Impact of sociodemographic status and sex on chronic rhinosinusitis and olfaction in people with cystic fibrosis.

BACKGROUND: Sociodemographic status (SDS) including race/ethnicity and socioeconomic status as approximated by education, income, and insurance status impact pulmonary disease in people with cystic fibrosis (PwCF). The relationship between SDS and chronic rhinosinusitis (CRS) remains understudied. METHODS: In a prospective, multi-institutional study, adult PwCF completed the 22-Question SinoNasal Outcome Test (SNOT-22), Smell Identification Test (SIT), Questionnaire of Olfactory Disorder Negative Statements (QOD-NS), and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Lund-Kennedy scores, sinus computed tomography, and clinical data were collected. Data were analyzed across race/ethnicity, sex, and socioeconomic factors using multivariate regression. RESULTS: Seventy-three PwCF participated with a mean age of 34.7 ± 10.9 years and 49 (67.1%) were female. Linear regression identified that elexacaftor/tezacaftor/ivacaftor (ETI) use (ß = â€’4.09, 95% confidence interval [CI] [‒6.08, ‒2.11], p < 0.001), female sex (ß = â€’2.14, 95% CI [‒4.11, ‒0.17], p = 0.034), and increasing age (ß = â€’0.14, 95% CI [‒0.22, ‒0.05], p = 0.003) were associated with lower/better endoscopy scores. Private health insurance (ß = 17.76, 95% CI [5.20, 30.32], p = 0.006) and >16 educational years (ß = 13.50, 95% CI [2.21, 24.80], p = 0.020) were associated with higher baseline percent predicted forced expiratory volume in one second (ppFEV1). Medicaid/Medicare insurance was associated with worse endoscopy scores, CFQ-R respiratory scores, and ppFEV1 (all p < 0.017), and Hispanic/Latino ethnicity was associated with worse SNOT-22 scores (p = 0.047), prior to adjustment for other cofactors. No other SDS factors were associated with SNOT-22, QOD-NS, or SIT scores. CONCLUSIONS: Differences in objective measures of CRS severity exist among PwCF related to sex, age, and ETI use. Variant status and race did not influence patient-reported CRS severity measures or olfaction in this study. Understanding how these factors impact response to treatment may improve care disparities among PwCF. CLINICAL TRIALS: NCT04469439.

Multi-institutional validation of an AI-based sinus CT analytic platform with olfactory assessments.

KEY POINTS: AI-based CT sinus analysis may have advantages over visual based systems, for example, Lund-Mackay score. Here, we show multi-institutional validation of an AI algorithm using novel OMC classification. Significant, robust correlations are seen between algorithm outputs and clinical outcomes.

Assessing Mobility in Patients With Glioblastoma Using Digital Phenotyping-Piloting the Digital Assessment in Neuro-Oncology.

BACKGROUND AND OBJECTIVES: Digital phenotyping (DP) enables objective measurements of patient behavior and may be a useful tool in assessments of quality-of-life and functional status in neuro-oncology patients. We aimed to identify trends in mobility among patients with glioblastoma (GBM) using DP. METHODS: A total of 15 patients with GBM enrolled in a DP study were included. The Beiwe application was used to passively collect patient smartphone global positioning system data during the study period. We estimated step count, time spent at home, total distance traveled, and number of places visited in the preoperative, immediate postoperative, and late postoperative periods. Mobility trends for patients with GBM after surgery were calculated by using local regression and were compared with preoperative values and with values derived from a nonoperative spine disease group. RESULTS: One month postoperatively, median values for time spent at home and number of locations visited by patients with GBM decreased by 1.48 h and 2.79 locations, respectively. Two months postoperatively, these values further decreased by 0.38 h and 1.17 locations, respectively. Compared with the nonoperative spine group, values for time spent at home and the number of locations visited by patients with GBM 1 month postoperatively were less than control values by 0.71 h and 2.79 locations, respectively. Two months postoperatively, time spent at home for patients with GBM was higher by 1.21 h and locations visited were less than nonoperative spine group values by 1.17. Immediate postoperative values for distance traveled, maximum distance from home, and radius of gyration for patients with GBM increased by 0.346 km, 2.24 km, and 1.814 km, respectively, compared with preoperative values. CONCLUSIONS: :Trends in patients with GBM mobility throughout treatment were quantified through the use of DP in this study. DP has the potential to quantify patient behavior and recovery objectively and with minimal patient burden.

Recurrent Glioblastoma-Molecular Underpinnings and Evolving Treatment Paradigms.

Glioblastoma is the most common and lethal central nervous system malignancy with a median survival after progression of only 6-9 months. Major biochemical mechanisms implicated in glioblastoma recurrence include aberrant molecular pathways, a recurrence-inducing tumor microenvironment, and epigenetic modifications. Contemporary standard-of-care (surgery, radiation, chemotherapy, and tumor treating fields) helps to control the primary tumor but rarely prevents relapse. Cytoreductive treatment such as surgery has shown benefits in recurrent glioblastoma; however, its use remains controversial. Several innovative treatments are emerging for recurrent glioblastoma, including checkpoint inhibitors, chimeric antigen receptor T cell therapy, oncolytic virotherapy, nanoparticle delivery, laser interstitial thermal therapy, and photodynamic therapy. This review seeks to provide readers with an overview of (1) recent discoveries in the molecular basis of recurrence; (2) the role of surgery in treating recurrence; and (3) novel treatment paradigms emerging for recurrent glioblastoma.

How to be a good reviewer: A step-by-step guide for approaching peer review of a scientific manuscript.

Objectives: The peer review process is critical to maintaining quality, reliability, novelty, and innovation in the scientific literature. However, the teaching of scientific peer review is rarely a component of formal scientific or clinical training, and even the most experienced peer reviewers express interest in continuing education. The objective of this review article is to summarize the collective perspectives of experienced journal editors about how to be a good reviewer in a step-by-step guide that can serve as a resource for the performance of peer review of a scientific manuscript. Methods: This is a narrative review. Results: A review of the history and an overview of the modern-day peer review process are provided with attention to the role played by the reviewer, including important reasons for involvement in scientific peer review. The general components of a scientific peer review are described, and a model for how to structure a peer review report is provided. These concepts are also summarized in a reviewer checklist that can be used in real-time to develop and double-check one's reviewer report before submitting it. Conclusions: Peer review is a critically important service for maintaining quality in the scientific literature. Peer review of a scientific manuscript and the associated reviewer's report should assess specific details related to the accuracy, validity, novelty, and interpretation of a study's results. We hope that this article will serve as a resource and guide for reviewers of all levels of experience in the performance of peer review of a scientific manuscript.

University of Washington Quality of Life subdomain outcomes after treatment of sinonasal malignancy: A prospective, multicenter study.

PURPOSE: Sinonasal malignancies (SNMs) adversely impact patients' quality of life (QOL) and are frequently identified at an advanced stage. Because these tumors are rare, there are few studies that examine the specific QOL areas that are impacted. This knowledge would help improve the care of these patients. METHODS: In this prospective, multi-institutional study, 273 patients with SNMs who underwent definitive treatment with curative intent were evaluated. We used the University of Washington Quality of Life (UWQOL) instrument over 5 years from diagnosis to identify demographic, treatment, and disease-related factors that influence each of the 12 UWQOL subdomains from baseline to 5 -years post-treatment. RESULTS: Multivariate models found endoscopic resection predicted improved pain (vs. nonsurgical treatment CI 2.4, 19.4, p = 0.01) and appearance versus open (CI 27.0, 35.0, p < 0.001) or combined (CI 10.4, 17.1, p < 0.001). Pterygopalatine fossa involvement predicted worse swallow (CI -10.8, -2.4, p = 0.01) and pain (CI -17.0, -4.0, p < 0.001). Neck dissection predicted worse swallow (CI -14.8, -2.8, p < 0.001), taste (CI -31.7, -1.5, p = 0.02), and salivary symptoms (CI -28.4, -8.6, p < 0.001). Maxillary involvement predicted worse chewing (CI 9.8, 33.2; p < 0.001) and speech (CI -21.8, -5.4, p < 0.001) relative to other sites. Advanced T stage predicted worse anxiety (CI -13.0, -2.0, p = 0.03). CONCLUSIONS: Surgical approach, management of cervical disease, tumor extent, and site of involvement impacted variable UWQOL symptom areas. Endoscopic resection predicted better pain, appearance, and chewing compared with open. These results may aid in counseling patients regarding potential QOL expectations in their SNM treatment and recovery course.

Dural Venous Sinus Thrombosis After Vestibular Schwannoma Surgery: Should We Anticoagulate?

BACKGROUND: The incidence of dural venous sinus thrombosis (DVST) following vestibular schwannoma (VS) surgery remains understudied. The diverse clinical presentation complicates forming anticoagulation treatment guidelines. This meta-analysis aimed to investigate the incidence of DVST post-VS surgery and to evaluate the role of anticoagulation. METHODS: A systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, was conducted. Studies reporting DVST incidence after VS surgery were included. DVST incidence stratified by detection method was the primary outcome. Adverse events per treatment strategy (anticoagulation or no anticoagulation) were the secondary outcome. Pooled incidence with respective 95% confidence intervals were calculated using the random-effects model via the DerSimonian and Laird method. RESULTS: The overall DVST incidence post-VS resection was 15.5% (95% confidence interval: 10.3%, 22.5%; 10 studies). Stratification by detection method revealed 29.4% (19.2%, 42.3%) for magnetic resonance imaging, 8.2% (3.2%, 19.5%) for computed tomography, and 0.7% (0.2%, 2.8%) upon clinical suspicion. The pooled incidence of adverse events was 16.1% (6.4%, 35.0%) for the anticoagulation treatment and 4.4% (1.4%, 12.9%) for no anticoagulation treatment, with one mortality case being among the adverse events in this latter group. CONCLUSIONS: DVST after VS surgery is more common than initially perceived, predominantly presenting asymptomatically. Variability in anticoagulation protocols hinders the establishment of definitive therapeutic stances; nevertheless, there is no supporting evidence to promote anticoagulation administration for DVST. This begs the need for further institutional comparative studies with a proper adjustment for confounding and well-defined anticoagulation regimens.

The Case for Neurosurgical Intervention in Cancer Neuroscience.

The emerging field of cancer neuroscience reshapes our understanding of the intricate relationship between the nervous system and cancer biology; this new paradigm is likely to fundamentally change and advance neuro-oncological care. The profound interplay between cancers and the nervous system is reciprocal: Cancer growth can be induced and regulated by the nervous system; conversely, tumors can themselves alter the nervous system. Such crosstalk between cancer cells and the nervous system is evident in both the peripheral and central nervous systems. Recent advances have uncovered numerous direct neuron-cancer interactions at glioma-neuronal synapses, paracrine mechanisms within the tumor microenvironment, and indirect neuroimmune interactions. Neurosurgeons have historically played a central role in neuro-oncological care, and as the field of cancer neuroscience is becoming increasingly established, the role of neurosurgical intervention is becoming clearer. Examples include peripheral denervation procedures, delineation of neuron-glioma networks, development of neuroprostheses, neuromodulatory procedures, and advanced local delivery systems. The present review seeks to highlight key cancer neuroscience mechanisms with neurosurgical implications and outline the future role of neurosurgical intervention in cancer neuroscience.

From Operating Room to Courtroom: Analyzing Malpractice Trajectories in Cranial Neurosurgery.

BACKGROUND AND OBJECTIVES: Nearly all neurosurgeons in the United States will be named defendants in a malpractice claim before retirement. We perform an assessment of national malpractice trends in cranial neurosurgery to inform neurosurgeons on current outcomes, trends over time, benchmarks for malpractice coverage needs, and ways to mitigate lawsuits. METHODS: The Westlaw Edge and LexisNexis databases were searched to identify medical malpractice cases relating to open cranial surgery between 1987 and 2023. Extracted data included date of verdict, jurisdiction, outcome, details of sustained injuries, and any associated award/settlement figures. RESULTS: Of 1550 cases analyzed, 252 were identified as malpractice claims arising from open cranial surgery. The median settlement amount was $950 000 and the average plaintiff ruling was $2 750 000. The highest plaintiff ruling resulted in an award of $28.1 million. Linear regression revealed no significant relationship between year and defendant win (P-value = .43). After adjusting for inflation, award value increased with time (P-value = .01). The most common cranial subspecialties were tumor (67 cases, 26.6%), vascular (54 cases, 21.4%), infection (23 cases, 9.1%), and trauma (23 cases, 9.1%). Perioperative complications was the most common litigation category (96 cases, 38.1%), followed by delayed treatment (40 cases, 15.9%), failure to diagnose (38 cases, 15.1%), and incorrect choice of procedure (29 cases, 11.5%). The states with most claims were New York (40 cases, 15.9%), California (24 cases, 9.5%), Florida (21 cases, 8.3%), and Pennsylvania (20 cases, 7.9%). CONCLUSION: Although a stable number of cases were won by neurosurgeons, an increase in award sizes was observed in the 37-year period assessed. Perioperative complications and delayed treatment/diagnosis were key drivers of malpractice claims.

From masks to muscles: Mapping facial structure of Nycticebus.

Facial musculature in mammals underlies mastication and nonverbal communicative facial displays. Our understanding of primate facial expression comes primarily from haplorrhines (monkeys and apes), while our understanding of strepsirrhine (lemurs and lorises) facial expression remains incomplete. We examined the facial muscles of six specimens from three Nycticebus species (Nycticebus coucang, Nycticebus javanicus, and Nycticebus menagensis) using traditional dissection methodology and novel three-dimensional facial scanning to produce a detailed facial muscle map, and compared these results to another nocturnal strepsirrhine genus, the greater bushbaby (Otolemur spp.). We observed 19 muscles with no differences among Nycticebus specimens. A total of 17 muscles were observed in both Nycticebus and Otolemur, with little difference in attachment and function but some difference in directionality of movement. In the oral region, we note the presence of the depressor anguli oris, which has been reported in other primate species but is absent in Otolemur. The remaining muscle is a previously undescribed constrictor nasalis muscle located on the lateral nasal alar region, likely responsible for constriction of the nares. We propose this newly described muscle may relate to vomeronasal organ functioning and the importance of the use of nasal musculature in olfactory communication. We discuss how this combined methodology enabled imaging of small complex muscles. We further discuss how the facial anatomy of Nycticebus spp. relates to their unique physiology and behavioral ecology.

Prevalence and risk factors for milk allergy overdiagnosis in the BEEP trial cohort.

BACKGROUND: Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual-level and primary care practice-level risk factors. METHODS: We analysed data from 1394 children born in England in 2014-2016 (BEEP trial, ISRCTN21528841). Participants underwent formal CMA diagnosis at ≤2 years. CMA overdiagnosis was defined in three separate ways: parent-reported milk reaction; primary care record of milk hypersensitivity symptoms; and primary care record of low-allergy formula prescription. RESULTS: CMA was formally diagnosed in 19 (1.4%) participants. CMA overdiagnosis was common: 16.1% had parent-reported cow's milk hypersensitivity, 11.3% primary care recorded milk hypersensitivity and 8.7% had low-allergy formula prescription. Symptoms attributed to cow's milk hypersensitivity in participants without CMA were commonly gastrointestinal and reported from a median age of 49 days. Low-allergy formula prescriptions in participants without CMA lasted a median of 10 months (interquartile range 1, 16); the estimated volume consumed was a median of 272 litres (26, 448). Risk factors for CMA overdiagnosis were high practice-based low-allergy formula prescribing in the previous year and maternal report of antibiotic prescription during pregnancy. Exclusive formula feeding from birth was associated with increased low-allergy formula prescription. There was no evidence that practice prescribing of paediatric adrenaline auto-injectors or anti-reflux medications, or maternal features such as anxiety, age, parity and socioeconomic status were associated with CMA overdiagnosis. CONCLUSION: CMA overdiagnosis is common in early infancy. Risk factors include high primary care practice-based low-allergy formula prescribing and maternal report of antibiotic prescription during pregnancy.

Developmental milestones in captive Galago moholi.

Systems of the body develop in a modular manner. For example, neural development in primates is generally rapid, whereas dental development varies much more. In the present study, we examined development of the skull, teeth, and postcrania in a highly specialized leaping primate, Galago moholi. Eighteen specimens ranging from birth to adult were studied. Bones, teeth, and the cranial cavity (i.e., endocast) were reconstructed with Amira software based on microCT cross-referenced to histology. Amira was also used to compute endocast volume (as a proxy for brain size). Reconstructions of the wrist and ankle show that ossification is complete at 1 month postnatally, consistent with the onset of leaping locomotion in this species. Endocranial volume is less than 50% of adult volume at birth, ~80% by 1 month, and has reached adult volume by 2 months postnatal age. Full deciduous dentition eruption occurs by 2 weeks, and the young are known to begin capturing and consuming arthropods on their own by 4 weeks, contemporaneous with the timing of bone and ankle ossification that accompanies successful hunting. The modular pattern of development of body systems in Galago moholi provides an interesting view of a "race" to adult morphology for some joints that are critical for specialized leaping and clinging, rapid crown mineralization to begin a transitional diet, but perhaps more prolonged reliance on nursing to support brain growth.

The first complete T2T Assemblies of Cattle and Sheep Y-Chromosomes uncover remarkable divergence in structure and gene content.

Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. We assembled complete and gapless telomere to telomere (T2T) Y chromosomes for these species. The pseudo-autosomal regions were similar in length, but the total chromosome size was substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity was accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 18MYA. The centromeres also differed dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosome have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.

Development of a novel self-assessment tool following endoscopic sinus surgery in the management of chronic rhinosinusitis.

OBJECTIVE: To propose a novel quality metric tool for retrospectively examining ESS performed on chronic rhinosinusitis (CRS) patients, ultimately to facilitate clinician self-assessment and optimize care provision within this population. DESIGN: Quality improvement study. SETTING: Multi-center. PARTICIPANTS: Observational, prospective research database of adult patients with medically recalcitrant CRS, presenting to seven North-American academic rhinology centers, who underwent ESS between 2011 and 2021. Participant characteristics, comorbidities, and preoperative study measures were collected. MAIN OUTCOMES AND MEASURES: A simple ratio of preoperative Lund-Mackay (LM) score to the number of sinus regions operated on during the course of ESS was determined for each participant and dichotomized into ratios of >1.0 or <1.0. RESULTS: 828 study participants with medically recalcitrant CRS met final study inclusion, of which 47.8 % were male with an average age of 49.0 years. Approximately 50.9 % of participants had a history of previous ESS. Overall mean ratio between preoperative LM scores and numbers of surgically addressed sinuses for all patients with CRS (n = 828) was 1.61 (range: 0.00-6.00), with a minority of subjects (n = 108; 13.0 %) found to have ratios below 1.00. Mean ratios between patients who underwent primary ESS versus revision ESS were not statistically different (2.00 [±0.83] vs 1.98 [±0.88]; 0.02 %, 95 % CI -0.10, 0.14; P = 0.76), whereas differences in mean ratios between CRSsNP patients (without nasal polyposis) and CRSwNP patients (with nasal polyposis) were statistically significant (1.78 [±0.93] vs 2.26 [±0.67]; 0.48 %, 95 % CI 0.37, 0.59; P ≤ 0.001). CONCLUSIONS AND RELEVANCE: This quality metric ratio represents a simple operational means for clinicians to integrate qualitative methodology into self-reflection when evaluating the extent of ESS performed on CRS patients. Its use as a clinical tool for retrospective self-reflection enables the surgeon to identify areas for improvement, assess situational specifics, and hone their craft.

Engineered IgM and IgG cleaving enzymes for mitigating antibody neutralization and complement activation in AAV gene transfer.

Systemic dosing of adeno-associated viral (AAV) vectors poses potential risk of adverse side effects including complement activation triggered by anti-capsid immunity. Due to the multifactorial nature of toxicities observed in this setting, a wide spectrum of immune modulatory regimens are being investigated in the clinic. Here, we discover an IgM cleaving enzyme (IceM) that degrades human IgM, a key trigger in the anti-AAV immune cascade. We then engineer a fusion enzyme (IceMG) with dual proteolytic activity against human IgM and IgG. IceMG cleaves B cell surface antigen receptors and inactivates phospholipase gamma signaling in vitro. Importantly, IceMG is more effective at inhibiting complement activation compared with an IgG cleaving enzyme alone. Upon IV dosing, IceMG rapidly and reversibly clears circulating IgM and IgG in macaques. Antisera from these animals treated with IceMG shows decreased ability to neutralize AAV and activate complement. Consistently, pre-conditioning with IceMG restores AAV transduction in mice passively immunized with human antisera. Thus, IgM cleaving enzymes show promise in simultaneously addressing multiple aspects of anti-AAV immunity mediated by B cells, circulating antibodies and complement. These studies have implications for improving safety of AAV gene therapies and possibly broader applications including organ transplantation and autoimmune diseases.

Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study.

Objectives: Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens, comparing normosmic and dysosmic CRS patients without polyps (CRSsNP). Methods: Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery. Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic (n = 7) and normosmic (n = 4) patients. Results: Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes. Using stringent criteria for multiple comparisons, one upregulated gene (Immediate Early Response 3 [IER3]) had an false discovery rate (FDR) correction adjusted P value considered statistically significant (P < 0.001, fold change 2.69). Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients (P < 0.05, FDR correction) including IL-4 and IL-13 signaling, IL-10 signaling, and rhodopsin-like receptors. Conclusions: RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction. This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP. This study also prompts questions regarding the role of IL-10, rhodopsin-like receptors, and IER3 in the pathogenesis of olfactory dysfunction.

Pilot trial of perampanel on peritumoral hyperexcitability and clinical outcomes in newly diagnosed high-grade glioma.

Background: Glutamatergic neuron-glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the AMPA-R antagonist, perampanel, on intraoperative electrophysiologic hyperexcitability and clinical outcomes. Methods: An open-label trial was performed comparing perampanel to standard of care (SOC) in patients undergoing resection of newly-diagnosed radiologic high-grade glioma. Perampanel was administered as a pre-operative loading dose followed by maintenance therapy until progressive disease or up to 12-months. SOC treatment involved levetiracetam for 7-days or as clinically indicated. The primary outcome of hyperexcitability was defined by intra-operative electrocorticography high frequency oscillation (HFO) rates. Seizure-freedom and overall survival (OS) were estimated by the Kaplan-Meier method. Tissue concentrations of perampanel, levetiracetam, and metabolites were measured by mass spectrometry. Results: HFO rates were similar between perampanel-treated and SOC cohorts. The trial was terminated early after interim analysis for futility, and outcomes assessed in 11 patients (7 perampanel-treated, 4 SOC). Over a median 281 days of post-enrollment follow-up, 27% of patients had seizures, including 14% treated with perampanel and 50% treated with SOC. OS in perampanel-treated patients was similar to a glioblastoma reference cohort (p=0.81). Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations. Conclusions: A peri-operative loading regimen of perampanel was safe and well-tolerated, with similar peritumoral hyperexcitability as in levetiracetam-treated patients. Maintenance anti-glutamatergic therapy was not observed to impact survival outcomes.

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis.

OBJECTIVES: The 22-question SinoNasal Outcome Test (SNOT-22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT-22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT-22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF). METHODS: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT-22 scores were obtained at baseline and after 3-6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution-based methods were used to assess internal consistency and calculate the MCID of the SNOT-22. RESULTS: A total of 184 PwCF participated with mean baseline SNOT-22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre- and post-HEMT data reported improvement in SNOT-22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT-22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02-1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14-18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39-20.11) were associated with greater SNOT-22 improvement. The mean MCID calculated via distribution-based methods was 8.5. CONCLUSION: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT-22 in PwCF is 8.5 points, similar to non-CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT-22 has strong internal consistency in PwCF. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Cardiovascular risk, social vigilance, and stress profiles of male law enforcement officers versus civilians.

This study examined the cardiovascular disease (CVD) risk profiles of male law enforcement officers (LEOs) and civilians. CVD risk profiles were based on data collected using traditional objective (e.g., resting BP, cholesterol), novel objective (e.g., ambulatory BP) and self-report measures (e.g., EMA social vigilance). A subset of male LEOs (n = 30, M age = 41.47, SD = 8.03) and male civilians (n = 120, M age = 40.73, SD = 13.52) from a larger study were included in analyses. Results indicated LEOs had significantly higher body mass index [BMI], 31.17 kg/m2 versus 28.87 kg/m2, and exhibited significantly higher trait and state social vigilance across multiple measures, whereas perceived stress was higher among civilians. Findings highlight the need for future research examining CVD risk associated with occupational health disparities, including attributes of individuals entering certain professions as well as experiential and environmental demands of the work.