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Mechanical forces are critical for fetal lung development. Using surfactant protein C (SP-C) as a marker, we previously showed that stretch-induced fetal type II cell differentiation is mediated via the ERK pathway. Caveolin-1, a major component of the plasma membrane microdomains, is important as a signaling protein in blood vessels exposed to shear stress. Its potential role in mechanotransduction during fetal lung development is unknown. Caveolin-1 is a marker of type I epithelial cell phenotype. In this study, using immunocytochemistry, Western blotting, and immunogold electron microscopy, we first demonstrated the presence of caveolin-1 in embryonic day 19 (E19) rat fetal type II epithelial cells. By detergent-free purification of lipid raft-rich membrane fractions and fluorescence immunocytochemistry, we found that mechanical stretch translocates caveolin-1 from the plasma membrane to the cytoplasm. Disruption of the lipid rafts with cholesterol-chelating agents further increased stretch-induced ERK activation and SP-C gene expression compared with stretch samples without disruptors. Similar results were obtained when caveolin-1 gene was knocked down by small interference RNA. In contrast, adenovirus overexpression of the wild-type caveolin-1 or delivery of caveolin-1 scaffolding domain peptide inside the cells decreased stretch-induced ERK phosphorylation and SP-C mRNA expression. In conclusion, our data suggest that caveolin-1 is present in E19 fetal type II epithelial cells. Caveolin-1 is translocated from the plasma membrane to the cytoplasm by mechanical stretch and functions as an inhibitory protein in stretch-induced type II cell differentiation via the ERK pathway. caveolin; lung development; surfactant protein C doi: 10.1152/ajplung.00327.2009.

An imbalance between pro-inflammatory and anti-inflammatory cytokines is a key factor in the lung injury of premature infants exposed to mechanical ventilation. Previous studies have shown that lung cells exposed to stretch produces reduced amounts of the anti-inflammatory cytokine IL-10. The objective of these studies was to analyze the signaling mechanisms responsible for the decreased IL-10 production in fetal type II cells exposed to mechanical stretch. Fetal mouse type II epithelial cells isolated at embryonic day 18 were exposed to 20% stretch to simulate lung injury. We show that IL-10 receptor gene expression increased with gestational age. Mechanical stretch decreased not only IL-10 receptor gene expression but also IL-10 secretion. In contrast, mechanical stretch increased release of IL-6. We then investigated IL-10 signaling pathway-associated proteins and found that in wild-type cells, mechanical stretch decreased activation of JAK1 and TYK2 and increased STAT3 and SOCS3 activation. However, opposite effects were found in cells isolated from IL-10 knockout mice. Reduction in IL-6 secretion by stretch was observed in cells isolated from IL-10 null mice. To support the idea that stretch-induced SOCS3 expression via IL-6 leads to reduced IL-10 expression, siRNA-mediated inhibition of SOCS3 restored IL-10 secretion in cells exposed to stretch and decreased IL-6 secretion. Taken together, these studies suggest that the inhibitory effect of mechanical stretch on IL-10 secretion is mediated via activation of IL-6-STAT3-SOCS3 signaling pathway. SOCS3 could be a therapeutic target to increase IL-10 production in lung cells exposed to mechanical injury.

Summary: Background: Significantly more patients with moderate‐to‐severe plaque psoriasis treated with the interleukin (IL)‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab in the IXORA‐R head‐to‐head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12. Objectives: To compare skin and nail clearance and patient‐reported outcomes for ixekizumab vs. guselkumab, up to week 24. Methods: IXORA‐R enrolled adults with moderate‐to‐severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran–Mantel–Haenszel test stratified by pooled site. Time‐to‐first‐event comparisons were performed using Kaplan–Meier analysis, and P‐values were generated using adjusted log‐rank tests stratified by treatment group. Cumulative days at clinical and patient‐reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323). Results: Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference −2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals. Conclusions: Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate‐to‐severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab. What is already known about this topic?Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.Ixekizumab is a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A.In the 12‐week report of the IXORA‐R study, ixekizumab demonstrated significantly higher efficacy at early timepoints than the IL‐23p19 inhibitor guselkumab, with more patients achieving 100% improvement in Psoriasis Area and Severity Index (PASI 100) and improved quality of life as early as week 4. What does this study add?Patients on ixekizumab vs. guselkumab achieved similar levels of skin clearance and superior efficacy in the resolution of nail psoriasis at week 24.Patients on ixekizumab vs. guselkumab had a greater cumulative benefit, with more days at PASI 90 and 100, more days when psoriasis did not impact their quality of life, and more itch‐free days.The safety profiles of both drugs were consistent with those in previous studies. Linked Comment: Puig. Br J Dermatol 2021; 184:992–993. [ABSTRACT FROM AUTHOR]

Summary: Background: Patients with psoriasis value rapid and complete skin clearance. No head‐to‐head studies have focused on early responses to interleukin (IL)‐17 vs. IL‐23 inhibitors. Objectives: To compare early and complete skin clearance by the IL‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab. Methods: IXORA‐R, a 24‐week, randomized, double‐blinded study, enrolled adults with moderate‐to‐severe plaque psoriasis [static Physician's Global Assessment of Disease (sPGA) score of ≥ 3, Psoriasis Area and Severity Index (PASI) ≥ 12, and ≥ 10% body surface area]. Patients were randomized (1 : 1) to receive the approved dose of subcutaneous ixekizumab or guselkumab. Primary end point was 100% improvement in PASI (PASI 100) at week 12. Major secondary end points included other levels of improved PASI and sPGA at different time points. Comparisons were made using the Cochran–Mantel–Haenszel test with a multiple testing strategy. Nonresponder imputation was used for missing data. After the completion of the study, the final secondary end point (PASI 100 at 24 weeks) and safety data through week 24 will be reported. Results: In total, 1027 patients were randomized. The primary end point PASI 100 at week 12 was met [215/520 ixekizumab (41%); 126/507 guselkumab (25%); P < 0·001]. All major secondary end points measured up to week 12 were met, including PASI 50 at week 1 and PASI 75 at week 2. Serious adverse event frequency was 3% for each group; no new safety signals were identified. Conclusions: Ixekizumab was superior to guselkumab for rapidly improving signs and symptoms in patients with moderate‐to‐severe plaque psoriasis by week 12. Adverse events were similar to previous ixekizumab and guselkumab studies. Compared with the IL‐23 inhibitor guselkumab, ixekizumab can offer complete skin clearance more rapidly to patients with moderate‐to‐severe plaque psoriasis. What's already known about this topic? Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.Ixekizumab, a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A, has demonstrated greater and faster skin clearance than etanercept and ustekinumab, with consistent long‐term efficacy, safety and durability of response.Clinical trial data and systematic reviews have suggested that IL‐17 inhibitors can improve a patient's psoriasis more rapidly than IL‐23 inhibitors. What does this study add? The head‐to‐head study design directly compares the efficacy and speed of response of ixekizumab and the IL‐23 inhibitor guselkumab in moderate‐to‐severe plaque psoriasis.The primary end point was met, showing superiority of ixekizumab over guselkumab for achieving complete skin clearance at week 12.The safety profile of ixekizumab was consistent with previous studies.Ixekizumab can deliver patients complete skin clearance and improved quality of life more rapidly than guselkumab. Linked Comment:Veysey. Br J Dermatol 2020; 182:1321–1322. Plain language summary available online [ABSTRACT FROM AUTHOR]

Mechanical forces are critical for fetal lung development. Using surfactant protein C (SP-C) as a marker, we previously showed that stretch-induced fetal type II cell differentiation is mediated via the ERK pathway. Caveolin-1, a major component of the plasma membrane microdomains, is important as a signaling protein in blood vessels exposed to shear stress. Its potential role in mechanotransduction during fetal lung development is unknown. Caveolin-1 is a marker of type I epithelial cell phenotype. In this study, using immunocytochemistry, Western blotting, and immunogold electron microscopy, we first demonstrated the presence of caveolin-1 in embryonic day 19 (E19) rat fetal type II epithelial cells. By detergent-free purification of lipid raft-rich membrane fractions and fluorescence immunocytochemistry, we found that mechanical stretch translocates caveolin-1 from the plasma membrane to the cytoplasm. Disruption of the lipid rafts with cholesterol-chelating agents further increased stretch-induced ERK activation and SP-C gene expression compared with stretch samples without disruptors. Similar results were obtained when caveolin-1 gene was knocked down by small interference RNA. In contrast, adenovirus overexpression of the wild-type caveolin-1 or delivery of caveolin-1 scaffolding domain peptide inside the cells decreased stretch-induced ERK phosphorylation and SP-C mRNA expression. In conclusion, our data suggest that caveolin-1 is present in E19 fetal type II epithelial cells. Caveolin-1 is translocated from the plasma membrane to the cytoplasm by mechanical stretch and functions as an inhibitory protein in stretch-induced type II cell differentiation via the ERK pathway. [ABSTRACT FROM AUTHOR]

Summary: 银屑病是一种皮肤病,会导致全身皮肤出现红色、鳞屑和瘙痒的斑块。 它影响着全球约 1.25 亿人。除了导致生活质量下降外,更广泛的银屑病往往会影响内在健康。过去几年开发的新药经常可以帮助银屑病患者实现完全清除皮损,并改善整体健康状况。 其中两种药物是 ixekizumab (IXE) 和 guselkumab (GUS)。然而,IXE 和 GUS 的工作方式不同,之前的一些研究表明,IXE 可能比 GUS 起效更快。 在这项研究中,来自美国和加拿大的研究人员对这些药物进行了直接对比测试,测量了开始用药后头 12 周的清除速度和皮肤完全清除率。 这项研究中的人接受了 IXE 或 GUS。12 周后,接受 IXE 治疗的人皮损完全清除者所占比例比接受 GUS 治疗的人高 16%(使用 IXE 的人为 41%,使用 GUS 的人为 25%)。 无论使用一周后皮肤清除率达 50% 的人数,还是使用两周后皮肤清除率达 75% 的人数,IXE 都比 GUS 多。与 GUS 相比,IXE 对瘙痒、皮肤疼痛和生活质量的改善也更快。IXE 和 GUS 出现严重副作用的患者数量相似。 总体而言,与使用 GUS 的患者相比,使用 IXE 的银屑病患者皮肤清除干净的速度更快,也更为迅速感觉好转。 本摘要涉及研究: 来自一项随机分配、双盲试验的 Ixekizumab 与 Guselkumab 治疗中度至重度斑块型银屑病患者的直接比较: 12 周疗效、安全性和应答速度 Linked Article: Blauvelt et al. Br J Dermatol 2020; 182:1348–1358 [ABSTRACT FROM AUTHOR]

Summary: Psoriasis is a skin disease that causes red, scaly and itchy patches of skin all over the body. It affects about 125 million people worldwide. As well as causing decreased quality of life, more widespread psoriasis often affects internal health. New drugs developed in the last few years often help people with psoriasis to achieve completely clear skin, and improve overall health. Two of these drugs are ixekizumab (IXE) and guselkumab (GUS). IXE and GUS work in different ways, however, and some prior research showed that IXE may work faster than GUS. In this study, researchers from the U.S.A. and Canada tested these drugs head‐to‐head, measuring speed of clearance and complete skin clearance rates over the first 12 weeks after starting drug. People in this study received either IXE or GUS. After 12 weeks, completely clear skin was achieved by 16% more people if they were treated with IXE compared to GUS (41% of people who took IXE versus 25% of people who took GUS). More people on IXE than GUS had 50% clearer skin after just one week and 75% clearer skin after two weeks. Itching, skin pain, and quality of life also improved faster with IXE compared to GUS. The number of patients with serious side effects was similar for IXE and GUS. Overall, people with psoriasis who take IXE may get clear skin faster and feel better more quickly than people who take GUS. This is a summary of the study: A head‐to‐head comparison of ixekizumab vs. guselkumab in patients with moderate‐to‐severe plaque psoriasis: 12‐week efficacy, safety and speed of response from a randomized, double‐blinded trial Linked Article: Blauvelt et al. Br J Dermatol 2020; 182:1348–1358 [ABSTRACT FROM AUTHOR]

Objective: To investigate the importance of hepcidin and paraoxonase in obstructive sleep apnea syndrome (OSAS)., Methods: Eighty-eight patients with sleep disorders were included and divided into four groups: simple snoring (SS), mild, moderate, and severe OSAS. All patients underwent polysomnography. The hepcidin and paraoxonase levels were examined and compared between the groups., Results: There were significant differences between the four groups in terms of paraoxonase levels. In the SS group, the paraoxonase value was significantly higher than in the other three groups. In the analysis, Apnea Hypopnea Index (AHI) was negatively correlated with paraoxonase levels., Conclusion: A significant difference was found between the OSAS groups with respect to paraoxonase enzyme, and a negative correlation with AHI was observed. Paraoxonase level could be used as a biomarker in OSAS. No significant data was found for hepcidin levels; therefore, hepcidin cannot be used as a biomarker in OSAS.

Objective: It was aimed to investigate the role of tonsil ultrasonography(USG) in the diagnosis of pediatric OSAS., Methods: Before tonsillectomy (±adenoidectomy) for OSAS, all patients tonsil USG and polysomnography (PSG) tests were performed. Tonsil volume was measured preoperatively with the Brodsky tonsil grading scale and by postoperative water displacement test., Results: In total, 47 patients were included in the study. We observed a positive correlation between tonsil volumes measured by preoperative USG and water displacement test postoperatively. There was a statistically significant correlation between tonsil sizes measured by tonsil USG, PSG AHI and questionnaire scores( p  < .05)., Conclusion: Preoperative tonsil USG may be helpful test in children with suspected OSAS.

Objective: Signal peptide CUB-EGF domain-containing protein 1 (SCUBE-1) is a cell surface protein, wherein inflammation causes an increase in serum. The aim of this study was to compare serum SCUBE-1 levels in OSA patients and to investigate the serum SCUBE-1 change with CPAP treatment., Methods: Blood samples were obtained from 61 severe OSA patients and from 25 control subjects evaluated as simple snorers. The 61 patients with severe OSA were treated with CPAP therapy and were recalled for follow up after 1 year. Evaluation was made after 1 year of CPAP therapy., Results: Serum SCUBE-1 values were significantly higher in patients with severe OSA. The SCUBE-1 values significantly decreased after treatment with CPAP., Conclusion: Serum SCUBE-1 values in OSA patients showed a significant reduction in SCUBE-1 levels following 1 year of CPAP treatment.

Background: Psoriasis is characterized by thick and scaly plaques. The Dermatology Life Quality Index (DLQI) and Physician Global Assessment (PGA) can be used to define its severity., Objective: To assess the impact of complete clearance of skin versus almost clear skin across various disease measures., Methods: Data were collected in a survey of US dermatologists and patients with psoriasis from November 2016-January 2017. Dermatologists completed a 6-point PGA (0 = clear skin, 1 = almost clear skin). Patients completed the DLQI and Work Productivity and Activity Impairment questionnaire (WPAI). Patients with clear and almost clear skin were compared using analysis of covariance for continuous variables, and multivariate logistic regression analysis for categorical variables., Results: Data for 99 and 160 patients with clear and almost clear skin, respectively, were included in the analyses. Patients with clear skin reported less frequent and lower intensity itching, lower total DLQI score (indicating better health-related quality of life), and less impairment of overall work productivity than patients with almost clear skin (all: p  < 0.05)., Limitations: Limitations relating to general survey methodology., Conclusion: Patients perceived a meaningful difference between clear and almost clear skin. Clear skin is now a realistic treatment target with newer biologics approved in psoriasis.

Introduction: Mucosal contact headache is a referred pain that arises from contact between the nasal septum and the lateral nasal wall. Evidence supports the role of substance P in a contact headache such that release of substance P from sensory nerve endings causes inflammation and allergy., Objectives: This study aimed to determine possible differences in substance P levels in inferior turbinate hypertrophy creating a contact headache., Methods: 28 patients who had contact headaches (study group) and 16 volunteers with no complaints were included in the study. Substance P levels in the inferior turbinate tissue samples were quantified using a commercially available substance P EIA kit., Results: In the study group average substance P levels were 2.65±0.27pg/mg tissue (range: 0.61-5.44) and in the control group it was 1.77±0.27pg/mg tissue (range: 0.11-4.35). The difference was statistically significant between the two groups (p=0.0215). Average preoperative headache group visual analog scale scores was 5.93±0.38 (2-9) and the turbinate volume was 6.56±0.35cm 3 (3.50-10.30). The control group turbinate volume was 4.71±0.39cm 3 (2.50-7.70). We found a correlation between the visual analog scale scores and substance P levels such that substance P levels were higher in visual analog scale scores above 5 (p=0.001)., Conclusion: This study demonstrates the relationship between intranasal contact headaches and increased mucosal substance P levels. We also found that there is no correlation with substance P levels and volume of the inferior turbinate., (Copyright © 2019 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Introduction: Biologics used to treat moderate-to-severe plaque psoriasis may cause injection site reactions (ISRs) characterized by erythema, edema, itch, and sometimes pain. The Federal Adverse Event Reporting System (FAERS) is a repository of spontaneous post-marketing reports of adverse events (AEs) that are reported to the US Food and Drug Administration (FDA). Our objective was to perform a pharmacovigilance analysis of FAERS reports of ISRs associated with the use of subcutaneously administered biologic products approved to treat moderate-to-severe plaque psoriasis., Methods: The products included in our assessment were adalimumab, etanercept, ixekizumab, secukinumab, and ustekinumab. Reports from the date of US approval for each biologic as treatment for plaque psoriasis through 2 years were included using the search term "injection site.", Results: The results show that the FAERS database contained reports of ISRs for all of the included biologics during the 2 years following FDA approval. The most common reports on ISRs were on pain, irritation, and erythema for adalimumab; reaction, pain, and erythema for etanercept; erythema, pain, and reaction for ixekizumab; bruising, pain, hemorrhage for secukinumab; and pain, induration, and swelling for ustekinumab. FAERS does not include data on total patient exposure; therefore, ISR rates could not be calculated., Conclusions: Specific ISRs varied among the biologic therapies assessed. The findings presented could be helpful when patients consider switching therapies due to ISRs., Funding: Eli Lilly and Company.

Introduction: Long-term safety data are critical for evaluating therapies for psoriasis. Ixekizumab has demonstrated efficacy and is well tolerated for the treatment of moderate-to-severe plaque psoriasis. We examined the safety and tolerability of up to 5 years of ixekizumab therapy in patients with psoriasis., Methods: Integrated safety data were analyzed from 13 ixekizumab clinical studies. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for the 12-week induction period in the combined pivotal studies, and for all pooled studies by year(s) of therapy and overall, reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (p-y) and/or frequencies., Results: Total ixekizumab exposure was 17,003.4 p-y (N = 5898); 2749 patients had ≥ 4 years of exposure. When compared across years of exposure, rates for AEs remained largely stable or declined, including TEAEs leading to discontinuation (3.8/100 p-y in year 1, declining to 2.0/100 p-y in year 5); SAEs (range 6.2-7.0/100 p-y); serious infections (range 1.3-1.7/100 p-y); nonmelanoma skin cancer (ranging from 0.5/100 p-y in year 1 to 0.2/100 p-y in years 4-5); other malignancies (range 0.4-0.6/100 p-y); inflammatory bowel disease including ulcerative colitis and Crohn's disease (IR 0.2/100 p-y); and major adverse cardiovascular events (MACE) (range 0.3-0.7/100 p-y). Candidiasis was reported in 327 patients (IR 1.9/100 p-y), with the majority identified as mucocutaneous. The rate of injection site reactions was 15.5/100 p-y during year 1 and 2.0-2.3/100 p-y by years 3-5., Conclusions: The decrease in rates of TEAEs and the stable rates of SAEs, other malignancies and MACE during up to 5 years of ixekizumab dosing are consistent with previous reports describing a favorable safety profile of ixekizumab following shorter durations of exposure., Funding: Eli Lilly and Company.

Objective: There is no useful tool to clinically predict the occurrence of osteoradionecrosis (ORN) of the mandible quantitatively. The aim was to investigate the risk factors, including different modalities of radiotherapy, for developing mandibular ORN in patients undergoing marginal mandibulectomy and postoperative radiotherapy., Methods: Between January 2006 and December 2012, 167 subjects who underwent marginal mandibulectomy and postoperative radiotherapy with different modalities were enrolled. The association of ORN with mandibular bone measurements and patient variables was analyzed, and a nomogram was established., Results: Fifteen (8.98%) of the 167 patients developed ORN during the follow-up period, and ORN was significantly associated with diabetes mellitus (DM), body mass index (BMI), remaining bone height, remaining bone height to original bone height ratio, resected bone height to original bone height ratio, and mandibular dose (P: < 0.001, 0.004, 0.042, 0.018, 0.010, 0.020, respectively). Interestingly, the risk of ORN had no significant difference between conformal and intensity modulation radiation therapy (P = 0.407). Multivariate analysis revealed that DM and resected bone height to original bone height ratio ≥ 50% were independent risk factors for postoperative ORN. A nomogram consisting of BMI, DM, resected bone height to original bone height ratio, mandibulotomy, and mandibular dose for predicting the ORN-free probability was established; and the c-index of the nomogram for ORN status was 0.803., Conclusion: A nomogram based on the risk factors was plotted to strengthen the prediction of ORN quantitatively. Surgeons should be more discrete regarding the treatment plan for patients with higher probability of ORN., Level of Evidence: 3b Laryngoscope, 130:101-107, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: The goal of psoriasis (PsO) treatment is to improve quality of life by lessening the extent and severity of the disease. Traditional systemic drugs and biologic agents are used for the treatment of moderate to severe PsO and recent research emphasizes understanding patient goals and preferences for treatment, to improve overall outcomes., Methods: An online survey was administered to collect data from 500 adult patients with moderate to severe PsO in the USA. Patients were required to have current or previous systemic therapy use and were excluded if aged 75 or older. Data on demographics, disease burden, treatment use, and patients' treatment goals and expectations were collected. Descriptive and multivariate analyses examined the factors that predict treatment goals. Subgroup analyses were performed for age, gender, severity, comorbid psoriatic arthritis (PsA), location of PsO, and biologic experience. All analyses were conducted using SAS v9.4 and R v3.4., Results: Of the 500 adult patients included, 71.6% reported moderate PsO. Patients had a mean (SD) score of 62.4 (23.0) for skin pain, 60.0 (26.3) for fatigue, and 6.6 (2.1) for itch on a scale of 0-100, 0-100, and 0-10 respectively. Mean (SD) score for quality of life (QoL), assessed using Dermatology Life Quality Index (DLQI), was 18.3 (7.3), with more than 90% having moderate/very large/extremely large effect on life. The majority of patients considered "keeping skin clear for 2-3 years" (94%), "overall relief of symptoms" (93.8%), and effective in clearing certain areas" (92.2%) as important attributes of a systemic treatment. Overall, patients expected 50% clear skin in about 2 weeks and completely clear skin in about 4 weeks., Conclusions: Overall, in this study with more than 70% of patients with moderate disease, patients reported high burden of disease and impact on QoL. This study demonstrates the importance of considering patient perspectives in treatment decisions that are critical for optimizing patient outcomes., Funding: Eli Lilly and Company.

Background/aim: Tinnitus is seen in 15% of the general population; in 1%–6% of this number, the quality of life is seriously affected by this chronic condition. Chemical, oxidative, and emotional stressors are important in terms of the clinical course of tinnitus. Apelin is an endogenous peptide which is an oxidative stress mediator. It has been shown that the apelin/APJ (apelin junction receptor) system plays various roles in the physiology and pathophysiology of many organs. However, the role of the apelin/APJ system as an oxidative stress mediator in tinnitus is unknown. We investigated the level of apelin in patients with normal hearing and bilateral tinnitus., Materials and Methods: We enrolled patients diagnosed with bilateral idiopathic tinnitus. Tinnitus severity was determined using the tinnitus handicap inventory (THI). We recorded the levels of plasma apelin-13 and biochemical parameters., Results: The mean apelin level of the control group was higher than that of the patient group (P = 0.002). A significant negative correlation was evident between the apelin level and the THI (r = –0.460, P = 0.003). The triglyceride (TG) level was significantly higher in the patient group than in the control group (P < 0.001)., Conclusion: In our study, we found a negative correlation between apelin and tinnitus severity. Thus, apelin may play a role in the pathophysiology of idiopathic tinnitus, and may be prescribed during follow-up to reduce oxidative stress in the future. Further clinical studies on the effects of the apelin/APJ (apelin junction receptor) system and the effects of antioxidants in patients with inflammatory diseases are required., (This work is licensed under a Creative Commons Attribution 4.0 International License)

Background: Allergic rhinitis (AR) is a disease that reduces athletic performance. Environmental allergen exposure is higher in outdoor sports (such as orienteering) than indoor sports. The main purpose of this study was to investigate the AR frequency in orienteers comparing with indoor athletes., Methods: Sixty adolescent athletes (33 orienteers, 27 basketball players) enrolled this prospective study. AR diagnosis was made by both history (ISAAC questionnaire) and physical examination. Nasal endoscopy was performed to observe objective findings (concha hypertrophy, mucosal paleness, serosity, septum deviation, adenoid hypertrophy). Epidermal prick test, pulmonary function test, total IgE and serum eosinophil levels were also assessed., Results: AR was diagnosed in 21 (35%) athletes. 14 (42.4%) were orienteers and 7 (25.9%) were basketball players (P=0.144). Endoscopic findings and skin test positivity were also seen at higher percentages in orienteers with no significance. Training age (sport duration), total IgE levels and skin test positivity were significantly higher in rhinitic orieenters than non-rhinitic orieenters (P=0.046, P=0.0001, and P=0.004, respectively)., Conclusions: Although adolescent orieenters had some higher allergic parameters than indoor athletes, they were not found more susceptible to AR. It seems that the frequency of AR increases with longer training age in orieentering sport. This study is the first report about AR in adolescent orienteers. Future researchs should more focus on comparing allergic conditions between outdoor and indoor sports.

Introduction: One of the most common otological complaints is tinnitus in adults. When there is a complaint of unilateral tinnitus and retrocochlear pathology is suspected, imaging methods are applied. However, the imaging findings obtained may not always be compatible with the severity and localization of the tinnitus., Aim: The aim of the present study was to determine whether or not there was a significant correlation between the findings on magnetic resonance imaging (MRI) and the presence and severity of tinnitus in patients with the complaint of unilateral tinnitus., Method: The study included 44 patients with no loss of hearing who presented with the complaint of unilateral tinnitus. The relationship between tinnitus severity and vascular loop presence was investigated., Results: Various types of vascular loop were determined in 14 patients. No statistically significant relationship was determined between the presence of vascular loop and the Tinnitus Handicap Inventory scores., Conclusion: The results of this study showed no significant difference in respect of the presence of vascular loop on the MRI findings of symptomatic and healthy ears. The presence of vascular loop on MRI is not always a pathological event and should be considered only as an examination finding that could be an anatomic variation.

The role of IL-25 and IL-33 in the aetiology and pathogenesis of nasal polyps has been controversial in the literature. The objective of the study is to detect serum and tissue levels of IL-25 and IL-33 in patients with (CRSwNP) or without (CRSsNP) nasal polyps using enzyme-linked immunosorbent assay (ELISA). Study group consisted of 20 CRSwNP and 20 CRSsNP patients. Control group comprised of 20 volunteers who had been operated with septum deviation without any additional sinonasal pathology, allergy, systemic disease, or medication use. All groups preoperatively underwent paranasal CT examinations and sinonasal pathologies were recorded based on Lund-Mackay radiological staging system. IL-25 and IL-33 levels in serum and tissue samples were analyzed using the ELISA method. Serum IL-25 and IL-33 levels in CRSsNP, CRSwNP, and control groups did not differ statistically significantly (p = 0.345 and p = 0.338). Any statistically significant difference was not detected in mean tissue IL-25 levels among CRSsNP, CRSwNP, and control groups (p = 0.698). Mean tissue IL-33 level in the CRSwNP group was statistically significantly lower when compared with those of CRSsNP and control groups (p < 0.001 and p < 0.001, respectively). A statistically significant negative correlation was detected between tissue IL-33 levels and Lund-Mackay CT scores (r = -0.436 and p = 0.005). In the present study, we conceivably contributed to scarce number of studies conducted on this issue and we think that further studies will better clarify the role of IL-25 and IL-33 in the development of nasal polyps.

Objectives: (1) To evaluate the effects of a platelet-rich fibrin (PRF) membrane in the repair of traumatic tympanic membrane (TM) perforations; and (2) to compare the use of a PRF membrane with the paper patch technique with regard to recovery rates, healing time, and correction of the mean air-bone gap., Methods: A randomized, prospective analysis was performed for 60 patients who were treated for traumatic TM perforations using one of the two methods. Closure rate, speed of healing, and hearing gain were compared between the PRF (Group 1) and paper patch (Group 2) groups., Results: Closure was obtained in 28 (93%) perforations in Group 1 and 25 (83%) perforations in Group 2 (p > 0.05). On day 10, full closure of the TM was observed in 24 (80%) patients in Group 1 and 16 (53%) patients in Group 2 (p < 0.05). The improvement in the mean air-bone gap was 14.1 dB in Group 1 and 12.4 dB in Group 2 on post-operative day 45 (p < 0.05)., Conclusions: In comparison with the paper patch method, PRF, a new method, provided more rapid healing with more successful audiological results, and with no requirement for a second procedure.

Objective: Silent sinus syndrome (SSS) is a clinical syndrome that occurs as a result of chronic maxillary sinus atelectasis (CMA) and is seen with progressive enophthalmos and hypoglobus. The aim of this study was to investigate the correlation between radiological findings and clinical findings in patients with radiologically asymmetrical reduced maxillary sinus volume., Material and Method: A comparison was made of patients with CMA through evaluation of paranasal sinus computed tomography, magnetic resonance imaging examination of maxillary sinus volume of the CMA side and the contralateral side, thickness of the retroantral fat tissue, infraorbital bone curve, uncinate process lateralisation measurement, middle concha diameter, and calculation of the change in location of the inferior rectus muscle., Results: The study included 16 patients. Although a statistically significant difference was determined between the healthy and the pathological sides in respect to maxillary sinus volume, thickness of the retroantral fat tissue, infraorbital bone curve, uncinate process lateralisation measurement, and middle concha diameter (p = 0.00, p = 0.002, p = 0.020, p = 0.020, p = 0.007), no significant difference was determined in respect to the change in location of the inferior rectus muscle (p = 0.154). A positive correlation was determined between the increase in sulcus depth and maxillary sinus volume and inferior orbital bone curve (p < 0.05)., Conclusion: In CMA patients suspected of having SSS, radiological maxillary sinus volume analysis, determination of retroantral fat thickness, measurement of the infraorbital bone curve, and measurement of the uncinate process lateralisation can be used as objective tests. However, it should be kept in mind that radiological findings may not always be compatible with the ophthalmological examination findings., (Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the hearing levels of participants of a randomized group using a smartphone hearing application and to compare these results with the results from a pure-tone audiogram., Materials and Methods: A heterogenous group consisting of both normal-hearing and hearing-impaired participants were included in this study. Pure-tone audiogram thresholds were measured from 250 Hz to 8000 Hz, while smartphone measurements were obtained with a Samsung Galaxy GT-19500 S4 with a bundled headphone running the Hearing Test™ software (e-audiologia.pl), which was downloaded from the Google Play Store as a free application. We compared these results with those obtained from pure-tone audiograms performed by an audiologist as a reference., Results: Validity analysis indicated that the results for each ear and each frequency were excellent (>0.75). We assessed the mean difference between the pure-tone audiogram and the smartphone hearing test results and found the absolute difference to be less than 8.8 dB., Conclusion: Smartphone hearing test applications are providing alternative tests that present low-cost solutions. Using the hearing application test may decrease the demand for audiological services in underserved areas. The study suggests that smartphone hearing test results are comparable to pure-tone audiometry results.

Objectives: Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease in children. HT is a multifaceted disease with a variable clinicopathological presentation, including hearing impairment. It is known that hearing function is negatively affected in patients with thyroid disorders. The literature includes a very limited number of studies on hearing function in euthyroid pediatric patients with HT. The aim of this study was to determine the relationship between cochlear function and HT, independent of thyroid function., Materials and Methods: The study included 48 children and adolescents (42 females and 6 males) aged 9-18 years that were diagnosed as HT, and 30 gender- and age-matched healthy controls. Hearing was assessed via otoscopy, tympanometry, pure-tone audiometry, and measurement of distortion product otoacoustic emissions., Results: There weren't any significant differences in pure tone thresholds between the 2 groups based on pure-tone audiometry, except in the right ear at 6kHz and 8kHz. Distortion product otoacoustic emissions signal to noise ratios were significantly lower in the HT group than in the control group at 4 different frequencies (6kHz [left ear], 8kHz [left ear], 1.5kHz [right ear], and 6kHz [right ear]) (P<0.05). The signal to noise ratios at all frequencies were <6dB in 3% of left ears and 2.5% of right ears in the control group, versus 12.5% of left ears and 9.6% of right ears in the HT group. Distortion product amplitudes were significantly lower in the HT group than in the control group for both left and right ears at 1kHz, 1.5kHz, 3kHz, and 8kHz, and at 2kHz for left ears only (P<0.05)., Conclusions: The present findings show that cochlear function was lower in the HT group than in the control group. Accordingly, we think that hearing in patients with HT should be monitored periodically, even if their hearing thresholds are within normal limits. Thyroid autoimmunity appears to play an important role in a decrease in cochlear activity in pediatric HT patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Auditory system abnormalities commonly occur in patients with chronic renal disease and end-stage renal disease undergoing hemodialysis. The aim of this study was to determine the relationship between cochlear sensitivity and hemodialysis in dialytic and non-dialytic chronic kidney disease patients., Methods: The study included children aged 6-18 years that were divided into 3 groups: 36 non-dialytic patients with chronic kidney disease, 16 end-stage renal disease patients undergoing hemodialysis, and 30 healthy controls. Blood urea nitrogen, serum cystatin C levels, duration of chronic kidney disease, and the duration of hemodialysis were compared between the chronic kidney disease patients and end-stage renal disease patients undergoing hemodialysis. Hearing health was measured via tympanometry, pure-tone audiometry and distortion product otoacoustic emissions testing., Results: Distortion product otoacoustic emission amplitudes and signal-to-noise ratios were significantly lower at all frequencies tested in the non-dialytic and dialytic groups than in the control group (p<0.05). Patients with normal hearing had significantly lower distortion product otoacoustic emission amplitudes and signal-to-noise ratios than the healthy controls (p<0.05). The duration of CKD, the cystatin C level, and the blood urea level were not associated with hearing loss. The present findings suggest that there was a significant association between the duration of HD and hearing loss., Conclusion: The present findings show that there was impaired cochlear function in the dialytic and non-dialytic patient groups, regardless of hearing loss, as compared to the control group. Patients with chronic renal disease-both dialytic and non-dialytic-should be monitored to prevent any further deterioration by avoiding potential ototoxic agents, even if their hearing thresholds are within normal limits., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate the effect of climate and altitude differences on the volume of paranasal sinuses and on the frequency of anatomic variations by comparing the paranasal sinus tomograms (PNSCT) of patients who were born and living in a cold, dry climate at high altitude with those of patients who were born and living on the coast at sea level in a temperate climate. We also aimed to determine differences relating to gender., Material and Methods: A total of 55 PNSCTs of 55 patients from the city center of Antalya and 60 PNSCTs of 60 patients from the city center of Agrı were evaluated and compared prospectively. The study included a total of 115 patients with a mean age of 44.75 ± 9.64 years (range, 27-63 years). Group 1 (Antalya) comprised 26 females (47.3%) and 29 males (52.7%) with a mean age of 36.7 ± 12.4 years. Group 2 (Agrı) comprised 25 females (41.7%) and 35 males (58.3%) with a mean age of 35.1 ± 13.4 years. Maxillary sinus volumes were 18.27 cm(3) (range, 5.04-37.62) and 15.06 cm(3) (4.11-41.40); sphenoid sinus volumes were 7.81 cm(3) (1.80-20.63) and 6.35 cm(3) (0.54-16.50); frontal sinus volumes were 5.51 cm(3) (0.50-29.25) and 3.76 cm(3) (0.68-22.81) respectively., Results: There was no statistically significant difference between the groups in term of volumes (p > 0.025). Both maxillary and frontal sinus volumes were greater in males compared to females (p < 0.025). The mean value of the maxillary sinus volume was 15.7 ± 5.3 cm(3) and was significantly larger in males than in females (p = 0.004). There was no statistically significant correlation between the volume of maxillary sinuses with age or side. There was no statistically significant difference between the groups in terms of septum deviation and concha bullosa rates (p = 0.469 and p = 0.388)., Conclusion: There have been many studies of nasal cavity changes due to climatic conditions but this is the first study to measure the difference of paranasal sinus volumes. No difference was determined in the anatomic variations and volumes of the maxillary, frontal, sphenoid sinuses on PNSCT of patients from different climates and altitudes., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to compare serum copeptin levels in patients with obstructive sleep apnea syndrome (OSA) and simple snorers without sleep apnea; and to investigate relationships between copeptin levels and polysomnographic parameters., Methods: Serum copeptin levels were determined using enzyme-linked immunosorbent assay in 47 patients with OSA and 12 patients without OSA (control group). Full-night polysomnography was performed in each patient. Patients with OSA were divided into three groups according to their Apnea Hypopnea Index (AHI) scores: mild OSA (5 < AHI < 15), moderate OSA (15 < AHI < 30), and severe OSA (AHI > 30)., Results: A total of 59 patients were included in the study. There were 23 female (39.0%) and 36 male (61.0%) subjects. The range of ages of study subjects was between 27 and 63 (mean 44.75 ± 9.64) years. According to the AHI values, patients were classified into four groups: simple snoring (n = 13), mild OSA (n = 10), moderate OSA (n = 15), and severe OSA (n = 21). Statistically significant differences between AHI groups in terms of age, Epworth score, and neck circumference. According to multiple comparison results for age, the difference between simple snoring and moderate OSA was statistically significant. According to multiple comparison results for Epworth score, the difference between simple snoring and severe OSA was statistically significant. According to multiple comparison results for neck circumference, a similar result was found like Epworth Sleepiness Scale score. The difference between AHI groups by gender was tested by a Pearson χ(2) test and was found to be statistically significant. There was no statistically significant difference among AHI groups in terms of copeptin. There was a statistically significant correlation of copeptin with AHI during rapid eye movement (REM) sleep; however, the correlation coefficient was not sufficiently large., Conclusions: Increased serum copeptin concentration may reflect a response to stress in some diseases. This is well documented especially in cardiovascular diseases; however, we could not find any difference in OSA groups in terms of copeptin levels., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Leiomyosarcoma (LMS) of the larynx is a very rare malignancy that originates from blood vessel, smooth muscle or from the heterotopic mesenchymal tissue in the larynx. The histological diagnosis of LMS depends on the immunohistochemical investigation. The case is here presented of an 82-year-old man with shortness of breath and hoarseness. Indirect laryngoscopy showed a pedunculated large glottic lesion causing airway obstruction. Direct laryngoscopy was performed and biopsies were taken. From the pathological examination, the diagnosis of LMS was made. This case is presented of laryngeal LMS with the clinical, radiological, and histological findings.