Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Πέμπτη 15 Οκτωβρίου 2015

OtoLaryngology New Articles


IMRT and 3D conformal radiotherapy with or without elective nodal irradiation in locally advanced NSCLC

Abstract

Aim

The potential of intensity-modulated radiation therapy (IMRT) as opposed to three-dimensional conformal radiotherapy (3D-CRT) is analyzed for two different concepts of fluorodeoxyglucose positron emission tomography (FDG PET)-based target volume delineation in locally advanced non-small cell lung cancer (LA-NSCLC): involved-field radiotherapy (IF-RT) vs. elective nodal irradiation (ENI).

Methods

Treatment planning was performed for 41 patients with LA-NSCLC, using four different planning approaches (3D-CRT-IF, 3D-CRT-ENI, IMRT-IF, IMRT-ENI). ENI included a boost irradiation after 50 Gy. For each plan, maximum dose escalation was calculated based on prespecified normal tissue constraints. The maximum prescription dose (PD), tumor control probability (TCP), conformal indices (CI), and normal tissue complication probabilities (NTCP) were analyzed.

Results

IMRT resulted in statistically significant higher prescription doses for both target volume concepts as compared with 3D-CRT (ENI: 68.4 vs. 60.9 Gy, p < 0.001; IF: 74.3 vs. 70.1 Gy, p < 0.03). With IMRT-IF, a PD of at least 66 Gy was achieved for 95 % of all plans. For IF as compared with ENI, there was a considerable theoretical increase in TCP (IMRT: 27.3 vs. 17.7 %, p < 0.00001; 3D-CRT: 20.2 vs. 9.9 %, p < 0.00001). The esophageal NTCP showed a particularly good sparing with IMRT vs. 3D-CRT (ENI: 12.3 vs. 30.9 % p < 0.0001; IF: 15.9 vs. 24.1 %; p < 0.001).

Conclusion

The IMRT technique and IF target volume delineation allow a significant dose escalation and an increase in TCP. IMRT results in an improved sparing of OARs as compared with 3D-CRT at equivalent dose levels.

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From the Editor
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Surgical Considerations and Choices in the Management of Velopharyngeal Dysfunction
Determining the type of secondary surgical management to treat velopharyngeal dysfunction requires the incorporation of surgical indications and principles to the perceptual, acoustic/airflow, and imaging results of a comprehensive evaluation by a speech-language pathologist. In addition, how the specific type of surgical technique (primary and/or secondary) may affect velopharyngeal function also should be considered. The purpose of this paper is to consider three standard techniques commonly employed in speech surgery—Pharyngeal Flap; Sphincter Pharyngoplasty; and Furlow Double Opposing Z-Plasty—and provide examples of the specific imaging parameters that support the choice of surgical technique. In addition, information is provided regarding the characteristics of different primary surgical techniques for cleft palate which can influence velopharyngeal closure, given that the most common cause of velopharyngeal dysfunction seen in the clinic is a patient with a history of repaired cleft palate.
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Speech Science Applications for Practicing Clinicians and Audiology or Speech-Language Pathology Students
The advent of widely available, free, and user-friendly speech analysis software in the late 1990s has made it possible to perform acoustic analyses in clinical and educational settings. However, despite the widespread availability and relative ease of use of speech analysis programs, some clinicians are reluctant to adopt hands-on acoustic analyses into their practice. The purpose of the present paper is threefold: (1) to dispel the myth that speech science and acoustic analyses are difficult and only marginally useful for clinical practice, (2) to demonstrate the practical utility—even necessity—of acoustic analyses for practicing as well as future audiologists and speech-language pathologists, and (3) to briefly outline a highly interactive speech science course with integrated hands-on acoustic analyses. Today, more than ever before, a solid background in speech science and extensive experience with acoustic analyses is a necessary part of audiologists' and speech-language pathologists' education, because incorporating speech analyses can enhance clinical practice. Moreover, new technologies demand that clinicians understand the principles behind the programs they and their clients use.
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How To Get Started With Ultrasound Technology for Treatment of Speech Sound Disorders
Although providing visual feedback with ultrasound is becoming more and more popular among speech-language pathologists, it is still not widely used, perhaps because many speech-language pathologists are unfamiliar with its application to treatment of speech sound disorders. This report introduces basic information on ultrasound for new users and summarizes existing studies conducted with ultrasound to provide clinical evidence for speech treatment. This report also presents a clinical case using ultrasound and discusses a treatment protocol for establishing postvocalic /r/ to illustrate an example of how ultrasound was used in a clinical setting.
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SIG 5 Perspectives Vol. 25, No. 2, October 2015: Earn 0.2 CEUs on This Issue
Download the CE Questions PDF from the toolbar, above. Use the questions to guide your Perspectives reading. When you're ready, purchase the activity from the ASHA Store and follow the instructions to take the exam in ASHA's Learning Center. Available until August 3, 2018.
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Coordinator's Column
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Gastrointestinal tract perforation in the newborn and child: Imaging Assessment
Gastrointestinal tract perforation can arise from various underlying etiologies ranging from congenital causes to ingested foreign bodies in the pediatric patient population. Imaging assessment in patients with suspected gastrointestinal perforation plays a central role in making the diagnosis and follow up evaluation. This article reviews the more common etiologies of gastrointestinal perforation in pediatric patients, their imaging manifestations, and strategies for imaging assessment in order to assist the radiologist in arriving at a timely and accurate diagnosis.
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Acute perforated diverticulitis: Assessment with Multidetector computed tomography
Colonic diverticulitis is a common condition in the western population. Complicated diverticulitis is defined as the presence of extraluminal air or abscess, peritonitis, colon occlusion or fistulas. MDCT is the modality of choice for the diagnosis and the staging of diverticulitis and its compications, able to perform an accurate differential diagnosis and to address the patients to a correct management. MDCT is accurate in diagnosing the site of perforation in about 85% of cases, by the detection of direct signs (focal bowel wall discontinuity, extraluminal gas and extraluminal enteric contrast) and indirect signs which are represented by segmental bowel wall thickening, abnormal bowel wall enhancement, perivisceral fat stranding of fluid and abscess.
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Higher cord blood 25-hydroxyvitamin D concentrations reduce the risk of early childhood eczema: in children with a family history of allergic disease
Background: In recent years the role of vitamin D status in early life on the development of allergic disease has generated much interest. The aim of this study was to determine whether cord blood vitamin D concentrations were associated with risk of early childhood allergic disease. Methods: Measurements of cord blood 25-hydroxyvitamin D [25(OH)D] concentrations were available in 270 mother-child pairs who were participating in the allergy follow-up (n = 706) of the Docosahexaenoic Acid to Optimise Mother Infant Outcome randomised controlled trial. All of the children had a hereditary risk of allergic disease. The diagnosis of allergic disease was made during medical assessments at 1 and 3 years of age. Results: The mean (standard deviation) standardised cord blood 25(OH)D concentration was 57.0 (24.1) nmol/L. The cumulative incidence of eczema to 3 years of age, n = 101/250 (40 %) was associated with standardised cord blood 25(OH)D concentration, with a 10 nmol/L rise in 25(OH)D concentration reducing the risk of eczema by 8 % (relative risk 0.92, 95 % confidence interval 0.86–0.97; P = 0.005). This association was stronger at 1 year of age, when a 10 nmol/L rise in standardised cord blood 25(OH)D concentration reduced the risk of eczema by 12 % (relative risk 0.88, 95 % confidence interval 0.81–0.96; P = 0.002). No associations between cord blood 25(OH)D concentrations and development of allergic sensitisation, allergic rhinitis or asthma in early childhood were found. Conclusion: In children with a family history of allergic disease, a higher cord blood 25(OH)D concentration appears to be associated with reduced risk of eczema in early childhood.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12610000735055 (DOMInO trial: ACTRN12605000569606).
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Future Meetings
Thyroid Oct 2015, Vol. 25, No. 10: 1175-1176.

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Survival rates of anterior composites in managing tooth wear: systematic review

Summary

The use of composite restorations for patients with tooth wear is considered as a more conservative treatment option. The aim of this study was to systematically review the literature investigating the survival rates of anterior composite restorations when used in managing tooth wear in patients. PubMed and MEDLINE (Ovid) databases were screened for studies from 1995 to 2015. Cross-referencing was used to further identify articles. Article selection and data extraction were performed in duplication. Languages were restricted to English. A quality appraisal of included studies was carried out using the Strength of Recommendation Taxonomy system. Six hundred and sixty-six articles were initially identified from which eight articles were full-text reviewed. Six articles involving five studies were selected for inclusion. Three studies were prospective and two retrospective. Included studies involved placement of 772 direct and indirect anterior composite restorations in 100 patients with follow-up periods between 5 months and 10 years. The survival rates of anterior composites were >90% and 50% at 2·5 and 5 years, respectively. Posterior occlusion was re-established in 91% of patients within 18 months. Meta-analysis could not be performed due to the heterogeneity of included studies. The systematic review's overall strength of recommendation was graded B. There is evidence to support the use of anterior composite restorations at an increased vertical dimension of occlusion in the short/medium-term management of tooth wear. Long-term reporting of outcomes remains limited. Further research is needed with standardised study design, detailed reporting of outcomes and long-term review.

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Treatment of Meniere's Syndrome or Disease

Syed et al (2015) evaluated the evidence-based treatments of Meniere's Syndrome and/or Meniere's Disease (MS/D) over the last two decades. One hundred and four (104) studies from the first decade (1994-2003) and 101 from the second decade (2004-2013) were included. They report a statistical decline in surgeries (from 43 percent to 27 percent, from the first decade to the second, respectively) and an increase in intratympanic steroid injections and an increase in use of the Meniett device.

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De Gruyter to Publish the Journal Advanced Nonlinear Studies



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Increased expression of C-C motif ligand 2 associates with poor prognosis in patients with gastric cancer after gastrectomy

Abstract

Previous studies have demonstrated the clinical significance of polarized tumor-associated macrophages (TAMs) in gastric cancer whereas the cytokines orchestrating TAM polarization remain elusive. This study aims to evaluate the prognostic value of C-C motif ligand 2 (CCL2) expression in gastric cancer patients after surgery. We examined CCL2 expression in tumor tissues by immunohistochemical staining in retrospectively enrolled 414 gastric cancer patients receiving gastrectomy at Zhongshan Hospital during 2008. We used Kaplan-Meier analysis and Cox regression models to assess the prognostic value of CCL2 expression. We generated a predictive nomogram from integrating CCL2 expression with the TNM staging system to evaluate 3- and 5-year overall survival. High intratumor CCL2 expression associated with adverse clinical outcome. Intratumor CCL2 expression provided additional prognostic value in gastric cancer patients. CCL2 expression, as well as well-established TNM staging parameters, was identified as independent prognostic factor for overall survival. The generated nomogram corresponded well with the ideal model in predicting the 3- and 5-year overall survival of gastric cancer patients. CCL2, an identified potential independent adverse prognosticator, could be integrated with TNM staging system to improve the predictive accuracy for overall survival in gastric cancer patients especially with advanced stages.

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Diagnostic value of soluble receptor-binding cancer antigen expressed on SiSo cells and carcinoembryonic antigen in differentiating malignant from benign pleural effusion

Abstract

Diagnosis of malignant pleural effusion (MPE) remains a major clinical challenge. The aim of this study was to evaluate the diagnostic value of combined detection of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) and carcinoembryonic antigen (CEA) in patients with MPE and benign pleural effusion (BPE). The serum and pleural fluid samples were collected from 53 patients diagnosed with MPE and 49 patients with BPE. Enzyme-linked immunosorbent assay was used to detect the concentration of RCAS1 in serum and pleural effusion. The clinical data and laboratory information, including CEA levels, were gathered from these cases. The concentration of RCAS1 in MPE was significantly higher than that of BPE (P < 0.001). There was no significant difference between the two serum groups. The diagnostic sensitivity and specificity of pleural fluid RCAS1 were 67.92 and 81.63 %, respectively, at the optimized cutoff value of 7.326 U/mL; meanwhile, the sensitivity and specificity of pleural fluid CEA were 83.02 and 91.84 % at the cutoff value of 3.93 ng/mL. The specificity could be elevated to 98.50 % in serial detection, while the sensitivity may be improved to 94.55 % in parallel detection. Serum RCAS1 concentration was only detected in 53 serum samples out of the 102 samples, indicating that serum RCAS1 may not be a better option in differential diagnosis of malignancies compared with serum CEA, of which the diagnostic sensitivity and specificity were 64.15 and 83.67 % at the cutoff value of 3.90 ng/mL. No significant differences were found in pleural fluid RCAS1 concentration in MPE patients with different ages, gender, and pathological types of lung cancers. The detection of RCAS1 concentration in pleural fluid is informative for the diagnosis of MPE. Joint detection of RCAS1 and CEA can improve the diagnostic sensitivity and specificity. However, the diagnostic value of RCAS1 is not higher than that of CEA.

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Significance of Onodera's prognostic nutritional index in patients with colorectal cancer: a large cohort study in a single Chinese institution

Abstract

The preoperative nutritional and immunological statuses have an important impact in predicting the survival outcome of patients with various types of malignant tumors. Our study aimed to explore the clinical significance and predictive prognostic potential of Onodera's prognostic nutritional index (PNI) in patients with colorectal carcinoma. This retrospective study included a total of 1321 patients who were diagnosed with colorectal cancer and who had been surgically treated between January 1994 and December 2007. The PNI level was determined according the following formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). The impact of PNI on clinicopathological features and overall survival (OS) was determined. The optimal cutoff value of PNI was set at 45. Patients in the low-PNI group had a greater potential to have aggressive histological features, advanced tumors (T), nodal involvement (N), metastasis (M), and TNM stage than those in the high-PNI group. The low-PNI group had a worse OS than the high-PNI group (5-year survival rate 56.1 vs 64.8 %, respectively; P < 0.05). Furthermore, the PNI value was an independent prognostic factor for colorectal cancer in this study. The OS was significantly lower in the low-PNI group than in the high-PNI group in patients with TNM stage II and III diseases. Preoperative PNI is a simple and useful marker to predict clinicopathological features and long-term survival outcome in patients with colorectal carcinoma. PNI analysis should be included in the routine assessment of patients with locally advanced colorectal cancer.

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Polymorphisms of 5,10-methylenetetrahydrofolate reductase and thymidylate synthase, dietary folate intake, and the risk of leukemia in adults

Abstract

The 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are critical enzymes in folate metabolism. Previous studies have reported conflicting results on the associations between MTHFR/TS polymorphisms and adult leukemia risk, which may due to the lack of information on folate intake. We investigated the risks of adult leukemia with genetic polymorphisms of folate metabolic enzymes (MTHFR C677T, A1298C, and TS) and evaluated if the associations varied by dietary folate intake from a multicenter case-control study conducted in Chinese. This study comprised 442 incident adult leukemia cases and 442 outpatient controls, individually matched to cases by gender, birth quinquennium, and study site. Genotypes were determined by a polymerase chain reaction (PCR) or PCR-based restriction fragment length polymorphism assay. Dietary folate intake was assessed by face-to-face interviews using a validated food-frequency questionnaire. The MTHFR 677TT genotype conferred a significant higher risk of leukemia in males than in females and exhibited an increased risk of acute myeloid leukemia (AML) but a decreased risk of acute lymphoblastic leukemia (ALL). The MTHFR 1298AC genotype appeared to decrease the risks of leukemia in both genders, in AML and ALL. Stratified analysis by dietary folate intake showed the increased risks of leukemia with the MTHFR 677TT and TS 2R3R/2R2R genotypes were only significant in individuals with low folate intake. A significant interaction between TS polymorphism and dietary folate intake was observed (P = 0.03). This study suggests that dietary folate intake and gender may modify the associations between MTHFR/TS polymorphisms and adult leukemia risk.

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Ultrastructural changes of mitochondria in human retinoblastoma: correlation with tumor differentiation and invasiveness

Abstract

Retinoblastoma still represents a challenge for pediatric tumors. Mitochondria have been implicated in tumor progression, cell differentiation, and apoptotic pathways. Electron microscopy allows the study of mitochondrial morphology and it is still debated in human retinoblastoma. Demographic, clinical, and histopathological parameters were recorded in 17 enucleated retinoblastoma specimens. Hematoxylin and eosin staining was performed to study tumor characteristics and the extent of invasion in ocular structures. The aim of this study was to describe and analyze the mitochondrial morphology in human retinoblastoma by transmission electron microscopy (TEM). There was a male preponderance in our study. Ages ranged from 2 to 78 months. Histopathological analysis revealed that 15 (88.2 %) tumors were poorly differentiated retinoblastomas. Massive choroidal invasion was the most frequent histopathological high-risk factor among the others. Histopathological high-risk factors were found in 7/17 (41.1 %) cases. Tumor samples of all patients were examined by means of TEM. All cases showed tumor cells with high nucleocytoplasmic ratio. Poorly differentiated retinoblastoma cases showed fewer mitochondria, scant cytoplasm, disorganized organelles (mitochondria), and necrosis, whereas well-differentiated retinoblastomas had larger number of mitochondria and more organized organelles. However, there was no significant difference in mitochondrial changes between invasive and noninvasive tumors. Our study observed that cristolysis and swollen mitochondria were more frequent in retinoblastoma tumors. Understanding the structural and functional characteristics of mitochondria in retinoblastoma might be essential for the design of future therapeutic strategies. The authors have no proprietary or commercial interest in any materials discussed in this article.

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Kleinzellig strukturierte Zellnester des Endometriumstromas

Zusammenfassung

In endometrialem diagnostischem Kürettagematerial können kleinherdig zusammengeschobene Stromazellen („stromal collapse") bei sogenanntem „glandular and stromal breakdown" zur Fehldiagnose eines kleinzellig strukturierten Karzinoms möglicherweise neuroendokriner oder basalzelliger Herkunft führen. Immunhistochemische Untersuchungen (Östrogenrezeptor, epitheliale und neuroendokrine Marker, Proliferationsmarker) sind in dieser differenzialdiagnostischen Abgrenzung hilfreich.

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Erratum zu: Die wichtigsten Studienergebnisse in der Primärtherapie von Kopf-Hals-Tumoren
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Treatment of keloid scars with a 1210-nm diode laser in an animal model

Background and Objective

A temperature increase can improve wound healing by activation of heat shock protein 70 and stimulation of fibroblasts. Since keloids are a dysfunction of collagen fiber synthesis and organization, this study aimed to evaluate if a 1,210 nm diode laser could have effects in a new animal model of keloid scars.

Study Design/Materials and Methods

A total of 39 nude mice were used for this study. Phototypes IV and V human keloids were grafted into their backs and after 1 month of healing, the mice were divided into four groups: Control, Laser, Resection, Resection/Laser. In the Laser group, the keloids were treated with a 1,210-nm diode-laser with the following parameters: 4 W; 10 seconds; fluence: 51 J/cm2; spot: 18.9 × 3.7 mm2. In the Resection group, surgical intra-lesional excision was performed. In the Resection/Laser group, keloids were treated with the 1,210-nm laser-diode after surgical intra-lesional excision. Temperature measurements were made during the laser treatment. Clinical examination and histological study were performed on the day of treatment and 1 month, 2 months, and 3 months later.

Results

Mean temperature measurement was of 44.8°C (42–48°) in the Laser groups. No healing complications or keloid proliferation was observed in any group. Keloid histologic characters were confirmed in all grafts. No histologic particularity was observed in the laser groups in comparison with the Control and Resection groups.

Conclusion

First, this keloid animal model appears to be adapted for laser study. Secondly, the 1,210-nm diode laser does not induce keloid thermal damage in vivo. Further studies with different 1,210-nm laser diode parameters should be performed in order to observe significant effects on keloids. Lasers Surg. Med. © 2015 Wiley Periodicals, Inc.

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360° versus localized demarcation laser photocoagulation for macular-sparing retinal detachment in silicone oil-filled eyes with undetected breaks: A retrospective, comparative, interventional study

Background and Objective

Recurrent retinal detachment (RD) in silicone oil-filled eyes is a serious condition. At the initial stage, it usually spares the macular and is localized in the inferior retina. The inability to locate the retinal breaks has been reported to be associated with a poor prognosis and has limited the use of conventional vitreoretinal surgeries. Demarcation laser photocoagulation (DLP) is widely accepted for treating macular-sparing RDs. For laser treatments to be effective, an adequate extent and the correct placement of the laser is of great importance. The purpose of this research was to compare the efficacy of 360° and localized DLP in the management of macular-sparing RD in silicone oil-filled eyes with no detected retinal breaks.

Materials and Methods

This is a retrospective, comparative, interventional study. The medical records of 48 consecutive eyes with macular-sparing RD in silicone oil-filled eyes with no detected retinal breaks were reviewed. Twenty-six patients (group I) received 360° DLP, and the remaining 22 patients (group II) underwent localized DLP. The anatomical and visual outcomes of the two groups were compared.

Results

The mean follow-up period was 12.54 ± 1.17 months. No significant difference was identified in the baseline characteristics. The single-operation success rate of 92.31% was achieved in group I, which was significantly higher than that of group II (59.09%, P = 0.01), and this trend was not weakened after adjusting for confounding factors (odds ratio: 0.002, P = 0.02). After salvage management of vitreoretinal surgeries, both groups had equivalent visual outcomes with silicone oil removal. Multivariate logistic regression also indicated that the radial extent of RD (odds ratio: 11.10, P = 0.04) was an independent predictor for laser treatment failure. Significant complications sufficient to require further operations included proliferative vitreoretinopathy in two (4.17%) eyes and epiretinal membrane in four (8.33%) eyes.

Conclusions

The 360° DLP achieved a better primary success rate and equivalent visual outcomes with localized DLP for macular-sparing RD in silicone oil-filled eyes with no detected retinal breaks. Lasers Surg. Med. © 2015 Wiley Periodicals, Inc.

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A new contemporary prostate cancer grading system
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Extension of the frontal sinus into the roof of the optic canal: a cadaveric case report

Abstract

This case reports a bilateral asymmetrical posterior extension of the frontal sinuses into the orbital roof with an unusual expansion into the roof of the optic canal in a 55-year-old male cadaver. The posterior extensions of the sinus were lined by mucoperiosteum and were separated from the underlying orbital contents and optic nerve by a thin plate of bone. This knowledge of an unusual anatomic variation of the frontal sinus may help understand better the ocular and intracranial complications associated with frontal sinus pathologies.

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Predicting asthma outcomes
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4
Author(s): Malcolm R. Sears
This review addresses predictors of remission or persistence of wheezing and asthma from early childhood through adulthood. Early childhood wheezing is common, but predicting who will remit or have persistent childhood asthma remains difficult. By adding parental history of asthma and selected infant biomarkers to the history of recurrent wheezing, the Asthma Predictive Index and its subsequent modifications provide better predictions of persistence than simply the observation of recurrent wheeze. Sensitization, especially to multiple allergens, increases the likelihood of development of classic childhood asthma. Remission is more likely in male subjects and those with milder disease (less frequent and less severe symptoms), less atopic sensitization, a lesser degree of airway hyperresponsiveness, and no concomitant allergic disease. Conversely, persistence is linked strongly to allergic sensitization, greater frequency and severity of symptoms, abnormal lung function, and a greater degree of airway hyperresponsiveness. A genetic risk score might predict persistence more accurately than family history. Remission of established adult asthma is substantially less common than remission during childhood and adolescence. Loss of lung function can begin early in life and tracks through childhood and adolescence. Despite therapy which controls symptoms and exacerbations, the outcomes of asthma appear largely resistant to pharmacologic therapy.


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News & Notes
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4




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Association of eosinophilic esophagitis and hypertrophic cardiomyopathy
Publication date: Available online 5 October 2015
Source:Journal of Allergy and Clinical Immunology
Author(s): Benjamin P. Davis, Tolly Epstein, Leah Kottyan, Priyal Amin, Lisa J. Martin, Avery Maddox, Margaret H. Collins, Joseph D. Sherrill, J. Pablo Abonia, Marc Rothenberg



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Advances in environmental and occupational disorders in 2014
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4
Author(s): David B. Peden, Robert K. Bush
In 2014, the Journal published a number of studies that have advanced our understanding of the effects of various environmental factors and immune responses in patients with allergic diseases. In this review we emphasize reports that have appeared in the Journal over the past year that deal with environmental and occupational respiratory disorders and novel approaches to their treatment. The review will focus on the effects of environmental factors and immune responses in allergic airway diseases, identification of new allergens, and risk factors in stinging insect allergy, development of asthma in different age groups, effects of viral infections, and benefits of new therapies.


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Higher B-cell activating factor levels at birth are positively associated with maternal dairy farm exposure and negatively related to allergy development
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4
Author(s): Anna-Carin Lundell, Bill Hesselmar, Inger Nordström, Ingegerd Adlerberth, Agnes E. Wold, Anna Rudin
BackgroundA high proportion of circulating immature/naive CD5+ B cells during early infancy is a risk factor for allergy development. B-cell activating factor (BAFF) is an important cytokine for B-cell maturation.ObjectiveWe sought to investigate whether BAFF levels are related to environmental exposures during pregnancy and early childhood and whether BAFF levels are associated with postnatal B-cell maturation and allergic disease.MethodsIn the FARMFLORA study, including both farming and nonfarming families, we measured BAFF levels in plasma from mothers and their children at birth and at 1, 4, 18, and 36 months of age. Infants' blood samples were also analyzed for B-cell numbers and proportions of CD5+ and CD27+ B cells. Allergic disease was clinically evaluated at 18 and 36 months of age.ResultsCirculating BAFF levels were maximal at birth, and farmers' children had higher BAFF levels than nonfarmers' children. Higher BAFF levels at birth were positively associated with proportions of CD27+ memory B cells among farmers' children and inversely related to proportions of CD5+ immature/naive B cells among nonfarmers' children. Children with allergic disease at 18 months of age had lower cord blood BAFF levels than nonallergic children. At birth, girls had higher BAFF levels and lower proportions of CD5+ B cells than boys.ConclusionsFarm exposure during pregnancy appears to induce BAFF production in the newborn child, and high neonatal BAFF levels were associated with more accelerated postnatal B-cell maturation, which lend further strength to the role of B cells in the hygiene hypothesis.


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CME Activities Calendar
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4




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Expression of activation markers in circulating basophils and the relationship to allergen-induced bronchoconstriction in subjects with mild allergic asthma
Publication date: Available online 5 October 2015
Source:Journal of Allergy and Clinical Immunology
Author(s): Brittany M. Salter, Graeme Nusca, Damian Tworek, John-Paul Oliveria, Steve G. Smith, Rick M. Watson, Tara Scime, Catie Obminski, Roma Sehmi, Gail M. Gauvreau



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Predicting asthma outcomes
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4




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Cover 1
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4




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Diverse activation and differentiation of multiple B-cell subsets in patients with atopic dermatitis but not in patients with psoriasis
Publication date: Available online 5 October 2015
Source:Journal of Allergy and Clinical Immunology
Author(s): Tali Czarnowicki, Juana Gonzalez, Kathleen M. Bonifacio, Avner Shemer, Peng Xiangyu, Norma Kunjravia, Dana Malajian, Judilyn Fuentes-Duculan, Hitokazu Esaki, Shinji Noda, Yeriel Estrada, Hui Xu, Xiuzhong Zheng, James G. Krueger, Emma Guttman-Yassky
BackgroundAtopic dermatitis (AD) and psoriasis pathogeneses involve skin barrier impairment and immune dysregulation; however, the contribution of B-cell imbalances to these diseases has not yet been determined.ObjectiveWe sought to quantify B-cell populations and antibody-secreting cells in the blood of patients with AD, patients with psoriasis, and control subjects.MethodsWe studied 34 adults with moderate-to-severe AD (mean SCORAD score, 65), 24 patients with psoriasis (mean Psoriasis Area and Severity Index score, 16), and 27 healthy subjects using an 11-color flow cytometric antibody panel. IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies of plasmablasts and naive, memory, transitional, and activated B cells.ResultsWe measured increased CD19+CD20+ B-cell counts in the skin and blood of patients with AD (P < .01). Significantly higher frequencies of chronically activated CD27+ memory and nonswitched memory B cells were observed in patients with AD (P < .05), with lower values of double-negative populations (4% for patients with AD vs 7% for patients with psoriasis [P = .001] and 6% for control subjects [P = .02]). CD23 expression was highest in patients with AD and correlated with IgE levels (P < .01) and disease severity (r = 0.6, P = .0002). Plasmablast frequencies and IgE expression were highest in all memory subsets of patients with AD (P < .01). Finally, CD19+CD24++CD38++ transitional and CD19+CD24CD38 new memory B-cell counts were higher in patients with AD versus those in patients with psoriasis (2.8% vs 1.4% [P = .001] and 9.2% vs 5.7% [P = .02], respectively).ConclusionsAD is accompanied by systemic expansion of transitional and chronically activated CD27+ memory, plasmablast, and IgE-expressing memory subsets. These data create a critical basis for the future understanding of this debilitating skin disease.


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Brief Overview of This Month's JACI
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4




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Correlation between CCL26 production by human bronchial epithelial cells and airway eosinophils: Involvement in patients with severe eosinophilic asthma
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4
Author(s): Marie-Chantal Larose, Jamila Chakir, Anne-Sophie Archambault, Philippe Joubert, Véronique Provost, Michel Laviolette, Nicolas Flamand
BackgroundHigh pulmonary eosinophil counts are associated with asthma symptoms and severity. Bronchial epithelial cells (BECs) produce CC chemokines, notably CCL26 (eotaxin-3), which recruits and activates eosinophils from asthmatic patients. This suggests that CCL26 production by BECs might be involved in persistent eosinophilia in patients with severe asthma despite treatment with high corticosteroid doses.ObjectiveWe sought to determine whether CCL26 levels correlate with eosinophilia and asthma severity.MethodsHuman CC chemokine expression was assessed by means of quantitative PCR or a quantitative PCR array in vehicle- or IL-13–treated BECs. CCL26 was quantitated by means of ELISA. Immunohistochemistry analyses of CCL26 and major basic protein were done on bronchial biopsy specimens.ResultsIL-13 selectively induced CCL26 expression by BECs. This increase was time-dependent and more prominent in BECs from patients with severe eosinophilic asthma. CCL26 levels measured in supernatants of IL-13–stimulated BECs also increased with asthma severity as follows: patients with severe eosinophilic asthma > patients with mild asthma ≈ healthy subjects. Immunohistochemistry analyses of bronchial biopsy specimens confirmed increased levels of CCL26 in the epithelium of patients with mild and those with severe eosinophilic asthma. Tissue eosinophil counts did not correlate with CCL26 staining. However, sputum CCL26 levels significantly correlated with sputum eosinophil counts (P < .0001), suggesting that CCL26 participates in the movement of eosinophils from the tissues to the airway lumen.ConclusionsThese results show a relation between CCL26 production by IL-13–stimulated BECs, sputum eosinophil counts, and asthma severity. They also suggest a role for CCL26 in the sustained inflammation observed in patients with severe eosinophilic asthma and reveal CCL26 as a potential target for treating patients with eosinophilic asthma that are refractory to classic therapies.


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Clinical features and hematopoietic stem cell transplantations for CD40 ligand deficiency in Japan
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4
Author(s): Kanako Mitsui-Sekinaka, Kohsuke Imai, Hiroki Sato, Daisuke Tomizawa, Michiko Kajiwara, Masayuki Nagasawa, Tomohiro Morio, Shigeaki Nonoyama
BackgroundThe long-term outcome of X-linked hyper-IgM syndrome (XHIM) caused by mutations in CD40LG is poor, and the only curative treatment is hematopoietic stem cell transplantation (HSCT).ObjectiveWe sought to determine the clinical features and factors affecting outcomes in patients with XHIM.MethodsWe enrolled and retrospectively analyzed data from 56 Japanese patients with XHIM, including 29 patients who received HSCT.ResultsThe long-term survival rate was poor in those not undergoing HSCT (overall survival rate at 40 years of age, 28.2%). The overall survival rate of patients undergoing HSCT (n = 29) was significantly higher than that of those not undergoing HSCT (n = 27, P = .0231). Moreover, event-free and disease-free survival rates were significantly greater in patients 5 years old or younger at the time of transplantation (n = 14) than in older patients (n = 15).ConclusionOn the basis of these results, we concluded that HSCT improved the outcomes of patients with XHIM and that an age of 5 years or younger was optimal for the timing of HSCT because persistent infections and severe organ damage were frequently observed in patients older than 6 years.


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News Beyond Our Pages
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4
Author(s): Marc E. Rothenberg, Jean Bousquet



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Table of Contents
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4




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Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4
Author(s): Julie Wang, Stacie M. Jones, Jacqueline A. Pongracic, Ying Song, Nan Yang, Scott H. Sicherer, Melanie M. Makhija, Rachel G. Robison, Erin Moshier, James Godbold, Hugh A. Sampson, Xiu-Min Li
BackgroundFood Allergy Herbal Formula-2 (FAHF-2) is a 9-herb formula based on traditional Chinese medicine that blocks peanut-induced anaphylaxis in a murine model. In phase I studies FAHF-2 was found to be safe and well tolerated.ObjectiveWe sought to evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy.MethodsIn this double-blind, randomized, placebo-controlled study 68 subjects aged 12 to 45 years with allergies to peanut, tree nut, sesame, fish, and/or shellfish, which were confirmed by baseline double-blind, placebo-controlled oral food challenges (DBPCFCs), received FAHF-2 (n = 46) or placebo (n = 22). After 6 months of therapy, subjects underwent DBPCFCs. For those who demonstrated increases in the eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy.ResultsTreatment was well tolerated, with no serious adverse events. By using intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose (P = .05) at the end-of-treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions (P = .55). There were no significant differences in allergen-specific IgE and IgG4 levels, cytokine production by PBMCs, or basophil activation between the active and placebo groups. In vitro immunologic studies performed on subjects' baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 levels, and increased numbers of regulatory T cells than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one third of the study period.ConclusionFAHF-2 is a safe herbal medication for subjects with food allergy and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used.


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Editorial Board
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4




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Revisiting the hygiene hypothesis for allergy and asthma
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4
Author(s): Andrew H. Liu
The hygiene hypothesis, which describes the protective influence of microbial exposures in early life on the development of allergy and asthma, has continued its swell of academic interest, investigation, and evolution. This article is focused on studies published in the past 3 years that have furthered the substance and shape of hygiene theory, primarily as it relates to allergic airways and asthma. Recent investigations have furthered an overarching "microbiome hypothesis" to home features, medical practices, and cleanliness behaviors that are suspects in the hygiene effect. Relatively crude markers of the protective microbial environment have been supplanted by culture-independent microbiome science, distinguishing the characteristics of potentially protective microbiomes from pathologic features. Understanding how the microbiome is shaped and affects healthful versus harmful outcomes in the human host is relatively nascent. Good clues are emerging that give mechanistic substance to the theory and could help guide microbe-based therapeutics to fill the allergy and asthma management gap in prevention and disease modification.


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Information for Readers
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4




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The Editors' Choice
Publication date: October 2015
Source:Journal of Allergy and Clinical Immunology, Volume 136, Issue 4
Author(s): Donald Y.M. Leung, Stanley J. Szefler



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Headache attributed to masticatory myofascial pain: impact on facial pain and pressure pain threshold

Summary

There is no clear evidence on how a headache attributed to temporomandibular disorder (TMD) can hinder the improvement of facial pain and masticatory muscle pain. The aim of this study was to measure the impact of a TMD-attributed headache on masticatory myofascial (MMF) pain management. The sample was comprised of adults with MMF pain measured according to the revised research diagnostic criteria for temporomandibular disorders (RDC/TMD) and additionally diagnosed with (Group 1, n = 17) or without (Group 2, n = 20) a TMD-attributed headache. Both groups received instructions on how to implement behavioural changes and use a stabilisation appliance for 5 months. The reported facial pain intensity (visual analogue scale – VAS) and pressure pain threshold (PPT – kgf cm−2) of the anterior temporalis, masseter and right forearm were measured at three assessment time points. Two-way anova was applied to the data, considering a 5% significance level. All groups had a reduction in their reported facial pain intensity (P < 0·001). Mean and standard deviation (SD) PPT values, from 1·33 (0·54) to 1·96 (1·06) kgf cm−2 for the anterior temporalis in Group 1 (P = 0·016), and from 1·27 (0·35) to 1·72 (0·60) kgf cm−2 for the masseter in Group 2 (P = 0·013), had significant improvement considering baseline versus the 5th-month assessment. However, no differences between the groups were found (P > 0·100). A TMD-attributed headache in patients with MMF pain does not negatively impact pain management, but does change the pattern for muscle pain improvement.

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Shortcomings of prosthodontic rehabilitation of patients living in long-term care facilities

Summary

Removable dentures are a non-invasive, cost-effective prosthodontic solution for the reduced dentition. Their intended purpose is the rehabilitation of harmonious oral function and aesthetics on a long-term basis. The prevalence of removable dentures among patients of advanced age is high and the quality of the dentures is often poor. The aim of this study was to find the most important shortcomings of removable dentures and address the main targets for improving the quality of prosthodontic rehabilitation. The records from dental check-ups in Austrian residential homes were analysed retrospectively. Dental anamnesis questionnaires and data from the clinical examinations of 105 denture wearers were analysed. The functional condition and retention of 192 dentures had been assessed, as well as the impact of the dentures on the intra-oral tissues. Insufficient denture retention was very common, particularly in the lower jaw (56·0%). Problems with the masticatory function were reported by 26.7% of the denture wearers, 11·4% were dissatisfied with the denture aesthetics, and 4·8% had difficulties with phonetics. Traumatic ulcers were found in 18·1%. Cracks, broken pieces (6·3%) or missing denture teeth (2·1%) were rare. It may be assumed that the findings of the present study also apply to a great percentage of community-dwelling seniors. The most important issues in prosthodontic rehabilitation with removable dentures are denture retention and masticatory function. Regular dental check-ups, denture adjustment and, when necessary, relining can maintain the primary denture quality and prevent damages of the oral tissues caused by ill-fitting dentures.

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Loss of Afferent Vestibular Input Produces Central Adaptation and Increased Gain of Vestibular Prosthetic Stimulation

ABSTRACT

Implanted vestibular neurostimulators are effective in driving slow phase eye movements in monkeys and humans. Furthermore, increases in slow phase velocity and electrically evoked compound action potential (vECAP) amplitudes occur with increasing current amplitude of electrical stimulation. In intact monkeys, protracted intermittent stimulation continues to produce robust behavioral responses and preserved vECAPs. In lesioned monkeys, shorter duration studies show preserved but with somewhat lower or higher velocity behavioral responses. It has been proposed that such changes are due to central adaptive changes in the electrically elicited vestibulo-ocular reflex (VOR). It is equally possible that these differences are due to changes in the vestibular periphery in response to activation of the vestibular efferent system. In order to investigate the site of adaptive change in response to electrical stimulation, we performed transtympanic gentamicin perfusions to induce rapid changes in vestibular input in monkeys with long-standing stably functioning vestibular neurostimulators, disambiguating the effects of implantation from the effects of ototoxic lesion. Gentamicin injection was effective in producing a large reduction in natural VOR only when it was performed in the non-implanted ear, suggesting that the implanted ear contributed little to the natural rotational response before injection. Injection of the implanted ear produced a reduction in the vECAP responses in that ear, suggesting that the intact hair cells in the non-functional ipsilateral ear were successfully lesioned by gentamicin, reducing the efficacy of stimulation in that ear. Despite this, injection of both ears produced central plastic changes that resulted in a dramatically increased slow phase velocity nystagmus elicited by electrical stimulation. These results suggest that loss of vestibular afferent activity, and a concurrent loss of electrically elicited vestibular input, produces an increase in the efficacy of a vestibular neurostimulator by eliciting centrally adapted behavioral responses without concurrent adaptive increase of galvanic afferent activation in the periphery.

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Prospective case-controlled sound localization study after cochlear implantation in adults with single-sided deafness and ipsilateral tinnitus

Abstract

Objectives

To analyze the sound localization skills of subjects with profound single-sided deafness (SSD) and accompanied ipsilateral tinnitus who are using a cochlear implant (CI) for between 4 and 11 years.

Design

Sound localization skills were tested using nine loudspeakers in a frontal semicircle ranging from -90° to +90°. Subjects were tested in the CION and the CIOFF condition via 3 localization stimuli: broadband noise (BB), low-pass noise (LP), and high-pass noise (HP).

Participants

The test group consisted of 10 adult subjects with profound sensorineural SSD, ipsilateral tinnitus and a CI. Normative data of a control group of 30 normal hearing subjects were used for comparison.

Main outcome measures

Sound location accuracy was analyzed via the Root Mean Square Error (RMSE), the Mean Absolute Error (MAE), the localization bias ('b'), and the bias-adjusted deviation ('db'). Subjective dynamic aspects of hearing were assessed via a reduced version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ5).

Results

For all 3 stimuli, the RMSE improved significantly in SSD subjects in the CION condition compared to the CIOFF condition. The localization accuracy of subjects with SSD improved significantly for BB and HP stimuli. A significant bias-adjusted deviation 'db' was found for the BB and HP stimuli. Subjects' mean SSQ5 scores were significantly higher in the CION condition at test date than in the CIOFF condition preoperatively.

Conclusions

Subjects can better locate sound in the CION condition than in the CIOFF condition.
This article is protected by copyright. All rights reserved.

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Validation of a family-centred outcome questionnaire for pinnaplasty: a cross-sectional pilot study

Abstract

Objectives

Comparison of pinnaplasty techniques is difficult due to variation in the reporting of outcomes. We aimed to develop a family-centered outcome questionnaire for use after pinnaplasty and assess it for reliability and validity.

Design

Cross-sectional study.

Setting

Tertiary referral paediatric otolaryngology center.

Participants

20 prospective and 71 retrospective pinnaplasty patients and their parent(s).

Methods

The Post-Operative Pinnaplasty Questionnaire (POPQ) was developed after semi-structured interview with families of children undergoing pinnaplasty. Children aged 4-16 were recruited. 3 different ear measurements (auriculocephalic angle, helix-mastoid distance and Walker's ratio) were performed pre-operatively. Children were reviewed 3 months post-operatively and asked to complete a POPQ and GCBI (Glasgow Children's Benefit Inventory) with their parent(s). Ear measurements were repeated and data collected on surgical technique and complications. 200 retrospective pinnaplasty patients were posted a POPQ & GCBI and data collected on surgical technique, complication rate and Walker's angle.

Main outcomes measures

Validity and reliability of the POPQ.

Results

Age range was 4-16 (median 12). POPQ correlated well with GCBI (Spearman's rho= 0.776, p<0.001). There was no correlation of POPQ scores with age, sex, complication or surgical technique. POPQ score was not associated with severe prominence pre-op nor change or degree of prominence post-op. POPQ displayed good internal consistency (Cronbach's alpha 0.850) and ease of use scores.

Conclusions

We have developed a family- focused outcome tool for pinnaplasty that displays good face validity, internal consistency, correlation with HRQoL and that is simple and easy to use. No correlation was seen with more traditional measures of outcome such as complications or ear measurements. Further refinement and testing of validity and reliability on a larger sample is planned.
This article is protected by copyright. All rights reserved.

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Distance and Interference in the Reference Management of African American Adults

Purpose
The purpose of this study was to examine the effect of distance and interference on the adequacy of reference management in 2 contrasting narrative conditions among age-defined groups of healthy African American adults.
Methods
Twenty middle-aged (M = 51 years) and 20 older (M = 72 years) women produced a complex story retelling and a personal narrative of a childhood experience. All narratives were transcribed orthographically, parsed into terminal units (T-units), and analyzed for surface structure markings of referents.
Results
Results varied on the basis of task complexity and specific dependent variables. Older adults produced shorter T-unit distances between nouns and pronouns in story retelling compared with middle-aged adults. Middle-aged adults, but not older adults, exhibited longer T-unit distances between referents on story retelling than on personal narratives. Both groups performed similarly in the management of intervening information between referents. The presence of African American English features was related to interference but not to referential distance.
Conclusions
Older adults demonstrated an effective age-related strategy for simplifying complex story retelling by producing shorter T-unit distances and, thus, less intervening information between referents. These findings suggest that referential distance may be a more important factor in mediating story recall. (For a summary and guidelines for therapy, see Bunce, 1991.)
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Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis

Atopic dermatitis (AD) is a chronic relapsing allergic skin disorder with increasing prevalence in western societies (1). Histamine is a well-known mediator of allergic skin diseases, but classical histamine H1 receptor (H1R) antagonists show insufficient efficacy in treatment of AD (2). With the discovery of the histamine H4 receptor (H4R) in 2000, the role of histamine in allergic diseases is re-evaluated (3, 4). A variety of cell types relevant in the pathogenesis of AD such as T cells, antigen presenting cells and keratinocytes express the H4R, and it has been shown that the H4R influences activation, migration, and cytokine and chemokine production of these cells (5).
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Bilateral Vestibulopathy Documented by Video Head Impulse Tests in Superficial Siderosis.
Objective: Superficial siderosis (SS) of the CNS is associated with cerebellar ataxia, sensorineural hearing loss, and pyramidal symptoms, which result from iron depositions on CNS surfaces. SS can produce bilateral vestibulopathy as the vestibulo-cochlear nerve is particularly vulnerable. To our knowledge, however, vestibular dysfunction in SS has not been reported thoroughly in the literature. Here, we describe a case of bilateral vestibulopathy, documented quantitatively by the video head impulse test (vHIT), in a patient with SS. Patient: A 60-year-old man presented with slowly progressing bilateral hearing loss, oscillopsia, and a severe gait disturbance that worsened in the dark. Intervention: After noticing deficits in the bedside head impulse test in all six semicircular canals, the patient underwent vHIT and brain MRI. Main Outcome Measure: MRI demonstrated a rim of hypointensities and signal losses in T2-weighted and gradient echo images around the cerebellum, brainstem, and vestibulo-cochlear nerve, which were compatible with an SS diagnosis. In addition, vHIT revealed reduced vestibule-ocular reflex (VOR) gains, and abnormal catch-up saccades (both covert and overt saccades) in all semicircular canals. Results: The vHIT showed impaired VOR gains that were 0.55, 0.59, and 0.45 in the horizontal, anterior, and posterior canals, respectively. Conclusion: SS may result in chronic bilateral vestibulopathy with SNHL. Bilateral vestibulopathy originated peripherally in our participant, without cerebellar dysfunctions such as those reported in the literature. vHIT findings have not been previously reported in patients with SS, and our study suggests that vHIT is a useful tool to document vestibular dysfunction. Copyright (C) 2015 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company
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Bilateral Vestibulopathy Documented by Video Head Impulse Tests in Superficial Siderosis.
Objective: Superficial siderosis (SS) of the CNS is associated with cerebellar ataxia, sensorineural hearing loss, and pyramidal symptoms, which result from iron depositions on CNS surfaces. SS can produce bilateral vestibulopathy as the vestibulo-cochlear nerve is particularly vulnerable. To our knowledge, however, vestibular dysfunction in SS has not been reported thoroughly in the literature. Here, we describe a case of bilateral vestibulopathy, documented quantitatively by the video head impulse test (vHIT), in a patient with SS. Patient: A 60-year-old man presented with slowly progressing bilateral hearing loss, oscillopsia, and a severe gait disturbance that worsened in the dark. Intervention: After noticing deficits in the bedside head impulse test in all six semicircular canals, the patient underwent vHIT and brain MRI. Main Outcome Measure: MRI demonstrated a rim of hypointensities and signal losses in T2-weighted and gradient echo images around the cerebellum, brainstem, and vestibulo-cochlear nerve, which were compatible with an SS diagnosis. In addition, vHIT revealed reduced vestibule-ocular reflex (VOR) gains, and abnormal catch-up saccades (both covert and overt saccades) in all semicircular canals. Results: The vHIT showed impaired VOR gains that were 0.55, 0.59, and 0.45 in the horizontal, anterior, and posterior canals, respectively. Conclusion: SS may result in chronic bilateral vestibulopathy with SNHL. Bilateral vestibulopathy originated peripherally in our participant, without cerebellar dysfunctions such as those reported in the literature. vHIT findings have not been previously reported in patients with SS, and our study suggests that vHIT is a useful tool to document vestibular dysfunction. Copyright (C) 2015 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company
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Tissue-Sparing Uvulopalatopharyngoplasty for OSA: Conservative, Compassionate and Possibly just as Effective

Abstract

A common surgical treatment for obstructive sleep apnea (OSA) is uvulopalatopharyngoplasty (UPPP). Unfortunately, traditional UPPP can cause a foreign body sensation, chronic discomfort and in rare cases, nasopharyngeal stenosis or velopharyngeal insufficiency. Modifications to traditional UPPP have been developed over the years to help decrease side effects, while trying to maintain or improve OSA outcomes. Conservative, tissue-sparing UPPP techniques include preservation of soft palate tissues (muscle and/or mucosa), avoidance of plication or conservative plication of the uvula, partial instead of complete uvulectomy, and suture plication of the palatopharyngeus-superior pharyngeal constrictor-palatoglossus muscles with complete preservation of surrounding tissues after tonsillectomy.

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Loss of Afferent Vestibular Input Produces Central Adaptation and Increased Gain of Vestibular Prosthetic Stimulation

ABSTRACT

Implanted vestibular neurostimulators are effective in driving slow phase eye movements in monkeys and humans. Furthermore, increases in slow phase velocity and electrically evoked compound action potential (vECAP) amplitudes occur with increasing current amplitude of electrical stimulation. In intact monkeys, protracted intermittent stimulation continues to produce robust behavioral responses and preserved vECAPs. In lesioned monkeys, shorter duration studies show preserved but with somewhat lower or higher velocity behavioral responses. It has been proposed that such changes are due to central adaptive changes in the electrically elicited vestibulo-ocular reflex (VOR). It is equally possible that these differences are due to changes in the vestibular periphery in response to activation of the vestibular efferent system. In order to investigate the site of adaptive change in response to electrical stimulation, we performed transtympanic gentamicin perfusions to induce rapid changes in vestibular input in monkeys with long-standing stably functioning vestibular neurostimulators, disambiguating the effects of implantation from the effects of ototoxic lesion. Gentamicin injection was effective in producing a large reduction in natural VOR only when it was performed in the non-implanted ear, suggesting that the implanted ear contributed little to the natural rotational response before injection. Injection of the implanted ear produced a reduction in the vECAP responses in that ear, suggesting that the intact hair cells in the non-functional ipsilateral ear were successfully lesioned by gentamicin, reducing the efficacy of stimulation in that ear. Despite this, injection of both ears produced central plastic changes that resulted in a dramatically increased slow phase velocity nystagmus elicited by electrical stimulation. These results suggest that loss of vestibular afferent activity, and a concurrent loss of electrically elicited vestibular input, produces an increase in the efficacy of a vestibular neurostimulator by eliciting centrally adapted behavioral responses without concurrent adaptive increase of galvanic afferent activation in the periphery.

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Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma
Background: Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are expected to have inferior outcome after liver transplantation (LT) and are therefore currently not considered for LT in many countries. The purpose of this study was to identify predictive factors for overall survival following LT for HCC that may support the Milan criteria in the selection of appropriate transplant candidates. Methods: Clinicopathological data on 364 patients with HCC who underwent LT between 1989 and 2010 were retrospectively evaluated. Predictors of overall survival in the entire cohort as well as in subsets of patients within (n = 214) and beyond (n = 150) the Milan criteria were analyzed. Results: Multivariate analysis in the entire cohort identified DNA index >1.5 (p 200 ng/ml (p = 0.005), and HCC beyond the Milan criteria (p = 0.002) to be associated with worse overall survival. In patients within the Milan criteria (median survival: 170 months), DNA index >1.5 (p 1.5, AFP >200 ng/ml, microvascular invasion, patient age >60 years, and DNA index >1.5 concomitant with AFP >200 ng/ml were associated with worse overall survival in univariate analysis. Multivariate analysis identified DNA index >1.5 concomitant with AFP >200 ng/ml (p Conclusions: DNA index and AFP level predict overall survival following LT in patients with advanced HCC beyond the Milan criteria. A combined assessment of these markers during the evaluation of transplant candidates can contribute to the selection of patients with HCC who may benefit from LT independently of their tumor burden.
Eur Surg Res 2015;55:302-318
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Synchronous Ipsilateral Parotid Tumors with Cytologic–Histologic Correlation

Abstract

Synchronous ipsilateral tumor formation within a major salivary gland is a very rare event. In this case, a 54-year-old female tobacco smoker presented with a slowly enlarging left parotid gland. Computed tomography of the neck demonstrated a solid mass superficial to a cystic mass in the deep lobe of the gland. Ultrasound-guided fine needle aspiration yielded oncocytic cells, lymphoid cells, and granular debris along with rare cohesive groups of basaloid cells. Parotidectomy was performed, and the resected gland was found to contain two adjacent but distinct masses. One mass, a predominantly solid, well-circumscribed lesion composed of ribbons of double-layered oncocytic cells and a lymphoid stroma with germinal center formation, was a Warthin tumor. The other mass, a predominantly cystic lesion composed of cords and nests of basaloid cells with associated deposits of basement membrane-like material, was a basal cell adenoma of the membranous type. To our knowledge, this is the first reported case of synchronous Warthin tumor and basal cell adenoma of the parotid gland with cytologic–histologic correlation attributable to each tumor.

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Quantifying the Ototoxicity of Mitomycin: Before versus after Myringotomy
Objectives: Recent research has focused on mitomycin C (MMC) application as a means to circumvent complications that arise when using ventilation tubes during myringotomy. This study has two aims: (1) to synergize the current literature to create a standardized clinical approach for using MMC, and (2) to determine at which point during the myringotomy the application of MMC proves the safest (i.e., before or after incision). Methods: We measured the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) in 9 female chinchillas to determine whether applying MMC before or after incision was also the safest. The tests were then repeated on days 3, 10 and 17. Results: The change in the ABR thresholds from baseline was greater in the experimental than in the control group; however, after stratification, the 'after' group experienced a statistically significant change (19.38 ± 8.26) on day 17, whereas the 'before' group did not (2.00 ± 3.26; p = 0.003). No such changes were seen with DPOAE testing. Conclusions: Mitomycin is less ototoxic to the middle ear when applied before myringotomy is done. We recommend future studies to apply the clinical approach we have designed to standardize its use in selected cases.
ORL 2015;77:346-350
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