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1.
Am J Otolaryngol ; 44(5): 103932, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37245324

RESUMO

BACKGROUND: Overcoming non-standardization, vagueness, and subjectivity in sinus CT radiology reports is an ongoing need, particularly in keeping with data-driven healthcare initiatives. Our aim was to explore otolaryngologists' perceptions of quantitative objective disease measures as enabled by AI-based analysis, and determine preferences for sinus CT interpretation. METHODS: A multi-methods design was used. We administered a survey to American Rhinologic Society members and conducted semi-structured interviews with a purposeful sample of otolaryngologists and rhinologists from varying backgrounds, practice settings and locations during 2020-2021. Interview topics included sinus CT reports, familiarity with AI-based analysis, and potential requisites for its future implementation. Interviews were then coded for content analysis. Differences in survey responses were calculated using Chi-squared test. RESULTS: 120 of 955 surveys were returned, and 19 otolaryngologists (8 rhinologists) were interviewed. Survey data revealed more trust in conventional radiologist reports, but that AI-based reports would be more systematic and comprehensive. Interviews expanded on these results. Interviewees believed that conventional sinus CT reports had limited utility due to inconsistent content. However, they described relying on them for reporting incidental extra-sinus findings. Reporting could be improved with standardization and more detailed anatomical analysis. Interviewees expressed interest in AI-derived analysis given potential for standardization, although they desired evidence of accuracy and reproducibility to gain trust in AI-based reports. CONCLUSIONS: Sinus CT interpretation has shortcomings in its current state. Standardization and objectivity could be aided with deep learning-enabled quantitative analysis, although clinicians desire thorough validation to gain trust in the technology prior to its implementation.


Assuntos
Otorrinolaringologistas , Seios Paranasais , Humanos , Estados Unidos , Reprodutibilidade dos Testes , Seios Paranasais/diagnóstico por imagem , Inquéritos e Questionários , Tomografia Computadorizada por Raios X/métodos
2.
Sensors (Basel) ; 23(16)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37631803

RESUMO

Multiphase flowmeters (MPFMs) measure the flow rates of oil, gas, and brine in a pipeline. MPFMs provide remote access to real-time well production data that are essential for efficient oil field operations. Most MPFMs are complex systems requiring frequent maintenance. An MPFM that is operationally simple and accurate is highly sought after in the energy industry. This paper describes an MPFM that uses only pressure sensors to measure gas and liquid flow rates. The design is an integration of a previously developed densitometer with an innovative Venturi-type flowmeter. New computing models with strong analytical foundations were developed, aided by empirical correlations and machine-learning-based flow-regime identification. A prototype was experimentally validated in a multiphase flow loop over a wide range of field-like conditions. The accuracy of the MPFM was compared to that of other multiphase metering techniques from similar studies. The results point to a robust, practical MPFM.

3.
J Allergy Clin Immunol ; 149(5): 1513-1521, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35300985

RESUMO

Chronic rhinosinusitis (CRS) is a complex, heterogenous condition that is likely associated with infectious and inflammatory causative factors. Renewed interest in the role that microbes play in this condition has stemmed from advancements in microbe identification and parallel research implicating the microbiome as having a role in other chronic inflammatory conditions. This clinical commentary provides a review of the current literature relevant to chronic rhinosinusitis. Particular focus is placed on factors specific to investigation of the sinonasal microbiome, evidence for the role of dysbiosis in the disease state, and influences that may affect the microbiome. Possible mechanisms of disease and therapeutic implications through microbial manipulation are also reviewed, as are deficiencies and limitations of the current body of research.


Assuntos
Microbiota , Rinite , Sinusite , Doença Crônica , Disbiose , Humanos , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico
4.
J Allergy Clin Immunol ; 149(4): 1296-1308.e6, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863854

RESUMO

BACKGROUND: Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Currently, little is known about possible underlying distinguishing factors between these inflammatory differences. OBJECTIVE: Our aim was to interrogate differences in CRSwNP disease between White/non-Asian patients and Japanese patients by using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs). METHODS: We performed whole transcriptome RNA sequencing with endotype stratification of NPs from 8 White patients (residing in the United States) and 9 Japanese patients (residing in Japan). Reproducibility was confirmed by quantitative PCR in an independent validation set of 46 White and 31 Japanese patients. Single-cell RNA sequencing (scRNAseq) was used to stratify key cell types for contributory transcriptional signatures. RESULTS: Unsupervised clustering analysis identified 2 major endotypes that were present within both cohorts of patients with NPs and had previously been reported at the cytokine level: (1) type 2 endotype and (2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct subgroups with NPs (P = .03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells. CONCLUSION: NPs from both racial groups harbor the same 2 major endotypes, which we have determined to be present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Humanos , Japão , Pólipos Nasais/genética , Reprodutibilidade dos Testes , Rinite/genética , Sinusite/genética
5.
J Allergy Clin Immunol ; 147(5): 1732-1741.e1, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33549569

RESUMO

BACKGROUND: Although chronic rhinosinusitis (CRS) is considered the most treatable form of olfactory dysfunction, there has been relatively little clinical attention focused on assessing endotypes as they pertain to olfactory loss. OBJECTIVES: The goal of this study was to explore inflammatory endotypes in CRS using an unsupervised cluster analysis of olfactory cleft (OC) biomarkers in a phenotype-free approach. METHODS: Patients with CRS were prospectively recruited and psychophysical olfactory testing, Questionnaire of Olfactory Dysfunction (QOD-NS), and bilateral OC endoscopy were obtained. Mucus was collected from the OC and evaluated for 26 biomarkers using principal component analysis. Cluster analysis was performed using only OC biomarkers and differences in olfactory measures were compared across clusters. RESULTS: A total of 198 subjects (128 with CRS and 70 controls) were evaluated. Evaluation of OC biomarkers indicated 6 principal components, explaining 69.50% of the variance, with type 2, mixed type 1/Th17-cell, growth factor, and neutrophil chemoattractant inflammatory signatures. A total of 10 clusters were identified that differed significantly in frequency of controls, and subjects with CRS with nasal polyps, and subjects with CRS without nasal polyps across the clusters (likelihood ratio test, χ182=178.64; P < .001). Olfactory measures differed significantly across clusters, including olfactory testing, QOD-NS, and OC endoscopy (P < .001 for all). CONCLUSIONS: Clustering based solely on OC biomarkers can organize patients into clinically meaningful endotypes that discriminate between subjects with CRS and controls. Validation studies are necessary to confirm these findings and further refine olfactory endotypes.


Assuntos
Citocinas/imunologia , Muco/imunologia , Transtornos do Olfato/imunologia , Rinite/imunologia , Sinusite/imunologia , Adulto , Idoso , Biomarcadores , Doença Crônica , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal , Transtornos do Olfato/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico , Olfato , Adulto Jovem
6.
J Allergy Clin Immunol ; 147(5): 1704-1719, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33453291

RESUMO

BACKGROUND: Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD). OBJECTIVE: Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists. METHODS: A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD. RESULTS: The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction. CONCLUSIONS: The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Transtornos do Olfato , SARS-CoV-2/imunologia , Esteroides/uso terapêutico , Vitamina A/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/imunologia , Consenso , Medicina Baseada em Evidências , Transtornos do Olfato/tratamento farmacológico , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/imunologia , Guias de Prática Clínica como Assunto
7.
BMC Genomics ; 22(1): 224, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781205

RESUMO

BACKGROUND: Understanding viral infection of the olfactory epithelium is essential because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection. RESULTS: Herein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of mCherry as a marker for olfactory sensory neurons and for eGFP in OMP-H2B::mCherry/TRPM5-eGFP transgenic mice (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells compared to olfactory sensory neurons. CONCLUSION: Our study provides new insights into a potential role for TRPM5-expressing microvillous cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.


Assuntos
Neurônios Receptores Olfatórios , Canais de Cátion TRPM , Viroses , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mucosa Olfatória , Canais de Cátion TRPM/genética
8.
Chem Senses ; 462021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34473227

RESUMO

OBJECTIVE: Compare machine learning (ML)-based predictive analytics methods to traditional logistic regression in classification of olfactory dysfunction in chronic rhinosinusitis (CRS-OD) and identify predictors within a large multi-institutional cohort of refractory CRS patients. METHODS: Adult CRS patients enrolled in a prospective, multi-institutional, observational cohort study were assessed for baseline CRS-OD using a smell identification test (SIT) or brief SIT (bSIT). Four different ML methods were compared to traditional logistic regression for classification of CRS normosmics versus CRS-OD. RESULTS: Data were collected for 611 study participants who met inclusion criteria between 2011 April and 2015 July. Thirty-four percent of enrolled patients demonstrated olfactory loss on psychophysical testing. Differences between CRS normosmics and those with smell loss included objective disease measures (CT and endoscopy scores), age, sex, prior surgeries, socioeconomic status, steroid use, polyp presence, asthma, and aspirin sensitivity. Most ML methods performed favorably in terms of predictive ability. Top predictors include factors previously reported in the literature, as well as several socioeconomic factors. CONCLUSION: Olfactory dysfunction is a variable phenomenon in CRS patients. ML methods perform well compared to traditional logistic regression in classification of normosmia versus smell loss in CRS, and are able to include numerous risk factors into prediction models. Several actionable features were identified as risk factors for CRS-OD. These results suggest that ML methods may be useful for current understanding and future study of hyposmia secondary to sinonasal disease, the most common cause of persistent olfactory loss in the general population.


Assuntos
Transtornos do Olfato , Rinite , Adulto , Anosmia , Doença Crônica , Humanos , Aprendizado de Máquina , Transtornos do Olfato/complicações , Transtornos do Olfato/diagnóstico , Estudos Prospectivos , Rinite/complicações , Rinite/diagnóstico , Olfato
9.
Haematologica ; 104(10): 2061-2074, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30846494

RESUMO

Despite recent advances in the treatment of multiple myeloma, patients with this disease still inevitably relapse and become refractory to existing therapies. Mutations in K-RAS, N-RAS and B-RAF are common in multiple myeloma, affecting 50% of patients at diagnosis and >70% at relapse. However, targeting mutated RAS/RAF via MEK inhibition is merely cytostatic in myeloma and largely ineffective in the clinic. We examined mechanisms mediating this resistance and identified histone deacetylase inhibitors as potent synergistic partners. Combining the MEK inhibitor AZD6244 (selumetinib) with the pan-histone deacetylase inhibitor LBH589 (panobinostat) induced synergistic apoptosis in RAS/RAF mutated multiple myeloma cell lines. Interestingly, this synergy was dependent on the pro-apoptotic protein BIM. We determined that while single-agent MEK inhibition increased BIM levels, the protein remained sequestered by antiapoptotic BCL-2 family members. LBH589 dissociated BIM from MCL-1 and BCL-XL, which allowed it to bind BAX/BAK and thereby initiate apoptosis. The AZD6244/LBH589 combination was specifically active in cell lines with more BIM:MCL-1 complexes at baseline; resistant cell lines had more BIM:BCL-2 complexes. Those resistant cell lines were synergistically killed by combining the BH3 mimetic ABT-199 (venetoclax) with LBH589. Using more specific histone deacetylase inhibitors, i.e. MS275 (entinostat) and FK228 (romidepsin), and genetic methods, we determined that concomitant inhibition of histone deacetylases 1 and 2 was sufficient to synergize with either MEK or BCL-2 inhibition. Furthermore, these drug combinations effectively killed plasma cells from myeloma patients ex vivo Given the preponderance of RAS/RAF mutations, and the fact that ABT-199 has demonstrated clinical efficacy in relapsed/refractory multiple myeloma, these drug combinations hold prom ise as biomarker-driven therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Mieloma Múltiplo/tratamento farmacológico , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Inibidores de Histona Desacetilases/farmacologia , Humanos , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Mieloma Múltiplo/enzimologia , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Mutação , Panobinostat/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quinases raf/genética , Quinases raf/metabolismo , Proteínas ras/genética , Proteínas ras/metabolismo
10.
Chem Senses ; 44(9): 663-671, 2019 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-31504289

RESUMO

Forkhead box protein J1 (FOXJ1), a member of the forkhead family transcription factors, is a transcriptional regulator of motile ciliogenesis. The nasal respiratory epithelium, but not olfactory epithelium, is lined with FOXJ1-expressing multiciliated epithelial cells with motile cilia. In a transgenic mouse where an enhanced green fluorescent protein (eGFP) transgene is driven by the human FOXJ1 promoter, robust eGFP expression is observed not only in the multiciliated cells of the respiratory epithelium but in a distinctive small subset of olfactory sensory neurons in the olfactory epithelium. These eGFP-positive cells lie at the extreme apical part of the neuronal layer and are most numerous in dorsal-medial regions of olfactory epithelium. Interestingly, we observed a corresponding small number of glomeruli in the olfactory bulb wherein eGFP-labeled axons terminate, suggesting that the population of eGFP+ receptor cells expresses a limited number of olfactory receptors. Similarly, a subset of vomeronasal sensory neurons expresses eGFP and is distributed throughout the full height of the vomeronasal sensory epithelium. In keeping with this broad distribution of labeled vomeronasal receptor cells, eGFP-labeled axons terminate in many glomeruli in both anterior and posterior portions of the accessory olfactory bulb. These findings suggest that Foxj1-driven eGFP marks a specific population of olfactory and vomeronasal sensory neurons, although neither receptor cell population possess motile cilia.


Assuntos
Fatores de Transcrição Forkhead/genética , Proteínas de Fluorescência Verde/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Animais , Axônios/metabolismo , Cílios/metabolismo , Feminino , Proteínas de Fluorescência Verde/genética , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Bulbo Olfatório/metabolismo , Mucosa Olfatória/metabolismo , Regiões Promotoras Genéticas , RNA-Seq , Mucosa Respiratória/metabolismo , Órgão Vomeronasal/metabolismo
11.
Chem Senses ; 44(7): 511-521, 2019 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-31300812

RESUMO

Mucins are a key component of the surface mucus overlying airway epithelium. Given the different functions of the olfactory and respiratory epithelia, we hypothesized that mucins would be differentially expressed between these 2 areas. Secondarily, we evaluated for potential changes in mucin expression with radiation exposure, given the clinical observations of nasal dryness, altered mucus rheology, and smell loss in radiated patients. Immunofluorescence staining was performed to evaluate expression of mucins 1, 2, 5AC, and 5B in nasal respiratory and olfactory epithelia of control mice and 1 week after exposure to 8 Gy of radiation. Mucins 1, 5AC, and 5B exhibited differential expression patterns between olfactory and respiratory epithelium (RE) while mucin 2 showed no difference. In the olfactory epithelium (OE), mucin 1 was located in a lattice-like pattern around gaps corresponding to dendritic knobs of olfactory sensory neurons, whereas in RE it was intermittently expressed by surface goblet cells. Mucin 5AC was expressed by subepithelial glands in both epithelial types but to a higher degree in the OE. Mucin 5B was expressed by submucosal glands in OE and by surface epithelial cells in RE. At 1-week after exposure to single-dose 8 Gy of radiation, no qualitative effects were seen on mucin expression. Our findings demonstrate that murine OE and RE express mucins differently, and characteristic patterns of mucins 1, 5AC, and 5B can be used to define the underlying epithelium. Radiation (8 Gy) does not appear to affect mucin expression at 1 week. LEVEL OF EVIDENCE: N/A (Basic Science Research).IACUC-approved study [Protocol 200065].


Assuntos
Mucinas/biossíntese , Mucosa Nasal/metabolismo , Mucosa Respiratória/metabolismo , Animais , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mucinas/análise , Mucosa Nasal/química , Mucosa Respiratória/química
12.
Chem Senses ; 44(7): 483-495, 2019 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-31231752

RESUMO

Some bitter taste receptors (TAS2R gene products) are expressed in the human sinonasal cavity and may function to detect airborne irritants. The expression of all 25 human bitter taste receptors and their location within the upper airway is not yet clear. The aim of this study is to characterize the presence and distribution of TAS2R transcripts and solitary chemosensory cells (SCCs) in different locations of the human sinonasal cavity. Biopsies were obtained from human subjects at up to 4 different sinonasal anatomic sites. PCR, microarray, and qRT-PCR were used to examine gene transcript expression. The 25 human bitter taste receptors as well as the sweet/umami receptor subunit, TAS1R3, and canonical taste signaling effectors are expressed in sinonasal tissue. All 25 human bitter taste receptors are expressed in the human upper airway, and expression of these gene products was higher in the ethmoid sinus than nasal cavity locations. Fluorescent in situ hybridization demonstrates that epithelial TRPM5 and TAS2R38 are expressed in a rare cell population compared with multiciliated cells, and at times, consistent with SCC morphology. Secondary analysis of published human sinus single-cell RNAseq data did not uncover TAS2R or canonical taste transduction transcripts in multiciliated cells. These findings indicate that the sinus has higher expression of SCC markers than the nasal cavity in chronic rhinosinusitis patients, comprising a rare cell type. Biopsies obtained from the ethmoid sinus may serve as the best location for study of human upper airway taste receptors and SCCs.


Assuntos
Células Quimiorreceptoras/metabolismo , Cavidade Nasal/metabolismo , Receptores Acoplados a Proteínas G/genética , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Acoplados a Proteínas G/metabolismo
13.
Curr Allergy Asthma Rep ; 19(4): 21, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-30859336

RESUMO

PURPOSE OF REVIEW: Staphylococcus aureus (S. aureus) is correlated with the development of persistent severe inflammatory disease of the upper airway including chronic rhinosinusitis with nasal polyps (CRSwNP). The presence of S. aureus is associated with atopic disease including allergic rhinitis and atopic dermatitis and is associated with poor outcomes. RECENT FINDINGS: Several different strains of S. aureus generate different toxins and gene products that can account for organism pathogenicity. S. aureus bacteria and its antigens shape the bacterial and fungal microbiome and the mucosal niche which generates host responses that can account for inflammation. The multiple disease phenotypes and molecular endotypes seen in CRSwNP can be characterized by T-helper cell environment within the inflammatory milieu, the presence of epithelial barrier dysfunction, aberrant eicosanoid metabolism, poor wound healing, and dysfunctional host-bacteria interactions which lead to recalcitrant disease and worse surgical outcomes. Understanding the pathomechanisms that S. aureus utilizes to promote nasal polyp formation, prolonged tissue inflammation, and bacterial dysbiosis are essential in our efforts to identify new therapeutic approaches to resolve this chronic inflammatory process.


Assuntos
Pólipos Nasais/microbiologia , Rinite Alérgica/microbiologia , Sinusite/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/patogenicidade , Antígenos de Bactérias/imunologia , Doença Crônica , Enterotoxinas/imunologia , Humanos , Pólipos Nasais/diagnóstico , Pólipos Nasais/imunologia , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Sinusite/diagnóstico , Sinusite/imunologia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Superantígenos/imunologia
15.
Acta Neurochir (Wien) ; 161(4): 729-735, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30715605

RESUMO

BACKGROUND: Olfaction is an undervalued sense in neurosurgery. Attempted surgical resection of anterior cranial fossa meningiomas puts the olfactory pathway at risk. Preservation of olfaction may increase the postoperative quality of life. Objective assessment of olfaction may inform clinical decision-making and influence the selection of operative approaches for surgical resection. METHODS: We reviewed all patients who underwent surgical resection for midline anterior skull base meningiomas from July 1, 2014, through December 31, 2017. Patient demographics, tumor size, operative approach, pre- and postoperative deficits, and Simpson grade were collected and analyzed. Postoperative olfaction was assessed by clinical evaluation as well as objective evaluation using the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: Twenty-eight patients (10 male, 18 female) were included with an average age of 53.8 years (range 27-80 years). Twenty-six patients underwent craniotomy for resection, while 2 patients had endoscopic approaches. Average tumor volume was 402.1 cm3 (6.6-2507.7 cm3). Preoperatively, five patients (17.8%) presented with olfactory impairment. Objectively, 50% of patients (14/28) consented and completed the UPSIT. The average postoperative UPSIT score was 25.8/40 (9/40-38/40). Two patients not identified on clinical assessment alone demonstrated postoperative olfactory deficit on UPSIT (2/14). CONCLUSION: There are limited published studies evaluating olfaction in patients who undergo skull-based approaches for anterior fossa meningiomas. Our series showed the highest olfaction preservation rate (87.5%) using a comprehensive strategy and multitude of surgical approaches based on the olfactory function and tumor characteristics.


Assuntos
Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Transtornos do Olfato/etiologia , Neoplasias da Base do Crânio/cirurgia , Olfato/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Craniotomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/prevenção & controle , Período Pós-Operatório , Qualidade de Vida , Base do Crânio/cirurgia
16.
J Craniofac Surg ; 29(3): 709-711, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29723950

RESUMO

Sino-orbital fistulas can occur after orbital exenteration. Chronic nonhealing fistulas lead to bothersome symptoms including malodorous discharge, hypernasal speech, crusting, wound breakdown, or inability to wear an ocular prosthesis. Reconstruction can be difficult due to the complexity of the defects and the multitude of treatments patients often undergo for the management of the primary disease. Prior radiation, lack of available local tissue, or compromised blood supply are some of the issues that make successful fistula closure problematic. This report describes a method for autologous vascularized tissue coverage using a contralateral nasoseptal flap to successfully close a sino-orbital fistula.


Assuntos
Fístula/cirurgia , Nariz/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Seios Paranasais/cirurgia , Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos/cirurgia , Traumatismos Oculares/cirurgia , Humanos
17.
Clin Immunol ; 179: 66-76, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28279811

RESUMO

Severe forms of chronic rhinosinusitis (CRS), a common upper airway inflammatory disorder, are associated with nasal polyps (NPs). NP disease is ameliorated by glucocorticoid (GC) treatment, whose cellular effects are poorly understood. We therefore assessed the influence of GC therapy on NPs in CRS patients, focusing on regulatory T (Treg) cells. Treg cell populations were analyzed by flow cytometry in NPs and control tissues from GC-treated CRS patients and controls. After GC exposure, selective expansion of Treg cells was seen within NPs, and not blood or adjacent ethmoid tissues. To confirm direct GC effects, NPs from the same patients were biopsied prior to, and following, 1week of oral GC exposure. Direct expansion of Tregs into the same NP bed was detected in 4/4 CRS patients following GC exposure. Treg cell spikes into NPs were secondary to cellular recruitment given limited Ki67 expression within these regulatory cells. Chemokine gene expression profiling identified several chemokines, notably CCL4, induced within NPs upon GC treatment. Neutralization of chemokine receptor/ligand interactions using CCR4 small molecule antagonists reduced Treg migration towards GC-treated NPs in an ex vivo migration assay. Our findings suggest that the common use of GCs in the treatment of NP disease leads to recruitment of Treg cells from peripheral sites into NP tissues, which may be critical to the anti-inflammatory effect of GCs. Mechanistically Treg expansion appears to be conferred, in part, by chemokine receptor/ligand interactions induced following corticosteroid therapy.


Assuntos
Glucocorticoides/farmacologia , Pólipos Nasais/imunologia , Prednisona/farmacologia , Rinite/imunologia , Sinusite/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Biópsia , Quimiocinas/genética , Doença Crônica , Fatores de Transcrição Forkhead/imunologia , Perfilação da Expressão Gênica , Glucocorticoides/uso terapêutico , Humanos , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/genética , Pólipos Nasais/patologia , Prednisona/uso terapêutico , Rinite/tratamento farmacológico , Rinite/genética , Rinite/patologia , Sinusite/tratamento farmacológico , Sinusite/genética , Sinusite/patologia , Linfócitos T Reguladores/imunologia
18.
Ann Allergy Asthma Immunol ; 119(4): 317-323.e1, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28958373

RESUMO

BACKGROUND: Immunoglobulin (Ig) D is largely localized to the upper airway and reacts with colonizing respiratory pathogens. OBJECTIVE: To determine whether chronic rhinosinusitis (CRS) is associated with increased IgD expression. METHODS: We performed immunofluorescent staining for cytoplasmic IgD, IgA, IgM, and surface plasma cell marker CD138 (syndecan-1) in sinus tissue of patients with CRS with and without nasal polyps (CRSwNP and CRSsNP, respectively) and control subjects without CRS (n = 6 each). Sinonasal mucus antibody levels of patients with CRSwNP or CRSsNP and control subjects were measured by enzyme-linked immunosorbent assay (n = 13, 11, and 9 subjects, respectively). Cells per square millimeter and antibody levels were compared by analysis of variance. Histopathology was performed with sinus tissue from subjects in the 3 groups (n = 6, 8, and 13 subjects respectively). RESULTS: Cells expressing cytoplasmic IgD exceeded those with cytoplasmic IgA and IgM and represented most CD138+ plasma cells in the lamina propria. The frequencies of IgD+ plasma cells were significantly higher in patients with CRSsNP and CRSwNP compared with control subjects (P < .01). Only patients with CRSwNP showed increased frequencies of IgM and IgA plasma cells (P < .01). In contrast to high plasma cell frequencies in tissues, the levels of secreted IgD were lower than those of IgA, IgM, and IgG but were highest in the CRSwNP group compared with the other groups (P < .05). CONCLUSION: IgD plasma cells are prominent in sinus tissues and are increased in CRS. That IgD protein also shows the lowest concentration of antibodies in secretions suggests that its activity might be targeted to the tissue rather than secretions.


Assuntos
Imunoglobulina D/genética , Pólipos Nasais/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Doença Crônica , Feminino , Expressão Gênica , Humanos , Imunoglobulina A/genética , Imunoglobulina G/genética , Imunoglobulina M/genética , Masculino , Pessoa de Meia-Idade , Muco/química , Pólipos Nasais/complicações , Pólipos Nasais/genética , Pólipos Nasais/imunologia , Seios Paranasais/imunologia , Seios Paranasais/patologia , Plasmócitos/imunologia , Plasmócitos/patologia , Rinite/complicações , Rinite/genética , Rinite/imunologia , Sinusite/complicações , Sinusite/genética , Sinusite/imunologia , Sindecana-1/genética
19.
J Craniofac Surg ; 28(1): 36-39, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27875509

RESUMO

Management of anterior skull base defects is an area of continued innovation for skull base surgeons. Various grafting materials have been advocated for the repair of skull base defects depending on needs, availability, harvest site morbidity, and surgeon preference. Spontaneous bony closure of small skull defects is known to occur in animal models without bone grafts, but this phenomenon has been unexplored in the human skull base. The objective of this study was to evaluate osseous skull base closure in patients undergoing endoscopic repair of skull base defects. A retrospective review was performed on 13 patients who underwent endoscopic repair of skull base defects with free bone grafts who were followed with postoperative computed tomography scans. This cohort was compared to postoperative radiology from patients undergoing transsphenoidal surgery without rigid reconstruction to evaluate for spontaneous osseous closure of sellar defects. Free bone grafts are incorporated into the bony skull base in the majority of patients (84.6% with at least partial incorporation) at mean of 5.3 years postoperatively. By comparison, patients undergoing pituitary surgery did not demonstrate spontaneous osseous closure on postoperative imaging. Human anterior skull base defects do not appear to spontaneously close, even when small, suggesting that there is no "critical size defect" in the human skull base, in contrast to the robust wound healing in animal models of skull convexity and mandibular defects. Free bone grafts incorporate into the skull base over the long-term and may be utilized whenever a rigid skull base reconstruction is desired, regardless of the defect size.


Assuntos
Transplante Ósseo/métodos , Fossa Craniana Anterior/cirurgia , Endoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Regeneração Óssea/fisiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Retalhos Cirúrgicos/cirurgia , Tomografia Computadorizada por Raios X
20.
Acta Neurochir (Wien) ; 158(8): 1625-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27339269

RESUMO

BACKGROUND: Fixed retraction of the internal carotid artery (ICA) has previously been described for use during transcranial microscopic surgery. We report the novel use of a self-retaining microvascular retractor for static repositioning and protection of the ICA during expanded endonasal endoscopic approaches to the paramedian skull base. METHODS: The transmaxillary, transpterygoid approach was performed in five cadaver heads (ten sides). The self-retaining microvascular retractor was used to laterally reposition the pterygopalatine fossa contents during exposure of the pterygoid base/plates and the paraclival ICA to expose the petrous apex. Maximum ICA retraction distance was measured in the x-axis for all ten sides. RESULTS: The average horizontal distance of ICA retraction measured at the mid-paraclival segment for all ten sides was 4.75 mm. In all cases, the carotid artery was repositioned without injury to the vessel or disruption of the surrounding neurovascular structures. CONCLUSIONS: Static repositioning of the ICA and other delicate neurovascular structures was effectively performed during endonasal, endoscopic cadaveric surgery of the skull base and has potential merits in live patients.


Assuntos
Artérias Carótidas/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Procedimentos Neurocirúrgicos/métodos , Base do Crânio/cirurgia , Cadáver , Humanos , Nariz/cirurgia
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