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BACKGROUND: Epithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including chronic rhinosinusitis (CRS). Cell-type shifts and their relationship to CRS endotypes and severity are incompletely described. OBJECTIVE: We sought to understand the relationship of epithelial cell remodeling to inflammatory endotypes and disease outcomes in CRS. METHODS: Using cell-type transcriptional signatures derived from epithelial single-cell sequencing, we analyzed bulk RNA-sequencing data from sinus epithelial brushings obtained from patients with CRS with and without nasal polyps in comparison to healthy controls. RESULTS: The airway epithelium in nasal polyposis displayed increased tuft cell transcripts and decreased ciliated cell transcripts along with an IL-13 activation signature. In contrast, CRS without polyps showed an IL-17 activation signature. IL-13 activation scores were associated with increased tuft cell, goblet cell, and mast cell scores and decreased ciliated cell scores. Furthermore, the IL-13 score was strongly associated with a previously reported activated ("polyp") tuft cell score and a prostaglandin E2 activation signature. The Lund-Mackay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, prostaglandin E2, and IL-13 signatures and negatively with ciliated cell transcriptional signatures. CONCLUSIONS: These results demonstrate that cell-type alterations and prostaglandin E2 stimulation are key components of IL-13-induced epithelial remodeling in nasal polyposis, whereas IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13-driven epithelial remodeling.
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Pólipos Nasais , Rinite , Sinusite , Humanos , Interleucina-13 , Pólipos Nasais/patologia , Rinite/patologia , Interleucina-17 , Dinoprostona , Sinusite/patologia , Doença Crônica , Mucosa Nasal/patologiaRESUMO
OBJECTIVE: Life expectancy has increased over the past century, causing a shift in the demographic distribution toward older age groups. Elderly patients comprise up to 14% of all patients with pituitary tumors, with most lesions being nonfunctioning pituitary adenomas (NFPAs). Here, the authors evaluated demographics, outcomes, and postoperative complications between nonelderly adult and elderly NFPA patients. METHODS: A retrospective review of 908 patients undergoing transsphenoidal surgery (TSS) for NFPA at a single institution from 2007 to 2019 was conducted. Clinical and surgical outcomes and postoperative complications were compared between nonelderly adult (age ≥ 18 and ≤ 65 years) and elderly patients (age > 65 years). RESULTS: There were 614 and 294 patients in the nonelderly and elderly groups, respectively. Both groups were similar in sex (57.3% vs 60.5% males; p = 0.4), tumor size (2.56 vs 2.46 cm; p = 0.2), and cavernous sinus invasion (35.8% vs 33.7%; p = 0.6). Regarding postoperative outcomes, length of stay (1 vs 2 days; p = 0.5), extent of resection (59.8% vs 64.8% gross-total resection; p = 0.2), CSF leak requiring surgical revision (4.3% vs 1.4%; p = 0.06), 30-day readmission (8.1% vs 7.3%; p = 0.7), infection (3.1% vs 2.0%; p = 0.5), and new hypopituitarism (13.9% vs 12.0%; p = 0.3) were similar between both groups. Elderly patients were less likely to receive adjuvant radiation (8.7% vs 16.3%; p = 0.009), undergo future reoperation (3.8% vs 9.5%; p = 0.003), and experience postoperative diabetes insipidus (DI) (3.7% vs 9.4%; p = 0.002), and more likely to have postoperative hyponatremia (26.7% vs 16.4%; p < 0.001) and new cranial nerve deficit (1.9% vs 0.0%; p = 0.01). Subanalysis of elderly patients showed that patients with higher Charlson Comorbidity Index scores had comparable outcomes other than higher DI rates (8.1% vs 0.0%; p = 0.006). Elderly patients' postoperative sodium peaked and troughed on postoperative day 3 (POD3) (mean 138.7 mEq/L) and POD9 (mean 130.8 mEq/L), respectively, compared with nonelderly patients (peak POD2: mean 139.9 mEq/L; trough POD8: mean 131.3 mEq/L). CONCLUSIONS: The authors' analysis revealed that TSS for NFPA in elderly patients is safe with low complication rates. In this cohort, more elderly patients experienced postoperative hyponatremia, while more nonelderly patients experienced postoperative DI. These findings, combined with the observation of higher DI in patients with more comorbidities and elderly patients experiencing later peaks and troughs in serum sodium, suggest age-related differences in sodium regulation after NFPA resection. The authors hope that their results will help guide discussions with elderly patients regarding risks and outcomes of TSS.
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Adenoma , Hipopituitarismo , Neoplasias Hipofisárias , Adenoma/cirurgia , Adulto , Idoso , Feminino , Humanos , Hipopituitarismo/epidemiologia , Hipopituitarismo/etiologia , Masculino , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Nonfunctioning pituitary adenomas present without biochemical or clinical signs of hormone excess and are the second most common type of pituitary adenomas. The 2017 WHO classification scheme of pituitary adenomas differentiates null-cell adenomas (NCAs) and silent gonadotroph adenomas (SGAs). The present study sought to highlight the differences in patient characteristics and clinical outcomes between NCAs and SGAs. METHODS: The records of 1166 patients who underwent transsphenoidal surgery for pituitary adenoma between 2012 and 2019 at a single institution were retrospectively reviewed. Patient demographics and clinical outcomes were collected. RESULTS: Of the overall pituitary adenoma cohort, 12.8% (n = 149) were SGAs and 9.2% (n = 107) NCAs. NCAs were significantly more common in female patients than SGAs (61.7% vs 26.8%, p < 0.001). There were no differences in patient demographics, initial tumor size, or perioperative and short-term clinical outcomes. There was no significant difference in the amount of follow-up between patients with NCAs and those with SGAs (33.8 months vs 29.1 months, p = 0.237). Patients with NCAs had significantly higher recurrence (p = 0.021), adjuvant radiation therapy usage (p = 0.002), and postoperative diabetes insipidus (p = 0.028). NCA pathology was independently associated with tumor recurrence (HR 3.64, 95% CI 1.07-12.30; p = 0.038), as were cavernous sinus invasion (HR 3.97, 95% CI 1.04-15.14; p = 0.043) and anteroposterior dimension of the tumor (HR 2.23, 95% CI 1.09-4.59; p = 0.030). CONCLUSIONS: This study supports the definition of NCAs and SGAs as separate subgroups of nonfunctioning pituitary adenomas, and it highlights significant differences in long-term clinical outcomes, including tumor recurrence and the associated need for adjuvant radiation therapy, as well as postoperative diabetes insipidus. The authors also provide insight into independent risk factors for these outcomes in the adenoma population studied, providing clinicians with additional predictors of patient outcomes. Follow-up studies will hopefully uncover mechanisms of biological aggressiveness in NCAs and associated molecular targets.
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Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Gonadotrofos/patologia , Linfócitos Nulos/patologia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral/fisiologia , Adulto JovemRESUMO
It is increasingly recognized that chronic rhinosinusitis (CRS) comprises a spectrum of different diseases with distinct clinical presentations and pathogenic mechanisms. Defining the distinct phenotypes and endotypes of CRS affects prognosis and, most importantly, is necessary as the basis for making therapeutic decisions. The need for individualized definitions of pathogenic mechanisms before initiating therapy extends to virtually all therapeutic considerations. This is clearly crucial with antibiotics, where, barring an influence from their off-target anti-inflammatory pharmacologic effects, an understanding of the role of the individual biome predicts likelihood of therapeutic benefit. However, this need for identifying individual phenotypes and endotypes also extends to the agent that is currently considered the mainstay of treatment of CRS, specifically glucocorticoids. As with asthma, it is recognized that a large minority of patients with CRS have a steroid-resistant phenotype, identification of which will preclude use of these agents with their potential side effects. Identification of endotypes is also becoming increasingly imperative because targeted biotherapeutic agents, such as anti-IgE and anti-cytokine antibodies, are becoming available. These agents are likely to benefit patients in whom the targeted mediator is not only expressed but demonstrably driving a central mechanism in that patient. In summary, the treatment of CRS is at an exciting crossroad. On the positive side, numerous therapeutics are in development that seem likely to have a positive effect in our patients with this condition. The challenge is that these therapies will require targeted individualized treatments based on identifying subjects with the relevant endotype.
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Anticorpos Monoclonais/uso terapêutico , Glucocorticoides/uso terapêutico , Rinite/diagnóstico , Sinusite/diagnóstico , Biomarcadores/metabolismo , Doença Crônica , Citocinas/imunologia , Humanos , Imunoglobulina E/imunologia , Fenótipo , Medicina de Precisão , Rinite/terapia , Sinusite/terapia , Resultado do TratamentoRESUMO
Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) > 0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness.
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Etnicidade/genética , Evolução Molecular , Exoma/genética , Variação Genética/genética , Perda Auditiva/genética , Perda Auditiva/patologia , Estudos de Casos e Controles , Conexina 26 , Conexinas , Frequência do Gene , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Humanos , FilogeniaRESUMO
OBJECTIVES: The purpose of this study is to investigate the 10-year postoperative quality of life outcomes in smokers and nonsmokers with chronic rhinosinusitis. STUDY DESIGN: This is a single-institution prospective cohort study. METHODS: 235 patients who have previously been enrolled in a 4-year follow-up study were identified and contacted for a telephone interview. Rates of revision surgery, smoking status and 20-item sinonasal outcomes test (SNOT-20) scores were obtained. Preoperative SNOT-20 scores were compared with those obtained at the 10-year follow-up. RESULTS: Of the patients enrolled in the initial 4-year study, 22.5% were available for a telephone interview, including 43 out of 185 nonsmokers (23.2%) and 9 out of 50 smokers (18%). Demographic data including age, sex and race were analyzed and found to be similar between the two groups. Preoperative SNOT-20 scores were similar between nonsmokers and smokers (28.9 vs. 25.8, p = 0.89). There was no significant difference in long-term SNOT-20 scores (10 years postoperatively) between nonsmokers and smokers (31.5 vs. 28.2, p = 0.629). CONCLUSIONS: While cigarette smoke may have long-term adverse effects on the sinonasal mucosa, we found no difference in quality of life outcomes between smokers and nonsmokers 10 years after functional endoscopic sinus surgery.
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Endoscopia , Qualidade de Vida , Rinite/cirurgia , Sinusite/cirurgia , Fumar , Idoso , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
The endoscopic endonasal approach for resection of craniopharyngiomas has gained popularity because of its minimal need for retraction and superior visualization of and access to the optic chiasm.1-4 Despite these advantages, the proximity of craniopharyngiomas to the optic apparatus still challenges the preservation of visual function.5-10 Indocyanine green (ICG) angiography can evaluate the perfusion of the chiasm and can predict visual outcomes after endonasal approaches, in addition to known uses of the dye.3 ICG angiography may therefore hold promise in the real-time assessment of optic chiasm perfusion during resection of craniopharyngiomas by delineating details of the superior hypophyseal artery (SHA) system. Here, we present a case in which ICG angiogram was used to assess the perfusion of the chiasm before, during, and after tumor resection. This technique signaled thrombosis of the left principal SHA during tumor resection that was compensated by the anastomotic SHA system from the right. The case shows an endoscopic endonasal approach for the resection of a third ventricular craniopharyngioma in a 21-year-old woman presenting with unremitting headaches, endocrine dysfunction, and vision loss. Postoperatively, the patient's neurological examination remained unchanged and visual function improved within 2 weeks. This case underscores the potential for real-time intraoperative ICG angiography to assist in the careful resection of craniopharyngiomas while improving visual outcomes. Institutional review board approval was not required; the patient consented to the procedure and to publishing of the operative video.
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OBJECTIVE: Socioeconomic status (SES) is known to affect presentations and outcomes in pituitary neuroendocrine tumor resections, but there is a paucity of literature examining its impact specifically on patients with prolactinomas, who may be treated medically or surgically. The authors sought to determine whether SES was associated with differences in treatment choice or outcomes for prolactinoma patients. METHODS: The authors retrospectively reviewed patient records at a high-volume academic pituitary center for prolactinoma diagnoses. Patients were split into medically and surgically treated cohorts. Race, ethnicity, insurance status, primary care physician (PCP) status, and zip code-based income data were collected and examined as socioeconomic covariates. Outcomes of interest included pretreatment likelihood of surgical cure, medical versus surgical treatment allocation, and posttreatment remission rates. RESULTS: The authors analyzed 568 prolactinoma patients (351 medically treated and 217 surgically treated). Patients receiving surgery were more likely to have Medicaid or private insurance (p < 0.001) and have lower incomes (p < 0.001) than medically treated patients. Lower-income surgical patients were more likely to require surgical intervention for an indication such as tumor decompression than higher-income patients (p = 0.023). Surgical patients with a PCP had a higher estimated likelihood of surgical cure (p = 0.008), while no SES-based differences in surgical remission likelihood existed in the medical cohort. After surgery, surgical patients who achieved remission had significantly higher income than those who did not (p < 0.001). Other SES factors were not associated with surgical remission, and among medically treated patients, remission rates were not affected by any SES factor. Income was inversely related to prolactinoma size in both cohorts (surgical, p < 0.001; medical, p = 0.005) but was associated more prominently in surgical patients (surgical, -0.65 mm per $10,000; medical, -0.37 mm per $10,000). CONCLUSIONS: While surgical prolactinoma patients were prone to income and PCP-related disparities, no SES disparities were found among medically treated patients. Income had a more pronounced association with tumor size in the surgical cohort and likely contributed to the increased need for surgical intervention seen in low-income surgical patients. Addressing socioeconomic healthcare disparities is needed among surgical prolactinoma patients to increase rates of early presentation and improve the outcomes of low-SES populations.
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Neoplasias Hipofisárias , Prolactinoma , Estados Unidos , Humanos , Prolactinoma/cirurgia , Estudos Retrospectivos , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/diagnóstico , Hipófise/cirurgia , Fatores SocioeconômicosRESUMO
The extreme genetic heterogeneity of nonsyndromic hearing loss (NSHL) makes genetic diagnosis expensive and time consuming using available methods. To assess the feasibility of target-enrichment and massively parallel sequencing technologies to interrogate all exons of all genes implicated in NSHL, we tested nine patients diagnosed with hearing loss. Solid-phase (NimbleGen) or solution-based (SureSelect) sequence capture, followed by 454 or Illumina sequencing, respectively, were compared. Sequencing reads were mapped using GSMAPPER, BFAST, and BOWTIE, and pathogenic variants were identified using a custom-variant calling and annotation pipeline (ASAP) that incorporates publicly available in silico pathogenicity prediction tools (SIFT, BLOSUM, Polyphen2, and Align-GVGD). Samples included one negative control, three positive controls (one biological replicate), and six unknowns (10 samples total), in which we genotyped 605 single nucleotide polymorphisms (SNPs) by Sanger sequencing to measure sensitivity and specificity for SureSelect-Illumina and NimbleGen-454 methods at saturating sequence coverage. Causative mutations were identified in the positive controls but not in the negative control. In five of six idiopathic hearing loss patients we identified the pathogenic mutation. Massively parallel sequencing technologies provide sensitivity, specificity, and reproducibility at levels sufficient to perform genetic diagnosis of hearing loss.
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Testes Genéticos/métodos , Perda Auditiva/genética , Análise de Sequência de DNA/métodos , Análise Mutacional de DNA , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , SoftwareRESUMO
BACKGROUND AND OBJECTIVES: To date, there are no tools to intraoperatively predict postoperative visual function after endoscopic endonasal surgery (EES) for suprasellar lesions. The objective of this study was to retrospectively evaluate the utility of indocyanine green (ICG) angiography as an intraoperative tool to measure optic chiasm perfusion and determine its relationship with postoperative visual function. METHODS: Videos of patients undergoing EES for resection of suprasellar lesions were reviewed, where 5 mg of ICG was diluted in 10 mL of saline and administered. Time between luminescence of the anterior cerebral artery and the superior hypophyseal artery branches supplying the optic chiasm was noted, and the percentage of optic chiasm vessels that luminesced was recorded. Postoperative examinations and imaging studies were used to assess visual function. Patients with and without new deficits were compared with examination of trends in ICG findings. RESULTS: A total of 7 trials were reviewed on 6 patients, with no complications occurring from ICG administration. Mean time to chiasm peak luminescence was 3.8 seconds, and 81.8% of chiasm vessels luminesced. Patients with stable or improved vision after resection demonstrated over 90% chiasm luminescence in every case, and mean chiasm time in these postresection ICG administrations was 4.0 seconds. One patient experienced new postoperative visual deficits; on review of their ICG administration, 11.5% of chiasm vessels luminesced, and the chiasm itself failed to display robust luminescence after 30 seconds of direct observation. CONCLUSION: This pilot study showed the capability of intraoperative ICG angiography to demonstrate perfusion of the optic chiasm during EES for resection of suprasellar lesions. While larger studies are required, preliminary results suggest chiasm times under 5 seconds and over 90% chiasm vessel illumination may reflect adequate chiasm perfusion, while those with delayed or absent chiasm luminescence may have compromised chiasm perfusion.
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Artérias , Verde de Indocianina , Humanos , Estudos Retrospectivos , Projetos Piloto , Angiografia Cerebral/métodosRESUMO
OBJECTIVE: Risk factors for a postoperative cerebrospinal fluid leak (CSF) after surgery include an intraoperative high flow of CSF, elevated body mass index, defect size, and defect site. In our prior series, a high postoperative CSF leak rate for tumors of the central skull base (planum, sella, and clivus) appeared to be due to graft migration. We changed our closure technique from a single layer of collagen +/- fat graft to a novel graft, termed a "Bow tie" (a tri-layer fat graft with two pieces of collagen matrix), and report our results in this study. METHODS: Retrospective temporal epoch study of a single otolaryngologist's experience of closing skull base defects in our skull base center from 2005 to 2017. RESULTS: One hundred and forty-nine patients met inclusion criteria in two time periods, pre- and post-introduction of the Bow tie technique. In epoch I, from 2005 to 2013, 79 patients had reconstruction with a single layer of dural graft (25 had additional free fat graft). In epoch II, from 2014 to 2017, 70 patients had reconstruction with the Bow tie. RESULTS: CSF leak rates were 8.7% overall: 15.2% in epoch I and 1.4% in epoch II (p = 0.01). After controlling the procedure, defects with a size greater than 2 cm had a 5.7 greater likelihood of failure. Epoch II had a lower incidence of major complications. CONCLUSION: Using a single surgeon's experience, the multilayer Bow tie has a significant reduction in postoperative CSF leak and associated major complications for defects of the central skull base. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1568-1575, 2023.
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Vazamento de Líquido Cefalorraquidiano , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias , Neoplasias da Base do Crânio , Retalhos Cirúrgicos , Cirurgia Endoscópica Transanal , Humanos , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Base do Crânio/cirurgia , Retalhos Cirúrgicos/cirurgia , Cirurgia Endoscópica Transanal/métodos , Neoplasias da Base do Crânio/cirurgiaRESUMO
In recent decades, perovskite-type compounds (ABB'O3) have been exhaustively studied due to their unique ferroelectric properties. In this work, a systematic study aiming to prepare fine particles in the binary system SrZrO3-SrTiO3 was conducted under hydrothermal conditions in a KOH (5 M) solution at 200 °C for 4 h under a constant stirring speed of 130 rpm. The precursors employed were SrSO4 powder (<38 µm size) and coprecipitated hydrous gels of Zr(OH)4â¢9.64 H2O (Zr-gel) and Ti(OH)4â¢4.5H2O (Ti-gel), which were mixed according to the stoichiometry of the SrZr1-xTixO3 in the compositional range of 0.0 > x > 100.0 mol% Ti4+. The XRD results revealed the formation of two crystalline phases rich in Zr4+, an orthorhombic structured SrZr0.93Ti0.07O3 and a cubic structured SrZr0.75Ti0.25O3 within the compositional range of 0.1-0.5 mol of Ti4+. A cubic perovskite structured solid solution, SrTi1-xZrxO3, was preferentially formed within the compositional range of 0.5 > x > 0.1 mol% Ti4+. The SrZrO3 and SrZr0.93Ti0.07O3-rich phases had particle sizes averaging 3 µm with a cubic morphology. However, a remarkable reduction in the particle size occurred on solid solutions prepared with hydrous Ti-gel over contents of 15 mol% Ti4+ in the reaction media, resulting in the formation of nanosized particle agglomerates with a cuboidal shape self-assembled via a 3D hierarchical architecture, and the sizes of these particles varied in the range between 141.0 and 175.5 nm. The limited coarsening of the particles is discussed based on the Zr-gel and Ti-gel dehydration capability differences that occurred under hydrothermal processing.
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Mutations in SLC26A4 cause nonsyndromic hearing loss associated with an enlarged vestibular aqueduct (EVA, also known as DFNB4) and Pendred syndrome (PS), the most common type of autosomal-recessive syndromic deafness. In many patients with an EVA/PS phenotype, mutation screening of SLC26A4 fails to identify two disease-causing allele variants. That a sizable fraction of patients carry only one SLC26A4 mutation suggests that EVA/PS is a complex disease involving other genetic factors. Here, we show that mutations in the inwardly rectifying K(+) channel gene KCNJ10 are associated with nonsyndromic hearing loss in carriers of SLC26A4 mutations with an EVA/PS phenotype. In probands from two families, we identified double heterozygosity in affected individuals. These persons carried single mutations in both SLC26A4 and KCNJ10. The identified SLC26A4 mutations have been previously implicated in EVA/PS, and the KCNJ10 mutations reduce K(+) conductance activity, which is critical for generating and maintaining the endocochlear potential. In addition, we show that haploinsufficiency of Slc26a4 in the Slc26a4(+/-) mouse mutant results in reduced protein expression of Kcnj10 in the stria vascularis of the inner ear. Our results link KCNJ10 mutations with EVA/PS and provide further support for the model of EVA/PS as a multigenic complex disease.
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Proteínas de Transporte de Ânions/genética , Perda Auditiva/genética , Proteínas de Membrana Transportadoras/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Doenças da Glândula Tireoide/genética , Aqueduto Vestibular/anormalidades , Animais , Proteínas de Transporte de Ânions/fisiologia , Feminino , Heterozigoto , Humanos , Técnicas In Vitro , Proteínas de Membrana Transportadoras/fisiologia , Camundongos , Camundongos Mutantes , Mutação , Oócitos/fisiologia , Técnicas de Patch-Clamp , Linhagem , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Estria Vascular/metabolismo , Transportadores de Sulfato , XenopusRESUMO
OBJECTIVE: Prolactinoma is the most common pituitary adenoma and can be managed medically or surgically. The authors assessed the correlation between tumor volume and prolactin level and its effect on surgical outcomes. METHODS: The authors reviewed 219 patients who underwent transsphenoidal prolactinoma resection at a single institution from 2012 to 2019. Outcomes were compared between patients with and without biochemical remission. Tumor volumes were quantified with BrainLab Smartbrush. Correlation analysis and linear regression were used to examine the association between tumor volume and serum prolactin level. Volume-adjusted prolactin level was defined as serum prolactin level divided by tumor volume. The authors utilized receiver operating characteristic (ROC) curve analysis to determine the thresholds for predicting biochemical remission status. RESULTS: The mean tumor volume was 5.66 cm3, and the mean preoperative prolactin level was 752.3 µg/L. Men had larger prolactinomas than women (mean volume 11.32 vs 2.54 cm3; p < 0.001), and women had a greater volume-adjusted prolactin level (mean 412.5 vs 175.9 µg/L/cm3, p < 0.001). In total, 66.7% of surgical patients achieved biochemical remission 6 weeks after surgery, whereas a similar cohort of medically treated patients during the same time frame demonstrated a 69.4% remission rate. Pearson correlation and linear regression analysis revealed a strong association between preoperative tumor volume and prolactin levels, with an increase in serum prolactin level of 101.31 µg/L per 1-cm3 increase in tumor volume (p < 0.001). This held true for men (R = 0.601, p < 0.001) and women (R = 0.935, p < 0.001), with women demonstrating a greater increase in prolactin level per 1-cm3 increase in volume (185.70 vs 79.77 µg/L, p < 0.001). Patients who achieved remission exhibited a 66.08-µg/L increase in preoperative prolactin level per 1 cm3 of preoperative tumor volume (p < 0.001), which was less than the 111.46-µg/L increase per 1 cm3 in patients without remission (p < 0.001). Patients who failed to achieve remission had residual tumors with a 77.77-µg/L increase in prolactin per 1 cm3 of remaining tumor volume after resection (p < 0.001). ROC curve analysis revealed significant thresholds that optimally predicted lack of postoperative remission on the basis of preoperative prolactin and tumor volume. These thresholds were rendered nonsignificant in patients with documented Knosp grade ≥ 3. CONCLUSIONS: Although the authors found a correlation between prolactinoma volume and serum prolactin level, patients without remission had a greater increase in serum prolactin level per increase in preoperative tumor volume than those who achieved remission, suggesting unique tumor composition. The authors also identified prolactin and tumor volume thresholds that optimally predicted biochemical remission status. The authors hope that their results can be used to identify prolactinomas for which surgery could achieve remission as an alternative to medical management.
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Chronic type 2 (T2) inflammatory diseases of the respiratory tract are characterized by mucus overproduction and disordered mucociliary function, which are largely attributed to the effects of IL-13 on common epithelial cell types (mucus secretory and ciliated cells). The role of rare cells in airway T2 inflammation is less clear, though tuft cells have been shown to be critical in the initiation of T2 immunity in the intestine. Using bulk and single-cell RNA sequencing of airway epithelium and mouse modeling, we found that IL-13 expanded and programmed airway tuft cells toward eicosanoid metabolism and that tuft cell deficiency led to a reduction in airway prostaglandin E2 (PGE2) concentration. Allergic airway epithelia bore a signature of PGE2 activation, and PGE2 activation led to cystic fibrosis transmembrane receptor-dependent ion and fluid secretion and accelerated mucociliary transport. These data reveal a role for tuft cells in regulating epithelial mucociliary function in the allergic airway.
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Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Animais , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Dinoprostona , Interleucina-13/metabolismo , Camundongos , Sistema RespiratórioRESUMO
While the use of image-guided navigation is an excellent adjunct to the use of anatomical landmarks, dynamic changes that may occur in the position of critical structures are not accounted for during and after tumor resection. Unlike navigation, Doppler ultrasonography provides real-time imaging of the anterior skull base and can be used to accurately identify the location of vital structures during skull base surgery. A 56-year-old female initially presented with new onset left eye visual deficits. She previously underwent sublabial transsphenoidal subtotal resection of the tumor, confirmed as clival chordoma. She subsequently presented to our institution. She was treated with an expanded endonasal resection of the remaining chordoma followed by CyberKnife radiosurgery. Two years later, surveillance imaging identified tumor recurrence within the right clivus posterior to the carotid artery. Intraoperatively, in the previously operated irradiated skull base, the normal bony architecture of the sella was absent, resulting in the inability to distinguish the anterior genu of the internal carotid artery (ICA) from the adjacent tumor. Using Doppler ultrasonography, the course of the ICA was imaged in real time, allowing for safe, gross total tumor resection. In the setting of prior operation, radiation, or extensive disease, the normal bony architecture of the sella may be disrupted, placing the cavernous ICA at risk. We report what we believe is the first use of intraoperative ultrasound during the endoscopic endonasal approach in the setting of a previously operated, radiated sella.
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Objective: To identify differentiation features of chemosensory dysfunction in COVID-19 infection and their primary drivers. Study Design: Cross-sectional cohort comparison. Methods: A national anonymous survey was used to query participants regarding nasal symptoms and chemosensory dysfunction including sensitivity levels, and presence or absence of distortions and phantoms within the 6-week time window surrounding their COVID-19 testing and survey completion. Results: Three-hundred and sixty-four respondents who reported COVID-19 positive (COVID+; n = 176) or COVID-19 negative (COVID-; n = 188) test results completed the survey. The COVID+ cohort had higher occurrence rates for: (a) chemosensory sensitivity impairments (67.0% vs 30.3%; P < .01), where the rate of complete loss of smell (anosmia) or taste (ageusia) was higher (35.8% vs 4.8%; P < .01), and (b) chemosensory distortions (39.8% vs 19.1%; P < .01), where the rate of anosmia or ageusia with distortions was also higher in the COVID+ cohort (19.9% vs 2.7%; P < .01). Occurrence rates in the two cohorts were similar for chemosensory phantoms (COVID+ 17.0%, COVID- 18.6%; P = .70) and nasal discharge or stuffiness in the presence of sensitivity impairment (COVID+ 63.6%, COVID- 52.6%; P = .17). Conclusion: Chemosensory dysfunction in COVID-19 is associated with higher rates of smell or taste sensitivity impairments and distortions. Higher rates of anosmia and ageusia drive these key findings. Chemosensory phantoms and nasal symptoms in the presence of sensitivity impairment occur at rates that should demand clinical attention, but they do not appear to be specific to COVID-19 positivity. Level of Evidence: 2b.
RESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is characterized by significant accumulation and thickening of mucus in the sinonasal cavities. One contributor of aberrant mucus production and impaired mucociliary clearance (MCC) is altered function of the sinonasal submucosal glands (SMGs), yet contributions of SMGs to upper airway disease initiation and progression remain unknown. The objective of this study was to characterize the morphology and secretory cell identities of the nasal septum SMGs in both healthy and CRS adults. METHODS: Biopsies from adult participants with CRS without nasal polyps (CRSsNP, n = 4), CRS with nasal polyps (CRSwNP, n = 8), and non-CRS controls (n = 14) were collected from the posterior septum. Glandular morphology and mucus markers were investigated using histological techniques and high-resolution confocal microscopy. RESULTS: Analysis revealed a significant decrease in gland density in the posterior septum of CRSsNP (28% ± 6.15%) and CRSwNP (23% ± 3.09%) compared to control participants (53% ± 1.59%, p < 0.0001). Further analysis of the CRS SMG secretory function revealed an overall decrease in Mucin 5B+ gland mucus being produced. Dilated and cystic ductal structures filled with inspissated mucus were also common to CRS glands. CONCLUSION: Here, we describe a significant alteration in SMG structure and function in the adult CRS posterior septum suggesting reduced gland contribution to MCC. The SMGs of both the nose and sinuses may represent targets for future therapeutic approaches.
Assuntos
Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Humanos , Mucinas , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologiaRESUMO
While surgical approaches and techniques of expanded endonasal approach (EEA) surgery have been well described, little data exist regarding management of post-operative cerebrospinal fluid (CSF) leaks. In this study, we examined a surgeon's continuous 12-year experience with failed closure of sphenoclival skull base defects. We conducted a retrospective case series of patients identified with post-operative CSF leaks after EEA of the sphenoclival axis, managed by a single otolaryngologist at a minimally invasive skull base center. Ten out of 326 patients required therapeutic intervention for central skull base defect closure failure. Median time to presentation of CSF leak was 25 days (range 6-542 days). Symptoms included rhinorrhea (n = 7), meningitis (n = 6), and pneumocephalus (n = 1). The majority of patients (7 of 10) were first managed by lumbar drain placement - one of which had resolution of his/her CSF leak. Overall, 9 of 10 patients required endoscopic repair. The majority of the post-operative CSF leaks (9/13, 69.2%) were repaired using a vascularized mucosal flap. There were 3 patients who required a second revision surgery. All CSF leaks were repaired without completely deconstructing the initial repair. Failure sites most frequently occurred outside of the sella (80%), likely reflecting their direct relationship to the intracranial cisterns. Initial operative repair provided definitive treatment in most cases (70%). Correct placement of a vascularized local pedicle-based flap is essential for successful repair. Knowledge of alternative flaps is particularly important when the nasoseptal flap is no longer available.