 10.10 months and 12.10 ± 3.92 years, respectively. Mean scale scores were 81.5 ± 17.9 for appearance, 86.8 ± 12.4 for symptoms, and 79.3 ± 25.7 for psychosocial impact. Higher patient dissatisfaction with scar appearance correlated with more scar-related symptoms (r = 0.389; p = 0.028) and a greater psychosocial impact (r = 0.725; p < 0.001). SCAR-Q scales did not significantly correlate with age at surgery, age at survey completion, type of synostosis, or type of surgery; however, female patients reported lower mean appearance (65.4 vs. 86.0; p = 0.012) and psychosocial impact (57.3 vs. 85.5; p = 0.010) scores when compared to their male counterparts. CONCLUSIONS: It is vital that surgeons discuss patients' aesthetic satisfaction following craniosynostosis surgery in order to appropriately address and limit deleterious, long-term physical and psychosocial outcomes.

National Trends in Microtia Repair Cost and Hospital Length of Stay.

Microtia can have deleterious impacts on the functional, psychological, and aesthetic outcomes of affected young children. Reconstructive procedures can alleviate these negative outcomes and significantly improve the quality of life for patients; however, the cost and length of hospital stay (LOS) for such procedures and the factors that impact them have not been well-characterized. This study seeks to understand the hospital-level (institution type, size, and geographic region) and patient-level factors (race, age, and insurance status) that impact cost and LOS in patients who undergo microtia reconstructive surgery. A retrospective data analysis was conducted utilizing the National Inpatient Sample (NIS) database for the years 2008 to 2015. Inclusion criteria included patients who had an International Classification of Diseases, Ninth Revision (ICD-9) diagnostic code for microtia (744.23) as well as a procedure for microtia correction (186×/187×). A total of 714 microtia repair cases met the inclusion criteria and were sampled from the NIS database. Microtia repair cost was significantly increased on the West Coast compared with the Northeast ($34,947 versus $29,222, P =0.020), increased with patient age ($614/y, P =0.012), and gradually increased from 2008 to 2015 ($25,897-$48,985, P <0.001). Microtia LOS was significantly increased with government-controlled hospitals compared with private hospitals (1.93 versus 1.39 d, P =0.005), increased with patients on Medicaid compared with private insurance (2.33 versus 2.00 d, P =0.036), and overall decreased with patient age (-0.07 d/y, P =0.001). The results not only identify the multifactorial impacts that drive cost and LOS in microtia repair but provide insights into the financial and medical considerations patients and their families must navigate.

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.

Passive Immunotherapies for Central Nervous System Disorders: Current Delivery Challenges and New Approaches.

Passive immunotherapy, i.e., the administration of exogenous antibodies that recognize a specific target antigen, has gained significant momentum as a potential treatment strategy for several central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain cancer, among others. Advances in antibody engineering to create therapeutic antibody fragments or antibody conjugates have introduced new strategies that may also be applied to treat CNS disorders. However, drug delivery to the CNS for antibodies and other macromolecules has thus far proven challenging, due in large part to the blood-brain barrier and blood-cerebrospinal fluid barriers that greatly restrict transport of peripherally administered molecules from the systemic circulation into the CNS. Here, we summarize the various passive immunotherapy approaches under study for the treatment of CNS disorders, with a primary focus on disease-specific and target site-specific challenges to drug delivery and new, cutting edge methods.

Immunosuppressive strategies in face and hand transplantation: a comprehensive systematic review of current therapy regimens and outcomes.

Background: Recipients of Vascularized Composite Allotransplants require effective immunosuppressive therapy to prevent graft rejection. This systematic review summarizes the current body of literature on immunosuppressive regimens used in face and hand transplants while summarizing their outcome in terms of rejection, renal failure, and infections. Methods: A systematic search of electronic databases was conducted to identify relevant studies from 1998 until July 1st, 2023. We included all studies that discussed immunosuppressive strategies in face and hand transplant recipients according to PRISMA. Results: The standard triple maintenance therapy was mostly adjusted due to nephrotoxicity or high incidence of rejection. The most common alternative treatments utilized were sirolimus (25/91; 27.5%) or everolimus (9/91; 9.9%) following hand- and photophoresis (7/45; 15.6%), sirolimus (5/45; 11.1%) or belatacept (1/45; 2.2%) following face transplantation. Episodes of rejection were reported in 60 (65.9%) of hand- and 33 (73%) of face transplant patients respectively. Graft loss of 12 (13.2%) hand and 4 (8.9%) face transplants was reported. Clinical CMV infection was observed in 6 (6.6%) hand and 7 (15.5%) face transplant recipients. Conclusions: Based on the herein presented data, facial grafts exhibited a heightened incidence of rejection episodes and CMV infections. Facial mucosa adds complexity to the immunological graft composition highlighting the need of individualized immunosuppressive regimens and further research.

A Nationwide Analysis on Major Upper Extremity Amputations and Replantations.

BACKGROUND: The loss of an upper extremity is a severely disabling condition made medically challenging by the limited window for replantation. This study aims to investigate the burden of traumatic major upper extremity amputations in the United States and uncover possibilities for improvements in treatment. METHODS: The Healthcare Cost and Utilization Project's National Inpatient Sample was screened for International Classification of Diseases-9/10 diagnosis/procedure codes for traumatic and nontraumatic major upper extremity amputations and replantations within the years 2008 to 2017. The resulting pool of cases was analyzed for multiple variables, including level of injury, patient demographics, hospital type and location, length of stay, costs, comorbidities, and complications. RESULTS: A total of 15 155 major upper extremity amputations were recorded, of which 15.20% (n = 2305) were traumatic amputations-almost half of them related to the upper arm (49.6%; P = .0002). The great majority of replantations, however, was conducted at the lower arm level (87.4%; P < .0001), with an overall replantation rate of 22.3%. Nontraumatic amputations were overall associated with significantly higher burden of comorbidities relative to traumatic amputations except for long-term alcohol use (P < .0001). Both, amputations and replantations, were predominantly treated in large urban teaching hospitals, and were significantly more likely to occur in white men. The Southern region of the United States was handling the highest proportion of amputations in the United States, but had the lowest likelihood of replantation. CONCLUSION: This study provides an overview of the national trends in major traumatic upper extremity amputations and replantations, revealing potential health care shortcomings.

Understanding Epidemiological Trends in Geriatric Burn Injuries: A National Multicenter Analysis from NEISS 2004-2022.

Burn injuries pose a significant source of patient morbidity/mortality and reconstructive challenges for burn surgeons, especially in vulnerable populations such as geriatric patients. Our study aims to provide new insights into burn epidemiology by analyzing the largest national, multicenter sample of geriatric patients to date. Utilizing the National Electronic Injury and Surveillance System (NEISS) database (2004-2022), individuals with a "Burn" diagnosis were extracted and divided into two comparison age groups of 18-64 and 65+. Variables including sex, race, affected body part, incident location, burn etiology, and clinical outcomes were assessed between the two groups utilizing two proportion z-tests. 60,581 adult patients who sustained burns were identified from the NEISS database with 6,630 of those patients categorized as geriatric (65+). Geriatric patients had a significantly greater frequency of scald burns (36.9% vs. 35.4%; p<0.01), and third degree/full-thickness burns (10.4% vs 5.5%, p<0.01) relative to non-geriatric adult patients with most of these burns occurring at home (75.9% vs 67.4%; p<0.01). The top five burn sites for geriatric patients were the hand, face, foot, lower arm, and lower leg and the top five burn injury sources were hot water, cookware, oven/ranges, home fires, and gasoline. Geriatric patients had over two times greater risk of hospital admission (OR: 2.32, 95% CI: 2.17-2.49, p<0.01) and over five times greater risk of ED mortality (OR: 6.22, 95% CI: 4.00-9.66, p<0.01) after incurring burn injuries. These results highlight the need for stronger awareness of preventative measures for geriatric burn injuries.

From standard therapies to monoclonal antibodies and immune checkpoint inhibitors - an update for reconstructive surgeons on common oncological cases.

Malignancies represent a persisting worldwide health burden. Tumor treatment is commonly based on surgical and/or non-surgical therapies. In the recent decade, novel non-surgical treatment strategies involving monoclonal antibodies (mAB) and immune checkpoint inhibitors (ICI) have been successfully incorporated into standard treatment algorithms. Such emerging therapy concepts have demonstrated improved complete remission rates and prolonged progression-free survival compared to conventional chemotherapies. However, the in-toto surgical tumor resection followed by reconstructive surgery oftentimes remains the only curative therapy. Breast cancer (BC), skin cancer (SC), head and neck cancer (HNC), and sarcoma amongst other cancer entities commonly require reconstructive surgery to restore form, aesthetics, and functionality. Understanding the basic principles, strengths, and limitations of mAB and ICI as (neo-) adjuvant therapies and treatment alternatives for resectable or unresectable tumors is paramount for optimized surgical therapy planning. Yet, there is a scarcity of studies that condense the current body of literature on mAB and ICI for BC, SC, HNC, and sarcoma. This knowledge gap may result in suboptimal treatment planning, ultimately impairing patient outcomes. Herein, we aim to summarize the current translational endeavors focusing on mAB and ICI. This line of research may serve as an evidence-based fundament to guide targeted therapy and optimize interdisciplinary anti-cancer strategies.

The role of C4d and donor specific antibodies in face and hand transplantation-a systematic review.

To date, little is known about the mechanisms of rejection in vascularized composite allotransplantation, particularly for antibody mediated rejection. Additionally, no clear guidelines exist for the diagnosis and management of antibody-mediated rejection in vascularized composite allotransplantation. A systematic review of electronic databases (Embase and PubMed) was conducted to evaluate the relationship of donor specific antibodies and C4d deposition in correlation with cellular rejection following hand and face transplantation reported by centers between 1998 and July 2023. We extracted data on serum donor specific antibodies at the time of biopsy proven rejection according to Banff classification and C4d staining of target tissues. Mann-Whitney U tests were performed to compare rejection grade between groups divided by status of C4d deposition and serum donor specific antibodies, and Fisher's Exact test was used to assess association between the two markers. This review adhered to PRISMA guidelines. A total of 26 patients (5 face, 21 hand) were identified and data on 90 acute rejection episodes with information on Banff grade, donor specific antibody status, and C4d deposition were available. Donor specific antibodies were found to be associated with higher rejection grade (p = 0.005). C4d was not found to be associated with higher rejection grade (p = 0.33). Finally, no significant association was found between concurrent status of the two markers (p = 0.23). These findings suggest that the presence of donor specifc antibodies may be associated with higher grades of acute cellular rejection following hand and face transplantation. More consistent reporting on rejection episodes is needed in order to better understand antibody-mediated rejection in vascularized composite allotransplantation.

Risk of ADHD, Autism Spectrum Disorder, and Executive Function Impairment in Metopic Craniosynostosis.

INTRODUCTION: Favorable behavioral interactions are critical for academic and interpersonal success. An association between metopic synostosis and behavioral impairments has not been fully elucidated. Behavioral dysfunction in school age children with surgically corrected metopic synostosis was evaluated using targeted testing to detect the most common behavioral abnormalities in this population. METHODS: Parents of children 6-18 years old with metopic synostosis completed the Conners Short 3 rd edition (Conners-3: ADHD), Social Responsiveness Scale 2 nd edition (SRS-2: autism spectrum disorder), Behavior Rating Inventory of Executive Function 2 nd edition (BRIEF-2: executive functioning), and Child's Behavioral Checklist (CBCL: behavioral/emotional functioning). Children also completed neurocognitive testing. Multivariable regression was used to determine predictors of clinically significant behavioral impairments. RESULTS: 60 children were enrolled. Average age at surgery was 9.2 ± 7.9 months, with an average age at assessment of 10.3 ± 3.5 years. Nearly half of patients demonstrated symptoms associated with ADHD, demonstrated by reaching or exceeding borderline clinical levels for inattention and hyperactivity subscales of the Conners-3. Greater age at surgery was associated with worse executive function, measured by reaching or exceeding clinically significant levels of the executive function subscale of the Conners-3 (p=0.04) and subscales of the BRIEF-2 (behavioral regulator index [p=0.05], cognitive regulatory index [p=0.03], and global executive composite [p=0.04]). CONCLUSIONS: Nearly half of patients with surgically corrected metopic synostosis reached borderline clinical scores for inattention and hyperactivity. Greater age at surgery was associated with worse executive function. Prompt surgical correction of metopic synostosis may portend improved long-term emotional and behavioral function.

Effects of delayed ambulation following posterior spinal fusion for adolescent idiopathic scoliosis: a single institutional study.

OBJECTIVE: Mobilizing out of bed and ambulation are key components of recovery following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). However, there remains a paucity of studies identifying risk factors associated with delayed ambulation and its impact on postoperative outcomes. The aim of this study was to investigate patient- and surgical-level risk factors associated with delayed ambulation and the ramifications of delayed ambulation on healthcare utilization for patients undergoing PSF for AIS. METHODS: The medical records of 129 adolescent (10-18 years) patients diagnosed with AIS undergoing posterior spinal fusion at a major academic institution between 2013 and 2020 were reviewed. Patients were categorized based on days from surgery to ambulation: early (≤ 1 day), intermediate (2 days), or late (≥ 3 days). Patient demographics, comorbidities, spinal deformity characteristics, intraoperative variables, postoperative complications, LOS, and unplanned readmissions were assessed. The odds ratios for risk-adjusted delayed ambulation and extended LOS were determined via multivariate stepwise logistic regressions. RESULTS: One Hundred and Twenty Nine patients were included in this study, of which 10.8% (n = 14) were classified as Early ambulators, 41.9% (n = 54) Intermediate ambulators, and 47.3% (n = 61) were Late ambulators. Late ambulators were significantly younger than early and intermediate ambulators (Early: 15.7 ± 1.9 years vs. Intermediate: 14.8 ± 1.7 years vs. Late: 14.1 ± 1.9 years, p = 0.010). The primary and secondary spinal curves were significantly worse among Late ambulators (p < 0.001 and p = 0.002 respectively). Fusion levels (p < 0.01), EBL (p = 0.014), and the rate of RBC transfusions (p < 0.001) increased as time to ambulation increased. Transition time from IV to oral pain medications (Early: 1.6 ± 0.8 days vs. Intermediate: 2.2 ± 0.6 days vs. Late: 2.4 ± 0.6 days, p < 0.001) and total hospital length of stay (Early: 3.9 ± 1.4 days vs. Intermediate: 4.7 ± 0.9 days vs. Late: 5.1 ± 1.2 days, p < 0.001) were longer in Late ambulators. On multivariate analysis, significant predictors of delayed ambulation included primary curve degree ≥ 70° [aOR: 5.67 (1.29‒31.97), p = 0.030] and procedure time [aOR: 1.66 (1.1‒2.59), p = 0.019]. CONCLUSIONS: Our study suggests that there may be patient- and surgical-level factors that are independently associated with late ambulation following PSF for AIS, including extent of major curve and length of operative time. Additionally, delayed ambulation has implications to length of hospital stay and postoperative complications.

Impact of insurance status on healthcare resource utilization and outcomes in adolescent patients presenting with spinal cord injuries.

OBJECTIVE: Insurance disparities have been suggested to influence the medical and surgical outcomes of adult patients with spinal cord injury (SCI), with a paucity of studies demonstrating their impact on the outcomes of pediatric and adolescent SCI patients. The aim of this study was to assess the impact of insurance status on healthcare utilization and outcomes in adolescent patients presenting with SCI. METHODS: An administrative database study was performed using the 2017 admission year from 753 facilities using the National Trauma Data Bank. Adolescent patients (11-17 years old) with cervical/thoracic SCIs were identified using International Classification of Diseases, Tenth Revision, Clinical Modification coding. Patients were categorized by governmental insurance versus private insurance/self-pay. Patient demographics, comorbidities, imaging, procedures, hospital adverse events (AEs), and length of stay (LOS) data were collected. Multivariate regression analyses were used to determine the effect of insurance status on LOS, any imaging or procedure, or any AE. RESULTS: Of the 488 patients identified, 220 (45.1%) held governmental insurance while 268 (54.9%) were privately insured. Age was similar between the cohorts (p = 0.616), with the governmental insurance cohort (GI cohort) having a significantly lower proportion of non-Hispanic White patients than the private insurance cohort (PI cohort) (GI: 43.2% vs PI: 72.4%, p < 0.001). While transportation accident was the most common mechanism of injury for both cohorts, assault was significantly greater in the GI cohort (GI: 21.8% vs PI: 3.0%, p < 0.001). A significantly greater proportion of patients in the PI cohort received any imaging (GI: 65.9% vs PI: 75.0%, p = 0.028), while there were no significant differences in procedures performed (p = 0.069) or hospital AEs (p = 0.386) between the cohorts. The median (IQR) LOS (p = 0.186) and discharge disposition (p = 0.302) were similar between the cohorts. On multivariate analysis, with respect to governmental insurance, private insurance was not independently associated with obtaining any imaging (OR 1.38, p = 0.139), undergoing any procedure (OR 1.09, p = 0.721), hospital AEs (OR 1.11, p = 0.709), or LOS (adjusted risk ratio -2.56, p = 0.203). CONCLUSIONS: This study suggests that insurance status may not independently influence healthcare resource utilization and outcomes in adolescent patients presenting with SCIs. Further studies are needed to corroborate these findings.

Delivery of immunoglobulin G antibodies to the rat nervous system following intranasal administration: Distribution, dose-response, and mechanisms of delivery.

The intranasal route has been hypothesized to circumvent the blood-brain and blood-cerebrospinal fluid barriers, allowing entry into the brain via extracellular pathways along olfactory and trigeminal nerves and the perivascular spaces (PVS) of cerebral blood vessels. We investigated the potential of the intranasal route to non-invasively deliver antibodies to the brain 30 min following administration by characterizing distribution, dose-response, and mechanisms of antibody transport to and within the brain after administering non-targeted radiolabeled or fluorescently-labeled full length immunoglobulin G (IgG) to normal adult female rats. Intranasal [125I]-IgG consistently yielded highest concentrations in the olfactory bulbs, trigeminal nerves, and leptomeningeal blood vessels with their associated PVS. Intranasal delivery also resulted in significantly higher [125I]-IgG concentrations in the CNS than systemic (intra-arterial) delivery for doses producing similar endpoint blood concentrations. Importantly, CNS targeting significantly increased with increasing dose only with intranasal administration, yielding brain concentrations that ranged from the low-to-mid picomolar range with tracer dosing (50 µg) up to the low nanomolar range at higher doses (1 mg and 2.5 mg). Finally, intranasal pre-treatment with a previously identified nasal permeation enhancer, matrix metalloproteinase-9, significantly improved intranasal [125I]-IgG delivery to multiple brain regions and further allowed us to elucidate IgG transport pathways extending from the nasal epithelia into the brain using fluorescence microscopy. The results show that it may be feasible to achieve therapeutic levels of IgG in the CNS, particularly at higher intranasal doses, and clarify the likely cranial nerve and perivascular distribution pathways taken by antibodies to reach the brain from the nasal mucosae.