Delivering Therapy to the Olfactory Cleft: A Comparison of the Various Methods of Administering Topical Nasal Medications.

Background and objective Chronic rhinosinusitis (CRS) is an inflammatory condition affecting the nasal mucosa, and it causes olfactory dysfunction (OD) in up to 78.2% of patients. Corticosteroids are the mainstay of treatment to shrink nasal polyposis, reduce inflammation, and improve olfactory function. While many delivery methods for topical nasal corticosteroids exist, there is scarce data on the efficacy of the various medication delivery methods to the olfactory cleft (OC). In light of this, this study aimed to compare the following delivery methods to the OC: conventional nasal spray (NS), nasal drops in the Kaiteki position (KP), and exhalation delivery system (EDS). Methods We evaluated 16 sinonasal cavities from eight cadaver specimens in this study. Each sinonasal cavity was administered fluorescein dye solution via NS, KP, and EDS. Following administration, nasal endoscopy was employed to capture staining patterns in the OC. OC staining was rated with scores ranging from 0 (no staining) to 3 (heavy staining) after each administration of dye solution. Mean OC staining ratings were calculated and compared using the Kruskal-Wallis rank sum test and the Wilcoxon signed-rank test. Results The mean OC staining score for the different delivery methods was as follows - NS: 1.095 ± 1.008, EDS: 0.670 ± 0.674, and KP: 2.038 ± 1.097. Nasal drops in the KP had a significantly higher staining score compared to NS (p=0.041) and EDS (p=0.003). However, there was no significant difference in staining scores between NS and EDS. Conclusions Nasal drops in the KP are more effective at reaching the OC than NS or EDS and should be considered as a first-line modality for administering topical medications when treating OD.

Accessing the Eustachian tube: Conventional nasal spray vs. exhalation delivery system and the impact of targeted endoscopic sinus surgery on topical distribution patterns.

BACKGROUND: Eustachian tube dysfunction (ETD) may occur distinct from, or in conjunction with, chronic rhinosinusitis (CRS+ETD). Intranasal corticosteroid sprays are often prescribed for ETD, although ET distribution may be limited. To date, no anatomic studies compare nasopharynx (NP) distribution between conventional nasal sprays (NS) and exhalation delivery systems (EDS) after surgery. This study utilizes a cadaver model to examine topical NP delivery using EDS vs. NS before and after targeted endoscopic sinus surgery (ESS). METHODS: Sixteen sinonasal cavities were administered fluorescein solution via NS and EDS before and after maxillary antrostomy and anterior ethmoidectomy, followed by nasal endoscopy of the NP and ET orifice. Seven blinded experts submitted staining ratings of endoscopy images on a 0- to 3-point scale, with ratings averaged for analysis. RESULTS: Interrater reliability was excellent (intraclass correlation, 0.956). EDS was associated with significantly greater NP staining vs. NS in a pooled cohort of nonsurgical and ESS specimens (1.19 ± 0.81 vs. 0.78 ± 1.06; p = 0.043). Using a logistic regression model, EDS significantly outperformed NS in nonsurgical (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.21-10.09; p = 0.021) and post-ESS (OR, 9.00; 95% CI, 1.95-41.5; p = 0.005) specimens, with the greatest relative staining observed for EDS after targeted ESS (OR, 18.99; 95% CI, 3.44-104.85; p = 0.001). CONCLUSIONS: EDS is more effective than NS in topical delivery to the NP and ET orifices in cadavers. Targeted ESS may facilitate greater NP penetration by EDS compared with NS, with possible synergism after ESS for augmented delivery. These findings suggest a role for EDS delivery methods for ETD management and in CRS+ETD patients undergoing sinus surgery.

Nasoseptal Flap to Repair Large Maxillary Sinus Floor Defects.

This case highlights the successful use of a large nasoseptal flap to repair a large maxillary sinus floor defect. Surgeons can therefore rely on this flap for repairing maxillary sinus floor defects of most sizes and locations. Laryngoscope, 134:87-91, 2024.

Investigating the origin of the 13 C lactate signal in the anesthetized healthy rat brain in vivo after hyperpolarized [1-13 C]pyruvate injection.

The goal of this study was to investigate the origin of brain lactate (Lac) signal in the healthy anesthetized rat after injection of hyperpolarized (HP) [1-13 C]pyruvate (Pyr). Dynamic two-dimensional spiral chemical shift imaging with flow-sensitizing gradients revealed reduction in both vascular and brain Pyr, while no significant dependence on the level of flow suppression was detected for Lac. These results support the hypothesis that the HP metabolites predominantly reside in different compartments in the brain (i.e., Pyr in the blood and Lac in the parenchyma). Data from high-resolution metabolic imaging of [1-13 C]Pyr further demonstrated that Lac detected in the brain was not from contributions of vascular signal attributable to partial volume effects. Additionally, metabolite distributions and kinetics measured with dynamic imaging after injection of HP [1-13 C]Lac were similar to Pyr data when Pyr was used as the substrate. These data do not support the hypothesis that Lac observed in the brain after Pyr injection was generated in other organs and then transported across the blood-brain barrier (BBB). Together, the presented results provide further evidence that even in healthy anesthetized rats, the transport of HP Pyr across the BBB is sufficiently fast to permit detection of its metabolic conversion to Lac within the brain.

Deuterium metabolic imaging for 3D mapping of glucose metabolism in humans with central nervous system lesions at 3T.

PURPOSE: To explore the potential of 3T deuterium metabolic imaging (DMI) using a birdcage 2 H radiofrequency (RF) coil in both healthy volunteers and patients with central nervous system (CNS) lesions. METHODS: A modified gradient filter, home-built 2 H volume RF coil, and spherical k-space sampling were employed in a three-dimensional chemical shift imaging acquisition to obtain high-quality whole-brain metabolic images of 2 H-labeled water and glucose metabolic products. These images were acquired in a healthy volunteer and three subjects with CNS lesions of varying pathologies. Hardware and pulse sequence experiments were also conducted to improve the signal-to-noise ratio of DMI at 3T. RESULTS: The ability to quantify local glucose metabolism in correspondence to anatomical landmarks across patients with varying CNS lesions is demonstrated, and increased lactate is observed in one patient with the most active disease. CONCLUSION: DMI offers the potential to examine metabolic activity in human subjects with CNS lesions with DMI at 3T, promising for the potential of the future clinical translation of this metabolic imaging technique.

A Phase 1 Study of Oral Vitamin D3 in Boys and Young Men With X-Linked Adrenoleukodystrophy.

Background and Objectives: There are no therapies for preventing cerebral demyelination in X-linked adrenoleukodystrophy (ALD). Higher plasma vitamin D levels have been linked to lower risk of inflammatory brain lesions. We assessed the safety and pharmacokinetics of oral vitamin D dosing regimens in boys and young men with ALD. Methods: In this open-label, multicenter, phase 1 study, we recruited boys and young men with ALD without brain lesions to a 12-month study of daily oral vitamin D3 supplementation. Our primary outcome was attainment of plasma 25-hydroxyvitamin D levels in target range (40-80 ng/mL) at 6 and 12 months. Secondary outcomes included safety and glutathione levels in the brain, measured with magnetic resonance spectroscopy, and blood, measured via mass spectrometry. Participants were initially assigned to a fixed dosing regimen starting at 2,000 IU daily, regardless of weight. After a midstudy safety assessment, we modified the dosing regimen, so all subsequent participants were assigned to a weight-stratified dosing regimen starting as low as 1,000 IU daily. Results: Between October 2016 and June 2019, we enrolled 21 participants (n = 12, fixed-dose regimen; n = 9, weight-stratified regimen) with a median age of 6.7 years (range: 1.9-22 years) and median weight of 20 kg (range: 11.7-85.5 kg). The number of participants achieving target vitamin D levels was similar in both groups at 6 months (fixed dose: 92%; weight stratified: 78%) and 12 months (fixed dose: 67%; weight stratified: 67%). Among the 12 participants in the fixed-dose regimen, half had asymptomatic elevations in either urine calcium:creatinine or plasma 25-hydroxyvitamin D; no laboratory deviations occurred with the weight-stratified regimen. Glutathione levels in the brain, but not the blood, increased significantly between baseline and 12 months. Discussion: Our vitamin D dosing regimens were well tolerated and achieved target 25-hydroxyvitamin D levels in most participants. Brain glutathione levels warrant further study as a biomarker for vitamin D and ALD. Classification of Evidence: This study provides Class IV evidence that fixed or weight-stratified vitamin D supplementation achieved target levels of 25-hydroxyvitamin D in boys and young men with X-ALD without brain lesions.

Critical Degree of Orbital Floor Displacement Drives Operative Repair of Zygomaticomaxillary Complex Fractures: Findings from a 10-Year Retrospective Study.

Among zygomaticomaxillary complex (ZMC) fractures presenting to a tertiary urban academic center, the authors hypothesized the presence of both clinical and radiographic predictors of operative management. The investigators conducted a retrospective cohort study of 1,914 patients with facial fractures managed at an academic medical center in New York City between 2008 and 2017. The predictor variables were based on both clinical data and features of pertinent imaging studies, and the outcome variable was an operative intervention. Descriptive and bivariate statistics were computed and the p-value was set at 0.05. In total, 196 patients sustained ZMC fractures (5.0%) and 121 (61.7%) ZMC fractures were treated surgically. All patients who presented with globe injury, blindness, retrobulbar injury, restricted gaze, or enophthalmos and a concurrent ZMC fracture were managed surgically. The most common surgical approach was the gingivobuccal corridor (31.9% of all approaches), and there were no significant immediate postoperative complications. Younger patients (38.9 ± 18 years vs. 56.1 ± 23.5 years, p < 0.0001) and patients with greater than or equal to 4 mm of orbital floor displacement were more likely to receive surgical treatment than observation (82 vs. 56%, p = 0.045), as were patients with comminuted orbital floor fractures (52 vs. 26%, p = 0.011). In this cohort, patients more likely to undergo surgical reduction were young patients with ophthalmologic symptoms on presentation and at least 4 mm displacement of the orbital floor. Low kinetic energy ZMC fractures may warrant surgical management as often as high-energy ZMC fractures. While orbital floor comminution has been shown to be a predictor for operative reduction, in this study we also demonstrated a difference in the rate of reduction based on the severity of orbital floor displacement. This may have significant implications in both the triage and selection of patients most suitable for operative repair.

Demographic Disparities in the Federal Drug Approval Process for Allergic Rhinitis Medications.

OBJECTIVE: Demographic minorities are underrepresented in clinical trials. For the approval of new drug applications (NDAs), the Food and Drug Administration (FDA) has asserted that clinical trial enrollment should represent the demographics of patients likely to receive the trial drug. The aim of this study is to assess the demographics of clinical trials included in NDAs and biologics license applications (BLAs) approved by the FDA since 1990 for allergic rhinitis (AR), a condition whose demographic prevalence mirrors the US population. METHODS: Federal Freedom of Information Act requests were submitted to the US government to obtain documents related to all relevant NDAs and BLAs. The Drugs@FDA database was queried for all clinical trial documentation. Demographic data were extracted from clinical trials used to inform FDA approval for AR pharmacotherapies. Demographics were analyzed relative to national US Census data. RESULTS: Since 1990, 22 drugs have been approved for AR. The racial, ethnic, and sex composition of all included study populations differed significantly (p < 0.05) from the demographics of AR and from US Census data. Most NDAs and BLAs included overrepresentation of White participants and underrepresentation of Black, Asian, Pacific Island, Native American, and Hispanic participants. CONCLUSION: The patients enrolled in clinical trials used to inform FDA approval for AR pharmacotherapeutics do not represent the demographics of the United States or the demographics of AR. The clinical significance of unrepresentative demography between study and treatment populations has been examined for several medical disorders, but has not been studied for AR. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:755-763, 2023.

Contralateral Transmaxillary Approach to Petrous Apex Granuloma with Lateral Maxillotomy: 2-Dimensional Operative Video.

The endoscopic endonasal approach (EEA) has proven to be a valuable tool to access the petrous apex (PA).1 Although lesions located medial to the PA can be easily accessed through an EEA with minimal risk to the internal carotid artery (ICA), more laterally seated lesions represent a surgical challenge. The contralateral transmaxillary approach is an effective extension of the normal EEA to the PA, allowing a more lateral trajectory and thereby reducing the risks connected to paraclival ICA manipulation.2-4 This is a 47-year-old female presenting with tinnitus, hearing loss, and right facial twitching. The preoperative audiogram showed a 60 dB sensorineural hearing loss, and magnetic resonance imaging demonstrated an expansive lesion of the PA with high signal intensity in T1- and T2-weighted sequences. A high-riding jugular bulb ruled out the use of an infracochlear infralabyrinthine approach, and a middle cranial fossa approach was felt to render a high risk of recurrence due to the potential for incomplete resection. Ultimately, a contralateral transmaxillary approach was selected. Due to the extreme lateral position of the lesion, the maxillotomy was created in the lateral wall of the maxillary sinus to allow a coaxial approach to the PA. Postoperatively, the patient did not report new neurologic deficits. Anatomic pathology was consistent with cholesterol granuloma (Video 1). In the surgical management of PA granulomas, recognizing relevant anatomic structures such as the paraclival ICA, cochlea, jugular bulb, and vestibule preoperatively is of paramount importance to tailor the surgical approach and reduce its risks.

Impact of Race, Ethnicity, and Socioeconomic Status on Nasopharyngeal Carcinoma Disease-Specific and Conditional Survival.

Introduction Race, ethnicity, and socioeconomic status (SES) are complex, interconnected social determinants of health outcomes. This study uses multivariable analysis on a combination of large national datasets to examine the effects of these factors on 5-year disease-specific survival (DSS) and conditional DSS (CDSS) for nasopharyngeal carcinoma (NPC). Methods A retrospective study of adults with NPC between 2000 and 2017 from the Surveillance, Epidemiology, End Results (SEER) registry was performed, using the National Cancer Institute Yost Index, a census tract-level composite score of SES to categorize patients. Kaplan-Meier analysis and Cox's regression for DSS and CDSS were stratified by SES. Logistic regression was conducted to identify risk factors for advanced cancer stage at time of diagnosis and receiving multimodal therapy. Results Our analysis included 5,632 patients. DSS was significantly associated with race and SES ( p < 0.01). Asian/Pacific Islander patients exhibited increased survival when controlling for other variables (hazard ratio [HR] = 0.73, p < 0.01). Although Black patients were more likely to be diagnosed with advanced disease (Black odds ratio [OR] = 1.47, p < 0.01), Black patients were also less likely to receive multimodal therapy; however, this relationship lost statistical significance once SES was incorporated into the multivariable analysis. DSS was decreased among the lowest (first) and middle (second) tertiles of SES (first HR = 1.34, p < 0.01; second HR = 1.20, p < 0.01) compared with the highest (third). Conclusion Our results indicate that race, ethnicity, and SES significantly affect survival, stage at diagnosis, and treatment of NPC. An interplay of tumor biology and inequalities in access to care likely drives these disparities.

Exclusively endoscopic surgical resection of esthesioneuroblastoma: A systematic review.

Background: Historically sinonasal malignancies were always addressed via open craniofacial surgery for an oncologic resection. Increasingly esthesioneuroblastomas are excised using an exclusively endoscopic approach, however, the rarity of this disease limits the availability of long-term and large scale outcomes data. Objective: The primary objective is to evaluate the treatment modalities used and the overall survival of patients with esthesioneuroblastoma managed with exclusively endoscopic surgery. Methods: In accordance with PRISMA guidelines, PubMed was queried to identify studies describing outcomes associated with endoscopic management of esthesioneuroblastomas. Results: Forty-four out of 2462 articles met inclusion criteria, totaling 399 patients with esthesioneuroblastoma treated with an exclusively endoscopic approach. Seventy-two patients (18.0%) received adjuvant chemotherapy and 331 patients (83.0%) received postoperative radiation therapy. The average age was 50.6 years old (range 6-83). Of the 399 patients, 57 (16.6%) were Kadish stage A, 121 (35.2%) were Kadish stage B, 145 (42.2%) were Kadish stage C, and 21 (6.1%) were Kadish stage D. Pooled analysis demonstrated that 66.0% of patients had Hyams histologic Grade Ⅰ or Ⅱ, while 34.0% of patients had Grade Ⅲ or Ⅳ disease. Negative surgical margins were achieved in 86.9% of patients, and recurrence was identified in 10.3% of patients. Of those with 5-year follow-up, reported overall survival was 91.1%. Conclusion: Exclusively endoscopic surgery for esthesioneuroblastoma is performed for a wide range of disease stages and grades, and the majority of these patients are also treated with adjuvant chemotherapy or radiation therapy. Reported overall recurrence rate is 10.3% and 5-year survival is 91.1%.

Finite free convolutions of polynomials.

We study three convolutions of polynomials in the context of free probability theory. We prove that these convolutions can be written as the expected characteristic polynomials of sums and products of unitarily invariant random matrices. The symmetric additive and multiplicative convolutions were introduced by Walsh and Szegö in different contexts, and have been studied for a century. The asymmetric additive convolution, and the connection of all of them with random matrices, is new. By developing the analogy with free probability, we prove that these convolutions produce real rooted polynomials and provide strong bounds on the locations of the roots of these polynomials.

Proton magnetic resonance spectroscopy assessment of neonatal brain metabolism during cardiopulmonary bypass surgery.

Here, we report on the development and performance of a robust 3-T single-voxel proton magnetic resonance spectroscopy (1 H MRS) experimental protocol and data analysis pipeline for quantifying brain metabolism during cardiopulmonary bypass (CPB) surgery in a neonatal porcine model, with the overall goal of elucidating primary mechanisms of brain injury associated with these procedures. The specific aims were to assess which metabolic processes can be reliably interrogated by 1 H MRS on a 3-T clinical scanner and to provide an initial assessment of brain metabolism during deep hypothermia cardiac arrest (DHCA) surgery and recovery. Fourteen neonatal pigs underwent CPB surgery while placed in a 3-T MRI scanner for 18, 28, and 37°C DHCA studies under hyperglycemic, euglycemic, and hypoglycemic conditions. Total imaging times, including baseline measurements, circulatory arrest (CA), and recovery averaged 3 h/animal, during which 30-40 single-voxel 1 H MRS spectra (sLASER pulse sequence, TR/TE = 2000/30 ms, 64 or 128 averages) were acquired from a 2.2-cc right midbrain voxel. 1 H MRS at 3 T was able to reliably quantify (1) anaerobic metabolism via depletion of brain glucose and the associated build-up of lactate during CA, (2) phosphocreatine (PCr) to creatine (Cr) conversion during CA and subsequent recovery upon reperfusion, (3) a robust increase in the glutamine-to-glutamate (Gln/Glu) ratio during the post-CA recovery period, and (4) a broadening of the water peak during CA. In vivo 1 H MRS at 3 T can reliably quantify subtle metabolic brain changes previously deemed challenging to interrogate, including brain glucose concentrations even under hypoglycemic conditions, ATP usage via the conversion of PCr to Cr, and differential changes in Glu and Gln. Observed metabolic changes during CPB surgery of a neonatal porcine model provide new insights into possible mechanisms for prevention of neuronal injury.

Benign bony tumors of the paranasal sinuses, orbit, and skull base.

Benign bony tumors of the skull base and paranasal sinuses are uncommon entities, with an overall higher incidence in males. Benign bony tumors may lead to local expansion with resultant mass effect of potentially critical structures. Some benign bony tumors may undergo malignant transformation. This article reviews the presentation and management of benign bone tumors of the skull base and paranasal sinuses with special consideration to involvement of the adjacent orbit, intracranial and critical neurovascular structures. This review covers tumor incidence, location, gross and histologic appearance as well as radiographic findings, treatment, and recurrence rates. Tumors discussed in this article include osteochondromas, osteomas, osteoid osteomas, aneurysmal bone cysts, fibrous dysplasia, giant cell tumors, cemento-ossifying fibroma, ameloblastic fibro-odontoma, ecchordosis physaliphora, chondromyxoid fibroma, primary chronic osteomyelitis, primary chronic osteomyelitis, osteochondromyxoma, and dense bone islands.

Do Federal Regulations Affect Gender, Racial, and Ethnic Disparities in Chronic Rhinosinusitis Research?

OBJECTIVE: The Food and Drug Administration and the National Institutes of Health (NIH) have asserted that diverse demographic representation in clinical trials is essential. In light of these federal guidelines, the objective of this study is to assess the racial, ethnic, and gender demographics of patients enrolled in clinical trials registered with the NIH that evaluate chronic rhinosinusitis with nasal polyposis (CRSwNP) relative to the demographics of the US population. STUDY DESIGN: Cross-sectional study. SETTING: Not applicable. METHODS: ClinicalTrials.gov was queried to identify all prospective clinical trials for CRSwNP. Individual study and pooled data were compared with national US census data. RESULTS: Eighteen studies were included comprising 4125 patients and evaluating dupilumab, mepolizumab, omalizumab, fluticasone/OptiNose, MediHoney, mometasone, and SINUVA. Women constituted 42.7% of clinical trial participants. Of the 4125 participants, 69.6% identified as White, 6.6% as Black, 20.8% as Asian, 0.1% as Pacific Islander, 0.4% as American Indian, 8.0% as Hispanic, and 2.4% as other. The racial, ethnic, and gender composition of the pooled study population differs significantly from national US census data, with underrepresentation of Black, Hispanic, Pacific Island, and American Indian individuals, as well as females (P < .05). CONCLUSION: The racial, ethnic, and gender demographics of patients enrolled in CRSwNP clinical trials registered with the NIH differ significantly from the demographics of the US population, despite federal guidelines advising demographically representative participation. Proactive efforts to enroll participants that better represent anticipated treatment populations should be emphasized by researchers, institutions, and editorial boards.

The management of cystic fibrosis chronic rhinosinusitis: An evidenced-based review with recommendations.

BACKGROUND: Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. In recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, in this review we systematically evaluate the scientific literature and provide an evidenced-based review with recommendations (EBRR) for fundamental management principles of CF CRS. METHODS: A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms, and the overall grade of evidence. RESULTS: We evaluated the published literature on 5 unique topics. Each of the following therapeutic categories was investigated explicitly for treatment outcomes in patients with CF CRS: (1) nasal saline; (2) intranasal corticosteroids (INCS); (3) topical antibiotics; (4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and (5) endoscopic sinus surgery (ESS). CONCLUSION: Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder.

Hyperpolarized NMR study of the impact of pyruvate dehydrogenase kinase inhibition on the pyruvate dehydrogenase and TCA flux in type 2 diabetic rat muscle.

The role of pyruvate dehydrogenase in mediating lipid-induced insulin resistance stands as a central question in the pathogenesis of type 2 diabetes mellitus. Many researchers have invoked the Randle hypothesis to explain the reduced glucose disposal in skeletal muscle by envisioning an elevated acetyl CoA pool arising from increased oxidation of fatty acids. Over the years, in vivo NMR studies have challenged that monolithic view. The advent of the dissolution dynamic nuclear polarization NMR technique and a unique type 2 diabetic rat model provides an opportunity to clarify. Dynamic nuclear polarization enhances dramatically the NMR signal sensitivity and allows the measurement of metabolic kinetics in vivo. Diabetic muscle has much lower pyruvate dehydrogenase activity than control muscle, as evidenced in the conversion of [1-13C]lactate and [2-13C]pyruvate to HCO3- and acetyl carnitine. The pyruvate dehydrogenase kinase inhibitor, dichloroacetate, restores rapidly the diabetic pyruvate dehydrogenase activity to control level. However, diabetic muscle has a much larger dynamic change in pyruvate dehydrogenase flux than control. The dichloroacetate-induced surge in pyruvate dehydrogenase activity produces a differential amount of acetyl carnitine but does not affect the tricarboxylic acid flux. Further studies can now proceed with the dynamic nuclear polarization approach and a unique rat model to interrogate closely the biochemical mechanism interfacing oxidative metabolism with insulin resistance and metabolic inflexibility.

Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents.

Animal models of stress and related conditions, including depression, have shown that elevated peripheral levels of inflammatory cytokines have downstream consequences on glutamate (Glu) in the brain. Although studies in human adults with depression have reported evidence of higher inflammation but lower Glu in the anterior cingulate cortex (ACC), the extent to which peripheral inflammation contributes to glutamatergic abnormalities in adolescents with depression is not well-understood. It is also unclear whether antioxidants, such as ascorbate (Asc), may buffer against the effects of inflammation on Glu metabolism. Fifty-five depressed adolescents were recruited in the present cross-sectional study and provided blood samples, from which we assayed pro-inflammatory cytokines, and underwent a short-TE proton magnetic spectroscopy scan at 3T, from which we estimated Glu and Asc in the dorsal ACC. In the 31 adolescents with usable cytokine and Glu data, we found that IL-6 was significantly positively associated with dorsal ACC Glu (ß = 0.466 ± 0.199, p = 0.029). Of the 16 participants who had usable Asc data, we found that at higher levels of dorsal ACC Asc, there was a negative association between IL-6 and Glu (interaction effect: ß = -0.906 ± 0.433, p = 0.034). Importantly, these results remained significant when controlling for age, gender, percentage of gray matter in the dorsal ACC voxel, BMI, and medication (antidepressant and anti-inflammatory) usage. While preliminary, our results underscore the importance of examining both immune and neural contributors to depression and highlight the potential role of anti-inflammatory compounds in mitigating the adverse effects of inflammation (e.g., glutamatergic neuroexcitotoxicity). Future studies that experimentally manipulate levels of inflammation, and of ascorbate, and that characterize these effects on cortical glutamate concentrations and subsequent behavior in animals and in humans are needed.

Frontal Sinus Fractures: 10-Year Contemporary Experience at a Level 1 Urban Trauma Center.

ABSTRACT: Frontal sinus fractures account for 5% to 15% of all facial fractures, and have traditionally been associated with high kinetic energy blunt injury. Surgical management is largely focused on minimizing potentially serious sequelae including frontal sinus dysfunction, CSF leak, and significant cosmetic deformity. An institutional database of 1944 patients presenting with maxillofacial fractures over a 10-year period was queried. Demographics, mechanism of injury, yearly trends, surgical approaches, and follow-up data were examined. A total of 160 (8.3%) patients presented with at least 1 fracture of the frontal sinus anterior table, posterior table, or frontal sinus outflow tract during the study period. The average annual number of cases was 15.9 ±â€Š5.7 per year with a peak of 21.5 ±â€Š4.0 cases during the 2014 to 2015 period and a decline to 8.5 ±â€Š1.5 cases/year from 2016 to 2017. Among those patients with falls, 61.5% (n = 40) were a result of tripping or fainting at a height of <6 ft. 55.6% of fracture types were isolated to the anterior table, but fracture location was not significantly associated with operative intervention. Cases of operative fracture type had a higher rate of both displacement and comminution compared to nonoperative fractures (P < 0.00001). Of all patients presenting with frontal sinus fractures, 75% of cases were managed nonoperatively. However, many patients presented with falls and other seemingly low energy injuries which are not traditionally associated with frontal sinus trauma. These results highlight the need for continued follow-up even in otherwise low-risk urban populations in order to avoid long term sinus dysfunction.

Injury Patterns in Pediatric Facial Fractures Unique to an Urban Environment.

This study aimed to define better the clinical presentation, fracture patterns, and features predictive of associated injuries and need for surgery in pediatric facial trauma patients in an urban setting. Charts of patients 18 years or younger with International Classification of Disease 9th and 10th revision (ICD-9/ICD-10) codes specific for facial fractures (excluding isolated nasal fractures) at NY-Presbyterian/Weill Cornell Medical Center between 2008 and 2017 were retrospectively reviewed. Of 204 patients, most were referred to the emergency department by a physician's office or self-presented. Children (age 0-6 years) were most likely to have been injured by falls, while more patients 7 to 12 years and 13 to 18 years were injured during sporting activities (p < 0.0001). Roughly half (50.5%) of the patients had a single fracture, and the likelihood of surgery increased with greater numbers of fractures. Older patients with either orbital or mandibular fractures were more likely to undergo surgery than younger ones (p = 0.0048 and p = 0.0053, respectively). Cranial bone fractures, CSF leaks, and intracranial injuries were more common in younger patients (p < 0.0001) than older patients and were more likely after high energy injuries; however, 16.2% of patients sustaining low energy injuries also sustained cranial bone, CSF leak, or intracranial injury. In an urban environment, significant pediatric facial fractures and associated injuries may occur after nonclassic low kinetic energy traumatic events. The age of the patient impacts both the injuries sustained and the treatment rendered. It is essential to maintain a high index of suspicion for associated injuries in all pediatric facial trauma patients.