Inhibition of arachidonate 15‐lipoxygenase reduces the epithelial–mesenchymal transition in eosinophilic chronic rhinosinusitis with nasal polyps

Background

The epithelial–mesenchymal transition (EMT) is a distinguishing characteristic of chronic rhinosinusitis with nasal polyps (CRSwNP). The underlying mechanism remains largely unknown. Arachidonate 15‐lipoxygenase (ALOX15), an enzyme involved in arachidonic acid metabolism, has been reported to cause airway epithelial injury and thus may further promote the EMT. The aim of this study was to evaluate the role of ALOX15 during the EMT process in CRSwNP.

Methods

A total of 54 samples were obtained, including 10 from healthy control, 16 from non‐eosinophilic CRSwNP, and 28 from eosinophilic CRSwNP. Hematoxylin and eosin staining was performed to determine the basement membrane (BM) thickness. The concentration of molecules mediating remodeling was assayed by Luminex. The messenger RNA (mRNA) and protein levels of target genes were measured by quantitative real‐time polymerase chain reaction (PCR) and Western blotting.

Results

EMT was enhanced in eosinophilic CRSwNP compared with the healthy controls and non‐eosinophilic CRSwNP infiltrated with lymphocytes and/or plasma cells. The expression pattern of molecules related to remodeling, including matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and transforming growth factor β (TGF‐β) family members, differed between the subtypes of CRSwNP. The mRNA level of ALOX15 was correlated with the BM thickness and MMP‐1 and TGF‐β3 expression. The inhibition of ALOX15 by PD146176 could induce claudin‐1, claudin‐4, claudin‐7, zonula occludens (ZO)‐1, ZO‐2, E‐Cadherin, TIMP‐1, and TIMP‐3 expressions and reduce the levels of MMP‐1 and N‐Cadherin in epithelial cells acquired from eosinophilic CRSwNP patients.

Conclusion

The specific inhibition of ALOX15 could attenuate the EMT, which may provide an alternative method for the treatment of CRSwNP.

https://ift.tt/2qTNeXC

In‐office balloon sinus dilation versus medical therapy for recurrent acute rhinosinusitis: a randomized, placebo‐controlled study

Background

A limited number of studies have demonstrated symptomatic improvement for recurrent acute rhinosinusitis (RARS) patients after endoscopic sinus surgery. In this randomized, controlled study we evaluated 24‐week outcomes for balloon sinus dilation (BSD) performed in‐office (IO) with medical management (MM) as compared with MM only for RARS patients.

Methods

Adults diagnosed with RARS were randomized to groups with BSD plus MM (n = 29) or MM alone (n = 30). Patients who received MM alone also received a sham BSD‐IO procedure to blind them to group assignment. Patients were followed to 48 weeks posttreatment. The primary outcome was the difference between arms in change in Chronic Sinusitis Survey (CSS) score from baseline to 24 weeks. Secondary endpoints included comparisons of Rhinosinusitis Disability Index (RSDI) score, medication usage, medical care visits, and sinus infections.

Results

Change in patient‐reported quality of life (QOL), as measured by the CSS total score from baseline to 24 weeks, was significantly greater in the BSD plus MM group compared with the MM‐only group (37.3 ± 24.4 [n = 26] vs 21.8 ± 29.0 [n = 27]; p = 0.0424).

Conclusion

BSD plus MM proved superior to MM alone in enhancing QOL for RARS patients. BSD plus MM should be considered as a viable treatment option for properly diagnosed RARS patients.

https://ift.tt/2FuY806

Quality of recovery in patients undergoing endoscopic sinus surgery after general anesthesia: total intravenous anesthesia vs desflurane anesthesia

Background

For sinus surgery, some centers favor total intravenous anesthesia (TIVA) over inhalation anesthesia. However, whether TIVA affects the patient's perceived quality of recovery remains unclear. This study used the Quality of Recovery–40 questionnaire (QoR‐40) to compare patient recovery between surgical patients who received TIVA and those who received desflurane (DES) anesthesia.

Methods

Eighty patients (20 to 65 years old) undergoing endoscopic sinus surgery were prospectively enrolled and randomized to either the TIVA (propofol and remifentanil infusion) or DES (desflurane inhalation and remifentanil infusion) group. The QoR‐40 was administered before surgery, at 6 hours after surgery, and on postoperative day 1 (POD1). Incidence of nausea and vomiting, remifentanil consumption, blood loss, and pain treatment were recorded. The influence of lesion extent (indexed as Lund‐Mackay [LM] score) on recovery quality was also assessed.

Results

Forty patients were randomized into the TIVA group, and 40 patients were randomized into the DES group. The QoR‐40 score at 6 hours after surgery was significantly higher in the TIVA group compared with the DES group (188.2 vs 182.6, respectively; p = 0.049), indicating a better quality of recovery in the TIVA group. TIVA resulted in less blood loss (p < 0.0001). A high LM score (≥12) was associated with lower QoR‐40 scores at 6 hours after surgery (180.2 vs 187.2, p = 0.028) and on POD1 (181.5 vs 190.3, p = 0.003).

Conclusion

This study shows that the quality of recovery for endoscopic sinus surgery patients was better with TIVA than with desflurane anesthesia. A high LM score was related to poorer recovery quality.

https://ift.tt/2qW3EPo

Pediatricians’ proficiency in the care of the dysphonic child

Objectives/Hypothesis

Pediatricians are the first physicians to see a dysphonic child (DC), yet there are limited data on their proficiency in caring for them. The objective of this study was to understand how pediatricians' experience and their comfort in recognizing/diagnosing voice disorders affects their referral patterns and use of basic treatment options.

Study Design

Survey study.

Methods

A 13‐question survey was sent to pediatricians in the Children's Hospital of Philadelphia's primary care network; 45/216 were returned. Statistical analyses were performed using the Student t test, linear/logistic regression model, Fisher exact test, Kruskal‐Wallis test, and Spearman's correlation test.

Results

Pediatricians practicing longer are more comfortable recognizing dysphonia (P = .0022). They are significantly more likely to refer a DC, even without subjective complaints of hoarseness by the family/patient or compounding medical issues. For each year in practice, the probability of referring increases by 1.55% (P = .0017). Pediatricians with a higher percentage of dysphonic children in their practice are more likely to trust their own perceptual recognition when deciding to refer (P = .0496). Nearly all pediatricians (40/45) would refer to a pediatric otolaryngologist. None would refer to a laryngologist or a voice therapist. No factors significantly affected treatment options.

Conclusions

Veteran pediatricians feel more comfortable diagnosing a voice disorder and are more likely to refer a DC, regardless of patient/parent complaints or compounding factors. Pediatricians are most likely to refer to a pediatric otolaryngologist versus a voice specialist. These findings suggest that education of younger, less‐experienced pediatricians about recognizing voice disorders and options for referral is needed. This may improve the overall care of the DC.

Level of Evidence

4 Laryngoscope, 2018

https://ift.tt/2A5DLAU

Characterization of aged rat vocal fold fibroblasts

Objectives/Hypothesis

To elucidate the aging physiology of the vocal folds, we examined the characters of aged vocal fold fibroblasts (VFFs) in various conditions.

Study Design

In vitro study.

Methods

VFFs from young (12‐week‐old) and aged (19‐month‐old) Sprague‐Dawley rats were compared. Proliferative capacity, ratio of myofibroblast to fibroblast, myofibroblast function, and extracellular matrix production were examined in the following conditions: naïve, basic fibroblast growth factor (bFGF) supplemented, and hepatocyte growth factor (HGF) supplemented.

Results

Aged VFFs demonstrated reduced proliferation by cell counting, though the ratio of Ki‐67–positive cells showed no difference. Aged VFFs exhibited an increased expression of α‐smooth muscle actin (α‐SMA); however, they demonstrated no enhanced contractile ability in a gel contraction assay. Type I collagen protein was increased age dependently, accompanied with decreased Mmp1 and unchanged Col1a1 transcription. Type I collagen protein and α‐SMA represented quite similar reduction patterns to bFGF or HGF administration.

Conclusions

The following possible characteristics of aged VFFs were implied: long duration of mitosis, increased myofibroblast population size with certain dysfunctions, reduced type I collagen turnover, and correlation between α‐SMA expression and type I collagen metabolism. Further investigations of these features will help to clarify presbyphonia's pathology and establish treatment strategies.

Level of Evidence

NA Laryngoscope, 2018

https://ift.tt/2Tr8Qrl

Endoscopic endonasal resection of adenoid cystic carcinoma of the sinonasal tract and skull base

Objectives

Adenoid cystic carcinoma (ACC) is a locally aggressive salivary gland malignancy prone to perineural invasion and local recurrences. In the literature, few data exist to guide treatment when this tumor involves the paranasal sinuses and skull base. We report our experience in the management of sinonasal adenoid cystic carcinoma through an endoscopic endonasal approach.

Methods

Retrospective analysis of patients affected by sinonasal ACC treated through an endoscopic endonasal approach from 1997 to 2015, managed at the Universities of Varese and Brescia, Italy.

Results

Thirty‐four patients were included in the analysis. The ethmoid sinus (55.9%), nasal septum (17.7%), maxillary sinus (11.7%), and sphenoid sinus (5.9%) were the primary tumor sites encountered. Twenty patients (58.8%) presented with T3 or T4, without any systemic spreading. Twenty‐nine patients underwent endoscopic transnasal resection, whereas the involvement of the anterior skull base in five cases required a transnasal endoscopic craniectomy. Overall, 20 of 34 (58.8%) patients received some form of adjuvant radiotherapy. The follow‐up ranged from 12 to 202 months (mean of 73.2 months). The 5‐year overall, disease‐specific, and recurrence‐free survival rates were 86.5% ± 7.39%, 86.5% ± 7.39%, and 71.8% ± 8.67%, respectively.

Conclusions

The endoscopic approach is safe and effective for selected sinonasal ACC, reducing the comorbidities of the external approaches while producing similar oncological results. High T‐stage, grade III histology, positive surgical margins, and perineural infiltration all have an important negative prognostic value.

Level of Evidence

4. Laryngoscope, 2018

https://ift.tt/2A44tK4

Changing trends in management of vestibular schwannoma: A National Cancer Database study

Objective

To describe changes in management trends of vestibular schwannoma (VS) and the effects of median income, education level, insurance status, and tumor size on receipt of treatment.

Methods

Cross‐sectional analysis using the National Cancer Database from 2004 to 2014. All patients with a diagnosis of VS were identified between 2004 and 2014. Trends in treatment modality over time were analyzed. Correlation between demographics, institution type, median income, education level, and insurance status were assessed using univariate and multivariate logistic regressions.

Results

Of the 22,290 VS patients identified, 16,011 (71.8%) received treatment, whereas 6,279 (28.2%) received observation. Management trend analysis over the 11‐year period revealed patients with tumor size < 1 cm are more frequently observed (34.6% of cases in 2004 vs. 60.8% of cases in 2014) and less frequently received surgery (34.6% vs. 16.8%). Multivariate analysis showed observation was more frequently used in patients ≥ 65 years; black patients; and those on Medicaid, Medicare, and noninsured (P < 0.0001). All tumors > 2 cm were more likely to be treated with surgery, specifically subtotal resections (P < 0.0001). Patients treated at nonacademic centers were more likely to receive linear accelerator, or LINAC (Accuray Incorporated, Sunnyvale, CA) therapy than Gamma Knife (Elekta, Stockholm, Sweden) (P < 0.0001).

Conclusion

Management of VS is shifting toward increased observation, most significantly in tumors size < 1 cm. Insurance provider plays a significant role on receipt of treatment and modality, whereas income and education do not.

Level of Evidence

N/A Laryngoscope, 2018

https://ift.tt/2ToQuY8