410 results on '"Wang EW"'
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2. The bipedicled anterior septal flap: a radioanatomic and cadaveric study.
- Author
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Bleier BS, Curry WT, Wang EW, Schlosser RJ, Bleier, Benjamin S, Curry, William T, Wang, Eric W, and Schlosser, Rodney J
- Abstract
Objectives/hypothesis: Pedicled mucosal flaps are the preferred method of endoscopic skull base reconstruction. Vascularized coverage of the anterior and posterior frontal tables remains a challenge given the lack of large caliber vessels supplying the anterior septum. The objective of this study was to define a novel bipedicled anterior septal (BAS) flap that is hypothesized to be capable of providing reproducible coverage of these difficult areas.Study Design: Radioanatomic and cadaveric study.Methods: The flap outline was superimposed over nine midline sagittal computed tomography images. The pedicles are comprised of the septal branch of the superior labial artery and the nasopalatine artery. The flap length subtended the distance from the incisive canal to the sphenoid face at the level of the choanal arch. Radiometric analysis of the flap length to base ratio and anterior/posterior frontal table coverage were calculated. These projected values were confirmed in four cadaveric dissection specimens.Results: The mean flap length was 39.64 ± 4.26 mm with a mean length:base ratio of 3.29 ± 0.70 and a total surface area of 916.46 ± 262.66 mm(2) . The flap was estimated to provide coverage of 100.31 ± 21.34% of the frontal beak and 50.74 ± 32.54% of the posterior frontal table. In all cadaveric specimens the flap extended beyond the superior aspect of the frontal beak and at least 50% of the posterior table.Conclusions: The BAS flap represents a novel septal mucosal flap based on two well-defined arterial inputs. This flap is capable of providing reliable vascularized coverage of the posterior frontal table and the frontal beak following frontal drillout. [ABSTRACT FROM AUTHOR]- Published
- 2011
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3. Pseudomonas aeruginosa lipopolysaccharide induces osteoclastogenesis through a toll-like receptor 4 mediated pathway in vitro and in vivo.
- Author
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Zhuang L, Jung JY, Wang EW, Houlihan P, Ramos L, Pashia M, and Chole RA
- Published
- 2007
4. Transposon mutagenesis identifies novel genes associated with Staphylococcus aureus persister formation
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Wang ewenjie, Chen ejiazhen, Chen eGang, Du eXin, Cui ePeng, Wu eJing, Zhao eJing, Wu eNan, Zhang ewenhong, Li eMin, and Ying eZhang
- Subjects
Staphylococcus aureus ,antibiotics ,Persisters ,Stress conditions ,Transposon mutant library ,Microbiology ,QR1-502 - Abstract
Pathogenic bacterial persisters are responsible for the recalcitrance of chronic and persistent infections to antimicrobial therapy. Although the mechanisms of persister formation and survival have been widely studied in Escherichia coli, persistence mechanisms in S. aureus remain largely unknown. Here, we screened a transposon mutant library of a clinical methicillin-resistant Staphylococcus aureus(MRSA)strain, USA500 (ST8), under antibiotic pressure and identified 13 genes whose insertion mutations resulted in a defect in persistence. These candidate genes were further confirmed by evaluating the survival of the mutants upon exposure to levofloxacin and several other stress conditions. We found 13 insertion mutants with significantly lower persister numbers under several stress conditions, including sdhA, sdhB, ureG, mnhG1, fbaA, ctaB, clpX, parE, HOU_0223, HOU_0587, HOU_2091, HOU_2315 and HOU_2346, which mapped into pathways of oxidative phosphorylation, TCA cycle, glycolysis, cell cycle and ABC transporters, suggesting that these genes and pathways may play an important role in persister formation and survival. The newly constructed knockout strains of ureG, sdhA and sdhB and their complemented strains were also tested for defect in persisters following exposure to levofloxacin and several other stress conditions. The results from these experiments were consistent with the screening results, which indicated that deletion of these genes in MRSA USA500 leads to persister defect. These findings provide novel insights into the mechanisms of persister formation and survival in S. aureus and offer new targets for the development of persister-directed antibiotics for the improved treatment of chronic and persistent infections.
- Published
- 2015
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5. Ginsenoside Rd promotes glutamate clearance by up-regulating glial glutamate transporter GLT-1 via PI3K/AKT and ERK 1/2 pathways
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Zhang eXiao, shi eming, Magnar eBjørås, wang ewei, zhang eguangyun, han ejunliang, liu ezhirong, zhang eyunxia, wang ebing, chen ejing, zhu eyi, xiong elize, and Zhao eGang
- Subjects
Stroke ,Glutamate ,Neuroprotection ,astrocyte ,PI3K/AKT ,ginseng ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, has been showed to protect against ischemic cerebral damage both in vitro and in vivo. However, the underlying mechanism of Rd is largely unknown. Excessive extracellular glutamate causes excitatory toxicity, leading to cell death and neurodegenerative processes after brain ischemia. The clearance of extracellular glutamate by astrocytic glutamate transporter GLT-1 is essential for neuronal survival after stroke. Here we investigated the effects of Rd on the levels of extracellular glutamate and the expression of GLT-1 in vivo and in vitro. After rat middle cerebral artery occlusion (MCAO), Rd significantly increased the mRNA and protein expression levels of GLT-1, and reduced the burst of glutamate as revealed by microdialysis. Consistently, specific glutamate uptake by cultured astrocytes was elevated after Rd exposure. Furthermore, we showed that Rd increased the levels of phosphorylated protein kinase B (PKB/Akt) and phospho-ERK1/2 (p-ERK1/2) in astrocyte culture after oxygen-glucose deprivation(OGD). Moreover, the effect of Rd on GLT-1 expression and glutamate uptake can be abolished by PI3K/AKT agonist LY294002 or ERK1/2 inhibitor PD98059. Taken together, our findings provide the first evidence that Rd can promote glutamate clearance by up-regulating GLT-1 expression through PI3K/AKT and ERK1/2 pathways.
- Published
- 2013
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6. Endoscopic-assisted transorbital extended orbital exenteration: A multi-institutional preclinical study.
- Author
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Roccuzzo G, Vyskocil E, Hirtler L, Kandathil SA, Peris-Celda M, Agosti E, Kuan EC, Wang EW, Leong S, Sharma R, Borsetto D, Herman P, Vinciguerra A, Verillaud B, Bresson D, Taboni S, Erovic BM, Vural A, Dallan I, Doglietto F, Schreiber A, Mattavelli D, Rampinelli V, Arosio AD, Battaglia P, Valentini M, Turri-Zanoni M, Pozzi F, Volpi L, Bignami M, Castelnuovo P, Nicolai P, and Ferrari M
- Subjects
- Humans, Surveys and Questionnaires, Paranasal Sinus Neoplasms surgery, Paranasal Sinus Neoplasms pathology, Orbital Neoplasms surgery, Female, Male, Neoplasm Invasiveness pathology, Endoscopy methods, Orbit Evisceration, Feasibility Studies
- Abstract
Background: Sinonasal malignancies with orbital invasion have dismal prognosis even when treated with orbital exenteration (OE). Sugawara et al. developed a surgical strategy called "extended-OE (EOE)," showing encouraging outcomes. We hypothesized that a similar resection is achievable under endoscopic guidance through the exenterated orbit (endoscopic-EOE)., Methods: The study was conducted in three institutions: University of Vienna; Mayo Clinic; University of Insubria; 48 orbital dissections were performed. A questionnaire was developed to evaluate feasibility and safety of each step, scoring from 1 to 10, ("impossible" to "easy," and "high risk" to "low risk," respectively), most likely complication(s) were hypothesized., Results: The step-by-step technique is thoroughly described. The questionnaire was answered by 25 anterior skull base surgeons from six countries. Mean, median, range, and interquartile range of both feasibility and safety scores are reported., Conclusions: Endoscopic-EOE is a challenging but feasible procedure. Clinical validation is required to assess real-life outcomes., (© 2024 Wiley Periodicals LLC.)
- Published
- 2024
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7. Recurrence morbidity of olfactory neuroblastoma.
- Author
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Melder K, Mace JC, Choby G, Almeida JP, Champagne PO, Chan E, Ciporen J, Chaskes MB, Fernandez-Miranda J, Fung NK, Gardner P, Hwang P, Ji KSY, Kalyvas A, Kong KA, Patel C, Patel Z, Celda MP, Pinheiro-Neto CD, Snyderman C, Thorp BD, Van Gompel JJ, Zenonos G, Zwagerman NT, Sanusi O, Wang EW, and Geltzeiler M
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- Humans, Male, Female, Middle Aged, Retrospective Studies, Aged, Adult, Nasal Cavity pathology, Prognosis, Neoplasm Staging, Esthesioneuroblastoma, Olfactory pathology, Esthesioneuroblastoma, Olfactory mortality, Esthesioneuroblastoma, Olfactory therapy, Nose Neoplasms pathology, Nose Neoplasms mortality, Nose Neoplasms epidemiology, Nose Neoplasms diagnosis, Neoplasm Recurrence, Local epidemiology
- Abstract
Background: With modern treatment paradigms, olfactory neuroblastoma (ONB) has favorable overall survival (OS); however, the incidence of recurrence remains high. The primary aims of this study were to delineate the prognosis of recurrence of ONB and explore how recurrence subsites are associated with OS, disease-specific survival (DSS), and further recurrence., Methods: A retrospective chart review of ONB cases from nine academic centers between 2005 and 2021 was completed. Tumor characteristics, recurrence subsites, timelines to recurrence, additional recurrences, and survival estimates were determined using descriptive and time-to-event analyses., Results: A final cohort of 233 patients was identified, with 70 (30.0%) patients recurring within 50.4 (standard deviation ±40.9) months of diagnosis on average, consisting of local (50%), neck (36%), intracranial (9%), and distant (6%) recurrence. Compared with subjects without recurrence, patients with recurrence had significantly different primary American Joint Committee on Cancer T stage (p < 0.001), overall stage (p < 0.001), and modified Kadish scores (p < 0.001). Histopathology identified that dural involvement and positive margins were significantly greater in recurrent cases. First recurrence was significantly associated with worse 5-year DSS (hazard ratio = 5.62; p = 0.003), and subjects with neck or local recurrence had a significantly better DSS compared to intracranial or distant recurrence., Conclusions: Recurrent cases of ONB have significantly different stages and preoperative imaging factors. Patients with local or neck recurrence, however, have better DSS than those with intracranial or distant recurrence, independent of initial tumor stage or Hyams grade. Identifying specific factors that confer an increased risk of recurrence and DSS is important for patient counseling in addition to surveillance planning., (© 2024 ARS‐AAOA, LLC.)
- Published
- 2024
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8. American Rhinologic Society expert practice statement part 1: Skull base reconstruction following endoscopic skull base surgery.
- Author
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Douglas JE, Adappa ND, Choby G, Levine CG, Rabinowitz MR, Sindwani R, Wang EW, Woodworth BA, and Kuan EC
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- Humans, Societies, Medical, Surgical Flaps, United States, Endoscopy methods, Plastic Surgery Procedures methods, Skull Base surgery
- Abstract
The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence for technical factors that optimize outcomes in skull base reconstruction following endoscopic skull base surgery for intradural pathologies. These topics include the use of free mucosal grafts versus vascularized pedicled nasoseptal flaps; the use of autologous versus synthetic grafts; and the roles of lumbar drains, dural sealants, and nasal packing. This EPS was developed following the recommended methodology and approval process as previously outlined. As there are a myriad of techniques and limited agreement on the accepted principles of skull base reconstruction, this EPS aims to summarize the existing evidence and provide clinically meaningful guidance on these divergent practices. Following a modified Delphi approach, five statements were developed, four of which reached consensus and one of which reached near consensus. These statements and the accompanying evidence are summarized along with an assessment of future needs., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)
- Published
- 2024
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9. Carotid Plexus Sympathetic Nerves as a Landmark for the Abducens Nerve Within the Cavernous Sinus During Endoscopic Endonasal Surgery: Cadaveric Anatomic Study and Surgical Consideration.
- Author
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Phoominaonin IS, Vargas Rosales AF, Choby GW, Wang EW, Zenonos GA, Snyderman CH, and Gardner PA
- Abstract
Background and Objectives: The abducens nerve (CN VI) is vulnerable to injury during endoscopic endonasal transcavernous surgery. In this study, the authors aimed to develop the surgical anatomic landmark and explore the relationship between the sympathetic nerves (SNs) around the internal carotid artery (ICA) and CN VI within the cavernous sinus (CS)., Methods: The relationship and patterns between the SNs and CN VI were investigated in 15 cadaveric specimens. The intraoperative examples of anatomic landmark were presented., Results: There were SNs around the ICA running into the CN VI, classified into ascending SNs and accessory sympathetic branches. The ascending SNs were divided into 3 types: (1) Type I had a single ascending SN. There were 2 subtypes of Type I (Type IA [17/30, 56.7%] was defined as a single ascending branch that ran into the CN VI, and Type IB [4/30, 13.3%] was defined as a single ascending branch with a terminal bifurcation before merging into the CN VI or lateral CS wall), (2) Type II (7/30, 23.3%) was defined as 2 ascending branches that ran into the CN VI and the lateral CS wall, and (3) Type III (2/30, 6.7%) was defined as 3 ascending branches that ran into the CN VIs and the lateral wall of the CS. The accessory branches of the SNs were defined by sympathetic branches from the posterior genu or horizontal ICA and found in 6/30 sides (20%)., Conclusion: The authors propose a classification of the relationship between paraclival ICA SNs and the CN VI within the CS, as approached during endoscopic endonasal surgery. The consistent relationship of the ascending SN and CN VI within the CS provides a reliable anatomic landmark during the endonasal approach to the CS., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)
- Published
- 2024
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10. Limb reduction in an Esco2 cohesinopathy mouse model is mediated by p53-dependent apoptosis and vascular disruption.
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Strasser AS, Gonzalez-Reiche AS, Zhou X, Valdebenito-Maturana B, Ye X, Zhang B, Wu M, van Bakel H, and Jabs EW
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- Animals, Mice, Cell Cycle Proteins metabolism, Cell Cycle Proteins genetics, Female, Toluene analogs & derivatives, Toluene pharmacology, Ectromelia genetics, Ectromelia metabolism, Ectromelia pathology, Benzothiazoles pharmacology, Signal Transduction, Male, DNA Damage, Cell Cycle Checkpoints genetics, Cell Cycle Checkpoints drug effects, Limb Buds metabolism, Hemorrhage pathology, Hemorrhage genetics, Hypertelorism, Homeodomain Proteins, Craniofacial Abnormalities, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Protein p53 genetics, Apoptosis genetics, Disease Models, Animal, Cohesins, Chromosomal Proteins, Non-Histone metabolism, Chromosomal Proteins, Non-Histone genetics, Limb Deformities, Congenital genetics, Limb Deformities, Congenital pathology, Limb Deformities, Congenital metabolism
- Abstract
Roberts syndrome (RBS) is an autosomal recessive disorder with profound growth deficiency and limb reduction caused by ESCO2 loss-of-function variants. Here, we elucidate the pathogenesis of limb reduction in an Esco2
fl/fl ;Prrx1-CreTg/0 mouse model using bulk- and single-cell-RNA-seq and gene co-expression network analyses during embryogenesis. Our results reveal morphological and vascular defects culminating in hemorrhage of mutant limbs at E12.5. Underlying this abnormal developmental progression is a pre-apoptotic, mesenchymal cell population specific to mutant limb buds enriched for p53-related signaling beginning at E9.5. We then characterize these p53-related processes of cell cycle arrest, DNA damage, cell death, and the inflammatory leukotriene signaling pathway in vivo. In utero treatment with pifithrin-α, a p53 inhibitor, rescued the hemorrhage in mutant limbs. Lastly, significant enrichments were identified among genes associated with RBS, thalidomide embryopathy, and other genetic limb reduction disorders, suggesting a common vascular etiology among these conditions., (© 2024. The Author(s).)- Published
- 2024
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11. Cyclin A/B RxL Macrocyclic Inhibitors to Treat Cancers with High E2F Activity.
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Singh S, Gleason CE, Fang M, Laimon YN, Khivansara V, Xie S, Durmaz YT, Sarkar A, Ngo K, Savla V, Li Y, Abu-Remaileh M, Li X, Tuladhar B, Odeh R, Hamkins-Indik F, He D, Membreno MW, Nosrati M, Gushwa NN, Leung SSF, Fraga-Walton B, Hernandez L, Baldomero MP, Lent BM, Spellmeyer D, Luna JF, Hoang D, Gritsenko Y, Chand M, DeMart MK, Metobo S, Bhatt C, Shapiro JA, Yang K, Dupper NJ, Bockus AT, Doench JG, Aggen JB, Liu LF, Levin B, Wang EW, Vendrell I, Fischer R, Kessler B, Gokhale PC, Signoretti S, Spektor A, Kreatsoulas C, Singh R, Earp DJ, Garcia PD, Nijhawan D, and Oser MG
- Abstract
Cancer cell proliferation requires precise control of E2F1 activity; excess activity promotes apoptosis. Here, we developed cell-permeable and bioavailable macrocycles that selectively kill small cell lung cancer (SCLC) cells with inherent high E2F1 activity by blocking RxL-mediated interactions of cyclin A and cyclin B with select substrates. Genome-wide CRISPR/Cas9 knockout and random mutagenesis screens found that cyclin A/B RxL macrocyclic inhibitors (cyclin A/Bi) induced apoptosis paradoxically by cyclin B- and Cdk2-dependent spindle assembly checkpoint activation (SAC). Mechanistically, cyclin A/Bi hyperactivate E2F1 and cyclin B by blocking their RxL-interactions with cyclin A and Myt1, respectively, ultimately leading to SAC activation and mitotic cell death. Base editor screens identified cyclin B variants that confer cyclin A/Bi resistance including several variants that disrupted cyclin B:Cdk interactions. Unexpectedly but consistent with our base editor and knockout screens, cyclin A/Bi induced the formation of neo-morphic Cdk2-cyclin B complexes that promote SAC activation and apoptosis. Finally, orally-bioavailable cyclin A/Bi robustly inhibited tumor growth in chemotherapy-resistant patient-derived xenograft models of SCLC. This work uncovers gain-of-function mechanisms by which cyclin A/Bi induce apoptosis in cancers with high E2F activity, and suggests cyclin A/Bi as a therapeutic strategy for SCLC and other cancers driven by high E2F activity.
- Published
- 2024
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12. Immunotherapy in the Management of Sinonasal Mucosal Melanoma: A Systematic Review.
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Tang A, Taori S, Dang S, Gardner PA, Zenonos GA, Davar D, Kuan EC, Snyderman CH, Wang EW, and Choby G
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- Humans, Nasal Mucosa, Mutation, Immune Checkpoint Inhibitors therapeutic use, Melanoma therapy, Melanoma drug therapy, Immunotherapy methods, Paranasal Sinus Neoplasms therapy
- Abstract
Objective: The aim of this work is to comprehensively review and synthesize the literature related to sinonasal mucosal melanoma (SNMM) treatment with immunotherapy, including potentially targetable genetic mutations, survival outcomes, and adverse events., Data Sources: Embase, Cochrane, Scopus, and Web of Science., Review Methods: The study protocol was designed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Databases were searched from inception through May 23, 2023., Results: A total of 42 studies met inclusion criteria. Twenty-four of the included studies reported genetic mutations for a combined 787 patients with SNMM. 8.1% (95% confidence interval, CI: 7.6-8.6), 18.9% (95% CI: 18.1-19.8), and 8.5% (95% CI: 8.1-9.0) of reported patients were positive for BRAF, NRAS, and KIT mutations, respectively. The presence of brisk tumor-infiltrating lymphocytes was associated with improved recurrence-free survival and overall survival (OS). Six studies reported a combined 5-year OS after adjuvant immunotherapy treatment of 42.6% (95% CI: 39.4-45.8). Thirteen studies encompassing 117 patients reported adjuvant or salvage immune checkpoint inhibitor (ICI) immunotherapy response rates: 40.2% (95% CI: 36.8-43.6) had a positive response (tumor volume reduction or resolution). Eleven studies reported direct comparisons between SNMM patients treated with or without immunotherapy; the majority (7/11) reported survival benefit for their entire cohort or select subgroups of SNMM patients. With the transition to modern ICIs, there is a stronger trend toward survival improvement with adjuvant ICI. Tumors with Ki67 <40% may respond better to ICI's., Conclusion: ICI therapy can be an effective in select SNMM patients, especially those with advanced/metastatic disease., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)
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- 2024
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13. SNOT-22 subdomain outcomes following treatment for sinonasal malignancy: A prospective, multicenter study.
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Grimm DR, Beswick DM, Maoz SL, Wang EW, Choby GW, Kuan EC, Chan EP, Adappa ND, Geltzeiler M, Getz AE, Humphreys IM, Le CH, Abuzeid WM, Chang EH, Jafari A, Kingdom TT, Kohanski MA, Lee JK, Nayak JV, Palmer JN, Patel ZM, Pinheiro-Neto CD, Resnick AC, Sim MS, Smith TL, Snyderman CH, John MA St, Storm P, Suh JD, Wang MB, and Hwang PH
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- Humans, Male, Female, Middle Aged, Prospective Studies, Aged, Sino-Nasal Outcome Test, Treatment Outcome, Adult, Quality of Life, Paranasal Sinus Neoplasms surgery, Paranasal Sinus Neoplasms therapy
- Abstract
Background: Patients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22-item Sinonasal Outcomes Test (SNOT-22) has been shown to improve with treatment. This study aims to characterize SNOT-22 subdomain outcomes in SNM., Methods: Patients diagnosed with SNM were prospectively enrolled in a multi-center patient registry. SNOT-22 scores were collected at the time of diagnosis and through the post-treatment period for up to 5 years. Multivariable regression analysis was used to identify drivers of variation in SNOT-22 subdomains., Results: Note that 234 patients were reviewed, with a mean follow-up of 22 months (3 months-64 months). Rhinologic, psychological, and sleep subdomains significantly improved versus baseline (all p < 0.05). Subanalysis of 40 patients with follow-up at all timepoints showed statistically significant improvement in rhinologic, extra-nasal, psychological, and sleep subdomains, with minimal clinically important difference met between 2 and 5 years in sleep and psychological subdomains. Adjuvant chemoradiation was associated with worse outcomes in rhinologic (adjusted odds ratio (5.22 [1.69-8.66])), extra-nasal (2.21 [0.22-4.17]) and ear/facial (5.53 [2.10-8.91]) subdomains. Pterygopalatine fossa involvement was associated with worse outcomes in rhinologic (3.22 [0.54-5.93]) and ear/facial (2.97 [0.32-5.65]) subdomains. Positive margins (5.74 [2.17-9.29]) and surgical approach-combined versus endoscopic (3.41 [0.78-6.05])-were associated with worse psychological outcomes. Adjuvant radiation (2.28 [0.18-4.40]) was associated with worse sleep outcomes., Conclusions: Sinonasal QOL improvements associated with treatment of SNM are driven by rhinologic, extra-nasal, psychological, and sleep subdomains., (© 2024 ARS‐AAOA, LLC.)
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- 2024
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14. Neuropathological findings and in vivo imaging correlates of the red nucleus compared to those of the substantia nigra pars compacta in parkinsonisms.
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Johnson ML, Lewis MM, Wang EW, Jellen LC, Du G, De Jesus S, Kong L, Pu C, and Huang X
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- Humans, Male, Aged, Female, Aged, 80 and over, Middle Aged, tau Proteins metabolism, Neuroglia pathology, Neuroglia metabolism, alpha-Synuclein metabolism, Neurons pathology, Neurons metabolism, Red Nucleus diagnostic imaging, Red Nucleus pathology, Red Nucleus metabolism, Magnetic Resonance Imaging, Pars Compacta diagnostic imaging, Pars Compacta pathology, Pars Compacta metabolism, Parkinsonian Disorders diagnostic imaging, Parkinsonian Disorders pathology, Parkinsonian Disorders metabolism, Substantia Nigra diagnostic imaging, Substantia Nigra pathology, Substantia Nigra metabolism
- Abstract
Introduction: The substantia nigra pars compacta (SNc) is the key pathologic locus in neurodegenerative parkinsonian disorders. Recently, in vivo susceptibility MRI metrics were associated with postmortem glial cell density and tau burden in the SNc of parkinsonism subjects. This study investigated the red nucleus (RN), another iron-rich region adjacent to the SNc and a potential site of higher functionality in parkinsonisms., Methods: In vivo MRI and postmortem data were obtained from 34 parkinsonism subjects and 3 controls. Neuron density, glial cell density, and percentages of area occupied by α-synuclein and tau were quantified using digitized midbrain slides. R2* and quantitative susceptibility mapping (QSM) metrics in the RN and SNc were derived from multi-gradient echo images. Histopathology data were compared between the RN and SNc using paired t-tests. MRI-histology associations were analyzed using partial Pearson correlations., Results: The RN had greater neuron (t
23 = 3.169, P = 0.004) and glial cell densities (t23 = 2.407, P = 0.025) than the SNc, whereas the SNc had greater α-synuclein (t28 = 4.614, P < 0.0001) and tau burden (t24 = 4.513, P = 0.0001). In both the RN (R2*: r = 0.47, P = 0.043; QSM: r = 0.52, P = 0.024) and SNc (R2*: r = 0.57, P = 0.01; QSM: r = 0.58, P = 0.009), MRI values were associated with glial cell density but not neuron density or α-synuclein (Ps > 0.092). QSM associated with tau burden (r = 0.49, P = 0.038) in the SNc, but not the RN., Conclusions: The RN is resilient to parkinsonian-related pathological processes compared to the SNc, and susceptibility MRI captured glial cell density in both regions. These findings help to further our understanding of the underlying pathophysiological processes in parkinsonisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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15. Changes in pituitary adenoma patient presentation and outcomes during the COVID pandemic at a Pituitary Center of Excellence.
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Tang A, Abdallah HM, Chang YF, Zenonos GA, Gardner PA, Choby GW, Wang EW, and Snyderman CH
- Abstract
Purpose: The COVID-19 pandemic caused significant disruption to the surgical care of patients. The aim of this study was to analyze the impact of the pandemic on endoscopic endonasal surgery (EES) for patients with a pituitary adenoma., Methods: Patients from 2015 to 2022 that had EES for a pituitary adenoma were included in this study. Patients were separated into pre-COVID (January 2015-March 2020) and COVID (March 2020-September 2022) groups. Univariate analysis was done using chi-square, fisher exact tests, and t-tests to compare groups., Results: This study included 492 patients that had EES for their pituitary adenoma. There were 314 patients in the pre-COVID group and 178 patients in the COVID group. Patients in the COVID group had a higher risk analysis index (RAI) frailty score (15 ± 10 pre-COVID vs. 20 ± 9 COVID, P < 0.001) and a higher American Society of Anesthesiology (ASA) physical status score (3 or 4) (72.0% pre-COVID vs. 81.9% COVID, P = 0.02). There were significantly more macroadenoma cases (87.6% pre-COVID vs. 94.4% COVID, P = 0.02) and extrasellar surgical approaches (45.2% pre-COVID vs. 61.2% COVID, P < 0.001) during COVID. There was no significant difference in length of stay (LOS) and readmission rates between groups., Conclusions: Patients that presented during the pandemic tended to be more frail, have more comorbidities, and require additional extrasellar surgical approaches. Despite changes in clinical presentation and operative management, the LOS and readmission rate remained stable during COVID, supporting the safety of this procedure during the recent pandemic., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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16. A phenomenon not to be missed: delayed postoperative cerebrospinal fluid rhinorrhea following no identifiable intraoperative leak in sellar surgery.
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Kshirsagar RS, Eide JG, Abiri A, Asmaro KP, Filip P, Pangal D, Ruzevick J, Adappa ND, Batra PS, Bergsneider MS, Craig JR, Fernandez-Miranda JC, Gardner PA, Grady MS, Halderman AA, Hsu FPK, Mohyeldin A, Palmer JN, Papagiannopoulos P, Snyderman CH, Tajudeen BA, Wang EW, Wang MB, Zada G, Zenonos GA, and Kuan EC
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- 2024
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17. American Rhinologic Society expert practice statement part 2: Postoperative precautions and management principles following endoscopic skull base surgery.
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Douglas JE, Adappa ND, Choby G, Levine CG, Rabinowitz MR, Sindwani R, Wang EW, Woodworth BA, and Kuan EC
- Abstract
The goal of this American Rhinologic Society expert practice statement (EPS) is to summarize the best available evidence regarding postoperative precautions for patients following endoscopic skull base surgery for intradural pathology. These topics include the administration of postoperative nasal hygiene; patient mobilization and activity level; the resumption of continuous positive airway pressure in patients with obstructive sleep apnea; and the timing and capacity with which a patient may be subjected to barotrauma, such as air travel postoperatively. This EPS was developed following the recommended methodology and approval process as previously outlined. Given the diverse practices and limited agreement on the accepted principles regarding postoperative precautions for patients following skull base surgery, this EPS seeks to summarize the existing literature and provide clinically relevant guidance to bring clarity to these differing practice patterns. Following a modified Delphi approach, four statements were developed, all of which reached consensus. Because of the paucity of literature on these topics, these statements represent a summation of the limited literature and the experts' opinions. These statements and the accompanying evidence are summarized below, along with an assessment of future needs., (© 2024 ARS‐AAOA, LLC.)
- Published
- 2024
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18. The role of induction chemotherapy for orbital invasion in sinonasal malignancies: A systematic review.
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Tang A, Calcaterra M, Harris M, Gardner PA, Zenonos GA, Stefko ST, Geltzeiler M, Zandberg DP, Snyderman CH, Wang EW, and Choby G
- Subjects
- Humans, Neoplasm Invasiveness, Treatment Outcome, Orbit pathology, Paranasal Sinus Neoplasms drug therapy, Paranasal Sinus Neoplasms pathology, Induction Chemotherapy, Orbital Neoplasms drug therapy, Orbital Neoplasms pathology
- Abstract
Background: Sinonasal malignancies (SNMs) frequently present with orbital invasion. Orbital exenteration (OE) can lead to significant morbidity. Induction chemotherapy (IC) is a promising treatment alternative that may allow for orbit preserving (OP) treatments without compromising patient survival. This systematic review was conducted to synthesize the published data on SNM patients with orbital invasion who underwent IC, including tumor response, orbital outcomes, and survival., Methods: The study protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Databases Embase, Cochrane, Medline, and Scopus, from inception to July 17, 2023, were searched., Results: Nineteen studies were included, encompassing 305 SNM patients with orbital invasion treated with IC. Fourteen studies reported an overall IC response rate (positive response defined as complete or partial tumor volume reduction) of 77.2%. Among included studies, OE rates after IC ranged from 0 to 40%. Three studies reported a high rate of posttreatment functional orbital preservation (89.8-96.0%). Five studies specifically reported that 62.5% (60 out of 96) of patients were downgraded from planned OE to OP treatment following IC. Three studies reported a significant overall survival (OS) improvement in IC responders versus IC nonresponders. Following IC, 5-year OS ranged from 44.2 to 55.5%. Patients with olfactory neuroblastoma demonstrated the highest IC response rate and lowest OE rate (100 and 0%, respectively) versus those with sinonasal undifferentiated carcinomas (68.4 and 0%) or squamous cell carcinomas (76.7 and 16%)., Conclusions: For select patients, IC may allow for OP in locally advanced SNMs with orbital involvement., (© 2024 ARS‐AAOA, LLC.)
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- 2024
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19. The Prognostic Implications of Neutrophil-to-Lymphocyte Ratio in Olfactory Neuroblastoma.
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Mocharnuk J, Daniels KE, Filimonov A, North LM, Gardner PA, Wang EW, and Snyderman CH
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Objective: Olfactory neuroblastoma is a rare sinonasal malignancy with comparatively positive prognosis and survival, but with a range of biological behaviors that can be difficult to prognosticate with current means of risk stratification. Neutrophil-to-lymphocyte ratio (NLR) has been found across a diverse range of malignancies to be associated with poorer outcomes. This paper aims to elucidate the relationship of NLR with olfactory neuroblastoma to assess its prognostic value in this setting., Study Design: Retrospective chart review., Setting: A single tertiary care academic hospital., Methods: The study cohort included all patients treated for initial presentation of olfactory neuroblastoma from 2004 to 2020. NLR was calculated from preoperative labs, and each patient was evaluated for Kadish staging, Hyams grade, intraoperative positive margin, use of adjuvant therapy, posttreatment recurrence, and death. All statistical analysis was conducted using R and relationship between NLR and variables was assessed via binomial logistic regression., Results: Forty-four patients were included, 24 were male. Average age 52.8, average length of follow-up was 9.6 years. Patients were grouped by low (Kadish A/B) and advanced (Kadish C/D) stage, n = 23 and n = 21, respectively, and low (Hyams I/II) and high (Hyams III/IV) risk, n = 15 and n = 11, respectively. Advanced Kadish stage was associated with elevated NLR, odds ratio 5.69 [2.30, 20.7], P = .001. No other variables were associated with elevated NLR including Hyams grade, margin status, recurrence, and mortality., Conclusion: Higher Kadish grade is associated with elevated NLR which may provide novel prognostic value to current risk-stratifying systems., (© 2024 The Author(s). Otolaryngology–Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)
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- 2024
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20. University of Washington Quality of Life subdomain outcomes after treatment of sinonasal malignancy: A prospective, multicenter study.
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Maoz SL, Golzar A, Choby G, Hwang PH, Wang EW, Kuan EC, Adappa ND, Geltzeiler M, Getz AE, Humphreys IM, Le CH, Pinheiro-Neto CD, Fischer JL, Chan EP, Abuzeid WM, Chang EH, Jafari A, Kingdom TT, Kohanski MA, Lee JK, Lazor JW, Nabavizadeh A, Nayak JV, Palmer JN, Patel ZM, Resnick AC, Smith TL, Snyderman CH, St John MA, Storm PB, Suh JD, Wang MB, Sim MS, and Beswick DM
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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., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)
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- 2024
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21. Multi-center study on sellar reconstruction after endoscopic transsphenoidal pituitary surgery.
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Ali HM, Leland EM, Stickney E, Lohse CM, Iyoha E, Valappil B, Filimonov A, Goetschel K, Young SC, Shahin MN, Sanusi O, Sonfack DJN, Nadeau S, Champagne PO, Geltzeiler M, Zwagerman NT, Gardner PA, Wang EW, Zenonos GA, Snyderman C, Van Gompel J, Link M, Peris-Celda M, Stokken J, Choby G, and Pinheiro-Neto CD
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Introduction: Surgical techniques for sellar reconstruction include no reconstruction, use of synthetic materials, autologous grafts, and/or vascularized flaps. The aim of this study was to conduct a multi-center study comparing the efficacy and postoperative morbidity associated with different sellar reconstruction techniques., Methods: A retrospective chart review of patients who underwent endoscopic transsphenoidal surgery for pituitary tumors from five participating sites between January 2021 and March 2023 was performed. The variables included demographics, tumor characteristics, reconstruction technique, postoperative cerebrospinal fluid leak (CSF) leak, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Comparisons of postoperative complications, SNOT-22 scores, and duration of surgery by type of onlay reconstruction were evaluated using Fisher's exact test, analysis of variance, and Kruskal‒Wallis test., Results: Five hundred and one patients were identified. The median tumor size was 2.1 cm, and 64% were non-functioning. Intraoperative CSF leak was identified in 38% of patients. A total of 89% of patients underwent onlay reconstruction: 49% were reconstructed with mucosal grafts, 35% with nasoseptal flaps, and 5% with other onlay techniques. Nasoseptal flaps were utilized more frequently in the setting of giant pituitary adenomas (>3 cm), medial cavernous sinus wall resection, and high-flow intraoperative CSF leaks. Cases who utilized mucosal grafts had an overall shorter operating time (median: 183 min vs. 240 min; p < 0.001). Five postoperative CSF leaks were identified, and therefore, statistical analysis could not be performed for this complication., Conclusion: The effectiveness and morbidity of different sellar reconstruction techniques are comparable. Vascularized flaps were utilized more frequently in the setting of larger tumors and high-flow intraoperative CSF leaks., (© 2024 ARS‐AAOA, LLC.)
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- 2024
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22. Endoscopic endonasal resection of Rathke cleft cysts: a single-institution analysis of 148 consecutive patients.
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Algattas HN, Gersey ZC, Fernandes Cabral D, Alattar AA, Abdallah H, Muthiah N, Khiyami A, Mehrotra N, Abdulwahid T, Wang EW, Snyderman CH, Zenonos GA, Fazeli PK, and Gardner PA
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Objective: The traditional treatment of sellar Rathke cleft cysts (RCCs) generally involves transsellar drainage; however, suprasellar RCCs present unique challenges to appropriate management and technical complexity. Reports on overall outcomes for the endoscopic endonasal approach (EEA) for this pathology are limited. The EEA for RCCs allows three surgical techniques: marsupialization, fenestration, and fenestration with cyst wall resection., Methods: The authors performed a retrospective review of consecutive patients with RCCs that had been treated via an EEA at a single institution between January 2004 and May 2021. Marsupialization entailed the removal of cyst contents while maintaining a drainage pathway into the sphenoid sinus. Fenestration involved the removal of cyst contents, followed by separation from the sphenoid sinus, often with a free mucosal graft or vascularized nasoseptal flap. Cyst wall resection, either partial or complete, was added to select cases., Results: A total of 148 patients underwent an EEA for RCC. Marsupialization or fenestration was performed in 88 cases (59.5%) and cyst wall resection in 60 (40.5%). Cysts were classified as having a purely sellar origin (43.2%), sellar origin with suprasellar extension (37.8%), and purely suprasellar origin (18.9%). Radiological recurrence was demonstrated in 22 cases (14.9%) at an average 39.7 months' follow-up (median 45 months, range 0.5-99 months), including 13 symptomatic cases (8.8%). Cases with cyst wall resection had no significantly different rate of recurrence (11.7% vs 15.9%, p = 0.48) or postoperative permanent anterior pituitary dysfunction (21.6% vs 12.5%, p = 0.29) compared to those of fenestrated and marsupialized cases. There was no significant difference in postoperative permanent posterior pituitary dysfunction based on technique, although such dysfunction tended to worsen with cyst wall resection (13.6% vs 4.0%, p = 0.09). Based on cyst location, purely suprasellar cysts were more likely to have a radiological recurrence (28.6%) than sellar cysts with suprasellar extension (12.5%) and purely sellar cysts (9.4%; p = 0.008). Most notably, of the 28 purely suprasellar cysts, selective cyst wall resection significantly improved the long-term (10-year) recurrence risk compared to fenestration alone (17.4% vs 80.0%, p = 0.0005) without any significant added risk of endocrinopathy., Conclusions: Endoscopic endonasal marsupialization or fenestration of sellar RCCs may be the ideal treatment strategy, whereas purely suprasellar cysts benefit from partial cyst wall resection to prevent recurrence. Selective cyst wall resection reduced long-term recurrence rates without significantly increasing rates of hypopituitarism.
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- 2024
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23. Science-informed Policy Making for Protecting People and the Environment from Radiation.
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Borrego D, Nagata JS, Boyd MA, DeCair SD, Matakas LR, Wang EW, Pawel DJ, and Ansari AJ
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- Humans, United States, Policy Making, United States Environmental Protection Agency, Radiation Exposure prevention & control, Radiation Exposure adverse effects, Science, Environmental Exposure prevention & control, Radiation Protection legislation & jurisprudence, Radiation Protection standards
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Abstract: The process to arrive at the radiation protection practices of today to protect workers, patients, and the public, including sensitive populations, has been a long and deliberative one. This paper presents an overview of the US Environmental Protection Agency's (US EPA) responsibility in protecting human health and the environment from unnecessary exposure to radiation. The origins of this responsibility can be traced back to early efforts, a century ago, to protect workers from x rays and radium. The system of radiation protection we employ today is robust and informed by the latest scientific consensus. It has helped reduce or eliminate unnecessary exposures to workers, patients, and the public while enabling the safe and beneficial uses of radiation and radioactive material in diverse areas such as energy, medicine, research, and space exploration. Periodic reviews and analyses of research on health effects of radiation by scientific bodies such as the National Academy of Sciences, National Council on Radiation Protection and Measurements, United Nations Scientific Committee on the Effects of Atomic Radiation, and the International Commission on Radiological Protection continue to inform radiation protection practices while new scientific information is gathered. As a public health agency, US EPA is keenly interested in research findings that can better elucidate the effects of exposure to low doses and low dose rates of radiation as applicable to protection of diverse populations from various sources of exposure. Professional organizations such as the Health Physics Society can provide radiation protection practitioners with continuing education programs on the state of the science and describe the key underpinnings of the system of radiological protection. Such efforts will help equip and prepare radiation protection professionals to more effectively communicate radiation health information with their stakeholders., (Copyright © 2024 Health Physics Society.)
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- 2024
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24. Effects of Speaking Rate Changes on Speech Motor Variability in Adults.
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Wang EW and Grigos MI
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The relationship between speaking rate and speech motor variability was examined in three groups of neurotypical adults, n = 40; 15 young adults (18-30 years), 13 adults (31-40 years), and 12 middle-aged adults (41-50 years). Participants completed a connected speech task at three speaking rates (habitual, fast, and slow) where kinematic (lower lip movement) and acoustic data were obtained. Duration and variability were measured at each speaking rate. Findings revealed a complex relationship between speaking rate and variability. Adults from the middle age range (31-40 years) demonstrated shorter acoustic and kinematic durations compared with the oldest age group (41-50 years) during the habitual speaking rate condition. All adults demonstrated the greatest variability in the slow speaking rate condition, with no significant differences in variability between habitual and fast speaking rates. Interestingly, lip aperture variability was significantly lower in the youngest age group (18-30 years) compared with the two older groups during the fast speaking rate condition. Differences in measures of acoustic variability were not observed across the age levels. Strong negative correlations between kinematic/acoustic duration and lip aperture/acoustic variability in the youngest age group were revealed. Therefore, while a slow speaking rate does result in greater variability compared with habitual and fast speaking rates, longer durations of productions by the different age groups were not linked to higher spatiotemporal index (STI) values, suggesting that timing influences speech motor variability, but is not the sole contributor.
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- 2024
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25. Oral Health-Related Quality of Life in Rare Disorders of Congenital Facial Weakness.
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Liberton DK, Almpani K, Mishra R, Bassim C, Van Ryzin C, On Behalf Of The Moebius Syndrome Research Consortium, Webb BD, Jabs EW, Engle EC, Collins FS, Manoli I, and Lee JS
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- Humans, Male, Female, Adult, Young Adult, Adolescent, Child, Middle Aged, Facial Paralysis psychology, Facial Paralysis physiopathology, Case-Control Studies, Rare Diseases psychology, Quality of Life, Oral Health
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Congenital facial weakness (CFW) encompasses a heterogenous set of rare disorders presenting with decreased facial movement from birth, secondary to impaired function of the facial musculature. The aim of the present study is to provide an analysis of subject-reported oral health-related quality of life (OHRQoL) in congenital facial weakness (CFW) disorders. Forty-four subjects with CFW and age- and sex- matched controls were enrolled in an Institutional Review Board (IRB)-approved study. Demographic data, medical and surgical history, comprehensive oral examination, and the Oral Health Impact Profile (OHIP-14) were obtained. Compared to unaffected controls, subjects with CFW had higher OHIP-14 scores overall (mean ± SD: 13.11 ± 8.11 vs. 4.46 ± 4.98, p < 0.0001) and within five of seven oral health domains, indicating decreased OHRQoL. Although subjects with Moebius syndrome (MBS) were noted to have higher OHIP-14 scores than those with Hereditary Congenital Facial Paresis (HCFP), there was no significant correlation in OHIP-14 score to age, sex, or specific diagnosis. An increase in OHIP-14 scores in subjects was detected in those who had undergone reanimation surgery. In conclusion, subjects with CFW had poorer OHRQoL compared to controls, and subjects with MBS had poorer OHRQoL than subjects with HCFP. This study provides better understanding of oral health care needs and quality of life in a CFW cohort and suggests that guidelines for dental treatment are required.
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- 2024
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26. The utility of inflammatory biomarkers in predicting overall survival and recurrence in skull base chordoma.
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Hoppe M, Gersey ZC, Muthiah N, Abdallah HM, Plute T, Abou-Al-Shaar H, Wang EW, Snyderman CH, Zenonos GA, and Gardner PA
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- Humans, Male, Female, Middle Aged, Adult, Retrospective Studies, Aged, Biomarkers, Tumor blood, Prognosis, Lymphocytes metabolism, Neutrophils, Young Adult, Chordoma surgery, Chordoma mortality, Skull Base Neoplasms surgery, Skull Base Neoplasms mortality, Neoplasm Recurrence, Local, Inflammation blood
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Objective: Numerous studies have investigated the impact of inflammatory factors in cancer, yet few attempts have been made to investigate these markers in skull base chordoma (SBC). Inflammatory values including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) can serve as prognostic markers in various cancers. This study aimed to determine whether these inflammatory factors influence overall survival (OS) or progression-free survival (PFS) in patients with primary SBC., Methods: The electronic medical records of patients with primary SBC who underwent resection from 2001 to 2020 were retrospectively reviewed for the associations of sex, age at diagnosis, preoperative steroid use, tumor volume, extent of resection, adjuvant radiation after surgery, tumor metastasis, Ki-67 index, percent homozygous deletion of 9p23 and percent 1p36 loss, and potential prognostic inflammatory markers of NLR, PLR, LMR, SII, and SIRI with the primary outcome measures of OS and PFS. Maximum log-rank statistical tests were used to determine inflammatory marker thresholds for grouping prior to Kaplan-Meier and Cox proportional hazards analysis for OS and PFS of the elucidated groups., Results: The cohort included 115 primary SBC patients. The mean ± SD tumor volume was 23.0 ± 28.0 cm3, 73% of patients received gross-total resection, 40% received postoperative radiation, 25% had local recurrence, and 6% had subsequent metastatic disease (mean follow-up 47.2 months). Univariable Cox analysis revealed that NLR (p < 0.01), PLR (p = 0.04), LMR (p = 0.04), SII (p < 0.01), and SIRI (p < 0.01) were independently associated with PFS. Additionally, NLR (p = 0.05) and SII (p = 0.03) were significant in multivariable Cox analysis of PFS. However, both univariable and multivariable Cox analysis revealed no correlations with OS., Conclusions: The routine assessment of inflammatory biomarkers such as NLR and SIRI could have prognostic value in postresection SBC patients.
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- 2024
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27. Targeting PARG induces tumor cell growth inhibition and antitumor immune response by reducing phosphorylated STAT3 in ovarian cancer.
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Martincuks A, Zhang C, Austria T, Li YJ, Huang R, Lugo Santiago N, Kohut A, Zhao Q, Borrero RM, Shen B, Cristea M, Wang EW, Song M, Rodriguez-Rodriguez L, and Yu H
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- Animals, Female, Humans, Mice, Cell Line, Immunity, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Ovarian Neoplasms drug therapy, STAT3 Transcription Factor drug effects, STAT3 Transcription Factor metabolism, Glycoside Hydrolases antagonists & inhibitors, Glycoside Hydrolases metabolism
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Background: Ovarian cancer is the most lethal gynecological malignancy, with limited treatment options after failure of standard therapies. Despite the potential of poly(ADP-ribose) polymerase inhibitors in treating DNA damage response (DDR)-deficient ovarian cancer, the development of resistance and immunosuppression limit their efficacy, necessitating alternative therapeutic strategies. Inhibitors of poly(ADP-ribose) glycohydrolase (PARG) represent a novel class of inhibitors that are currently being assessed in preclinical and clinical studies for cancer treatment., Methods: By using a PARG small-molecule inhibitor, COH34, and a cell-penetrating antibody targeting the PARG's catalytic domain, we investigated the effects of PARG inhibition on signal transducer and activator of transcription 3 (STAT3) in OVCAR8, PEO1, and Brca1 -null ID8 ovarian cancer cell lines, as well as in immune cells. We examined PARG inhibition-induced effects on STAT3 phosphorylation, nuclear localization, target gene expression, and antitumor immune responses in vitro, in patient-derived tumor organoids, and in an immunocompetent Brca1 -null ID8 ovarian mouse tumor model that mirrors DDR-deficient human high-grade serous ovarian cancer. We also tested the effects of overexpressing a constitutively activated STAT3 mutant on COH34-induced tumor cell growth inhibition., Results: Our findings show that PARG inhibition downregulates STAT3 activity through dephosphorylation in ovarian cancer cells. Importantly, overexpression of a constitutively activated STAT3 mutant in tumor cells attenuates PARG inhibitor-induced growth inhibition. Additionally, PARG inhibition reduces STAT3 phosphorylation in immune cells, leading to the activation of antitumor immune responses, shown in immune cells cocultured with ovarian cancer patient tumor-derived organoids and in immune-competent mice-bearing mouse ovarian tumors., Conclusions: We have identified a novel antitumor mechanism underlying PARG inhibition beyond its primary antitumor effects through blocking DDR in ovarian cancer. Furthermore, targeting PARG activates antitumor immune responses, thereby potentially increasing response rates to immunotherapy in patients with ovarian cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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28. Endoscopic endonasal approach for resection of odontoid process, decompression of the cervicomedullary junction spinal cord, and resection of pannus.
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Fernandes Cabral DT, Fernández-de Thomas RJ, Alattar A, Paul DA, Wang EW, and Gardner PA
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Odontoid pannus is an abnormal collection of degenerative or inflammatory tissue on the C1-dens joint that can result in severe spinal cord compression myelopathy. Treatment options vary depending on severity and etiology. In cases of severe cord compression, surgical management could be either through a purely posterior approach or in combination with an anterior decompression via endoscopic endonasal approach (EEA). This case presents a 77-year-old female who underwent posterior cervical fixation for odontoid pannus causing dramatic cervical myelopathy who failed to improve over a 6-month period and required anterior transodontoid pannus resection and decompression via EEA. The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23176., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication.The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication., (© 2024, The Authors.)
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- 2024
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29. Anterolateral keyhole transorbital routes to the skull base: a comparative anatomical study.
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Karampouga M, Terrarosa AK, Patel B, Affolter K, Wang EW, Choby GW, Fu R, Bonhomme GR, Stefko ST, McDowell MM, Snyderman CH, Gardner PA, and Zenonos GA
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- Humans, Cranial Fossa, Middle surgery, Cranial Fossa, Anterior surgery, Orbit surgery, Cadaver, Skull Base surgery, Skull Base anatomy & histology, Craniotomy methods
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Objective: Although keyhole transorbital approaches are gaining traction, their indications have not been adequately studied comparatively. In this study the authors have defined them also as transwing approaches-meaning that they use the different facies of the sphenoid wing for cranial entry-and sought to compare the four major ones: 1) lateral orbitocraniotomy through a lateral canthal incision (LatOrb); 2) modified orbitozygomatic approach through a palpebral incision (ModOzPalp); 3) modified orbitozygomatic approach through an eyebrow incision (ModOzEyB); and 4) supraorbital craniotomy through an eyebrow incision (SupraOrb), coupled with its expanded version (SupraTransOrb)., Methods: Cadaveric dissections were performed at the neuroanatomy lab. To delineate the skull base exposure, four formalin-fixed heads were used, with two sides dedicated to each approach. The outer limits were assessed via image guidance and were mapped and illustrated accordingly. A fifth head was dissected purely endoscopically, just to facilitate an overview of the transwing concept. Qualitative features were also rigorously examined., Results: The LatOrb proves to be more versatile in the middle cranial fossa (MCF), whereas the anterior cranial fossa (ACF) exposure is limited to a small area above the sphenoid ridge. An anterior clinoidectomy is possible; however, the exposure of the roof of the optic canal is suboptimal. The ModOzPalp adequately exposes both the ACF and MCF. Its lateral trajectory allows the inferior to superior view, yet there is restricted access to the medial anterior skull base (olfactory groove). The ModOzEyB also provides extensive exposure of the ACF and MCF, but has a more superior to inferior trajectory compared to the ModOzPalp, making it more appropriate for pathology reaching the medial anterior skull base or even the contralateral side. The anterior clinoidectomy is performed with improved visualization of the optic canal. The SupraOrb provides mainly anterior cranial base exposure, with minimal middle fossa. An anterior clinoidectomy can be performed, but without any direct observation of the superior orbital fissure. Some MCF access can be accomplished if the lateral sphenoid wing is drilled inferiorly, leading to its highly versatile variant, the SupraTransOrb., Conclusions: All the aforementioned approaches use the sphenoid wing as skull base corridor from a specific orientation point; hence these are designated as transwing approaches. Their peculiarities mandate careful case selection for the effective and safe completion of the surgical goals.
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- 2024
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30. Predictive factors for decreased baseline quality of life in patients with sinonasal malignancies.
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Fleseriu CM, Beswick DM, Maoz SL, Hwang PH, Choby G, Kuan EC, Chan EP, Adappa ND, Geltzeiler M, Getz AE, Humphries IM, Le CH, Abuzeid WM, Chang EH, Jafari A, Kingdom TT, Kohanski MA, Lee JK, Nabavizadeh SA, Nayak JV, Palmer JN, Patel ZM, Pinheiro-Neto CD, Resnick AC, Smith TL, Snyderman CH, St John MA, Storm J, Suh JD, Wang MB, and Wang EW
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- Male, Humans, Female, Treatment Outcome, Quality of Life, Endoscopy, Skull Base, Chronic Disease, Skull Base Neoplasms, Rhinitis
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Background: The impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT-22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling., Methods: Patients with previously untreated SNMs were prospectively enrolled (2015-2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT-22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL., Results: Among 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT-22 QOL in patients with skull base erosion (p = 0.02). SNOT-rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005)., Conclusions: Our findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex-specific and symptom-related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T-staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL., (© 2023 ARS‐AAOA, LLC.)
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- 2024
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31. Endoscopic Endonasal Far-Medial Approach: 2-Dimensional Operative Video.
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Ali MS, Algattas H, Zenonos GA, Wang EW, Snyderman CH, and Gardner PA
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- Humans, Cadaver, Endoscopy methods, Cranial Fossa, Posterior surgery, Cranial Fossa, Posterior anatomy & histology, Skull Base anatomy & histology, Nose
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Indications Corridor and Limits of Exposure: Endoscopic endonasal far-medial approach provides an effective and safe corridor to access the parasagittal structures of the lower clivus such as the medial jugular tubercle (JT) and occipital condyle (OC) for lesions that displace neurovascular structures laterally., Anatomic Essentials Need for Preoperative Planning and Assessment: Parapharyngeal internal carotid arteries (ICAs) run posterolateral to the eustachian tubes and lateral to the OC. The supracondylar groove is a superficial landmark for the hypoglossal canal, which divides the lateral extension of clivus into the JT and OC., Essential Steps of the Procedure: Typically, approach starts with opening of the sphenoid sinus to localize the paraclival ICA. An "inverted U" rhinopharyngeal (RP) flap exposing the supracondylar groove and lower clivus. Doppler and navigation can confirm the course of the ICA. Drilling is started in the midline in the lower clivus and extended laterally to expose the hypoglossal canal, JT, and OC., Pitfalls/avoidance of Complications: Neurovascular injuries can be avoided by using intraoperative Doppler and nerve stimulator. Multilayer reconstruction with vascularized nasoseptal (NSF) and RP flaps minimize postoperative cerebrospinal fluid leak., Variants and Indications for Their Use: The contralateral transmaxillary approach provides an increased angle of access behind foramen lacerum and the petrous ICA.The endoscopic endonasal far-medial approach can be used for a variety of pathologies, including petroclival or JT meningiomas, chordomas and chondrosarcomas, and hypoglossal schwannomas, inferiorly extending cholesterol granulomas and even rare, ventral posterior inferior cerebellar artery aneurysms.The patients consented to the procedure., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)
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- 2024
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32. Anteromedial Petrous (Gardner's) Triangle: Surgical Anatomy and Relevance for Endoscopic Endonasal Approach to the Petrous Apex and Petroclival Region.
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Coutinho da Silva MB, Hernández Hernández V, Gupta P, Lavinsky J, Zenonos GA, Wang EW, Snyderman CH, and Gardner PA
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- Humans, Cadaver, Nose, Endoscopy, Petrous Bone surgery, Petrous Bone pathology, Neurosurgical Procedures
- Abstract
Background and Objectives: Triangular corridors have been used as reliable surgical entry points for open transcranial approaches to the petrous apex (PA) and petroclival region (PCR). The endoscopic endonasal approaches have grown rapidly in the last decade, and the indications have advanced. The knowledge of accurate and reliable anatomic landmarks through endoscopic endonasal route is essential and remain to be established. The purpose of this study was to describe the feasibility and surgical exposure of the anteromedial petrous (Gardner's) triangle as a novel corridor to the PA and PCR., Methods: Five anatomic specimens were dissected. The PA and PCR were accessed through endoscopic endonasal approaches and contralateral transmaxillary approach. The limits of the anteromedial petrous (Gardner's) triangle were identified and dissected and associated measurements performed., Results: The dissection was divided into 6 steps. The limits of the anteromedial petrous (Gardner's) triangle were identified and defined by the paraclival internal carotid artery anterolaterally, the abducens nerve posteromedially, and the petroclival synchondrosis inferiorly. Three lines were established following the limits of the triangle. The mean distance of the anterolateral limit was 10.03 mm (SD = 0.94), of the posteromedial limit was 20.06 mm (SD = 2.90), and of the inferior limit was 17.99 mm (SD = 2.99). The mean area was 87.56 mm 2 (SD = 20.06). The 3 anatomic landmarks with a critical role to safely define the triangle were the pterygosphenoidal fissure, the petrosal process of the sphenoid bone, and the petroclival synchondrosis., Conclusion: The anteromedial (Gardner's) triangle is a well-defined bone corridor which provides access to the entire petrous bone and petroclival junction through endoscopic endonasal route. Regardless of the anatomic variations or tumor location, the landmarks of the abducens nerve, paraclival internal carotid artery, and petroclival synchondrosis are key for understanding lateral access to tumors extending from the clivus., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)
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- 2024
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33. Associations between maternal periconceptional alcohol consumption and risk of omphalocele among offspring, National Birth Defects Prevention Study, 1997-2011.
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Fisher SC, Romitti PA, Tracy M, Howley MM, Jabs EW, and Browne ML
- Subjects
- Pregnancy, Infant, Female, Humans, United States epidemiology, Risk Factors, Case-Control Studies, Maternal Exposure, Alcohol Drinking adverse effects, Alcohol Drinking epidemiology, Hernia, Umbilical epidemiology, Hernia, Umbilical etiology, Binge Drinking
- Abstract
Objective: Previous studies of alcohol consumption during pregnancy and omphalocele have produced mixed results. We updated an earlier analysis of National Birth Defects Prevention Study (NBDPS) data, adding six years of participants, to examine associations between maternal alcohol consumption and omphalocele., Methods: NBDPS was a multi-site, population-based case-control study in the United States. Cases were identified from birth defect surveillance programs in 10 states; controls were liveborn infants without a birth defect randomly selected from the same catchment areas. Mothers self-reported alcohol consumption during the periconceptional period (one month before through the third gestational month) via telephone interview. Our study included mothers of 410 omphalocele cases and 11,219 controls with estimated dates of delivery (EDDs) during 1997-2011. We used logistic regression to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for periconceptional alcohol consumption and omphalocele. We performed a probabilistic bias analysis to evaluate the impact of alcohol exposure misclassification on our results., Results: Overall, 44% of case and 38% of control mothers reported periconceptional alcohol consumption; 22% and 17%, respectively, reported binge drinking. Any maternal periconceptional alcohol consumption was associated with modestly increased odds of omphalocele (AOR 1.35, 95% CI 1.09, 1.68), as was binge drinking (AOR 1.47, 95% CI 1.08, 2.01). Our bias analysis yielded estimates further from the null., Conclusions: We observed modest associations between maternal periconceptional alcohol consumption and omphalocele. Based on our bias analysis, studies of alcohol and birth defects not accounting for exposure misclassification may underestimate associations., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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34. Transcriptomic landscape of human induced pluripotent stem cell-derived osteogenic differentiation identifies a regulatory role of KLF16.
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Ru Y, Ma M, Zhou X, Kriti D, Cohen N, D'Souza S, Schaniel C, Motch Perrine SM, Kuo S, Pinto D, Housman G, Wu M, Holmes G, Schadt E, van Bakel H, Zhang B, and Jabs EW
- Abstract
Osteogenic differentiation is essential for bone development and metabolism, but the underlying gene regulatory networks have not been well investigated. We differentiated mesenchymal stem cells, derived from 20 human induced pluripotent stem cell lines, into preosteoblasts and osteoblasts, and performed systematic RNA-seq analyses of 60 samples for differential gene expression. We noted a highly significant correlation in expression patterns and genomic proximity among transcription factor (TF) and long noncoding RNA (lncRNA) genes. We identified TF-TF regulatory networks, regulatory roles of lncRNAs on their neighboring coding genes for TFs and splicing factors, and differential splicing of TF, lncRNA, and splicing factor genes. TF-TF regulatory and gene co-expression network analyses suggested an inhibitory role of TF KLF16 in osteogenic differentiation. We demonstrate that in vitro overexpression of human KLF16 inhibits osteogenic differentiation and mineralization, and in vivo Klf16
+/- mice exhibit increased bone mineral density, trabecular number, and cortical bone area. Thus, our model system highlights the regulatory complexity of osteogenic differentiation and identifies novel osteogenic genes., Competing Interests: Competing interests The authors declare no competing interests- Published
- 2024
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35. International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors.
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Kuan EC, Wang EW, Adappa ND, Beswick DM, London NR Jr, Su SY, Wang MB, Abuzeid WM, Alexiev B, Alt JA, Antognoni P, Alonso-Basanta M, Batra PS, Bhayani M, Bell D, Bernal-Sprekelsen M, Betz CS, Blay JY, Bleier BS, Bonilla-Velez J, Callejas C, Carrau RL, Casiano RR, Castelnuovo P, Chandra RK, Chatzinakis V, Chen SB, Chiu AG, Choby G, Chowdhury NI, Citardi MJ, Cohen MA, Dagan R, Dalfino G, Dallan I, Dassi CS, de Almeida J, Dei Tos AP, DelGaudio JM, Ebert CS, El-Sayed IH, Eloy JA, Evans JJ, Fang CH, Farrell NF, Ferrari M, Fischbein N, Folbe A, Fokkens WJ, Fox MG, Lund VJ, Gallia GL, Gardner PA, Geltzeiler M, Georgalas C, Getz AE, Govindaraj S, Gray ST, Grayson JW, Gross BA, Grube JG, Guo R, Ha PK, Halderman AA, Hanna EY, Harvey RJ, Hernandez SC, Holtzman AL, Hopkins C, Huang Z, Huang Z, Humphreys IM, Hwang PH, Iloreta AM, Ishii M, Ivan ME, Jafari A, Kennedy DW, Khan M, Kimple AJ, Kingdom TT, Knisely A, Kuo YJ, Lal D, Lamarre ED, Lan MY, Le H, Lechner M, Lee NY, Lee JK, Lee VH, Levine CG, Lin JC, Lin DT, Lobo BC, Locke T, Luong AU, Magliocca KR, Markovic SN, Matnjani G, McKean EL, Meço C, Mendenhall WM, Michel L, Na'ara S, Nicolai P, Nuss DW, Nyquist GG, Oakley GM, Omura K, Orlandi RR, Otori N, Papagiannopoulos P, Patel ZM, Pfister DG, Phan J, Psaltis AJ, Rabinowitz MR, Ramanathan M Jr, Rimmer R, Rosen MR, Sanusi O, Sargi ZB, Schafhausen P, Schlosser RJ, Sedaghat AR, Senior BA, Shrivastava R, Sindwani R, Smith TL, Smith KA, Snyderman CH, Solares CA, Sreenath SB, Stamm A, Stölzel K, Sumer B, Surda P, Tajudeen BA, Thompson LDR, Thorp BD, Tong CCL, Tsang RK, Turner JH, Turri-Zanoni M, Udager AM, van Zele T, VanKoevering K, Welch KC, Wise SK, Witterick IJ, Won TB, Wong SN, Woodworth BA, Wormald PJ, Yao WC, Yeh CF, Zhou B, and Palmer JN
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- Humans, Quality of Life, Hypersensitivity, Head and Neck Neoplasms, Paranasal Sinus Neoplasms therapy, Paranasal Sinus Neoplasms pathology
- Abstract
Background: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field., Methods: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication., Results: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention., Conclusion: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)
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- 2024
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36. Electromyographic predictors of abducens nerve palsy after endoscopic skull base surgery.
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Jimenez JE, Omar M, Adams GM, Costacou T, Thirumala PD, Crammond DJ, Anetakis KM, Balzer JR, Shandal V, Snyderman CH, Gardner PA, Zenonos GA, and Wang EW
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- Humans, Retrospective Studies, Male, Female, Middle Aged, Case-Control Studies, Adult, Aged, Skull Base Neoplasms surgery, Electromyography, Abducens Nerve Diseases etiology, Abducens Nerve Diseases physiopathology, Skull Base surgery, Postoperative Complications etiology
- Abstract
Objective: Recovery of abducens nerve palsy (ANP) after endoscopic endonasal skull base surgery (ESBS) has been shown to be potentially predicted by postoperative ophthalmological examination. Triggered electromyography (t-EMG) and free-run electromyography (f-EMG) activity provide an intraoperative assessment of abducens nerve function, but associations with long-term ANP outcomes have not been explored. The objective of this study was to describe intraoperative abducens EMG characteristics and determine whether these electrophysiological profiles are associated with immediately postoperative and long-term ANP outcomes after ESBS., Methods: The authors conducted a 5-year (2011-2016) retrospective case-control study of patients who underwent ESBS in whom the abducens nerve was stimulated (t-EMG). Electrophysiological metrics were compared between patients with a new postoperative ANP (cases) and those without ANP (controls). Pathologies included chordoma, pituitary adenoma, meningioma, cholesterol granuloma, and chondrosarcoma. Electrophysiological data included the presence of abnormal f-EMG activity, t-EMG stimulation voltage, stimulation threshold, evoked compound muscle action potential (CMAP) amplitude, onset latency, peak latency, and CMAP duration at various stages of the dissection. Controls were selected such that pathologies were similarly distributed between cases and controls., Results: Fifty-six patients were included, 26 with new postoperative ANP and 30 controls without ANP. Abnormal f-EMG activity (28.0% vs 3.3%, p = 0.02) and lack of response to stimulation (27% vs 0%, p = 0.006) were more frequent in patients with immediately postoperative ANP than in controls. Patients with immediately postoperative ANP also had a lower median CMAP amplitude (35.0 vs 71.2 μV, p = 0.02) and longer onset latency (5.2 vs 2.8 msec, p = 0.04). Comparing patients with transient versus persistent ANP on follow-up, those with persistent ANP tended to have a lower CMAP amplitude (12.8 vs 57 μV, p = 0.07) and higher likelihood of not responding to stimulation at the end of the case (45.5% vs 7.1%, p = 0.06). Abnormal f-EMG was not associated with long-term ANP outcomes., Conclusions: The presence of f-EMG activity, lack of CMAP response to stimulation, decreased CMAP amplitude, and increased CMAP onset latency were associated with immediately postoperative ANP. Long-term ANP outcomes may be associated with t-EMG parameters, including whether the nerve is able to be stimulated once identified and CMAP amplitude. Future prospective studies may be designed to standardize abducens nerve electrophysiological monitoring protocols to further refine operative and prognostic utility.
- Published
- 2023
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37. Impact of Sodium Thiosulfate on Prevention of Nephrotoxicities in HIPEC: An Ancillary Evaluation of Cisplatin-Induced Toxicities in Ovarian Cancer.
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Senguttuvan RN, Santiago NL, Han ES, Lee B, Lee S, Lin WC, Kebria M, Hakim A, Lin JF, Wakabayashi MT, Ruel N, Tinsley R, Eng M, Stewart DB, Wang EW, Paz BI, Wu X, Cho H, Liang WS, Rodriguez-Rodriguez L, Cristea MC, Raoof M, and Dellinger TH
- Subjects
- Humans, Female, Cisplatin therapeutic use, Hyperthermic Intraperitoneal Chemotherapy, Prospective Studies, Neoplasm Recurrence, Local, Carcinoma, Ovarian Epithelial, Cytoreduction Surgical Procedures adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Antineoplastic Agents therapeutic use, Hyperthermia, Induced adverse effects, Ovarian Neoplasms pathology
- Abstract
Purpose: Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary., Methods: A prospective, nonrandomized, clinical trial evaluated safety outcomes of HIPEC with cisplatin 75 mg/m
2 during cytoreductive surgery (CRS) in patients with EOC (n = 34) and endometrial cancer (n = 6). Twenty-one patients received no ST (nST), and 19 received ST. Adverse events (AEs) were reported according to CTCAE v.5.0. Serum creatinine (Cr) was collected preoperatively and postoperatively (Days 5-8). Progression-free survival (PFS) was followed. Normal peritoneum was biopsied before and after HIPEC for whole transcriptomic sequencing to identify RNAseq signatures correlating with AEs., Results: Forty patients had HIPEC at the time of interval or secondary CRS. Renal toxicities in the nST group were 33% any grade AE and 9% grade 3 AEs. The ST group demonstrated no renal AEs. Median postoperative Cr in the nST group was 1.1 mg/dL and 0.5 mg/dL in the ST group (p = 0.0001). Median change in Cr from preoperative to postoperative levels were + 53% (nST) compared with - 9.6% (ST) (p = 0.003). PFS did not differ between the ST and nST groups in primary or recurrent EOC patients. Renal AEs were associated with downregulation of metabolic pathways and upregulation of immune pathways., Conclusions: ST significantly reduces acute renal toxicity associated with HIPEC with cisplatin in ovarian cancer patients. As nephrotoxicity is high in HIPEC with cisplatin, nephroprotective agents should be considered., (© 2023. The Author(s).)- Published
- 2023
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38. Recurrence patterns among patients with sinonasal mucosal melanoma: A multi-institutional study.
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Pandrangi VC, Mace JC, Abiri A, Adappa ND, Beswick DM, Chang EH, Eide JG, Fung N, Hong M, Johnson BJ, Kohanski MA, Kshirsagar RS, Kuan EC, Le CH, Lee JT, Nabavizadeh SA, Obermeyer IP, Palmer JN, Pinheiro-Neto CD, Smith TL, Snyderman CH, Suh JD, Wang EW, Wang MB, Choby G, and Geltzeiler M
- Subjects
- Female, Humans, Male, Disease-Free Survival, Nasal Mucosa, Neoplasm Recurrence, Local epidemiology, Retrospective Studies, Survival Rate, Middle Aged, Aged, Aged, 80 and over, Melanoma therapy, Paranasal Sinus Neoplasms surgery
- Abstract
Objective: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM)., Methods: This was a multi-institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan-Meier tests were used to evaluate disease-free survival (DFS), overall survival (OS), and post-recurrence survival (PRS) reported with standard errors (SE) and log-rank testing used for comparison. Cox-regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported., Results: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60-month DFS (SE) was 15.5% (2.9%), 60-month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60-month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60-month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12-month PRS (HR = 0.32, 95% CI = 0.11-0.92, p = 0.034), and no treatment group was associated with improved 24- or 60-month PRS (p > 0.05)., Conclusion: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12-month PRS., (© 2023 ARS-AAOA, LLC.)
- Published
- 2023
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39. Inability to move one's face dampens facial expression perception.
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Japee S, Jordan J, Licht J, Lokey S, Chen G, Snow J, Jabs EW, Webb BD, Engle EC, Manoli I, Baker C, and Ungerleider LG
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- Humans, Facial Expression, Emotions, Perception, Social Perception, Mobius Syndrome complications, Facial Paralysis etiology, Facial Paralysis psychology, Facial Recognition
- Abstract
Humans rely heavily on facial expressions for social communication to convey their thoughts and emotions and to understand them in others. One prominent but controversial view is that humans learn to recognize the significance of facial expressions by mimicking the expressions of others. This view predicts that an inability to make facial expressions (e.g., facial paralysis) would result in reduced perceptual sensitivity to others' facial expressions. To test this hypothesis, we developed a diverse battery of sensitive emotion recognition tasks to characterize expression perception in individuals with Moebius Syndrome (MBS), a congenital neurological disorder that causes facial palsy. Using computer-based detection tasks we systematically assessed expression perception thresholds for static and dynamic face and body expressions. We found that while MBS individuals were able to perform challenging perceptual control tasks and body expression tasks, they were less efficient at extracting emotion from facial expressions, compared to matched controls. Exploratory analyses of fMRI data from a small group of MBS participants suggested potentially reduced engagement of the amygdala in MBS participants during expression processing relative to matched controls. Collectively, these results suggest a role for facial mimicry and consequent facial feedback and motor experience in the perception of others' facial expressions., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Published by Elsevier Ltd.)
- Published
- 2023
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40. POLD1 DEDD Motif Mutation Confers Hypermutation in Endometrial Cancer and Durable Response to Pembrolizumab.
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Wei CH, Wang EW, Ma L, Zhou Y, Zheng L, Hampel H, Shehayeb S, Lee S, Cohen J, Kohut A, Fan F, Rosen S, Wu X, Shen B, and Zhao Y
- Abstract
Background: Mutations in the DNA polymerase delta 1 (POLD1) exonuclease domain cause DNA proofreading defects, hypermutation, hereditary colorectal and endometrial cancer, and are predictive of immunotherapy response. Exonuclease activity is carried out by two magnesium cations, bound to four highly conserved, negatively charged amino acids (AA) consisting of aspartic acid at amino acid position 316 (p.D316), glutamic acid at position 318 (p.E318), p.D402, and p.D515 (termed DEDD motif). Germline polymorphisms resulting in charge-discordant AA substitutions in the DEDD motif are classified as variants of uncertain significance (VUSs) by laboratories and thus would be considered clinically inactionable. We hypothesize this mutation class is clinically pathogenic., Methods: A review of clinical presentation was performed in our index patient with a POLD1(p.D402N) heterozygous proband with endometrial cancer. Implications of this mutation class were evaluated by a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review, in silico analysis with orthogonal biochemical confirmation, and whole-exome and RNA sequencing analysis of the patient's tumor and engineered cell lines., Results: Our systematic review favored a Mendelian disease mutation class associated with endometrial and colorectal cancers. In silico analysis predicted defective protein function, confirmed by biochemical assay demonstrating loss of nuclease activity. A POLD1 -specific mutational signature was found in both the patient's tumor and POLD1 (p.D402N) overexpressing cell. Furthermore, paired whole-exome/transcriptome analysis of endometrial tumor demonstrated hypermutation and T cell-inflamed gene expression profile (GEP), which are joint predictive biomarkers for pembrolizumab. Our patient showed a deep, durable response to immune checkpoint inhibitor (ICI)., Conclusion: Charge-discordant AA substitution in the DEDD motif of POLD1 is detrimental to DNA proofreading and should be reclassified as likely pathogenic and possibly predictive of ICI sensitivity.
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- 2023
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41. Long-term quality of life after treatment in sinonasal malignancy: A prospective, multicenter study.
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Maoz SL, Wang EW, Hwang PH, Choby G, Kuan EC, Fleseriu CM, Chan EP, Adappa ND, Geltzeiler M, Getz AE, Humphreys IM, Le CH, Abuzeid WM, Chang EH, Jafari A, Kingdom TT, Kohanski MA, Lee JK, Lazor JW, Nabavizadeh A, Nayak JV, Palmer JN, Patel ZM, Pinheiro-Neto CD, Resnick AC, Smith TL, Snyderman CH, St John MA, Storm PB, Suh JD, Wang MB, Sim MS, and Beswick DM
- Abstract
Background: Quality of life (QOL) for individuals with sinonasal malignancy (SNM) is significantly under-studied, yet it is critical for counseling and may impact treatment. In this study we evaluated how patient, treatment, and disease factors impact sinonasal-specific and generalized QOL using validated metrics in a large cohort over a 5-year posttreatment time frame., Methods: Patients with SNM who underwent definitive treatment with curative intent were enrolled in a prospective, multisite, longitudinal observational study. QOL was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22) and University of Washington Quality of Life Questionnaire (UWQOL) instruments at pretreatment baseline and multiple follow-ups through 5 years posttreatment. Multivariable modeling was used to determine demographic, disease, and treatment factors associated with disease-specific and generalized physical and social/emotional function QOL., Results: One hundred ninety-four patients with SNM were analyzed. All QOL indices were impaired at pretreatment baseline and improved after treatment. SNOT-22 scores improved 3 months and UWQOL scores improved 6 to 9 months posttreatment. Patients who underwent open compared with endoscopic tumor resection had worse generalized QOL (p < 0.001), adjusted for factors including T stage. Pterygopalatine fossa (PPF) involvement was associated with worse QOL (SNOT-22, p < 0.001; UWQOL Physical dimension, p = 0.02). Adjuvant radiation was associated with worse disease-specific QOL (p = 0.03). Neck dissection was associated with worse generalized physical function QOL (p = 0.01). Positive margins were associated with worse generalized social/emotional function QOL (p = 0.01)., Conclusion: Disease-specific and generalized QOL is impaired at baseline in patients with SNM and improves after treatment. Endoscopic resection is associated with better QOL. PPF involvement, adjuvant radiation, neck dissection, and positive margins were associated with worse QOL posttreatment., (© 2023 ARS-AAOA, LLC.)
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- 2023
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42. Monozygotic twins discordant for a congenital cranial dysinnervation disorder with features of Moebius syndrome.
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Gates RW, Webb BD, Stevenson DA, Jabs EW, DeFilippo C, Ruzhnikov MRZ, and Tise CG
- Abstract
Moebius syndrome is a congenital cranial dysinnervation disorder (CCDD) that presents with nonprogressive cranial nerve (CN) VI and VII palsies resulting in facial weakness and inability to abduct the eye(s). While many CCDDs have an underlying genetic cause, the etiology of Moebius syndrome remains unclear as most cases are sporadic. Here, we describe a pair of monochorionic, diamniotic twin girls; one with normal growth and development, and one with micrognathia, reduced facial expression, and poor feeding. Magnetic resonance imaging of the brain performed on the affected twin at 19 months of age showed severely hypoplastic or absent CN IV bilaterally, left CN VI smaller than right, and bilateral hypoplastic CN VII and IX, consistent with a diagnosis of a CCDD, most similar to that of Moebius syndrome. Genomic sequencing was performed on each twin and data was assessed for discordant variants, as well as variants in novel and CCDD-associated genes. No pathogenic, likely pathogenic, or variants of uncertain significance were identified in genes known to be associated with CCDDs or other congenital facial weakness conditions. This family provides further evidence in favor of a stochastic event as the etiology in Moebius syndrome, rather than a monogenic condition., (© 2023 Wiley Periodicals LLC.)
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- 2023
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43. Determinants of physician assessment of chronic rhinosinusitis disease control using EPOS 2020 criteria and the importance of incorporating patient perspectives of disease control.
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Sedaghat AR, Caradonna DS, Chandra RK, Franzese C, Gray ST, Halderman AA, Hopkins C, Kuan EC, Lee JT, McCoul ED, O'Brien EK, Pletcher SD, Pynnonen MA, Wang EW, Wise SK, Woodworth BA, Yao WC, and Phillips KM
- Abstract
Background: We identify chronic rhinosinusitis (CRS) manifestations associated with how rhinologists assess CRS control, with a focus on patient perspectives (patient-reported CRS control)., Methods: Fifteen rhinologists were provided with real-world data from 200 CRS patients. Participating rhinologists first classified patients' CRS control as "controlled," "partly controlled," and "uncontrolled" using seven CRS manifestations reflecting European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) CRS control criteria (nasal obstruction, drainage, impaired smell, facial pain/pressure, sleep disturbance, use of systemic antibiotics/corticosteroids in past 6 months, and nasal endoscopy findings) and patient-reported CRS control. They then classified patients' CRS control without knowledge of patient-reported CRS control. Interrater reliability and agreement of rhinologist-assessed CRS control with patient-reported CRS control and EPOS guidelines were determined., Results: CRS control classification with and without knowledge of patient-reported CRS control was highly consistent across rhinologists (κ
w = 0.758). Rhinologist-assessed CRS control agreed with patient-reported CRS control significantly better when rhinologists had knowledge of patient-reported CRS control (κw = 0.736 vs. κw = 0.554, p < 0.001). Patient-reported CRS control, nasal obstruction, drainage, and endoscopy findings were most strongly associated with rhinologists' assessment of CRS control. Rhinologists' CRS control assessments weakly agreed with EPOS CRS control guidelines with (κw = 0.529) and without (κw = 0.538) patient-reported CRS control. Rhinologists classified CRS as more controlled than EPOS guidelines in almost 50% of cases., Conclusions: This study directly demonstrates the importance of patient-reported CRS control as a dominant influence on rhinologists' CRS control assessment. Knowledge of patient-reported CRS control may better align rhinologists' CRS control assessments and treatment decisions with patients' perspectives., (© 2023 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)- Published
- 2023
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44. Snapshot Mueller spectropolarimeter imager.
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Dai T, Phan T, Wang EW, Kwon S, Son J, Lee M, and Fan JA
- Abstract
We introduce an imaging system that can simultaneously record complete Mueller polarization responses for a set of wavelength channels in a single image capture. The division-of-focal-plane concept combines a multiplexed illumination scheme based on Fourier optics together with an integrated telescopic light-field imaging system. Polarization-resolved imaging is achieved using broadband nanostructured plasmonic polarizers as functional pinhole apertures. The recording of polarization and wavelength information on the image sensor is highly interpretable. We also develop a calibration approach based on a customized neural network architecture that can produce calibrated measurements in real-time. As a proof-of-concept demonstration, we use our calibrated system to accurately reconstruct a thin film thickness map from a four-inch wafer. We anticipate that our concept will have utility in metrology, machine vision, computational imaging, and optical computing platforms., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Aerospace Information Research Institute, Chinese Academy of Sciences 2023.)
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- 2023
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45. Radiographic predictors of occult intracranial involvement in olfactory neuroblastoma patients.
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Geltzeiler M, Choby GW, Ji KSY, JessMace C, Almeida JP, de Almeida J, Champagne PO, Chan E, Ciporen JN, Chaskes MB, Cornell S, Drozdowski V, Fernandez-Miranda J, Gardner PA, Hwang PH, Kalyvas A, Kong KA, McMillan RA, Nayak JV, Patel C, Patel ZM, Celda MP, Pinheiro-Neto C, Sanusi OR, Snyderman CH, Thorp BD, Van Gompel JJ, Zadeh G, Zenonos G, Zwagerman NT, and Wang EW
- Subjects
- Humans, Cohort Studies, Nasal Cavity pathology, Retrospective Studies, Esthesioneuroblastoma, Olfactory diagnostic imaging, Nose Neoplasms diagnostic imaging
- Abstract
Background: Traditional management of olfactory neuroblastoma (ONB) includes margin-negative resection with removal of cribriform plate, dura, and olfactory bulb, regardless of intracranial disease. This approach may be overtreating certain patients. Our investigation examines risk factors associated with occult intracranial disease to optimize therapeutic outcomes., Methods: This retrospective, multi-institutional cohort study examined clinical covariates associated with occult intracranial involvement. Patient demographics, staging, Hyam's grade, and pathologic involvement of dura, olfactory bulb/tract, and brain were collected. Diagnostic imaging was reviewed. Positive and negative predictive value (NPV) were estimated along with effect size estimates. Cox hazard regression examined associations with overall survival (OS) and disease-free survival (DFS)., Results: A total of 224 subjects with new diagnoses of ONB (2005-2021) were identified. Skull base bone involvement on computed tomography (CT) had the highest NPV for pathologic dura (88.0%), olfactory bulb (88%), and brain involvement (97.3%). Hyam's grade category was significantly associated with dural involvement (φ
C = 0.26; 95% confidence interval [CI]: 0.16, 0.42). Subjects without radiologic skull base involvement (n = 66) had pathologic positivity of 12.1%. Within this subgroup, Hyam's grade was clinically significant for dural positivity (φ = 0.34; 95% CI: -0.12, 0.71) with 28.6% involvement in high grade tumors. Neither clinical nor pathologic positivity of intracranial structures were associated with significantly different OS or DFS., Conclusions: Both CT and magnetic resonance imaging (MRI) had reasonably good NPV for involvement of dura and olfactory bulb. Higher Hyam's grade was associated with dural involvement. Patients with low-grade tumors not involving the skull base may be suitable for avoiding skull base resection; however, further investigation is warranted., (© 2023 ARS-AAOA, LLC.)- Published
- 2023
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46. Orbital resection by intranasal technique (ORBIT): A new classification system for reporting endoscopically resectable primary benign orbital tumors.
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Jafari A, Adappa ND, Anagnos VJ, Campbell RG, Castelnuovo P, Chalian A, Chambers CB, Chitguppi C, Dallan I, El Rassi E, Freitag SK, Fernandez Miranda JC, Ferreira M Jr, Gardner PA, Gudis DA, Harvey RJ, Huang Q, Humphreys IM, Kennedy DW, Lee JYK, Lehmann AE, Locatelli D, McKinney KA, Moreau A, Nyquist G, Palmer JN, Prepageran N, Pribitkin EA, Rabinowitz MR, Rosen MR, Sacks R, Sharma D, Snyderman CH, Tonya Stefko S, Stokken JK, Wang EW, Workman AD, Wu AW, Yu JY, Zhang MM, Zhou B, and Bleier BS
- Subjects
- Humans, Female, Adult, Middle Aged, Male, Retrospective Studies, Treatment Outcome, Nose surgery, Endoscopy, Orbital Neoplasms surgery, Orbital Neoplasms pathology, Hemangioma, Cavernous surgery
- Abstract
Background: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs., Methods: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class., Results: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05)., Conclusion: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs., (© 2023 ARS-AAOA, LLC.)
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- 2023
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47. Endoscopic endonasal repair of encephaloceles of the lateral sphenoid sinus: multiinstitution confirmation of a new classification.
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Tosi U, Jackson C, D'Souza G, Rabinowitz M, Farrell C, Parsel SM, Anand VK, Kacker A, Tabaee A, Zenonos GA, Snyderman CH, Wang EW, Evans J, Rosen M, Nyquist G, Gardner PA, and Schwartz TH
- Subjects
- Humans, Female, Male, Hypesthesia, Sphenoid Sinus diagnostic imaging, Sphenoid Sinus surgery, Endoscopy, Encephalocele diagnostic imaging, Encephalocele surgery, Dry Eye Syndromes
- Abstract
Objective: Encephaloceles of the lateral sphenoid sinus are rare. Originally believed to be due to defects in a patent lateral craniopharyngeal canal (Sternberg canal), they are now thought to originate more commonly from idiopathic intracranial hypertension, not unlike encephaloceles elsewhere in the skull base. A new classification of these encephaloceles was recently introduced, which divided them in relation to the foramen rotundum. Whether this classification can be applied to a larger cohort from multiple institutions and whether it might be useful in predicting outcome is unknown. Thus, the authors' goal was to divide a multiinstitutional cohort of patients with lateral sphenoid encephaloceles into four subtypes to determine their incidence and any correlation with surgical outcome., Methods: A multicenter retrospective review of prospectively acquired databases was carried out across three institutions. Cases were categorized into one of four subtypes (type I, Sternberg canal; type II, medial to rotundum; type III, lateral to rotundum; and type IV, both medial and lateral with rotundum enlargement). Demographic and outcome metrics were collected. Kaplan-Meyer curves were used to determine the rate of recurrence after surgical repair., Results: A total of 49 patients (71% female) were included. The average BMI was 32.8. All encephaloceles fell within the classification scheme. Type III was the most common (71.4%), followed by type IV (16.3%), type II (10.2%), and type I (2%). Cases were repaired endonasally, via a transpterygoidal approach. Lumbar drains were placed in 78% of cases. A variety of materials was used for closure, with a nasoseptal flap used in 65%. After a mean follow-up of 47 months, there were 4 (8%) CSF leak recurrences, all in patients with type III or type IV leaks and all within 1 year of the first repair. Two leaks were fixed with ventriculoperitoneal shunt and reoperation, 1 with ventriculoperitoneal shunt only, and 1 with a lumbar drain only. Of 45 patients in whom detailed information was available, there were 12 (26.7%) with postoperative dry eye or facial numbness, with facial numbness occurring in type III or type IV defects only., Conclusions: Endoscopic endonasal repair of lateral sphenoid wing encephaloceles is highly successful, but repair may lead to dry eye or facial numbness. True Sternberg (type I) leaks were uncommon. Failures and facial numbness occurred only in patients with type III and type IV leaks.
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- 2023
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48. A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer.
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Holloway RW, Thaker P, Mendivil AA, Ahmad S, Al-Niaimi AN, Barter J, Beck T, Chambers SK, Coleman RL, Crafton SM, Crane E, Ramez E, Ghamande S, Graybill W, Herzog T, Indermaur MD, John VS, Landrum L, Lim PC, Lucci JA, McHale M, Monk BJ, Moore KN, Morris R, O'Malley DM, Reid TJ, Richardson D, Rose PG, Scalici JM, Silasi DA, Tewari K, and Wang EW
- Subjects
- Humans, Female, Bevacizumab, Prospective Studies, Carcinoma, Ovarian Epithelial, Platinum, Tumor Microenvironment, Viral Vaccines, Ovarian Neoplasms drug therapy
- Abstract
Background: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer., Primary Objective: The primary objective is to evaluate the efficacy of intra-peritoneal Olvi-Vec followed by platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer., Study Hypothesis: This phase III study investigates Olvi-Vec oncolytic immunotherapy followed by platinum-based chemotherapy and bevacizumab as an immunochemotherapy evaluating the hypothesis that such sequential combination therapy will prolong progression-free survival (PFS) and bring other clinical benefits compared with treatment with platinum-based chemotherapy and bevacizumab., Trial Design: This is a multicenter, prospective, randomized, and active-controlled phase III trial. Patients will be randomized 2:1 into the experimental arm treated with Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or the control arm treated with platinum-doublet chemotherapy and bevacizumab., Major Inclusion/exclusion Criteria: Eligible patients must have recurrent, platinum-resistant/refractory, non-resectable high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer. Patients must have had ≥3 lines of prior chemotherapy., Primary Endpoint: The primary endpoint is PFS in the intention-to-treat population., Sample Size: Approximately 186 patients (approximately 124 patients randomized to the experimental arm and 62 to the control arm) will be enrolled to capture 127 PFS events., Estimated Dates for Completing Accrual and Presenting Results: Expected complete accrual in 2024 with presentation of primary endpoint results in 2025., Trial Registration: NCT05281471., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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49. Nasal disease with polyps: Need for clarity.
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Pezato R, Stamm AC, Douglas R, Han JK, Chen PG, Neto CDP, Tepedino MS, Singh N, Balsalobre L, Ryu CH, Gregório L, Almatrafi S, Felippu AWD, Iturriaga E, Toledo RN, Cascio F, Dassi C, Alkholaiwi F, Bezerra TFP, Javer A, Dutra DL, Psaltis AJ, Migueis DP, Almutari N, Avelino MAG, Gunaratne DA, Felippu A, Pinna FR, Nakanishi M, Perez-Novo CA, Singhera GK, Choby G, Wang EW, Patel ZM, and Thamboo A
- Subjects
- Humans, Chronic Disease, Nose Diseases, Nasal Polyps diagnosis, Nasal Polyps therapy
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- 2023
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50. Multicenter Survival Analysis and Application of an Olfactory Neuroblastoma Staging Modification Incorporating Hyams Grade.
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Choby G, Geltzeiler M, Almeida JP, Champagne PO, Chan E, Ciporen J, Chaskes MB, Fernandez-Miranda J, Gardner P, Hwang P, Ji KSY, Kalyvas A, Kong KA, McMillan R, Nayak J, O'Byrne J, Patel C, Patel Z, Peris Celda M, Pinheiro-Neto C, Sanusi O, Snyderman C, Thorp BD, Van Gompel JJ, Young SC, Zenonos G, Zwagerman NT, and Wang EW
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- Humans, Male, Female, Middle Aged, Retrospective Studies, Case-Control Studies, Nasal Cavity, Survival Analysis, Neoplasm Staging, Disease Progression, Esthesioneuroblastoma, Olfactory therapy, Esthesioneuroblastoma, Olfactory mortality, Esthesioneuroblastoma, Olfactory pathology, Nose Neoplasms pathology
- Abstract
Importance: Current olfactory neuroblastoma (ONB) staging systems inadequately delineate locally advanced tumors, do not incorporate tumor grade, and poorly estimate survival and recurrence., Objective: The primary aims of this study were to (1) examine the clinical covariates associated with survival and recurrence of ONB in a modern-era multicenter cohort and (2) incorporate Hyams tumor grade into existing staging systems to assess its ability to estimate survival and recurrence., Design, Setting, and Participants: This retrospective, multicenter, case-control study included patients with ONB who underwent treatment between January 1, 2005, and December 31, 2021, at 9 North American academic medical centers., Intervention: Standard-of-care ONB treatment., Main Outcome and Measures: The main outcomes were overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) as C statistics for model prediction., Results: A total of 256 patients with ONB (mean [SD] age, 52.0 [15.6] years; 115 female [44.9%]; 141 male [55.1%]) were included. The 5-year rate for OS was 83.5% (95% CI, 78.3%-89.1%); for DFS, 70.8% (95% CI, 64.3%-78.0%); and for DSS, 94.1% (95% CI, 90.5%-97.8%). On multivariable analysis, age, American Joint Committee on Cancer (AJCC) stage, involvement of bilateral maxillary sinuses, and positive margins were associated with OS. Only AJCC stage was associated with DFS. Only N stage was associated with DSS. When assessing the ability of staging systems to estimate OS, the best-performing model was the novel modification of the Dulguerov system (C statistic, 0.66; 95% CI, 0.59-0.76), and the Kadish system performed most poorly (C statistic, 0.57; 95% CI, 0.50-0.63). Regarding estimation of DFS, the modified Kadish system performed most poorly (C statistic, 0.55; 95% CI, 0.51-0.66), while the novel modification of the AJCC system performed the best (C statistic, 0.70; 95% CI, 0.66-0.80). Regarding estimation of DSS, the modified Kadish system was the best-performing model (C statistic, 0.79; 95% CI, 0.70-0.94), and the unmodified Kadish performed the worst (C statistic, 0.56; 95% CI, 0.51-0.68). The ability for novel ONB staging systems to estimate disease progression across stages was also assessed. In the novel Kadish staging system, patients with stage VI disease were approximately 7 times as likely to experience disease progression as patients with stage I disease (hazard ratio [HR], 6.84; 95% CI, 1.60-29.20). Results were similar for the novel modified Kadish system (HR, 8.99; 95% CI, 1.62-49.85) and the novel Dulguerov system (HR, 6.86; 95% CI, 2.74-17.18)., Conclusions and Relevance: The study findings indicate that 5-year OS for ONB is favorable and that incorporation of Hyams grade into traditional ONB staging systems is associated with improved estimation of disease progression.
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- 2023
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