Regulation of bone remodeling by vitamin K2

Abstract

All living tissues require essential nutrients such as amino acids, fatty acids, carbohydrates, minerals, vitamins, and water. The skeleton requires nutrients for development, maintaining bone mass and density. If the skeletal nutritional requirements are not met, the consequences can be quite severe. In recent years, there has been growing interest in promotion of bone health and inhibition of vascular calcification by Vitamin K2. This vitamin regulates bone remodeling, an important process necessary to maintain adult bone. Bone remodeling involves removal of old or damaged bone by osteoclasts and its replacement by new bone formed by osteoblasts. The remodeling process is tightly regulated; when the balance between bone resorption and bone formation shifts to a net bone loss results in the development of osteoporosis in both men and women. In this review, we focus on our current understanding of the effects of vitamin K2 on bone cells and its role in prevention and treatment of osteoporosis.

This article is protected by copyright. All rights reserved.

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Hyposalivation and xerostomia among Parkinson's disease patients and its impact on quality of life

Abstract

Objective

Parkinson's disease (PD) adversely affects oral health (OH). However, the informative value of xerostomia compared to objective parameters and its impact on quality of life (QoL) is still unclear. This study aimed to explore whether xerostomia correlates with hyposalivation and to define its impact on OH-related QoL.

Materials and methods

Whole stimulated saliva (WSS) was collected from 30 PD patients and 30 matched healthy controls. Objective parameters (Community Periodontal Index of Treatment Needs, plaque/ gingivitis index, mucosa situation and cheilitis angularis), and questionnaires (German Oral Health Impact Profile [OHIPG]-14, visual analogue scale [VAS], xerostomia [yes/no], and the Unified Parkinson's Disease Rating Scale-II) were assessed.

Results

87% PD patients showed hyposalivation versus 50% of controls (p=0.001). 50% of PD patients reported xerostomia, none of controls (p<0.001). The OHIPG-14 was impaired in PD patients compared to controls (p<0.001), PD patients with xerostomia reported mean VAS values of 4.1 (SD 2.2). WSS did not correlate with VAS values.

Conclusions

Half of PD patients reported xerostomia and underestimated their xerostomic status, with higher probability than healthy controls. WSS did not reflect the grade of xerostomia. PD patients suffered from impaired OH-related QoL. Dental teams should not overlook these oral health risks.

This article is protected by copyright. All rights reserved.

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Evaluation of the p-AKT, p-JNK and FoxO3a function in the oral epithelial dysplasia malignance

Abstract

Objectives

To evaluate the expression of p-AKT, p-JNK, FoxO3a and KI-67 in samples of Oral Squamous Cell Carcinoma (OSCC) and Oral Epithelial Dysplasias (OEDs) to understand their possible involvement in the malignant transformation process of oral lesions.

Materials And Methods

Tissue samples of 20 cases of OSCCs, 20 OEDs and normal oral mucosa were subjected to immunohistochemistry reactions for anti-p-Akt, anti-p-JNK, anti-FoxO3a and anti-Ki-67 antibodies. It was analyzed quantitative (number of immunostained cells) and qualitative (immunostaining intensity) parameters in different cell immunostaining sublocations.

Results

Nuclear p-AKT was observed significantly greater immunostaining in OSCC (21.2 ± 19.0) than in dysplasias (7.9 ± 8.1) and control (1.8 ± 4.7) (p = 0.002). Immunostaining of strong nuclear p-JNK was greater in controls (48.3 ± 13.7) than in OEDs (11.0 ± 10.3) and OSCCs (1.1 ± 1.3) (p<0.001). Strong nuclear immunostaining of FoxO3a proved to be absent in OSCCs (0.0 ± 0.1) with little staining on dysplasias (3.2 ± 5.4) and increased expression in controls (13.5 ± 4.8) (p<0.001). Immunostaining of strong nuclear ki-67 was grater in OSCCs (48.1±49.6) than in OED (11.8±10.6) and controls (1.9±2.0) (p<0.001).

Conclusions

Malignant process of OEDs in this research may involve the same mechanisms of established malignant lesions.

This article is protected by copyright. All rights reserved.

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An update on the implications of Cyclin D1 in oral carcinogenesis

Abstract

Cyclin D1 promotes cell cycle progression during G1 phase, a key event in G1-S transition. The protein is encoded by gene CCND1, located in chromosomal band 11q13. Cyclin D1 plays key roles in cell biology, including: cell proliferation and growth regulation, mitochondrial activity modulation, DNA repair, and cell migration control. CCND1 gene and its protein cyclin D1 are frequently altered by different molecular mechanisms, including amplification, chromosomal translocations, mutations, and activation of the pathways involved in cyclin D1 expression, alterations which appear to be essential in the development of human cancers, including oral carcinoma. This is the first published review of the specific features of cyclin D1 overexpression in oral oncogenesis. Starting with the physiological regulation of cyclin D1, there is an evaluation of its functions, overexpression mechanisms, and the implications of the oncogenic activation of CCND1/cyclin D1 in OSCC. The potential diagnostic and prognostic value of cyclin D1 is reviewed. The influence of CCND1/cyclin D1 on tumor size and clinical stage is reported, and an update is provided on the utilization of cyclin D1 as therapeutic target and on the combination of cyclin D1 inhibitors with cytotoxic agents. Future research lines in this field are also proposed.

This article is protected by copyright. All rights reserved.

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Phenotype and genotype analyses in seven families with dentinogenesis imperfecta or dentin dysplasia

Abstract

Objective

Hereditary dentin defects can be categorised into two classes according to their clinical manifestations: dentinogenesis imperfecta (DGI), which includes three types (DGI-I, DGI-II, and DGI-III) and dentin dysplasia (DD), which includes two types (DD-I and DD-II). This study investigated the phenotypic characteristics and genetic causes of hereditary dentin defects in seven Chinese families.

Materials And Methods

Seven families affected with DGI-II, DGI-III, or DD-II were enrolled. Clinical examinations were performed to determine the phenotypic characteristics, and DNA samples were collected for Sanger sequencing.

Results

Clinical diagnoses revealed DGI-II in five families, DGI-III in one family, and DD-II in one family. Variants of the dentin sialophosphoprotein (DSPP) gene were found in six of the seven families. Of these, c.52G>T was identified in two families. Each of the remaining four families had a different variant: c.2684delG, c.52-2A>G, c.1874-1877delACAG, and c.3509-3521del13bp; the last three variants were novel.

Conclusions

This is the first study to analyse all three important types of hereditary dentin defect and include comprehensive genetic analyses of both dentin sialoprotein and dentin phosphoprotein in Chinese families. This study expands the spectrum of DSPP variants, highlighting their associated phenotypic continuum.

This article is protected by copyright. All rights reserved.

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Could Calcified Triglyceride Bone Cement Be an Alternative Graft Material in Maxillary Sinus Augmentation?.

The ideal graft material for maxillary sinus augmentation is still a matter of controversy and the search for a more appropriate bone substitute for use continues. The aim of this study was to evaluate bone formation as a sign of the regeneration following maxillary sinus augmentation in rabbits using 3 different biomaterials, one of which is a newly developed graft material; calcified triglyceride bone cement (CTBC). Twenty-one New Zealand rabbits were used and randomly divided into 3 groups. Bilateral maxillary sinus augmentation was carried out and autogenous bone (AB), bovine hydroxyapatite (BHA), and CTBC were administered. Maxillary sinuses were dissected after fourth and eighth weeks of the operation. The bone formation was evaluated by stereological and histopathological analysis and the data were analyzed statistically. When the volume of primary bone is compared, statistically significant differences were found among all groups at both of the fourth and eighth weeks. The highest value was obtained from AB applied group. In BHA and CTBC applied groups, active bone formation, osseointegration of graft materials were observed at both fourth and eighth weeks. In CTBC applied group, primary bone formation was only seen as linked to the continuation of parent sinus bony wall. The efficiency of primary bone formation of CTBC was found less than AB and BHA. Of the 3 graft materials tested, BHA is the strongest alternative to AB graft for maxillary sinus augmentation. (C) 2016 by Mutaz B. Habal, MD.

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Analysis of Anatomical Characteristics and Morphometric Aspects of Infraorbital and Accessory Infraorbital Foramina.

Objective: This study aimed to perform a morphological and morphometric study of the characteristics of the infraorbital foramen (IOF) and accessory infraorbital foramen (AIOF) in Brazilian skulls. Methods: A sample calculation determined a total of 94 human skulls to be evaluated by a trained examiner for number, shape, diameters, and location of IOF in relation to anatomical landmarks. Number, size, shape, diameters, location, orientation, position, and distances in relation to anatomical landmarks were evaluated for the AIOF. Descriptive analysis, paired t test, Wilcoxon test, Pearson and Spearman correlations were used. Results: A total of 188 IOFs and 48 AIOFs were found. Circular outline was the predominant shape for both IOFs and AIOFs. Infraorbital foramens presented in left sides had a significantly greater transverse diameter and distance from medial margin of the orbit when compared with IOFs located on the right sides (P

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A Rare Patient with Facial Duplication.

Facial duplication, in whole or in part, is a very rare malformation. It may be symmetrical or asymmetric. Those cases that have been reported in the literature constitute a spectrum extending from simple nasal duplication to complete separation of 2 faces. Up to now there are some reports of eye, nose, mandible, or maxilla duplication separately. But there is no report of oral orifice or lips duplication. The present article reports a case of a newborn girl who presented with 2 mouths and also duplication of zygoma and maxilla. Then, we describe her stages of treatment from birth through now that she has 20 years. (C) 2016 by Mutaz B. Habal, MD.

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Microsurgical Forehead Reconstruction.

Reconstruction of the forehead remains challenging. Especially in cases of large or even complete forehead defects, local flaps and skin grafting may not be an option, necessitating free flap coverage. The aim of this retrospective case series was to develop an algorithmic surgical approach as well as to evaluate surgical and aesthetic outcomes of microvascular-based forehead reconstructions, using gracilis muscle or anterolateral thigh flaps in 15 cases. The mean size of the defects was 84.6 (range: 25-160, +/-44.1) cm2, all with significant area of bone exposure. The free flap reconstructions included 7 gracilis muscle flaps, covered with 1.2-mm-thick unmeshed split-thickness skin grafts, and 8 anterolateral thigh flaps with a mean size of the free flaps of 160 (range: 56-300, +/-78.6) cm2. In all patients, wound healing at the donor site was uneventful. Minor complications occurred in 3 patients and required small revision procedures. This case series demonstrates that microsurgical reconstruction of multiple entities of forehead defects poses a reliable method, especially in large and complex defects. In our opinion, given low risks for major complications and superior aesthetic results, the gracilis muscle flap covered with unmeshed split-thickness skin graft is ideally suited to reconstruct the forehead and should be one of first choices. (C) 2016 by Mutaz B. Habal, MD.

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Mandibular Contouring During Orthognathic Surgery Using the Modified Hunsuck Technique.

Square face or prominent mandibular angle is a major concern in Asian women. In class III patients, mandibular setback may lead to a wider lower face that is not preferred in Asian culture. In order to achieve better aesthetic outcomes, simultaneous mandibular contouring to reduce the width of the lower face is required for some patients. This article details the authors' procedures modified from Hunsuck techniques of sagittal split osteotomy. This modified Hunsuck technique provides an alternative option to obtain a desirable mandibular outline. The long-term stability is also comparable to traditional methods. (C) 2016 by Mutaz B. Habal, MD.

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Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn’s Disease in Remission: A Pilot Randomized Double-Blind Controlled Study

Abstract

Aim

To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD).

Methods

This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores.

Results

High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3.

Conclusions

Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted.

Clinicaltrials.gov registration no

NCT02615288.

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Inflammatory Bowel Disease-Related Abstracts Presented at National Conferences in the USA Are Frequently Unpublished as Full Manuscripts

Abstract

Background

Numerous abstracts related to inflammatory bowel disease (IBD) are presented at national conferences in the USA. The overall rate of publication of these abstracts as complete manuscripts is unknown .

Methods

Abstracts submitted to the 2010 American College of Gastroenterology (ACG), Advances in Inflammatory Bowel Diseases (AIBD), and the American Gastroenterological Association abstracts at Digestive Disease Week (DDW) were reviewed. Each abstract was reviewed manually by two authors for type of research, study design, patient population, and outcome. Both PubMed and Google were then searched to determine whether the abstract was published as a full manuscript within five years of the conference. Univariate and multivariate logistic regression analysis was carried out using Stata 14.1.

Results

In total, 872 abstracts were reviewed. 49% (426/872) were published as complete manuscripts within five years of the conference. The average length of time to publication was 1.87 years (range 0–5). 42% of abstracts from ACG, 58% from AIBD, and 23% from DDW were eventually published (p < 0.0001). However, abstracts presented at DDW had the shortest time to publication compared to the other conferences (p = 0.002). Factors predictive of eventual publication include: number of authors (mean 7.5 for published vs 6.4 for unpublished p = 0.0001), clinical research compared to basic and translational (p = 0.026), and studies assessing drug safety with no adverse effects reported (p = 0.006).

Conclusion

Nearly 50% of the abstracts presented at major gastroenterology conferences in the USA are published as full manuscripts 5 years after the conference. Further studies are needed to assess why so many abstracts are not published.

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Visual Context Enhanced: The Joint Contribution of Iconic Gestures and Visible Speech to Degraded Speech Comprehension

Purpose

This study investigated whether and to what extent iconic co-speech gestures contribute to information from visible speech to enhance degraded speech comprehension at different levels of noise-vocoding. Previous studies of the contributions of these 2 visual articulators to speech comprehension have only been performed separately.

Method

Twenty participants watched videos of an actress uttering an action verb and completed a free-recall task. The videos were presented in 3 speech conditions (2-band noise-vocoding, 6-band noise-vocoding, clear), 3 multimodal conditions (speech + lips blurred, speech + visible speech, speech + visible speech + gesture), and 2 visual-only conditions (visible speech, visible speech + gesture).

Results

Accuracy levels were higher when both visual articulators were present compared with 1 or none. The enhancement effects of (a) visible speech, (b) gestural information on top of visible speech, and (c) both visible speech and iconic gestures were larger in 6-band than 2-band noise-vocoding or visual-only conditions. Gestural enhancement in 2-band noise-vocoding did not differ from gestural enhancement in visual-only conditions.

Conclusions

When perceiving degraded speech in a visual context, listeners benefit more from having both visual articulators present compared with 1. This benefit was larger at 6-band than 2-band noise-vocoding, where listeners can benefit from both phonological cues from visible speech and semantic cues from iconic gestures to disambiguate speech.

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Propositional Density in Spoken and Written Language of Czech-Speaking Patients With Mild Cognitive Impairment

Purpose

Propositional density (PD) is a measure of content richness in language production that declines in normal aging and more profoundly in dementia. The present study aimed to develop a PD scoring system for Czech and use it to compare PD in language productions of older people with amnestic mild cognitive impairment (aMCI) and control participants matched on age, gender, and education.

Method

Groups of patients with aMCI and cognitively healthy control participants (N = 20 each) provided short spoken and written language samples. Two samples were elicited for each modality, 1 describing recent events and 1 describing childhood memories. Series of neuropsychological tests were administered. The groups were compared using t-tests and the relations between measures using correlation coefficients.

Results

PD was lower in spoken productions of patients with aMCI, compared with control participants, but only in language samples using remote memories. PD in these samples was related to verbal fluency and education but not to working memory. PD in written samples did not differ between participants with aMCI and control participants.

Conclusions

PD in spoken language reflects the cognitive decline in people with aMCI, but the effect is relatively mild. The results support the existing findings that PD is related to verbal fluency.

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Visual Context Enhanced: The Joint Contribution of Iconic Gestures and Visible Speech to Degraded Speech Comprehension

Purpose

This study investigated whether and to what extent iconic co-speech gestures contribute to information from visible speech to enhance degraded speech comprehension at different levels of noise-vocoding. Previous studies of the contributions of these 2 visual articulators to speech comprehension have only been performed separately.

Method

Twenty participants watched videos of an actress uttering an action verb and completed a free-recall task. The videos were presented in 3 speech conditions (2-band noise-vocoding, 6-band noise-vocoding, clear), 3 multimodal conditions (speech + lips blurred, speech + visible speech, speech + visible speech + gesture), and 2 visual-only conditions (visible speech, visible speech + gesture).

Results

Accuracy levels were higher when both visual articulators were present compared with 1 or none. The enhancement effects of (a) visible speech, (b) gestural information on top of visible speech, and (c) both visible speech and iconic gestures were larger in 6-band than 2-band noise-vocoding or visual-only conditions. Gestural enhancement in 2-band noise-vocoding did not differ from gestural enhancement in visual-only conditions.

Conclusions

When perceiving degraded speech in a visual context, listeners benefit more from having both visual articulators present compared with 1. This benefit was larger at 6-band than 2-band noise-vocoding, where listeners can benefit from both phonological cues from visible speech and semantic cues from iconic gestures to disambiguate speech.

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Propositional Density in Spoken and Written Language of Czech-Speaking Patients With Mild Cognitive Impairment

Purpose

Propositional density (PD) is a measure of content richness in language production that declines in normal aging and more profoundly in dementia. The present study aimed to develop a PD scoring system for Czech and use it to compare PD in language productions of older people with amnestic mild cognitive impairment (aMCI) and control participants matched on age, gender, and education.

Method

Groups of patients with aMCI and cognitively healthy control participants (N = 20 each) provided short spoken and written language samples. Two samples were elicited for each modality, 1 describing recent events and 1 describing childhood memories. Series of neuropsychological tests were administered. The groups were compared using t-tests and the relations between measures using correlation coefficients.

Results

PD was lower in spoken productions of patients with aMCI, compared with control participants, but only in language samples using remote memories. PD in these samples was related to verbal fluency and education but not to working memory. PD in written samples did not differ between participants with aMCI and control participants.

Conclusions

PD in spoken language reflects the cognitive decline in people with aMCI, but the effect is relatively mild. The results support the existing findings that PD is related to verbal fluency.

http://ift.tt/2huk7qP

Visual Context Enhanced: The Joint Contribution of Iconic Gestures and Visible Speech to Degraded Speech Comprehension

Purpose

This study investigated whether and to what extent iconic co-speech gestures contribute to information from visible speech to enhance degraded speech comprehension at different levels of noise-vocoding. Previous studies of the contributions of these 2 visual articulators to speech comprehension have only been performed separately.

Method

Twenty participants watched videos of an actress uttering an action verb and completed a free-recall task. The videos were presented in 3 speech conditions (2-band noise-vocoding, 6-band noise-vocoding, clear), 3 multimodal conditions (speech + lips blurred, speech + visible speech, speech + visible speech + gesture), and 2 visual-only conditions (visible speech, visible speech + gesture).

Results

Accuracy levels were higher when both visual articulators were present compared with 1 or none. The enhancement effects of (a) visible speech, (b) gestural information on top of visible speech, and (c) both visible speech and iconic gestures were larger in 6-band than 2-band noise-vocoding or visual-only conditions. Gestural enhancement in 2-band noise-vocoding did not differ from gestural enhancement in visual-only conditions.

Conclusions

When perceiving degraded speech in a visual context, listeners benefit more from having both visual articulators present compared with 1. This benefit was larger at 6-band than 2-band noise-vocoding, where listeners can benefit from both phonological cues from visible speech and semantic cues from iconic gestures to disambiguate speech.

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Propositional Density in Spoken and Written Language of Czech-Speaking Patients With Mild Cognitive Impairment

Purpose

Propositional density (PD) is a measure of content richness in language production that declines in normal aging and more profoundly in dementia. The present study aimed to develop a PD scoring system for Czech and use it to compare PD in language productions of older people with amnestic mild cognitive impairment (aMCI) and control participants matched on age, gender, and education.

Method

Groups of patients with aMCI and cognitively healthy control participants (N = 20 each) provided short spoken and written language samples. Two samples were elicited for each modality, 1 describing recent events and 1 describing childhood memories. Series of neuropsychological tests were administered. The groups were compared using t-tests and the relations between measures using correlation coefficients.

Results

PD was lower in spoken productions of patients with aMCI, compared with control participants, but only in language samples using remote memories. PD in these samples was related to verbal fluency and education but not to working memory. PD in written samples did not differ between participants with aMCI and control participants.

Conclusions

PD in spoken language reflects the cognitive decline in people with aMCI, but the effect is relatively mild. The results support the existing findings that PD is related to verbal fluency.

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Simulateur de suture – chirurgie des fentes vélopalatines

Publication date: Available online 14 December 2016
Source:Annales de Chirurgie Plastique Esthétique
Author(s): F. Devinck, S. Riot, A. Qassemyar, A. Belkhou, A. Wolber, V. Martinot Duquennoy, P. Guerreschi
IntroductionLes fentes vélopalatines imposent une fermeture chirurgicale au cours des premières années de vie. La réparation du voile et du palais de manière anatomique est complexe sur le plan chirurgical, du fait de la finesse des tissus et de la configuration locale endobuccale. L'apprentissage par la répétition sur simulateur est utile avant de réaliser le geste au bloc opératoire. Or, il n'existe aucun matériel dédié à l'apprentissage des sutures endobuccales dans la chirurgie vélopalatine. Nous en avons donc confectionné un de manière artisanale afin de s'entraîner avant le geste chirurgical.Construction du simulateurLe simulateur a été construit à partir de données anatomiques précises. Un tuyau en acier, fixé sur un socle rigide, formait la cavité buccale. Une cuillère fendue retravaillée permettait de reproduire le palais. L'ensemble était amovible, ce qui permettait d'appliquer un pansement hydrocellulaire avant l'entraînement aux sutures.Utilisation du simulateurNotre simulateur a été testé par 3 chirurgiens seniors de notre service dans des conditions proches de la réalité afin d'évaluer sa fidélité.ConclusionDisposer d'un simulateur de suture de fentes vélopalatines au sein des centres prenant en charge cette pathologie est bénéfique pour l'apprentissage. Notre simulateur a un coût de revient faible, il est facile à réaliser de manière artisanale et fidèle à la réalité anatomique des patients.IntroductionCleft palate requires surgery in the first years of life, furthermore repairing anatomically the soft and hard palate is complex on a surgical level because of the fine tissues and the local intraoral configuration. It is valuable to train first on simulators before going to the operating room. However, there is no material dedicated to learning how to perform intraoral sutures in cleft palate surgery. We made one, in an artisanal manner, in order to practice before the real surgical gesture.Building the simulatorThe simulator was designed based on precise anatomical data. A steel pipe, fixed on a rigid base represented the oral cavity. An adapted split spoon represented the palate. All pieces could be removed in order to apply a hydrocellular dressing before training for sutures.Use of the simulatorOur simulator was tested by 3 senior surgeons in our department in close to real-life conditions in order to evaluate its anatomical accuracy.ConclusionIt is valuable to have a simulator to train on cleft palate sutures within teaching university hospitals that manage this pathology. Our simulator has a very low cost, it is easy to make and is anatomically accurate.



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Perineal reconstruction: The use of a gracilis muscle flap for urethral fistula coverage, our point of view

Publication date: Available online 14 December 2016
Source:Annales de Chirurgie Plastique Esthétique
Author(s): N. Ouar, S. Mazouz-Dorval, M. Revol, T. Sorin




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“A safe-repositioning maneuver for the management of benign paroxysmal positional vertigo: Gans vs. Epley maneuver; a randomized comparative clinical trial”: something else about Gans maneuver

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Systematic Review of Hyperbaric Oxygen Therapy for the Treatment of Radiation-Induced Skin Necrosis

Publication date: Available online 14 December 2016
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Zachary Borab, Michael D. Mirmanesh, Madeleine Gantz, Alessandro Cusano, Lee L.Q. Pu
1.2 million cancer patients receive radiation therapy every year in the United States. Late radiation tissue injury occurs in an estimated 5-15% of these patients. The tissue injury can include skin necrosis, which can lead to chronic non-healing wounds. Despite many treatments available to help heal skin necrosis such as hyperbaric oxygen therapy, no clinical guidelines exist and evidence is lacking. The purpose of this review is to identify and comprehensively summarize studies published to date in order to evaluate the effectiveness of hyperbaric oxygen therapy for the treatment of radiation induced skin necrosis. Adhering to PRISMA guidelines, a systematic review was performed of currently published articles evaluating the use of hyperbaric oxygen to treat skin necrosis.Eight articles were identified, including one observational cohort, five case series, and two case reports. The articles describe changes in symptoms and alteration in wound healing of radiation induced skin necrosis after treatment with hyperbaric oxygen therapy. Hyperbaric oxygen therapy is a safe intervention with promising outcomes, however additional evidence is needed to endorse its application as a relevant therapy in the treatment of radiation induced skin necrosis.



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Fingertip reconstruction with a posterior interosseous artery perforator flap: a minimally invasive procedure for donor and recipient sites

Publication date: Available online 14 December 2016
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Satoshi Usami, Mutsumi Okazaki
BackgroundA posterior interosseous artery perforator flap is used for small defects, leaving no functional disturbance at the flap donor site. The purpose of this report is to describe our experience with the transfer of this flap for fingertip defects and the evaluation of postoperative function.MethodsEleven flaps were used for 13 fingertip reconstructions in 11 patients. Two patients had two finger defects covered simultaneously with one bridge flap, and five flaps were harvested in true perforator flap style.ResultsOver the mean follow-up of 10.6 months, static and moving two-point discrimination were 8.8 and 6.1 mm, respectively, and patients returned to work approximately 2 months after surgery. There were no complications at the donor sites.ConclusionsA posterior interosseous artery perforator flap was a useful choice for fingertip reconstruction, with good sensory recovery and no donor site morbidity, and the patients were able to return to daily living quickly.



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Autologous Fat Grafting: A comparison study of four current commercial protocols

Publication date: Available online 14 December 2016
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Vincent Hivernaud, Bruno Lefourn, Myriam Robard, Jérôme Guicheux, Pierre Weiss
BackgroundAutologous Fat Grafting is a widely used technique that gives natural results when treating soft tissue deficiencies. However, there is still no consensus on which is the best procedure to use, leading to unpredictable results due to fat graft resorption.ObjectivesThis study compared 4 commercial lipotransfer devices by analyzing the behavior of processed adipose tissue and the outcome of the adipose graft in an in vivo model.Methods4 different protocols that used manual, power or water assisted lipoaspiration and then decantation, centrifugation or filtration were used on each of 8 patients to process lipoaspirate. Harvested adipose tissue was assessed in vitro (tissue resorption, oil formation, cytokine secretion). Graft resorption rate was calculated and histological analyses were performed after subcutaneous injection in a murine model.ResultsAll protocols resulted in very low oil formation and histologically healthy grafts. The tissue volume was significantly greater after 2 days in culture when using manual lipoaspiration and soft centrifugations/washing steps (Microfill^®/Macrofill^®) compared to Water-Assisted Lipoaspiration/Decantation (BodyJet^®) and Power-Assisted Lipoaspiration/Filtration (PAL^®+PureGraft^®). These results were confirmed in mice one month after subcutaneous injection, with greater efficiency obtained with protocols that employed (A) manual aspiration, (B) soft centrifugations and (C) washing steps.ConclusionsWe have confirmed that the choice of technique used to process adipose tissue during lipotransfer surgery can highly influence fat grafting efficacy. In our study, the use of manual aspiration combined to soft centrifugations lead to the best results in the selected models.



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Venous Drainage of the Face

Publication date: Available online 14 December 2016
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): S. Onishi, N. Imanishi, Y. Yoshimura, Y. Inoue, Y. Sakamoto, H. Chang, T. Okumoto
The venous anatomy of the face was examined in 12 fresh cadavers. Venograms and arteriovenograms were obtained after injection of contrast medium. In eight of the 12 cadavers, a large loop was formed by the facial vein, the supratrochlear vein, and the superficial temporal vein, which became the main trunk vein of the face. In four of the 12 cadavers, the superior lateral limb of the loop vein was less well developed. The loop vein generally did not accompany the arteries of the face. Cutaneous branches of the loop vein formed a polygonal venous network in the skin, while communicating branches ran toward deep veins. These findings suggest that blood from the dermis of the face is collected by the polygonal venous network and enters the loop vein through the cutaneous branches, after which it flows away from the face via the superficial temporal vein, the facial vein, and the communicating branches and enters the deep veins.



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Nipple Reconstruction with Combination of Modified C-V Flap and Contralateral Nipple Composite Graft

Publication date: Available online 14 December 2016
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Young Chul Kim, Ji Young Yun, Hyung Chul Lee, Ji Hong Yim, Jin Sup Eom
BackgroundNumerous nipple reconstruction methods have been proposed including use of local flaps and composite grafts, but most have shown significant loss of projection. We combined a modified C-V flap with a composite graft (nipple-sharing), in order to maximize projection and volume of the new nipple and reduce the size of the contralateral nipple.MethodsThirty patients underwent nipple reconstruction using a combined method between January 2013 and November 2015. This technique was selected if the diameter of the contralateral nipple was large, and the thickness of the skin was less than 2 mm. After the modified C-V flap was created, a composite graft from the contralateral nipple was placed between the V flaps and C flap. The loss of projection and the ratio of the new nipple to the contralateral nipple were evaluated 12 months after surgery.ResultsNipple reconstruction was successful in all cases. The projection at 12 months after reconstruction was 68% of the initial projection, and the mean projection ratio of the new nipple to the contralateral nipple was 0.81. There was no complication in the donor nipple; the shape improved with nipple reduction and the scar was inconspicuous.ConclusionsNipple reconstruction that combines a modified C-V flap and composite graft can maximize the nipple projection and provides a chance for nipple symmetry, as the two components will act synergistically.



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Acceptable clinical outcomes and recommended reconstructive strategies of secondary maxillary reconstruction with vascularised fibula osteomyocutaneous flap: a retrospective analysis

Publication date: Available online 14 December 2016
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Yi Shen, Jun Li, Andrew Ow, Liang Wang, Ming-ming Lv, Jian Sun
BackgroundTo conduct a retrospective analysis of the clinical outcomes and evaluation of reconstructive strategies of patients who underwent secondary maxillary reconstruction with the vascularised fibula osteomyocutaneous flap (VFOF).MethodsFrom May of 2001 to June of 2014, 34 patients who underwent secondary maxillary reconstruction with VFOF, with or without titanium mesh, were reviewed. The patients were divided into 2 groups of maxillary reconstruction, according to different planning and treatment strategies. In Group 1, pre-surgical planning was achieved using 3-dimensional stereomodelling (n=12, Group 1). In Group 2, virtual surgical planning was done and guided templates produced (n=22, Group 2). The differences in the preoperative planning, intraoperative technique, postoperative complications and long-term results between the 2 groups were analysed. Statistical analysis was performed to determine the differences between the 2 groups and the risk factors for prognosis.ResultsSimilar and accurate secondary maxillary were successfully performed in Group 1 and 2, respectively. Postoperative complications were reported in 8 patients in Group 1 and 11 patients in Group 2. Complications were reported in patients who had undergone radiotherapy. The incidence of postoperative complications in Group 2 were lower than that of Group 1 with the exception of midfacial collapse (P > 0.05). The long-term results of some patients with class 3 defects were not satisfactory because of midfacial collapse and lower eyelid ectropion. Stepwise regression analysis showed radiotherapy to be risk factor for prognosis.ConclusionsThe long-term results of secondary maxillary reconstruction were reported to be acceptable in our study. Radiotherapy was the risk factor for prognosis in secondary maxillary reconstruction. Based on our results, we highly recommend our strategy for secondary maxillary reconstruction. Good functional results could be achieved after accurate restoration of maxillary alveolar ridge with several fibular segments using virtual surgical planning and dental restoration.



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Representations of workers with hearing loss in Canadian newspapers: a thematic analysis

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Representations of workers with hearing loss in Canadian newspapers: a thematic analysis

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Enhanced regeneration potential of mobilized dental pulp stem cells from immature teeth

Abstract

Objectives

We have previously demonstrated that dental pulp stem cell (DPSCs) isolated from mature teeth by granulocyte-colony stimulating factor (G-CSF)-induced mobilization method can enhance angiogenesis/vasculogenesis and improve pulp regeneration when compared with colony-derived DPSCs. However, the efficacy of this method in immature teeth with root-formative stage has never been investigated. Therefore, the aim of this study is to examine the stemness, biological characteristics and regeneration potential in mobilized-DPSCs compared with colony-derived DPSCs from immature teeth.

Materials And Methods

Mobilized-DPSCs isolated from immature teeth were compared to colony-derived DPSCs using methods including flow cytometry, migration assays, mRNA expression of angiogenic/neurotrophic factor, and induced differentiation assays. They were also compared in trophic effects of the secretome. Regeneration potential was further compared in an ectopic tooth transplantation model.

Results

Mobilized-DPSCs had higher migration ability and expressed more angiogenic/neurotrophic factors than DPSCs. The mobilized-DPSC secretome produced a higher stimulatory effect on migration, immunomodulation, anti-apoptosis, endothelial differentiation and neurite extension. In addition, vascularization and pulp regeneration potential were higher in mobilized-DPSCs than in DPSCs.

Conclusions

G-CSF-induced mobilization method enhances regeneration potential of colony-derived DPSCs from immature teeth.

This article is protected by copyright. All rights reserved.

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Amianto. Cáncer de laringe

Publication date: Available online 14 December 2016
Source:Acta Otorrinolaringológica Española
Author(s): Luis Sánchez Galán




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Electrocauterización endoscópica para el tratamiento de las fístulas congénitas del seno piriforme en pediatría. Serie de casos

Publication date: Available online 14 December 2016
Source:Acta Otorrinolaringológica Española
Author(s): Giselle Cuestas, Flavia Doormann, Verónica Rodríguez, Patricio Bellia Munzón, Gastón Bellia Munzón
Las fístulas del seno piriforme son anomalías infrecuentes de los arcos branquiales. La mayoría se localizan en el lado izquierdo y se extienden desde el ápex del seno piriforme de la hipofaringe hasta la glándula tiroides o el espacio peritiroideo.El diagnóstico se sospecha ante la presencia de tiroiditis aguda supurada o abscesos cervicales laterales recurrentes, y se confirma mediante la visualización endoscópica del orificio de la fístula. El tratamiento clásico consiste en la exéresis del trayecto fistuloso por vía cervical, con o sin lobectomía tiroidea. Sin embargo, se han desarrollado alternativas menos invasivas y con menos riesgos de complicaciones que obliteran el trayecto de la fístula, como la electrocauterización endoscópica.Describimos nuestra experiencia con 7 pacientes que presentaban esta afección, tratados con cauterización endoscópica utilizando electrobisturí de radiofrecuencia, y evaluamos la eficacia y la seguridad del tratamiento realizado.Pyriform sinus fistulas are rare anomalies of the branchial arches. Most of them are located on the left side. They extend from the apex of the pyriform sinus of the hypopharynx to the thyroid gland or adjacent tissues.The diagnosis is suspected in the presence of acute suppurative thyroiditis or recurrent cervical abscesses, and is confirmed by endoscopic visualization of the fistula hole. The traditional treatment consists of excision of the fistulous tract, with or without thyroid lobectomy, by cervical approach. However, less invasive alternatives that obliterate the path of the fistula have been developed, such as endoscopic electrocautery.We describe our experience with 7 patients with this condition, who were treated with endoscopic cauterization using radiofrequency electrocautery, and we evaluate the effectiveness and safety of the treatment performed.



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Estimating Subglottal Pressure From Neck-Surface Acceleration During Normal Voice Production

Purpose

The purpose of this study was to evaluate the potential for estimating subglottal air pressure using a neck-surface accelerometer and to compare the accuracy of predicting subglottal air pressure relative to predicting acoustic sound pressure level (SPL).

Method

Indirect estimates of subglottal pressure (P_sg′) were obtained from 10 vocally healthy speakers during loud-to-soft repetitions of 3 different /p/–vowel gestures (/pa/, /pi/, /pu/) at 3 pitch levels in the modal register. Intraoral air pressure, neck-surface acceleration, and radiated acoustic pressure were recorded, and the root-mean-square amplitude of the acceleration signal was correlated with P_sg′ and SPL.

Results

The coefficient of determination between accelerometer level and P_sg′ was high when data were pooled from all vowel and pitch contexts for each participant (r ² = .68–.93). These relationships were stronger than corresponding relationships between accelerometer level and SPL (r ² = .46–.81). The average 95% prediction interval for estimating P_sg′ using accelerometer level was ±2.53 cm H₂O, ranging from ±1.70 to ±3.74 cm H₂O across participants.

Conclusions

Accelerometer signal amplitude correlated more strongly with P_sg′ than with SPL. Future work is warranted to investigate the robustness of the relationship in nonmodal voice qualities, individuals with voice disorders, and accelerometer-based ambulatory monitoring of subglottal pressure.

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Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis

by Cong Tian, Belinda S. Harris, Kenneth R. Johnson

Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1^asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1^asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1^asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

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Ectopic Mineralization and Conductive Hearing Loss in Enpp1asj Mutant Mice, a New Model for Otitis Media and Tympanosclerosis

by Cong Tian, Belinda S. Harris, Kenneth R. Johnson

Otitis media (OM), inflammation of the middle ear, is a common cause of hearing loss in children and in patients with many different syndromic diseases. Studies of the human population and mouse models have revealed that OM is a multifactorial disease with many environmental and genetic contributing factors. Here, we report on otitis media-related hearing loss in asj (ages with stiffened joints) mutant mice, which bear a point mutation in the Enpp1 gene. Auditory-evoked brainstem response (ABR) measurements revealed that around 90% of the mutant mice (Enpp1^asj/asj) tested had moderate to severe hearing impairment in at least one ear. The ABR thresholds were variable and generally elevated with age. We found otitis media with effusion (OME) in all of the hearing-impaired Enpp1^asj/asj mice by anatomic and histological examinations. The volume and inflammatory cell content of the effusion varied among the asj mutant mice, but all mutants exhibited a thickened middle ear epithelium with fibrous polyps and more mucin-secreting goblet cells than controls. Other abnormalities observed in the Enpp1 mutant mice include over-ossification at the round window ridge, thickened and over-calcified stapedial artery, fusion of malleus and incus, and white patches on the inside of tympanic membrane, some of which are typical symptoms of tympanosclerosis. An excessive yellow discharge was detected in the outer ear canal of older asj mutant mice, with 100% penetrance by 5 months of age, and contributes to the progressive nature of the hearing loss. This is the first report of hearing loss and ear pathology associated with an Enpp1 mutation in mice. The Enpp1^asj mutant mouse provides a new animal model for studying tympanosclerotic otitis and otitis media with effusion, and also provides a specific model for the hearing loss recently reported to be associated with human ENPP1 mutations causing generalized arterial calcification of infancy and hypophosphatemic rickets.

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Sound-Induced Intracellular Ca2+ Dynamics in the Adult Hearing Cochlea

by Dylan K. Chan, Stephanie L. Rouse

Ca²⁺ signaling has been implicated in the initial pathophysiologic mechanisms underlying the cochlea's response to acoustic overstimulation. Intracellular Ca²⁺ signaling (ICS) waves, which occur in glia and retinal cells in response to injury to activate cell regulatory pathways, have been proposed as an early event in cochlear injury. Disruption of ICS activity is thought to underlie Connexin 26-associated hearing loss, the most common genetic form of deafness, and downstream sequelae of ICS wave activity, such as MAP kinase pathway activation, have been implicated in noise-induced hearing loss. However, ICS waves have only been observed in neonatal cochlear cultures and are thought to be quiescent after the onset of hearing. In this study, we employ an acute explant model of an adult, hearing cochlea that retains many in vivo physiologic features to investigate Ca²⁺ changes in response to sound. We find that both slow monotonic changes in intracellular Ca²⁺ concentration as well as discrete ICS waves occur with acoustic overstimulation. The ICS waves share many intrinsic features with their better-described neonatal counterparts, including ATP and gap-junction dependence, and propagation velocity and distance. This identification of ICS wave activity in the adult, hearing cochlea thus confirms and characterizes an important early detection mechanism for cochlear trauma and provides a target for interventions for noise-induced and Connexin 26-associated hearing loss.

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Review of "Preservation of the Nerves to the Frontalis Muscle During the Pterional Craniotomy" by Poblete T, Jiang X, Komune N, Matsushima K, Rhoton AL in J Neurosurg 122: 1274-1282, 2015.

No abstract available

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Are Three-Dimensional Monitors More Appropriate Than Two-Dimensional Monitors in the Three-Dimensional Analysis?.

In orthognathic surgery, three-dimensional (3D) program-based analysis of 3D reconstructions of computed tomography (CT) images is commonly used, and images viewed on a monitor. The authors compared the coordinates of facial landmarks on images in a 3D program displayed on a two-dimensional (2D) (standard) or 3D monitor. Facial bone CT data from 30 patients were reconstructed in 3D. Four researchers identified 33 facial landmarks, 3 times each on 2D and 3D monitors, for each patient, by their x-, y-, and z-coordinates. The time taken to complete these identifications was measured. For each set of coordinates, the average intraclass coefficient was >0.8 for 2D and 3D analyses, as well as among 4 readers. It took on average of 2 minutes 46 seconds to identify the landmarks on the 2D monitor, compared with 2 minutes 25 seconds on the 3D monitor. The variance of individual coordinates differed when measured on 2D or 3D monitor. The landmarks affected were located near the median region of the facial area, and are important for setting the reference sagittal plane during diagnosis for orthognathic surgery. Therefore, identifying facial landmarks using 3D monitors may be helpful for conducting accurate facial diagnoses. (C) 2016 by Mutaz B. Habal, MD.

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Off-Label Use of Bone Morphogenetic Protein 2 in the Reconstructions of Mandibular Continuity Defects.

This paper describes 3 patients of off-label use of bone morphogenetic protein 2 (rhBMP-2) in the reconstruction of mandibular continuity defects. In the first patient, rhBMP-2 was associated with iliac crest bone graft for late mandibular reconstruction after resection of osteosarcoma. In the 2 other patients, rhBMP-2 was used alone. In 1 patient the mandibular continuity defect was due to resection for treatment of osteomyelitis and in the other patient a continuity defect was created by unsuccessful osteogenic distraction for correction of mandibular hypoplasia. Despite the good results in those patients, the off-label use of rhBMP-2 is associated with increased rate of complications, so more studies are needed to assess the predictability of the use of rhBMP-2 in mandibular continuity defects. Therefore, at the moment the off-label use of rhBMP-2 should be restricted to complicated bone defects in which the conventional alternatives of reconstruction were unsuccessful. (C) 2016 by Mutaz B. Habal, MD.

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Assessment of the Postoperative Stability of Mandibular Orthognathic Surgery for Correction of Class III Skeletal Malocclusion.

To assess the stability of mandible position after orthognathic surgery for correction of class III skeletal malocclusion. Twenty adult males, aged 18 to 40 years, with Angle class III skeletal malocclusion underwent preoperative orthodontic treatment for elimination of dental compensations followed by combined maxillomandibular surgery with rigid internal fixation. Lateral cephalograms from each patient, obtained in the natural head position before surgery, immediately after surgery, and at 6-month follow-up, were retrieved from the files of the Pontifical Catholic University of Rio Grande do Sul outpatient Oral and Maxillofacial Surgery clinic and compared. Comparison of craniometric landmark measurements showed that the precision of mandibular setback was compromised in the horizontal plane, with a mean mandibular relapse of 37.75% at point B and 45.85% at point Pg. Improved intercuspation and adaptation of the musculature to the new position of the jaws after orthognathic surgery lead to counterclockwise rotation of the mandible, ultimately displacing the mandible more anteriorly than desired. (C) 2016 by Mutaz B. Habal, MD.

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Anatomical Study and Locating Nasolacrimal Duct on Computed Topographic Image.

Purpose: We performed a novel anatomical and radiological investigation to understand the structure of nasolacrimal duct (NLD) and to provide data to help surgeons locate the openings of NLD efficiently based on landmarks. Materials and methods: We examined the NLD region using computed tomography images of 133 individuals and 6 dry skull specimens. Multiplanar reconstruction of the computed tomography images was performed, and the anatomical features of the NLD were studied in the coronal, sagittal, and axial planes. The long and short diameters of NLD were measured along its cross-section. The position of NLD was localized using the nostril, concha nasalis media, and medial orbital corner as landmarks. The free and open source software, 3D Slicer, was used for the segmentation of the NLD and 3D visualization of the superior and inferior openings of the NLD. Results: The length, angle, and diameter of NLD were significantly influenced by the age in females compared to those in males. The inferior opening of the NLD could be located efficiently using the nostril and the midsagittal line while the superior opening of NLD could be located using the medial orbital corner. Third, 3D Slicer enabled us to measure the distance between the skin and the bony structure in the image. Conclusion: Our study indicates that the sex and age of the patient should be considered while selecting the optimal NLD stent for a patient, and that the precise location of NLD in reference to landmarks can simplify the surgical difficulties and reduce the risk of injury during the transnasal operation. (C) 2016 by Mutaz B. Habal, MD.

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The Need for Overcorrection When Using a Suborbital Cervicofacial Hike Flap.

Background: The senior author has previously described a deep-plane cervicofacial hike flap as a workhorse for reconstruction mid-cheek defects. One important modification commonly used involves overcorrection of the defect in order to reduce the incidence of ectropion. This report outlines the senior author's experience in surgical treating complex cheek defects with an overcorrected deep-plane cervicofacial hike flap. Methods: The authors performed a retrospective review of the senior author's patients with cheek and eyelid reconstruction. The authors initially identified all patients who had undergone a deep-plane cervicofacial hike flap, then filtered those charts for patients who had overcorrection of their deformity in order to prevent ectropion. Results: A total of 3 patients had an overcorrected flap. Overcorrection was accomplished either by cheek advancement with suture fixation to the deep temporal fascia, or by placement of drill holes and bone anchors. Lower eyelid malposition was avoided in all 3 patients. Patient satisfaction at long term follow-up was very high, and no revision surgery was needed. Conclusion: If gravitational or cicatricial forces can potentially distort the eyelid in patients with cheek or eyelid reconstruction, it is necessary to overcorrect the cheek flap. This modification of the deep-plane cervicofacial flap is an important tool in reconstructing defects in this area. (C) 2016 by Mutaz B. Habal, MD.

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Conjoined Twin Separation: Integration of Three-Dimensional Modeling for Optimization of Surgical Planning.

Conjoined twinning is a rare anomaly, with an incidence of approximately 1 in 100,000 live births. There is a high perinatal mortality rate, but twins who survive pose reconstructive challenges that require meticulous preoperative planning. The authors describe the senior surgeon's career experience with conjoined twin separation, and the evolution of medical modeling and 3-dimensional imaging as a critical component in presurgical planning. The authors performed a retrospective review of all consecutive patients of conjoined twin separation at a single institution from January 2004 to December 2013. Data were collected related to patient demographics, comorbidities, operative technique, perioperative complications, survival, long-term outcomes, and the type of medical modeling system used for preoperative planning. Five sets of conjoined twins underwent separation during the 10-year study period. There were 3 sets of thoraco-omphalopagus twins, 1 set of pyopagus twins, and 1 set of ischiopagus tetrapus twins. The mean age at separation was 70 days, with a mean of 3.5 surgical procedures performed per patient during the first year of life. One set of twins experienced postseparation complications that warranted immediate return to the operating room. The overall survival rate after separation was 70%. The imaging methods used were computed tomography scan with 3-dimensional reconstruction, plaster molds, medical modeling with composite printing, and virtual surgical planning. The use of imaging and medical modeling in presurgical planning has proven to be an important element in optimizing the outcomes for patients with this rare anomaly. (C) 2016 by Mutaz B. Habal, MD.

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A Modified Approach to Extensive Oromandibular Reconstruction Using Free Fibula Flaps.

In select patients with advanced disease resulting in large composite tissue defects, consideration is often given to multiple flap reconstruction. The authors propose an alternative option. Using virtual surgical planning the authors demonstrate how modest sacrifice in projection translates into a substantial decrease in the volume and surface area of soft tissue needed, in turn maximizing soft tissue coverage with a single fibula free flap. The authors used 3-dimensional virtual surgery to simulate angle-to-angle reconstructions using free fibula flaps. The reference 3-segment reconstruction was done using symphyseal projection to the plane perpendicular to the anterior nasal spine, a customary landmark. Additional simulations were then performed using recessed projections 0.5 mm, 1 cm, 1.5 cm, and 2 cm posterior to anterior nasal spine plane. Program analytics were used to calculate the surface area and volume of the floor of mouth. With projection recessed by 1 cm, surface area decreased 22% to 14 cm2. With projection recessed by 2 cm, surface area decreased 44% to 10 cm2. With a 3-segment construct converted to a 2-segment construct, surface area decreased 22% to 14 cm2. This demonstrates for the first time an official analysis of an intraoperative modification that sacrifices little and gains a lot. Ultimately, 1 compound flap can be used in extensive reconstructions with increased confidence that it will not be overly stressed. (C) 2016 by Mutaz B. Habal, MD.

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Wall teichoic acid is an essential component of Staphylococcus aureus for the induction of human dendritic cell maturation

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Sung Jun Hong, Sun Kyung Kim, Eun Byeol Ko, Cheol-Heui Yun, Seung Hyun Han
Staphylococcus aureus is a Gram-positive pathogen that can cause chronic skin inflammation, pneumonia, and septic shock. The immunomodulatory functions of wall teichoic acid (WTA), a glycopolymer abundantly expressed on the Gram-positive bacterial cell wall, are poorly understood. Here, we investigated the role of WTA in the phenotypic and functional activation of human monocyte-derived dendritic cells (DCs) treated with ethanol-killed S. aureus. WTA-deficient S. aureus mutant (ΔtagO) exhibited attenuated binding and internalization to DCs compared to the wild-type. ΔtagO induced lower expression of maturation markers on and cytokines in DCs than the wild-type S. aureus. Furthermore, autologous human peripheral blood mononuclear cells cocultured with ΔtagO-treated DCs exhibited a marked reduction in T cell proliferative activity, the expression of activation markers, and the production of cytokines compared to the wild-type S. aureus-stimulated DCs. Collectively, these results suggest that WTA is an important cell wall component of S. aureus for the induction of DC maturation and activation.



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Antibody-mediated targeting of antigen to C-type lectin-like receptors Clec9A and Clec12A elicits different vaccination outcomes

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Christophe Macri, Claire Dumont, Scott Panozza, Mireille H. Lahoud, Irina Caminschi, Jose A. Villadangos, Angus P.R. Johnston, Justine D. Mintern
Targeting antigen (Ag) to dendritic cell (DC) surface receptors is a potential new mode of vaccination. C-type lectin-like receptors Clec9A and Clec12A are attractive receptor targets however their targeting in vivo elicits significantly different outcomes for unknown reasons. To gain insight into the mechanisms responsible, we have examined the intrinsic capacity of Clec9A and Clec12A to elicit MHC I and MHC II Ag presentation following ex vivo targeting with primary murine DC. Both receptors exhibited high rates of internalization by CD8⁺ DCs, while Clec12A delivered a significantly higher Ag owing to its higher expression level. Targeting Ag to immature CD8⁺ DCs via both Clec9A and Clec12A failed to elicit MHC I cross-presentation above that of controls, while Clec12A was the superior receptor to target following CD8⁺ DC maturation. CD8⁻ DCs were unable to elicit MHC I cross-presentation regardless of the receptor targeted. For MHC II presentation, targeting Ag to Clec12A enabled significant responses by both immature CD8⁺ and CD8⁻ DCs, whereas Clec9A did not elicit significant MHC II Ag presentation by either DC subset, resting or mature. Therefore, Clec9A and Clec12A exhibit different intrinsic capacities to elicit MHC I and MHC II presentation following direct Ag targeting, though they can only elicit MHC I responses if the DC expressing the receptor is equipped with the capacity to cross-present. Our conclusions have consequences for the exploitation of these receptors for vaccination purposes, in addition to providing insight into their roles as Ag targets in vivo.



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Structural, mutational and biophysical studies reveal a canonical mode of molecular recognition between immune receptor TIGIT and nectin-2

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Dibyendu Samanta, Haisu Guo, Rotem Rubinstein, Udupi A. Ramagopal, Steven C. Almo
In addition to antigen-specific stimulation of T cell receptor (TCR) by a peptide-MHC complex, the functional outcome of TCR engagement is regulated by antigen-independent costimulatory signals. Costimulatory signals are provided by an array of interactions involving activating and inhibitory receptors expressed on T cells and their cognate ligands on antigen presenting cells. T cell immunoglobulin and ITIM domain (TIGIT), a recently identified immune receptor expressed on T and NK cells, upon interaction with either of its two ligands, nectin-2 or poliovirus receptor (PVR), inhibits activation of T and NK cells. Here we report the crystal structure of the human TIGIT ectodomain, which exhibits the classic two-layer β-sandwich topology observed in other immunoglobulin super family (IgSF) members. Biophysical studies indicate that TIGIT is monomeric in solution but can form a dimer at high concentrations, consistent with the observation of a canonical immunoglobulin-like dimer interface in the crystalline state. Based on existing structural data, we present a model of the TIGIT:nectin-2 complex and utilized complementary biochemical studies to map the nectin-binding interface on TIGIT. Our data provide important structural and biochemical determinants responsible for the recognition of nectin-2 by TIGIT. Defining the TIGIT:nectin-2 binding interface provides the basis for rational manipulation of this molecular interaction for the development of immunotherapeutic reagents in autoimmunity and cancer.



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Acute arsenic exposure induces inflammatory responses and CD4+ T cell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF-kB, and Nrf2

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Xiaoxu Duan, Shuang Gao, Jinlong Li, Liuzhong Wu, Yang Zhang, Wei Li, Lu Zhao, Jinli Chen, Shan Yang, Guifan Sun, Bing Li
Increasing lines of evidence indicate that arsenic may be associated with immune related problems, but its detailed effects on immune organs are poorly understood. The objective of this study was to explore inflammatory responses and T cell differentiation of arsenic exposure in spleen and thymus. Female C57BL/6 mice were used as a model to systemically administration 2.5, 5 and 10mg/kg NaAsO2 intra-gastrically for 24h. We found that arsenic significantly decreased the spleen and thymus weights and indices, and flow cytometry revealed that arsenic decreased the relative frequency of CD4⁺ T cell subpopulation and the ratios of CD4/CD8 in spleen. In contrast, serum concentration of tumor necrosis factor α (TNF-α), IL-1β and IL-6 as well as the mRNA of key inflammatory mediators in spleen and thymus, including transforming growth factor β (Tgf-β), Tnf-α, Il-12, Il-1β and Il-6 were significantly increased in arsenic-treated mice compared to the control as assayed by ELISA and real time PCR, respectively. In addition, arsenic increased the expression of T helper cell 1 (Th1), Th2 and regulatory T cell (Treg) −associated transcription factors and cytokines as well as decreased Th17-associated transcription factors and cytokines. Moreover, arsenic enhanced oxidative stress and induced the activation of extracellular-signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and p38 and their downstream transcription factors nuclear factor kappa B (NF-kB) and nuclear factor E2-related factor 2 (Nrf2), which comprise important mechanistic pathways involved in immune-inflammatory manifestations. Together, these results provide a novel strategy to block the arsenic-dependent impairments in immune responses.



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Interleukin 16 and CCL17/thymus and activation-regulated chemokine in patients with aspirin-exacerbated respiratory disease

Publication date: Available online 13 December 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Luis Manuel Teran, Fernando Ramirez-Jimenez, Gabriela Soid-Raggi, Juan Raymundo Velazquez
BackgroundInterleukin (IL) 16 and thymus and activation-regulated cytokine (TARC) are chemoattractant cytokines for eosinophils and TH2 cells. Differential levels of these components in aspirin-exacerbated respiratory disease (AERD) and allergic rhinitis with asthma (ARwA) may be related to a different inflammatory response in both asthma phenotypes.ObjectiveTo assess the nasal lavage immunoreactivity of IL-16 and TARC cytokines.MethodsWe used multienzyme-linked immunosorbent assays to detect IL-5, IL-13, IL-16, IL-33, I-309/CCL1, TARC/CCL17, monocyte-derived chemokine/CCL22, periostin, and eosinophil cationic protein levels in nasal lavages from patients with AERD and patients with ARwA.ResultsThe IL-13, IL-16, TARC, and periostin levels were significantly higher in patients with AERD compared with those of patients with ARwA. Correlation analysis of mediator levels in AERD revealed a possible role of IL-16 and TARC in eosinophil recruitment and activation.ConclusionIL-16, TARC, and periostin distinguish between patients with AERD and those with ARwA. These mediators, taken together rather than individually, may comprise good specific nasal markers in patients with AERD. The effects of IL-16 and TARC on TH1, TH2, and T-regulatory cell functions in AERD cannot be disregarded.



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Immunodominance in allergic T-cell reactivity to Japanese cedar in different geographic cohorts

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Carla Oseroff, John Pham, April Frazier, Denise Hinz, John Sidney, Sinu Paul, Jason A. Greenbaum, Randi Vita, Bjoern Peters, Véronique Schulten, Alessandro Sette
BackgroundJapanese cedar (JC) pollen is a common trigger for allergic rhinitis in Japan. Pollen proteins targeted by IgE, including Cry j 1 and Cry j 2, and isoflavone reductase (IFR) have been identified.ObjectiveTo compare antigen-specific IgE titers and T-cell responses to JC pollen–derived extract and peptides in cohorts with high and low pollen exposure.MethodsPeripheral blood mononuclear cells from JC pollen allergic or nonallergic patients who have lived in Japan for at least 1 year and JC pollen allergic patients who have never been to Japan were tested for T-cell responses against JC pollen extract and peptide pools derived from Cry j 1, Cry j 2, or IFR. T-cell reactivity was assessed by interleukin 5 and interferon γ production by ELISPOT.ResultsJC pollen–specific T-cell reactivity and IgE titers were significantly higher in the allergic compared with the nonallergic Japanese cohort, which was also associated with different patterns of polysensitization. Interestingly, a significant overlap was observed in the hierarchy of the T-cell epitopes in the allergic Japanese cohort compared with the allergic non-Japanese cohort. In all 3 cohorts, T-cell reactivity was dominantly directed against peptides from the major allergens Cry j 1 and 2, with few T-cell responses detected against IFR.ConclusionOur studies identify common denominators of T-cell reactivity in patient populations with different sensitization patterns, suggesting that generally applicable immunotherapeutic approaches might be developed irrespective of exposure modality.



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Information for Readers

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6





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Author Index to Volume 117, 2016

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6





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Table of Contents

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6





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Simplification of intradermal skin testing in Hymenoptera venom allergic children

Publication date: Available online 13 December 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Ewa Cichocka-Jarosz, Marcin Stobiecki, Piotr Brzyski, Iwona Rogatko, Marita Nittner-Marszalska, Krystyna Sztefko, Ewa Czarnobilska, Grzegorz Lis, Anna Nowak-Węgrzyn
BackgroundThe direct comparison between children and adults with Hymenoptera venom anaphylaxis (HVA) has never been extensively reported. Severe HVA with IgE-documented mechanism is the recommendation for venom immunotherapy, regardless of age.ObjectiveTo determine the differences in the basic diagnostic profile between children and adults with severe HVA and its practical implications.MethodsWe reviewed the medical records of 91 children and 121 adults.ResultsBee venom allergy was exposure dependent, regardless of age (P < .001). Atopy was more common in children (P = .01), whereas cardiovascular comorbidities were present almost exclusively in adults (P = .001). In the bee venom allergic group, specific IgE levels were significantly higher in children (29.5 kUA/L; interquartile range, 11.30-66.30 kUA/L) compared with adults (5.10 kUA/L; interquartile range, 2.03–8.30 kUA/L) (P < .001). Specific IgE levels for culprit insect venom were higher in bee venom allergic children compared with the wasp venom allergic children (P < .001). In adults, intradermal tests revealed higher sensitivity, accompanied by larger area of skin reactions, regardless of type of venom. At concentrations lower than 0.1 μg/mL, 16% of wasp venom allergic children and 39% of bee venom allergic children had positive intradermal test results. The median tryptase level was significantly higher in adults than in children for the entire study group (P = .002), as well as in bee (P = .002) and wasp venom allergic groups (P = .049).ConclusionsThe basic diagnostic profile in severe HVA reactors is age dependent. Lower skin test reactivity to culprit venom in children may have practical application in starting the intradermal test procedure with higher venom concentrations.



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Instructions for Authors

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6





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Editorial Board

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6





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A renewed focus on safety, efficacy, and use of inhaled corticosteroids in asthma

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Rohit K. Katial




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Measuring safety of inhaled corticosteroids in asthma

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Anthony N. Gerber
BackgroundDespite evidence demonstrating generally excellent therapeutic ratios for inhaled corticosteroids (ICSs) in asthma treatment, many clinicians and patients have ongoing concerns regarding their safety. To frame discussions of ICS safety, it is important to understand how safety is measured.ObjectiveTo discuss how ICS safety is and should be measured.MethodsDiscussion is augmented by relevant articles from the literature.ResultsThe therapeutic value of corticosteroids depends on the activation and repression of thousands of genes. However, it is not fully known which genes cause the desirable, therapeutic effects and which cause the adverse effects. The drug development process attempts to elucidate the clinically significant therapeutic effects and adverse effects of a candidate molecule and then compare them to those of currently available corticosteroids. Approaches to monitoring safety include clinical trials, retrospective comparison to historical efficacy and safety data, surrogate markers, animal models, and in vitro assays. Both preclinical and clinical data are used to compare safety among corticosteroids; however, no specific pathway or model that can robustly predict therapeutic ratios has been identified. Furthermore, variation in adverse effects is influenced by isoforms of the glucocorticoid receptor, differences in corticosteroid characteristics, differences among patients, and environmental variation.ConclusionAlthough some preclinical and patient-based metrics have predictive value, there is a clear need for improved biomarkers of corticosteroid adverse effects. Integrated analysis of preclinical and clinical data, including long-term safety data, could be used to address this important unmet need.



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A real-life comparison of the Asthma Control Test and Global Initiative for Asthma asthma control grading

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Giorgio Ciprandi, Fabio Gallo, Fabio L.M. Ricciardolo




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Pivotal efficacy trials of inhaled corticosteroids in asthma

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Ronina A. Covar
BackgroundInhaled corticosteroids (ICSs) are the mainstay of daily controller treatment for persistent and uncontrolled asthma. However, many clinicians are wary of ICSs because of safety concerns. Clinicians need to know the underlying efficacy data that support the use of ICSs to weigh efficacy against safety.ObjectiveTo discuss efficacy data from pivotal trials to aid clinicians in their decisions to use ICSs.MethodsKey efficacy studies were selected to augment discussion.ResultsClinical studies have revealed that ICSs are effective in reducing the risk of exacerbations in both children and adults. ICSs also reduce the risk of hospitalization and asthma-related death, improve asthma symptoms, and improve quality of life. In addition, ICSs improve lung function and airway responsiveness and reduce airway inflammation and remodeling. In young children, ICSs improve daytime and nighttime symptoms, improve lung function, reduce the risk of exacerbations, and reduce the need for rescue medications. To date, evidence is conflicting about whether intermittent ICS treatment is as effective as daily ICS treatment. The possibility of lower efficacy of intermittent therapy needs to be weighed against a reduced risk of slowed growth in children.ConclusionICSs effectively reduce the risk of exacerbations, hospitalizations, and asthma-related death and improve asthma symptoms, quality of life, lung function, and airway responsiveness. ICSs also reduce airway inflammation and remodeling. Intermittent therapy may not be as effective as daily therapy, and clinicians should weigh reduced efficacy against reduced risk of adverse effects, particularly slowed growth in children.



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Inhaled corticosteroids

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Warner W. Carr, Stanley J. Szefler
BackgroundInhaled corticosteroids (ICSs) effectively deliver corticosteroids to target sites in the lungs and reduce systemic effects compared with oral corticosteroids, but long-term systemic exposure from inhaled corticosteroids remains a concern.ObjectiveTo discuss ICS systemic effects on the eye and the hypothalamic-pituitary-adrenal (HPA) axis.MethodsRelevant publications were used to augment discussion.ResultsThe most common adverse effects of exogenous corticosteroids on the eye are secondary open-angle glaucoma and posterior subcapsular cataracts. Study findings conflict about whether ICS use is associated with increased risk of glaucoma or elevated intraocular pressure, but studies might not have addressed the question in the right population. Increased risk of glaucoma may be limited to a few susceptible individuals, such as individuals with a family history of glaucoma. Large population-based studies reveal that high daily doses or high lifetime exposure of ICSs is associated with a higher risk of posterior subcapsular cataracts. More research is needed to determine the risk from low to moderate doses during long periods. For the HPA axis, there are several measures for detecting systemic effects. Short-term measures are more sensitive for detecting the systemic effects of ICSs but have less predictive value in identifying clinically important adverse effects. Several studies have found that ICSs have a dose-dependent effects on cortisol suppression that can be used to estimate equivalent dosages among ICSs.ConclusionBecause of systemic effects on the HPA axis, high doses of ICS should be avoided where possible. Adult patients undergoing high-dose or long-term ICS therapy should be monitored for cataracts.



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Inhaled corticosteroids

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): David P. Skoner
BackgroundBoth slowed growth in children and reduced bone mineral density (BMD) are systemic effects of corticosteroids, and there is concern about the degree to which these systemic effects affect growth and BMD.ObjectiveTo engage in a data-driven discussion of the effects of inhaled corticosteroids (ICSs) on growth in children and BMD.MethodsArticles were selected based on their relevance to this review.ResultsStudies of ICSs in children in which growth was a secondary outcome have revealed slowed growth associated with low doses of budesonide, fluticasone propionate, and beclomethasone dipropionate. In the study of budesonide, the effect was permanent, and in the study of fluticasone propionate, the effect was long-lasting, but it is unclear whether the effect was permanent. However, the results of studies in which growth was the primary outcome were mixed. Slowed growth was detected in a study of beclomethasone dipropionate; however, slowed growth was not detected in a study of ciclesonide or flunisolide. A decrease in BMD acquisition in children was associated with high doses but not low to medium doses of ICSs. In adults, there was a dose-related effect of ICSs on BMD. Both higher daily dose and larger cumulative dose were associated with increased bone density loss.ConclusionBecause of the systemic effects on growth and bone health, children should be monitored for growth using stadiometry every 3 to 6 months and BMD should be monitored yearly in patients being treated with high doses of ICSs.



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IL-17RB+ granulocytes are associated with airflow obstruction in asthma

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Lin Li, Nicholas W. Lukacs, Matthew A. Schaller, Bryan Petersen, Alan P. Baptist
BackgroundInterleukin (IL)-25 (IL-17E) is a proinflammatory cytokine that plays an important role in the T-helper type 2 cell pathway. The effects of IL-25 are mediated by its specific receptor, IL-17RB. Previous studies have defined an IL-17RB⁺ granulocyte population known as type 2 myeloid (T2M) cells that express T-helper type 2 cell cytokines. The correlation of IL-17RB⁺ granulocytes, T2M cells, and asthma parameters is unknown.ObjectiveTo investigate the relation of IL-17RB⁺ granulocytes (and its subset, T2M cells) in patients with asthma with clinical parameters including spirometric values and the Asthma Control Test (ACT).MethodsPeripheral blood from subjects with asthma and healthy controls was collected and analyzed by flow cytometry. Granulocytes were gated for IL-17RB⁺, T2M (CD11b⁺CD16⁺CD177⁺IL-17RB⁺), and eosinophil (CD16⁻) populations. Spirometry testing was performed on subjects with asthma. ACT scores and medical histories were collected by questionnaire and chart review. Correlations of IL-17RB⁺ cells and T2M cells with spirometry and ACT score were analyzed.ResultsPercentages of IL-17RB⁺ granulocytes and T2M cells were larger in subjects with asthma than in controls. Furthermore, percentages of the 2 cell populations were negatively correlated with degree of airway obstruction as measured by the ratio of percentage-predicted forced expiratory volume in 1 second to force vital capacity (r = −0.17, P = .043 for IL-17RB⁺ granulocytes; r = −0.32, P = .03 for T2M cells). There was no correlation with ACT score. The percentage of eosinophils was increased in subjects with asthma. However, IL-17RB⁺ eosinophil percentages were similar between subjects with asthma and controls and did not correlate with any clinical parameter.ConclusionIL-17RB⁺ granulocytes and T2M cells from peripheral blood were increased in subjects with asthma, and the 2 cell types correlated with degree of airflow obstruction.



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Safety of intranasal corticosteroids

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Greg W. Bensch
BackgroundConcurrent use of intranasal corticosteroids (INCSs) and inhaled corticosteroids (ICSs) is indicated for patients who are comorbid for asthma and allergic rhinitis. Clinicians need to know the data regarding INCS safety for their patients with asthma.ObjectiveTo discuss INCS safety data for the use of INCSs in patients with asthma and allergic rhinitis.MethodsINCS safety studies were selected for their relevance to the discussion.ResultsTo date, most studies regarding INCS safety are performed in patients with allergic rhinitis. These studies reveal no evidence of increased risk of nasal atrophy, and only isolated cases of septal perforation have been reported. Evidence of hypothalamic-pituitary-adrenal axis suppression is inconsistent and not clinically significant. Early growth studies indicated that beclomethasone dipropionate but not other INCSs have systemic effects on growth; however, newer, larger, and better designed studies are detecting small but significant growth effects in other INCSs. INCSs do not increase the risk of cataracts or glaucoma, although there are anecdotal data on transient elevated intraocular pressure. Data on concurrent use of INCSs and ICSs are limited, but these limited data reveal no evidence of systemic effects on the hypothalamic-pituitary-adrenal axis.ConclusionMore studies of concurrent therapy are needed because concurrent use of ICSs and INCSs is common in practice. Clinicians might want to consider monitoring whether there are risk factors, such as a family history of glaucoma.



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Long-term effects of a house dust mite sublingual immunotherapy tablet in an environmental exposure chamber trial

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Petra Zieglmayer, Hendrik Nolte, Harold S. Nelson, David I. Bernstein, Amarjot Kaur, Henrik Jacobi, Patrick Lemell, René Schmutz, René Zieglmayer, Friedrich Horak
BackgroundTreatment with SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is effective for HDM respiratory allergic disease, but data on long-term effects are lacking.ObjectivePost hoc analyses were conducted to determine the long-term effect of SQ HDM SLIT-tablet on nasal, ocular, and cough symptoms 1 year after discontinuation of treatment.MethodsStudy participants underwent environmental exposure chamber (EEC) challenges at baseline and week 24 in a randomized, placebo-controlled, double-blind trial (NCT01644617) during which participants received daily 12 SQ-HDM, 6 SQ-HDM, or placebo for 24 weeks. Asthma had to be stable, well controlled, and nonsevere. The mean total asthma symptom score (TASS; sum of 3 symptoms: cough, wheeze, and dyspnea) during baseline and week 24 EEC challenge was analyzed in all participants who completed the trial (n = 106). Approximately 1 year after trial completion, another EEC challenge was conducted in a subset of participants (n = 51). Total nasal symptom score (sum of 4 symptoms), total ocular symptom score (sum of 2 symptoms), and cough were assessed.ResultsCompared with baseline and end-of-treatment values, sustained improvement of all symptoms assessed at the 1-year follow-up EEC challenge was evident in participants treated with 12 SQ-HDM. Results with 6 SQ-HDM were less notable. After 24 weeks of 12 SQ-HDM, TASS during EEC challenge was improved 65% vs baseline; at 1-year follow-up, cough was improved 57% vs baseline.ConclusionPersistent improvement of nasal and ocular symptoms was observed up to 1 year after completing 24 weeks of 12 SQ-HDM treatment. Beneficial effects on cough were also observed.Trial Registrationclinicaltrials.gov Identifier NCT01644617.



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Inhalation devices, delivery systems, and patient technique

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Harold S. Nelson
BackgroundIn real-life clinical settings, physicians often consider the properties of various inhaled corticosteroids (ICSs), but typically little consideration is given to the properties of different inhalers and formulations.ObjectiveTo discuss the effects of inhalation devices and user technique on efficacy, safety, and adherence with the aim of improving asthma management.MethodsRelevant publications were selected to augment discussion.ResultsThere are many types of devices available, each with advantages, disadvantages, ease of use, and rate of misuse. Aerosol particle size influences the deposition pattern of a drug in the lungs, and the optimal particle size range is 1 to 5 μm. Retrospective reviews suggest that smaller particles (1–2 μm) could provide improved asthma control, but randomized, prospective studies are needed. Multiple studies have demonstrated high misuse rates in patients for pressurized metered-dose inhalers and dry powder inhalers. Because of this, repeated education should include physical demonstrations of using the device, checking the patient's technique, correcting the technique, and rechecking the technique. This also means that dedicated, trained staff and placebo devices should be available for instructing patients. Furthermore, the device should be selected to be cost effective and to fit the patient's preference and ability to use it correctly to enhance compliance. Asthma management guidelines and algorithms are available to guide the clinician.ConclusionThe choice of inhaler device should depend on cost effectiveness and the patient's preference and ability to use it correctly. Patient inhaler technique should be checked and, if necessary, corrected and rechecked, with retraining if needed, at every opportunity.



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Patient adherence and effective communication

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Don A. Bukstein
BackgroundPoor adherence to inhaled corticosteroid medication is a critical problem for asthma because it contributes to morbidity and mortality through poor asthma control, frequent asthma exacerbations, acute care visits, and oral corticosteroid use.ObjectiveTo discuss evidence-based, time-efficient strategies that can be adopted by most practitioners to try to increase patient adherence.MethodsAsthma management guidelines and other key publications are used to enhance discussion.ResultsEstablishing patient-centered, collaborative care that permits effective patient-practitioner communication can improve adherence, thus leading to improved asthma outcomes. One critical strategy is shared decision making, in which the patient and the practitioner share relevant information, discuss risks vs benefits of various treatment options, express treatment preferences, deliberate the options, and agree on treatment. Asthma self-management education, which emphasizes self-efficacy, is also essential. The education necessary to provide those skills depends in part on consideration of the patient's health literacy. Practitioners also have at their disposal a variety of tips and techniques to improve communication and gather information not only at the patient-practitioner level but also at the practitioner-practitioner level, such as within a group practice or within a health care system.ConclusionTo improve patient adherence, clinicians need to consider a variety of factors and implement strategies that directly target underlying issues. Strategies may include customizing and simplifying learning and intervention regimens, identifying barriers to adherence and addressing them, ensuring patient support structures are in place, and improving self-efficacy and health literacy.



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Management of primary antibody deficiency syndromes

Publication date: December 2016
Source:Annals of Allergy, Asthma & Immunology, Volume 117, Issue 6
Author(s): Vincent R. Bonagura, Blanka Kaplan, Artemio M. Jongco




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Reconstruction of through-and-through oromandibular defects with combined fibula flap and anterolateral thigh flap

Publication date: Available online 13 December 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Zhao-Jian Gong, Shuai Zhang, Sheng Zhang, Jiang Liu, Yu-Ming Xu, Han-Jiang Wu
PurposeThe reconstruction of massive through-and-through oromandibular defects is still a challenge because no single adequate candidate for a donor site of vascularized bone and a large amount of soft tissue has yet been found. The aim of this study was to evaluate the feasibility and reconstructive efficacy of the combined fibula flap and anterolateral thigh (ALT) flap in tandem for the reconstruction of such defects.Patients and methodsA retrospective case series was performed of patients who had undergone reconstruction of through-and-through oromandibular defects with combined fibula flap and ALT flap in tandem from January 2012 through December 2014 at the Second Xiangya Hospital. The flap design and the methods for defect reconstruction are described, and the reconstructive efficacy is reported.ResultsOf the 14 patients, 13 were men and 1 was a woman, with an average age of 49.36 years. Postoperatively, all flaps survived completely, without vascular compromise or major wound complications. All of the donor sites were closed directly, leaving only linear scars and no thigh or leg motor dysfunctions. All patients were followed for approximately 12–48 months, and the appearance and oral functions were acceptably recovered in about 90% of the patients.ConclusionsBecause of the convenient flap design, satisfactory functional and esthetic results, and lower complication rates at the donor and recipient sites, the use of a combined fibula flap and ALT flap in tandem is a good choice for the reconstruction of complex through-and-through oromandibular defects.



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Only severe malocclusion correlates with mastication deficiency

Publication date: March 2017
Source:Archives of Oral Biology, Volume 75
Author(s): Pierre Bourdiol, Delphine Soulier-Peigue, Pauline Lachaze, Emmanuel Nicolas, Alain Woda, Martine Hennequin
ObjectivesThe relation between level of dentofacial deformity and extent of masticatory deficiency was studied.DesignThree groups of human young adults were formed: (i) subjects needing orthodontics plus orthognathic surgery (SevDFD, n=18), (ii) subjects needing orthodontic treatment only (ModDFD, n=12), and (iii) subjects needing no treatment (NoDFD, n=12). For mastication tests, carrot boluses were collected at the deglutition time. Bolus particle size range was expressed as d50 value, which was compared with the Masticatory Normative Indicator (MNI). Index of treatment need (IOTN), global oral health assessment index (GOHAI) and chewing kinematic characteristics were also recorded. We used a general linear model univariate procedure followed by a Student-Newman-Keuls test.ResultsAll the SevDFD subjects showed impaired mastication with MNI above the normal limit (d50 mean=7.23mm). All the ModDFD subjects but one were below this limit (d50 mean=2.54mm), and so could adapt to a low level of masticatory impairment as also indicated by kinematics. IOTN indicated a treatment need for ModDFD (3.7±0.5) and SevDFD (4.3±0.6) groups, while GOHAI values were unsatisfactory only for SevDFD (42.6±9.2 vs. 55.3±1.9).ConclusionsOur findings emphasize the need for an objective evaluation of masticatory function to discern truly deficient mastication from mild impairment allowing satisfactory adaptation of the function. However, malocclusions are known to worsen with time justifying thus their corrections as early as possible.



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