Δευτέρα, 5 Ιουνίου 2017

Managing the marginally raised aPTT—looking beyond the absolute number



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Current evidence for the use of sugammadex in children



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In this issue: July 2017



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Caudal analgesia, hypospadias, and urethrocutaneous fistula: Does association mean causality?



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Reducing risk in pediatric anesthesia: What are the implications from the APRICOT study?



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Issue Information



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Taking a sympathetic approach to posttraumatic stress disorder



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Development and validation of a claims-based measure as an indicator for disease status in patients with multiple sclerosis treated with disease-modifying drugs

Administrative healthcare claims data provide a mechanism for assessing and monitoring multiple sclerosis (MS) disease status across large, clinically representative “real-world” populations. The estimation of...

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Association between total-Tau and brain atrophy one year after first-ever stroke

Although the most serious consequence of neuronal ischemia is acute neuronal death, mounting evidence suggests similarities between stroke and neurodegenerative disease. Brain atrophy visualized on structural ...

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Endoscopic endonasal management of esthesioneuroblastoma: A retrospective multicenter study

The aim of the present study was to illustrate the safety and utility of the endoscopic endonasal approach (EEA) for the treatment of esthesioneuroblastomas (ENB).

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Functional and phenotypic analysis of basophils allows determining distinct subtypes in patients with chronic urticaria

Abstract

Background

Chronic urticaria (CU) is a frequent skin disease characterized by relapsing appearance of pruritic hives. While clinical symptoms are due to the release of histamine by cutaneous mast cells, the underlying pathophysiology is still unknown. However, previous studies indicate that basophils might be of relevance. Besides, the occurrence of autoantibodies against IgE or its receptor, FcεRI, and the therapeutic efficacy of anti-IgE antibodies imply that IgE-mediated mechanisms also play an important role in CU.

Methods

Reactivity of CU patients’ peripheral blood basophils (n=60) to specific anti-FcεRI and IgE-independent fMLP stimulation was determined by basophil activation test in comparison to patients suffering from IgE-mediated allergic rhinitis (n=10) and healthy controls (n=10). In addition, immunoglobulin receptor (FcεRI, FcγRII) expression and surface bound antibodies (IgE, IgG) were quantified on basophils. Furthermore, the autoreactive capacity of CU sera was evaluated and urticaria-related symptoms were assessed by both UCT and CU-Q2oL.

Results

Stimulating CU patients’ basophils via FcεRI, we identified three distinct immunological phenotypes. One subgroup of patients' basophils reacted to FcεRI stimulation, whereas the others had anti-FcεRI non-reactive basophils. Among the latter a subgroup with pronounced basopenia was identified. Of note, this group was characterized by augmented serum-induced basophil activation, increased levels of autoantibodies against thyroid peroxidase and also exhibited the strongest disease impact on their quality of life.

Conclusions

CU patients can be categorized into three immunological subgroups based on their basophil reactivity and frequency. These phenotypes are associated with different clinical characteristics, pointing to basophils as important players in CU pathophysiology.

This article is protected by copyright. All rights reserved.



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Patterns of antiepileptic drug prescription in Sweden: A register-based approach

Objectives

To determine drug utilization pathways from the incident healthcare visit due to epilepsy and three years onward.

Material and methods

Anti-epileptic drug utilization was calculated using individual information on inpatient- and outpatient care utilization and drug sales. Throughout, we used national register information pertaining to pharmaceutical sales linked to diagnosis-related healthcare utilization. Information on pharmaceutical sales was collected for the 2007-2013 period.

Results

For the entire studied period, a majority of new patients with epilepsy were initiated on anti-epileptic drug treatment with a monotherapy (98%); most of these patients remained on that first treatment (64%). The three most frequently prescribed drugs accounted for 72% of the initiated AED treatments. Patients with epilepsy (ICD-10: G40/41) were most commonly prescribed carbamazepine, lamotrigine and valproate. The most common second-line monotherapy was levetiracetam. About 12% of new patients with epilepsy who were initiated on AED treatment during the period eventually switched to an add-on therapy. The proportion of patients who were initiated on treatment with carbamazepine or valproate decreased, and the proportion of patients who remained on their initial monotherapy increased between 2007 and 2013.

Conclusions

A limited number of anti-epileptic drugs accounted for the treatment of a majority of new patients with epilepsy (carbamazepine, lamotrigine and valproate accounted for more than 70%). Add-on therapies showed the same pattern, as the most frequently prescribed add-on regimens were the same ones that accounted for most of the monotherapies. There was a tendency towards fewer patients being initiated on AED treatment with either carbamazepine or valproate.



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Rationale and protocol of MetNET-2 trial: Lanreotide Autogel plus metformin in advanced gastrointestinal or lung neuroendocrine tumors

Future Oncology Ahead of Print.


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Cover 2 - Masthead (p/u from previous issue)



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Information for authors (p/u from previous issue)



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Editorial Board (p/u from previous issue)



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Future and recent issues (p/u from previous issue and update)



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Contents



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Drug-induced sedation endoscopy (DISE) classification systems: a systematic review and meta-analysis

Abstract

Purpose

Drug-induced sedation endoscopy (DISE) classification systems have been used to assess anatomical findings on upper airway obstruction, and decide and plan surgical treatments and act as a predictor for surgical treatment outcome for obstructive sleep apnoea management. The first objective is to identify if there is a universally accepted DISE grading and classification system for analysing DISE findings. The second objective is to identify if there is one DISE grading and classification treatment planning framework for deciding appropriate surgical treatment for obstructive sleep apnoea (OSA). The third objective is to identify if there is one DISE grading and classification treatment outcome framework for determining the likelihood of success for a given OSA surgical intervention.

Methods

A systematic review was performed to identify new and significantly modified DISE classification systems: concept, advantages and disadvantages.

Results

Fourteen studies proposing a new DISE classification system and three studies proposing a significantly modified DISE classification were identified. None of the studies were based on randomised control trials.

Conclusion

DISE is an objective method for visualising upper airway obstruction. The classification and assessment of clinical findings based on DISE is highly subjective due to the increasing number of DISE classification systems. Hence, this creates a growing divergence in surgical treatment planning and treatment outcome. Further research on a universally accepted objective DISE assessment is critically needed.



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The effect of sleep duration on exhaled nitric oxide levels in U.S. adults

Abstract

Purpose

Poor sleep quality and duration are associated with systemic endothelial dysfunction. However, an association between poor sleep and pulmonary endothelial dysfunction has not been elucidated. We sought to determine if there is a relationship between sleep duration and fractional exhaled nitric oxide (FeNO) concentrations as a surrogate for pulmonary endothelial function.

Methods

We used three National Health and Nutrition Examination Survey (NHANES) cycles (2007–2012). Linear regression models were built with and without adjustment for age, sex, race, BMI, asthma/bronchitis, CRP, smoking, folate, renal function, respiratory infections, and steroid use. To examine a non-linear relationship, we introduced a spline, with single knot at mean sleep duration (7 h).

Results

Of 13,173 participants (50.8% male, 44.2% Caucasian), 78% slept 6–8 hours (h). FeNO was significantly higher in the group sleeping 6–8 h (17.3 ± 14.9 ppb) than in the other two groups (16.0 ± 13.0 ppb, 15.9 ± 12.7 ppb for <6 and >8 h respectively; P < 0.001). In unadjusted linear regression, FeNO increased by 1.1 ppb for each hour increase in sleep up to 7 h (P < 0.001). Increased sleep duration beyond 7 h saw a 0.96 ppb decrease in FeNO (P < 0.001). After adjustment for confounders, FeNO increased by 1.09 ppb for each hour of sleep up to 7 h (P = 0.001) and decreased by 0.71 ppb for each hour after (P = 0.02).

Conclusion

Sleeping less or more than 7 h is associated with pulmonary endothelial dysfunction as measured by FeNO. Further study is needed to evaluate mechanism(s) of this association and validity of FeNO as a marker of endothelial function.



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Severity of desaturation events differs between hypopnea and obstructive apnea events and is modulated by their duration in obstructive sleep apnea

Abstract

Purpose

Frequency of apnea and hypopnea events is used to estimate the severity of obstructive sleep apnea (OSA). However, comprehensive information on whether apneas and hypopneas cause an equal biological effect is not available. The purpose of the present work was to evaluate the effect of the breathing cessation event type (i.e., obstructive apnea or hypopnea) and duration on the severity of related SpO2 desaturation events.

Methods

Type 1 polysomnographies of 395 patients (220 males and 175 females) examined for suspected OSA were analyzed. Desaturation severity related to hypopnea and obstructive apnea events were compared and comparison was controlled for gender, sleep stage, sleeping position, age, and body mass index. Hypopneas and obstructive apneas were further divided into eight different durational categories and related desaturation event characteristics were compared between the categories.

Results

SpO2 desaturation events caused by obstructive apneas were statistically significantly (p ≤ 0.004) longer, greater in area, and deeper compared to the SpO2 desaturations caused by hypopneas. The increase in the duration of hypopnea and obstructive apnea events led to increase in the duration and area of related SpO2 desaturations. The increase in the obstructive apnea event duration also led to increase in the depth of related desaturation event.

Conclusions

Obstructive apneas led to more severe SpO2 desaturation compared to hypopneas. Increased event duration led to increase in the severity of the related SpO2 desaturation. In addition to considering event duration, obstructive apneas should have more weight than hypopneas when estimating severity of OSA and associated long-term cardiovascular risk.



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Combined interventional sialendoscopy and intraductal steroid therapy for recurrent sialadenitis in Sjögren's syndrome. Results of a pilot monocentric trial

Abstract

Objectives

To evaluate the effectiveness of interventional sialendoscopy alone or combined with outpatient intraductal steroid irrigations in patients with sialoadenitis due to Sjögren's syndrome (SS).

Design

A pilot therapeutic study.

Setting

ENT Clinics, Universities of Milan and Pavia.

Study Population

We included 22 patients with SS of whom 12 underwent interventional sialendoscopy followed by intraductal steroid irrigations (group A), and 10 interventional sialendoscopy alone (group B).

Outcomes measures

The following outcome measures were considered and recorded before and after the therapeutic intervention: (i) number of episodes of glandular swelling, (ii) cumulative prevalence of patients with glandular swelling assessed by the specific domain the EULAR SS Disease Activity Index (ESSDAI); (iii) severity of pain by means of a 0-10 pain visual analogue scale (VAS), (iv) severity of xerostomia and other disease symptoms assessed by the EULAR SS Patient Reported Index (ESSPRI) and the Xerostomia Inventory questionnaire.

Results

The post-operative reduction in the mean number of episodes of glandular swelling was 87% (95% CI: 77-93) and 75% (95% CI: 47-88%) in the group A and B, respectively. The percentage of patients with glandular swelling, decreased from 41.7% to 0.0% in the group A and from 30.0% to 0.0% in the group B, respectively. Most of the patients experienced a subjective clinical improvement documented by the statistically significant reductions in the post-operative mean pain VAS group A p<0.001; group B p=0.004), Xerostomia Inventory p<0.001 and p=0.003), and ESSPRI scores (p<0.001 and p=0.008). Interventional sialendoscopy followed by outpatient intraductal steroid irrigations was more effective than interventional sialendoscopy alone, when pain VAS, Xerostomia Inventory, and ESSPRI scores before and after treatment, were analysed together using the multivariate Hotelling T2 test (p=0.0173).

Conclusions

This pilot study confirms that interventional sialendoscopy with steroid duct irrigation significantly reduces the number of painful episodes of sialadenitis, and improves the subjective sensation of oral dryness and other disease symptoms in patients with SS. The study results also suggest that the improvement is greater when interventional sialendoscopy is combined with a cycle of outpatient steroid ductal irrigations. Larger controlled randomised studies are certainly needed to confirm these preliminary data.

This article is protected by copyright. All rights reserved.



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Rationale and protocol of MetNET-2 trial: Lanreotide Autogel plus metformin in advanced gastrointestinal or lung neuroendocrine tumors

Future Oncology Ahead of Print.


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Salvage Strategies for Management of Testicular Tumors

Abstract

Testicular germ cell tumors (GCTs) comprise 2% of all human male malignancies and are the most common solid tumors in men between ages 15 and 35 years. Risk of contralateral testicular GCT is between 1 and 5%. Partial orchidectomy (PO) was originally described in 1984 by Richie. The evolving indications include metachronous tumors and tumor in solitary testicles. Also, small non-palpable lesions detected only by ultrasonography (USG) in asymptomatic patients is another indication. Salvagability is only chosen for tumors less than 2 cm in size. The key feature of PO is an inguinal approach with early vascular control using a rubber tourniquet before testicular mobilization into the field to avoid systemic tumor seeding. After, mass excision with a margin mandatory frozen section is done to assess adequacy of resection. Intra-op USG may be beneficial in small non-palpable lesions. Post op tumor markers are assessed and patients are taught self-examination of testis. Recent series shows that PO is safe and gives adequate oncological control. Carcinoma in situ (CIS) in the affected testis at PO or after testicular sparing surgery remains a challenge. At most centers, 20 Gy is recommended when adjuvant local radiation treatment is chosen to treat CIS. But this dose may hamper Androgen production. Radical orchiectomy remains the gold standard and should be discussed as part of informed consent. It is mandatory to highlight the risks of local recurrence and CIS, and treatment (observation, radiation, or completion orchiectomy) as well as the need for androgen supplementation and fertility risks before choosing testicular salvage procedures.



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Current Concepts in the Management of Non-Muscle Invasive Bladder Cancer

Abstract

Non-muscle invasive bladder cancer, despite advances in the field of medicine, remains an enigmatic problem with no tangible solution of one-time treatment as it needs an invasive surveillance in the form of cystoscopy. There are issues related to diagnosis, ideal resection technique, BCG treatment, and follow-up. In this article, we review the recent developments in the diagnosis of the disease and describe optimal management strategies.



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Closure of the vertebral canal in human embryos and fetuses

Abstract

The vertebral column is the paradigm of the metameric architecture of the vertebrate body. Because the number of somites is a convenient parameter to stage early human embryos, we explored whether the closure of the vertebral canal could be used similarly for staging embryos between 7 and 10 weeks of development. Human embryos (5–10 weeks of development) were visualized using Amira 3D® reconstruction and Cinema 4D® remodelling software. Vertebral bodies were identifiable as loose mesenchymal structures between the dense mesenchymal intervertebral discs up to 6 weeks and then differentiated into cartilaginous structures in the 7th week. In this week, the dense mesenchymal neural processes also differentiated into cartilaginous structures. Transverse processes became identifiable at 6 weeks. The growth rate of all vertebral bodies was exponential and similar between 6 and 10 weeks, whereas the intervertebral discs hardly increased in size between 6 and 8 weeks and then followed vertebral growth between 8 and 10 weeks. The neural processes extended dorsolaterally (6th week), dorsally (7th week) and finally dorsomedially (8th and 9th weeks) to fuse at the midthoracic level at 9 weeks. From there, fusion extended cranially and caudally in the 10th week. Closure of the foramen magnum required the development of the supraoccipital bone as a craniomedial extension of the exoccipitals (neural processes of occipital vertebra 4), whereas a growth burst of sacral vertebra 1 delayed closure until 15 weeks. Both the cranial- and caudal-most vertebral bodies fused to form the basioccipital (occipital vertebrae 1–4) and sacrum (sacral vertebrae 1–5). In the sacrum, fusion of its so-called alar processes preceded that of the bodies by at least 6 weeks. In conclusion, the highly ordered and substantial changes in shape of the vertebral bodies leading to the formation of the vertebral canal make the development of the spine an excellent, continuous staging system for the (human) embryo between 6 and 10 weeks of development.



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The deep fascia and retinacula of the equine forelimb – structure and innervation

Abstract

Recent advances in human fascia research have shed new light on the role of the fascial network in movement perception and coordination, transmission of muscle force, and integrative function in body biomechanics. Evolutionary adaptations of equine musculoskeletal apparatus that assure effective terrestrial locomotion are employed in equestrianism, resulting in the wide variety of movements in performing horses, from sophisticated dressage to jumping and high-speed racing. The high importance of horse motion efficiency in the present-day equine industry indicates the significance of scientific knowledge of the structure and physiology of equine fasciae. In this study, we investigated the structure and innervation of the deep fascia of the equine forelimb by means of anatomical dissection, histology and immunohistochemistry. Macroscopically, the deep fascia appears as a dense, glossy and whitish lamina of connective tissue continuous with its fibrous reinforcements represented by extensor and flexor retinacula. According to the results of our histological examination, the general structure of the equine forelimb fascia corresponds to the characteristics of the human deep fasciae of the limbs. Although we did find specific features in all sample types, the general composition of all examined fascial tissues follows roughly the same scheme. It is composed of dense, closely packed collagen fibers organized in layers of thick fibrous bundles with sparse elastic fibers. This compact tissue is covered from both internal and external sides by loosely woven laminae of areolar connective tissue where elastic fibers are mixed with collagen. Numerous blood vessels running within the loose connective tissue contribute to the formation of regular vascular network throughout the compact layer of the deep fascia and retinacula. We found nerve fibers of different calibers in all samples analyzed. The fibers are numerous in the areolar connective tissue and near the blood vessels but scarce in the compact layers of collagen. We did not observe any Ruffini, Pacini or Golgi-Mazzoni corpuscles. In conclusion, the multilayered composition of compact bundles of collagen, sparse elastic fibers in the deep fascia and continuous transition into retinacula probably facilitate resistance to gravitational forces and volume changes during muscle contraction as well as transmission of muscle force during movement. However, further research focused on innervation is needed to clarify whether the deep fascia of the equine forelimb plays a role in proprioception and movement coordination.



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The teeth of non-mammalian vertebrates By Berkovitz Barry K. B., Shellis Peter Academic Press, 2016. ISBN-10: 0128028505



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Inside Front Cover - Editorial Board Page/Cover image legend if applicable

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Publication date: September 2017
Source:Journal of Environmental Radioactivity, Volumes 175–176





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Whole-Genome Sequence and Variant Analysis of W303, a Widely-Used Strain of Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae has emerged as a superior model organism. Selection of distinct laboratory strains of S. cerevisiae with unique phenotypic properties, such as superior mating or sporulation efficiencies, has facilitated advancements in research. W303 is one such laboratory strain that is closely related to the first completely sequenced yeast strain, S288C. In this work, we provide a high-quality, annotated genome sequence for W303 for utilization in comparative analyses and genome-wide studies. Approximately 9,500 variations exist between S288C and W303, affecting the protein sequences of about 700 genes. A listing of the polymorphisms and divergent genes is provided for researchers interested in identifying the genetic basis for phenotypic differences between W303 and S288C. Several divergent functional gene families were identified, including flocculation and sporulation genes, likely representing selection for desirable laboratory phenotypes. Interestingly, remnants of ancestor wine strains were found on several chromosomes. Finally, as a test of the utility of the high-quality reference genome, variant mapping revealed more accurate identification of accumulated mutations in passaged mismatch repair defective strains.



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Whole Genome Sequencing of the Braconid Parasitoid Wasp Fopius arisanus, an Important Biocontrol Agent of Pest Tepritid Fruit Flies

The braconid wasp Fopius arisanus (Sonan) is an important biological control agent of tropical and subtropical pest fruit flies including two important global pests, the Mediterranean fruit fly (Ceratitis capitata), and the oriental fruit fly (Bactrocera dorsalis). The goal of this study was to develop foundational genomic resources for this species to provide tools that can be used to answer questions exploring the multitrophic interactions between the host and parasitoid in this important research system. Here we present the a whole genome assembly of F. arisanus, derived from pooled haploid offspring from a single unmated female. The genome is approximately 154 Mb in size, with a N50 contig and scaffold size of 51,867 bp and 0.98 Mb, respectively. Utilizing existing RNA-Seq data for this species, as well as publicly available peptide sequences from related hymenopterans, a high quality gene annotation set, which includes 10,991 protein coding genes, was generated. Prior to this assembly submission, no RefSeq proteins were present for this species. Parasitic wasps play an important role in a diverse ecosystem as well as a role in biological control of agricultural pests. This whole genome assembly and annotation data represents the first genome-scale assembly for this species or any closely related Opiine, and are publicly available in the National Center for Biotechnology Information Genome and RefSeq databases, providing a much needed genomic resource for this hymenopteran group.



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Predictive factors of depressive symptoms of elderly patients with cancer: A critical comment



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Issue Information



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Extended endoscopic endonasal approach for pituitary adenoma: a single-center experience of 171 patients

Abstract

Background

Pituitary adenoma (PA) is a common intracranial tumor and surgical treatment is considered to be the best treatment for most patients. The extended endoscopic endonasal approach (EEEA) has been used to treat increasing numbers of patients with PA in recent years. We conducted this study to evaluate the safety and efficacy of this approach for PA resection.

Methods

We performed a retrospective analysis of all patients who underwent an EEEA to remove PA by a binostril, four-handed technique between October 2013 and April 2016 in our department. The medical information of the patients including gender, age, tumor size, hormone level, clinical outcome, and complications were collected and analyzed.

Results

From a total of 593 pituitary adenoma surgeries, 171 patients (101 male and 70 female, mean age 47.4 ± 12.8 years) underwent EEEA, including 96 with functional adenomas (56.14%) and 75 with nonfunctional adenomas (43.86%). The most common symptoms were headache and vision change. Gross total resection was achieved in 126 patients (73.68%). Common complications were hyposmia or anosmia, diabetes insipidus, hypopituitarism, postoperative cerebrospinal fluid leak, cerebral hemorrhage, and epistaxis. The mean duration of follow-up was 14.6 months (range: 6–31 months).

Conclusions

The application of EEEA for PA resection by a binostril, four-handed technique provided great surgical freedom with minimal invasion, and resulted in few complications. EEEA is a secure and effective surgical method that could be used for the majority of PAs.



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Drug-induced sedation endoscopy (DISE) classification systems: a systematic review and meta-analysis

Abstract

Purpose

Drug-induced sedation endoscopy (DISE) classification systems have been used to assess anatomical findings on upper airway obstruction, and decide and plan surgical treatments and act as a predictor for surgical treatment outcome for obstructive sleep apnoea management. The first objective is to identify if there is a universally accepted DISE grading and classification system for analysing DISE findings. The second objective is to identify if there is one DISE grading and classification treatment planning framework for deciding appropriate surgical treatment for obstructive sleep apnoea (OSA). The third objective is to identify if there is one DISE grading and classification treatment outcome framework for determining the likelihood of success for a given OSA surgical intervention.

Methods

A systematic review was performed to identify new and significantly modified DISE classification systems: concept, advantages and disadvantages.

Results

Fourteen studies proposing a new DISE classification system and three studies proposing a significantly modified DISE classification were identified. None of the studies were based on randomised control trials.

Conclusion

DISE is an objective method for visualising upper airway obstruction. The classification and assessment of clinical findings based on DISE is highly subjective due to the increasing number of DISE classification systems. Hence, this creates a growing divergence in surgical treatment planning and treatment outcome. Further research on a universally accepted objective DISE assessment is critically needed.



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The effect of sleep duration on exhaled nitric oxide levels in U.S. adults

Abstract

Purpose

Poor sleep quality and duration are associated with systemic endothelial dysfunction. However, an association between poor sleep and pulmonary endothelial dysfunction has not been elucidated. We sought to determine if there is a relationship between sleep duration and fractional exhaled nitric oxide (FeNO) concentrations as a surrogate for pulmonary endothelial function.

Methods

We used three National Health and Nutrition Examination Survey (NHANES) cycles (2007–2012). Linear regression models were built with and without adjustment for age, sex, race, BMI, asthma/bronchitis, CRP, smoking, folate, renal function, respiratory infections, and steroid use. To examine a non-linear relationship, we introduced a spline, with single knot at mean sleep duration (7 h).

Results

Of 13,173 participants (50.8% male, 44.2% Caucasian), 78% slept 6–8 hours (h). FeNO was significantly higher in the group sleeping 6–8 h (17.3 ± 14.9 ppb) than in the other two groups (16.0 ± 13.0 ppb, 15.9 ± 12.7 ppb for <6 and >8 h respectively; P < 0.001). In unadjusted linear regression, FeNO increased by 1.1 ppb for each hour increase in sleep up to 7 h (P < 0.001). Increased sleep duration beyond 7 h saw a 0.96 ppb decrease in FeNO (P < 0.001). After adjustment for confounders, FeNO increased by 1.09 ppb for each hour of sleep up to 7 h (P = 0.001) and decreased by 0.71 ppb for each hour after (P = 0.02).

Conclusion

Sleeping less or more than 7 h is associated with pulmonary endothelial dysfunction as measured by FeNO. Further study is needed to evaluate mechanism(s) of this association and validity of FeNO as a marker of endothelial function.



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Severity of desaturation events differs between hypopnea and obstructive apnea events and is modulated by their duration in obstructive sleep apnea

Abstract

Purpose

Frequency of apnea and hypopnea events is used to estimate the severity of obstructive sleep apnea (OSA). However, comprehensive information on whether apneas and hypopneas cause an equal biological effect is not available. The purpose of the present work was to evaluate the effect of the breathing cessation event type (i.e., obstructive apnea or hypopnea) and duration on the severity of related SpO2 desaturation events.

Methods

Type 1 polysomnographies of 395 patients (220 males and 175 females) examined for suspected OSA were analyzed. Desaturation severity related to hypopnea and obstructive apnea events were compared and comparison was controlled for gender, sleep stage, sleeping position, age, and body mass index. Hypopneas and obstructive apneas were further divided into eight different durational categories and related desaturation event characteristics were compared between the categories.

Results

SpO2 desaturation events caused by obstructive apneas were statistically significantly (p ≤ 0.004) longer, greater in area, and deeper compared to the SpO2 desaturations caused by hypopneas. The increase in the duration of hypopnea and obstructive apnea events led to increase in the duration and area of related SpO2 desaturations. The increase in the obstructive apnea event duration also led to increase in the depth of related desaturation event.

Conclusions

Obstructive apneas led to more severe SpO2 desaturation compared to hypopneas. Increased event duration led to increase in the severity of the related SpO2 desaturation. In addition to considering event duration, obstructive apneas should have more weight than hypopneas when estimating severity of OSA and associated long-term cardiovascular risk.



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Level of cystatin C in functional thyroid disorders and its relation to GFR

Abstract

Thyroid hormones affect the development and physiology of the kidneys. Hypothyroidism and hyperthyroidism affect glomerular filtration rate (GFR), tubular function, renal blood flow, and structure of the kidney. Cystatin C is a non-glycosylated neuroendocrine protein. It is freely filtered at the glomerulus and completely reabsorbed and catabolized by cells of tubules. Cystatin C levels, affected by the thyroid state, is being increased in hyperthyroidism and decreased in hypothyroidism. The current study was conducted on 66 patients of thyroid disorder and 21 healthy control subjects. Total T3, total T4, and TSH were measured by cobas e 411. Human Cystatin C was measured using ELISA kit based on sandwich enzyme-linked immunosorbent assay. Cystatin C was significantly increased in both total hyperthyroid and clinical hyperthyroid groups as compared to control (p < 0.001). eGFRCys C and eGFRCr-Cys C were significantly decreased in hyperthyroid and clinical hyperthyroid (p < 0.001). Cystatin C was significantly reduced in hypothyroid group and subgroups comparing to control group (p < 0.001, p < 0.001, and p = 0.004, respectively). As regard to eGFRCys C, it was significantly an overestimate clearance in hypothyroid group and subgroups when compared to normal subjects (p < 0.001, p < 0.001, and p = 0.002, respectively). Thyroid dysfunction affects cystatin C level as well as cystatin-based eGFR so it is not suitable in thyroid dysfunction specially in clinical dysfunction.



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TLR-3/9 Agonists Synergize with Anti-ErbB2 mAb—Letter



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Human Subjects Protection and Cancer Surveillance Research: Revised Regulations, Expanded Opportunities

On January 19, 2017, the United States federal government issued revisions to the Common Rule under which scientists who receive federal funding conduct research involving human subjects. The revised Common Rule expressly addresses public health surveillance in relation to scientific research and the protection of human subjects, and its impacts are anticipated to contribute to the efficiency of activities, including cancer registration and surveillance, and research that uses cancer registry data. Cancer Res; 77(12); 1–4. ©2017 AACR.

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FOXM1 in Cancer: Interactions and Vulnerabilities

FOXM1 is a transcription factor of the Forkhead family that is required for cell proliferation of normal cells. However, FOXM1 is repeatedly overexpressed in a variety of human cancers, and it has been implicated in all major hallmarks of cancer delineated by Hanahan and Weinberg. It has been postulated that the oncogenic potential of FOXM1 is determined by its capacity to transactivate target genes that are implicated in different phases of cancer development. However, FOXM1 may also play an oncogenic role by interacting with other proteins, such as β-catenin or SMAD3 to induce oncogenic WNT and TGFβ signaling pathways, respectively. In this review, I will discuss the protein–protein interactions of FOXM1 that are critical for cancer development and may represent novel targets for anticancer drugs. Cancer Res; 77(12); 1–5. ©2017 AACR.

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Nature and Nurture: What Determines Tumor Metabolic Phenotypes?

Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. Cancer Res; 77(12); 1–4. ©2017 AACR.

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Modeling the C9ORF72 repeat expansion mutation using human induced pluripotent stem cells

Abstract

C9ORF72 repeat expansion is the most frequent causal genetic mutation giving rise to amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). The relatively recent discovery of the C9ORF72 repeat expansion in 2011 and the complexity of the mutation have meant that animal models that successfully recapitulate human C9ORF72 repeat expansion-mediated disease are only now emerging. Concurrent advances in the use of patient-derived induced pluripotent stem cells (iPSCs) to model aspects of neurological disease offers an additional approach for the study of C9ORF72 mutation. This review focuses on the opportunities of human C9ORF72 iPSC platforms to model pathological aspects of disease and how findings compare with other existing models of disease and post mortem data.



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A 53-Year-Old Woman with a Subfascial Mass of the Back that Lasted for Years



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Modeling tau pathology in human stem cell derived neurons

Abstract

Tau pathology is a defining characteristic of multiple neurodegenerative disorders including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD) with tau pathology. There is strong evidence from genetics and experimental models to support a central role for tau dysfunction in neuronal death, suggesting tau is a promising therapeutic target for AD and FTD. However, the development of tau pathology can precede symptom onset by several years, so understanding the earliest molecular events in tauopathy is a priority area of research. Induced pluripotent stem cells (iPSC) derived from patients with genetic causes of tauopathy provide an opportunity to derive limitless numbers of human neurons with physiologically appropriate expression levels of mutated genes for in vitro studies into disease mechanisms. This review discusses the progress made to date using this approach and highlights some of the challenges and unanswered questions this technology has the potential to address.



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Modeling Parkinson's disease with induced pluripotent stem cells harboring α-synuclein mutations

Abstract

Parkinson's disease (PD) is a common neurodegenerative condition affecting more than 8 million people worldwide. Although, the majority of PD cases are sporadic in nature, there are a growing number of monogenic mutations identified to cause PD in a highly penetrant manner. Many of these familial mutations give rise to a condition that is clinically and neuropathologically similar, if not identical, to sporadic PD. Mutations in genes such as SNCA cause PD in an autosomal dominant manner and patients have motor and non-motor symptoms that are typical for sporadic PD. With the advent of reprogramming technology it is now possible to capture these mutations in induced pluripotent stem cells (iPSCs) to establish models of PD in a dish. There are multiple neuronal subtypes affected in PD including the midbrain dopaminergic (mDA) neurons of the substantia nigra. Robust neuronal differentiation into mDA or other relevant neural cell types are critical to accurately model the disease and ensure the findings are relevant to understanding the disease process. Another challenge for establishing accurate models of PD is being met by the generation of isogenic control iPSC lines with precise correction of mutations using advanced gene editing technology. The contributions of ageing and environmental factors present further challenges to this field, but significant progress is being made in these areas to establish highly relevant and robust models of PD. These human neuronal models, used in conjunction with other model systems, will vastly improve our understanding of the early stages of the PD, which will be key to identifying disease-modifying and preventative treatments.



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A 32-Year-Old Man with Headache and Visual Loss



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Understanding neurodevelopmental disorders using human pluripotent stem cell-derived neurons

Abstract

Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient-specific cells, which in principle can be differentiated into all disease-relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs-based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed. We also discuss the impact of the recently developed CRISPR/Cas9 genome editing tool in the disease modeling field. Genetically engineered mutation of disease risk alleles in well characterized reference “control” hPSCs or correction of disease risk variants in patient iPSCs has been used as a powerful means to establish causality of the identified cellular pathology. Together, iPSC reprogramming and CRISPR/CAS9 genome editing technology have already significantly contributed to our understanding of the developmental origin of some major psychiatric disorders. The challenge ahead is the identification of shared mechanisms in their etiology, which will ultimately be relevant to the development of new treatments.



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Issue Information



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19-Year-Old Male with Headaches and a Possible Seizure



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Astrocytes in a dish: Using pluripotent stem cells to model neurodegenerative and neurodevelopmental disorders

Abstract

Neuroscience and Neurobiology have historically been neuron biased, yet up to 40% of the cells in the brain are astrocytes. These cells are heterogeneous and regionally diverse but universally essential for brain homeostasis. Astrocytes regulate synaptic transmission as part of the tripartite synapse, provide metabolic and neurotrophic support, recycle neurotransmitters, modulate blood flow and brain blood barrier permeability and are implicated in the mechanisms of neurodegeneration. Using pluripotent stem cells (PSC), it is now possible to study regionalised human astrocytes in a dish and to model their contribution to neurodevelopmental and neurodegenerative disorders. The evidence challenging the traditional neuron-centric view of degeneration within the CNS is reviewed here, with focus on recent findings and disease phenotypes from human PSC-derived astrocytes. In addition we compare current protocols for the generation of regionalised astrocytes and how these can be further refined by our growing knowledge of neurodevelopment. We conclude by proposing a functional and phenotypical characterisation of PSC-derived astrocytic cultures that is critical for reproducible and robust disease modelling.



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AN 11-Year-Old Boy with a Leptomeningeal Tumor



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SOCIETY NEWS



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Endoscopic endonasal management of esthesioneuroblastoma: A retrospective multicenter study

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Publication date: Available online 5 June 2017
Source:Auris Nasus Larynx
Author(s): Takayuki Nakagawa, Satoru Kodama, Masayoshi Kobayashi, Tetsuji Sanuki, Shuho Tanaka, Nobuhiro Hanai, Toyoyuki Hanazawa, Hiroko Monobe, Hidenori Yokoi, Motohiko Suzuki, Masaru Yamashita, Koichi Omori
ObjectiveThe aim of the present study was to illustrate the safety and utility of the endoscopic endonasal approach (EEA) for the treatment of esthesioneuroblastomas (ENB).MethodsWe retrospectively reviewed patients with a diagnosis of ENB between March 2008 and February 2016 at 10 tertiary referral hospitals in Japan, and assessed demographic data, stage of disease, surgical approach, outcomes and postoperative complications.ResultsA total of 22 patients (10 males and 12 females; mean age at presentation, 49.0 years) underwent endoscopic endonasal resection of newly diagnosed ENBs. Dulguerov staging at presentation was T1, 6 patients; T2, 9 patients; T3, 5 patients; and T4, 2 patients. As surgical procedures, unilateral resection via EEA was performed in 12 patients aiming preservation of the contralateral olfactory system, and bilateral resection via EEA was done in 10 patients. Post-operative radiotherapy was done in 20 patients. Pathological margin studies revealed margin-free resections in 21 patients (95.5%). The mean period of follow-up was 44 months. Local recurrence was observed in one T2 patient 12 months after bilateral resection. All patients were alive at the last follow-up, and 21 patients showed no evidence of disease. No post-operative complications including bleeding, CSF leak and meningitis were identified. Preservation of olfactory function was achieved in 11 patients (91.7%).ConclusionThe results of the present study indicate the safety and utility of multilayer resection using EEA for treatment of ENBs.



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Effects of unilateral real-time biofeedback on propulsive forces during gait

In individuals with post-stroke hemiparesis, reduced push-off force generation in the paretic leg negatively impacts walking function. Gait training interventions that increase paretic push-off can improve wal...

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Erratum to: Physical human-robot interaction of an active pelvis orthosis: toward ergonomic assessment of wearable robots



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Effects of unilateral real-time biofeedback on propulsive forces during gait

In individuals with post-stroke hemiparesis, reduced push-off force generation in the paretic leg negatively impacts walking function. Gait training interventions that increase paretic push-off can improve wal...

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Erratum to: Physical human-robot interaction of an active pelvis orthosis: toward ergonomic assessment of wearable robots



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Morphometry and microsurgical anatomy of Bochdalek’s flower basket and the related structures of the cerebellopontine angle

Abstract

Background

Bochdalek’s flower basket (Bfb) is the distal part of the horizontal segment of the fourth ventricle’s choroid plexus protruding through the lateral aperture (foramen of Luschka). The microsurgical anatomy of the cerebellopontine angle, fourth ventricle and its inner choroid plexus is well described in the literature, but only one radiological study has investigated the Bfb so far. The goal of the present study was to give an extensive morphometric analysis of the Bfb for the first time and discuss the surgically relevant anatomical aspects.

Method

Forty-two formalin-fixed human brains (84 cerebellopontine angles) were involved in this study. Photomicrographs with scale bars were taken in every step of dissection to perform further measurements with Fiji software. The lengths and widths of the Bfb, rhomboid lip and lateral aperture of the fourth ventricle as well as the related neurovascular and arachnoid structures were measured. The areas of two sides were compared with paired t-tests using R software. Significance level was set at p < 0.05.

Results

Protruding choroid plexus was present in 77 cases (91.66%). In 6 cases (7.14%), the Bfb was totally covered by the rhomboid lip, and in one case (1.19%), it was absent. The mean width of the Bfb was 6.618 mm (2–14 mm), the mean height 5.658 mm (1.5–14 mm) and mean area 25.80 mm2 (3.07–109.83 mm2). There was no statistically significant difference between the two sides (p = 0.1744). The Bfb was in contact with 20 AICAs (23.80%), 6 PICAs (7.14%) and 39 vestibulocochlear nerves (46.42%). Arachnoid trabecules, connecting the lower cranial nerves to the Bfb or rhomboid lip, were found in 57 cases (67.85%).

Conclusions

The Bfb is an important landmark during various surgical procedures. Detailed morphology, dimensions and relations to the surrounding neurovascular structures are described in this study. These data are essential for surgeons operating in this region.



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“Cold-Steel” Phonosurgery of Reinke Edema Evaluated by the Multidimensional Voice Program

Publication date: Available online 5 June 2017
Source:Journal of Voice
Author(s): Ylva Margareta Schyberg, Kristian Hveysel Bork, Martin Kryspin Sørensen, Niels Rasmussen
Objectives“Cold-steel” phonosurgery (PS) of Reinke edema is challenging, as the delicate structures of the vocal folds are difficult to preserve. This study aimed to evaluate the results of PS using the Multidimensional Voice Program (MDVP) .Materials and MethodsFrom 2003 to 2007, 76 consecutive patients with Reinke edema were treated with PS for the first time. Reliable MDVP data were available in 37 female patients with both pre- and postoperative values in 14 patients. Voice quality and outcome after PS were evaluated by jitter, shimmer, soft phonation index, and fundamental frequency (f0) using MDVP, videostroboscopy, and a five-step voice outcome score.ResultsIn the 14 patients, the mean f0 increased from 172 to 222 (P = 0.01), and jitter decreased from 2.03 to 1.17 (P = 0.04) 3 months postoperatively. Vocal fold grading based on videostroboscopy correlated significantly with jitter (P = 0.01). Patients with high preoperative values of jitter, shimmer, or soft phonation index had larger reductions than those with normal values. All had a postoperative reduction of the edemas. The mean voice outcome score increased postoperatively. None of the 37 patients reported complications, but seven patients were reoperated. Preoperatively, 95% of the 37 patients were smokers and only 9 (24%) changed smoking habits. Pre- or postoperative voice therapy was used in 23 (62%) patients.Conclusionsf0 and jitter by MDVP adequately reflected the postoperative voice improvement and reduction of the edema. Removal of large amounts of edematous tissue, many years of vocal abuse, and unchanged smoking habits may prevent optimal results.



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Acoustic Analysis of Voice and Electroglottography in Patients With Laryngopharyngeal Reflux

Publication date: Available online 5 June 2017
Source:Journal of Voice
Author(s): Daphne Anahit Morales Ramírez, Víctor Manuel Valadez Jiménez, Xochiquetzal Hernández López, Pablo Antonio Ysunza
BackgroundLaryngopharyngeal reflux (LPR) refers to the flow of gastric acid content into the laryngopharynx. It has been reported that 10% of the patients consulting an otolaryngologist present with this condition. Signs of LPR can be identified during flexible or rigid laryngoscopy. The Voice Handicap Index (VHI) is a reliable tool for detecting the impact of voice disorders, and acoustic assessment of voice including acoustic analysis of voice (AAV) and electroglottography (EGG) provide objective data of voice production and voice disorders.ObjectiveThis study aimed to describe changes in AAV, EGG, and VHI in patients who present with LPR compared with a matched control group of healthy subjects.Materials and MethodsSeventeen patients with LPR were studied. A group of healthy subjects matched by age and gender without any history of voice disorder, LPR, or gastroesophageal reflux disease was assembled. Both groups of patients were studied by VHI, flexible laryngoscopy, AAV, and EGG.ResultsAll patients with LPR demonstrated abnormal VHI values. Shimmer, jitter, open quotient, and irregularity were significantly increased in the patients with LPR. Nonsignificant correlations were found between VHI scores and abnormal acoustic parameters in patients with LPR.ConclusionsAlthough abnormal acoustic parameters of patients with LPR were not predictive of the overall VHI score, the abnormal acoustic parameters of patients with LPR suggest a decrease in adequate laryngeal control during phonation.



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Menstrual Cycle, Vocal Performance, and Laryngeal Vascular Appearance: An Observational Study on 17 Subjects

Publication date: Available online 5 June 2017
Source:Journal of Voice
Author(s): Hagit Shoffel-Havakuk, Narin N. Carmel-Neiderman, Doron Halperin, Yael Shapira Galitz, Dan Levin, Yaara Haimovich, Oded Cohen, Jean Abitbol, Yonatan Lahav
ObjectiveTo assess the anatomical and functional features of the vocal folds during different phases of the female menstrual cycle.MethodsAn observational study of 17 healthy fertile female volunteers not using hormonal contraception was carried out. Each volunteer underwent two examinations: first, during the early days of the menstrual cycle when progesterone levels are low (p-depletion), and second, during premenstruation when progesterone levels are high (p-peak). The workup included blood hormone levels, Voice Handicap Index, acoustic analysis, rigid telescopy, stroboscopy, and narrow band imaging. The videos were evaluated by blinded observers.ResultsThe participants' mean age was 31.7 ± 5.6 (range 23–43). Progesterone levels were 13- to 45-fold higher in p-peak relative to p-depletion. No significant differences were detected in Voice Handicap Index scores, stroboscopic reports, or acoustic analysis between p-peak and p-depletion examinations. Analyzing the rigid telescopy and narrow band imaging videos, the observers tended to estimate the different laryngeal subsites more vascularized during the p-peak examination. Moreover, this tendency was significantly correlated with blood progesterone levels during the p-depletion examinations; the lower the blood progesterone levels were during p-depletion, the higher the probability for the observers to estimate the p-peak examinations more vascularized (P value = 0.024).ConclusionsAlterations in laryngeal vascular characteristics are evident throughout the menstrual cycle and may suggest increased congestion during premenstrual days. Variations in progesterone levels during the menstrual cycle correlate with laryngeal vascular changes. Hormone-related alterations in vocal folds' vascularity may have a role in the variability of vocal performance in certain women.



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Contribution of Simultaneous Breast Reconstruction by Deep Inferior Epigastric Artery Perforator Flap to the Efficacy of Vascularized Lymph Node Transfer in Patients with Breast Cancer-Related Lymphedema

J reconstr Microsurg
DOI: 10.1055/s-0037-1603738

Background The contribution of simultaneous breast reconstruction by deep inferior epigastric artery perforator (DIEP) flap to the efficacy of vascularized groin lymph node transfer (LNT) for breast cancer-related lymphedema (BCRL) was investigated. Methods Patients were divided into two groups: the first group underwent groin LNT + DIEP flap surgery for simultaneous breast reconstruction (groin LNT + DIEP flap group) and the second group underwent groin LNT only (groin flap alone group). Patients with BCRL were evaluated based on indocyanine green lymphography findings. LNT was indicated only in advanced-stage BCRL cases, and groin nodes nourished by superficial circumflex iliac artery (SCIA) were used as donors. The side for the vascular pedicle(s) was decided based on our algorithm. In patients with pendulous breast, the flap was vertically transferred on the chest. Lymphatic function was assessed after LNT using imaging tests, and transferred lymph nodes were evaluated using ultrasonography. Results In this study, 27 patients with advanced-stage BCRL underwent LNT. Of them, 13 belonged to the groin LNT + DIEP flap group and 14 belonged to the groin flap alone group. Although reduction volume was not significantly different between the groups, the number of patients in whom lymphatic function was improved and the need for compression therapy could be reduced was significantly higher in the groin LNT + DIEP flap group than in the groin flap alone group. Conclusion When a patient with advanced-stage BCRL undergoes LNT based on SCIA, simultaneous breast reconstruction using DIEP flap may reduce the need for compression therapy.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Indocyanine Green Fluorescence to Evaluate Nasoseptal Flap Viability in Endoscopic Endonasal Cranial Base Surgery

J Neurol Surg B
DOI: 10.1055/s-0037-1602777

Objectives The pedicled nasoseptal flap (NSF) has dramatically reduced postoperative cerebrospinal fluid leakage following endoscopic endonasal approach (EEA) surgery. Although rare, its arterial supply may be damaged during harvest or may be preoperatively damaged for numerous reasons. Early recognition permits harvesting a contralateral flap before sacrificing its pedicle as part of the surgical exposure or use of an alternative flap. Design Technical feasibility study and case series. Setting Tertiary care university-associated medical center. Participants Five patients requiring an EEA with NSF reconstruction. Main Outcome Measures During NSF harvest, intravenous indocyanine green (IVICG) was administered, and a customized endoscopic system was used to visualize the emerging fluorescence. At the end of each case, just before final positioning of the NSF, additional IVICG was administered, and the custom endoscope was again introduced to evaluate fluorescence. Results In four patients, the entire NSF fluoresced brightly with IVICG on initial harvest and before final positioning. One patient showed heterogeneous fluorescence of the pedicle and distal parts of the NSF at both stages. All NSFs healed well without complication. Conclusion IVICG facilitates real-time evaluation NSF's arterial supply. This may provide early recognition of arterial compromise, allowing the harvest of alternate flaps or modification of surgery.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Multimodality Management of Cavernous Sinus Hemangiomas—An Institutional Experience

J Neurol Surg B
DOI: 10.1055/s-0037-1602790

Objective Cavernous sinus hemangiomas (CSHs) are benign lesions accounting for less than 2% of the cavernous sinus tumors. They provide a formidable surgical challenge because of their vascularity and their being surrounded by critical neurovascular structures. In this study, one of the largest in available literature, we analyze our experience in the management of these unusual tumors and review the available literature. Materials This is a retrospective analysis of patients who were managed surgically (both microsurgical and Gamma knife radiosurgery [GKRS]) for CSH at our Institution from 2007 to 2015. Complete demographic, clinical-radiologic surgical records were analyzed. Follow-up data were collected from the hospital records. Results Total 23 patients were managed. Among these, 15 patients underwent microsurgery (group 1) whereas 8 underwent GKRS (group 2). Predominant clinical presentation in both the groups included headache and involvement of multiple cranial nerves. Five patients in group 1 had deteriorating vision. The volume of tumors ranged from 29 to 115 cm3 (mean = 64.57 cm3) in group 1 and from 2.1 to 11.6 cm3 in group 2. GKRS was performed with a mean dose of 13 Gy, an average isodose line of 50% with an average coverage of 96%. In group 1, the follow-up period ranged from 6 to 62 months (mean = 29.4 months). The extraocular movement (EOM) preservation rate in our series was not favorable, as most patients presented late with large tumors and established deficits. Recurrence/residual tumor was seen in two cases. In group 2, the follow-up was 5 to 48 months. All of them showed significant reduction in size. Conclusion Both surgery and radiosurgery are highly effective in the management of CSHs. They are complementary to each other, with individual characteristics—the size and volume of the lesion—being the main factors in deciding the choice of treatment.
[...]

Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Utility of Laryngeal High-speed Videoendoscopy in Clinical Voice Assessment

This study aimed to assess the utility of laryngeal high-speed videoendoscopy (HSV) as a clinical tool.

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Menstrual Cycle, Vocal Performance, and Laryngeal Vascular Appearance: An Observational Study on 17 Subjects

To assess the anatomical and functional features of the vocal folds during different phases of the female menstrual cycle.

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“Cold-Steel” Phonosurgery of Reinke Edema Evaluated by the Multidimensional Voice Program

“Cold-steel” phonosurgery (PS) of Reinke edema is challenging, as the delicate structures of the vocal folds are difficult to preserve. This study aimed to evaluate the results of PS using the Multidimensional Voice Program (MDVP) .

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Acoustic Analysis of Voice and Electroglottography in Patients With Laryngopharyngeal Reflux

Laryngopharyngeal reflux (LPR) refers to the flow of gastric acid content into the laryngopharynx. It has been reported that 10% of the patients consulting an otolaryngologist present with this condition. Signs of LPR can be identified during flexible or rigid laryngoscopy. The Voice Handicap Index (VHI) is a reliable tool for detecting the impact of voice disorders, and acoustic assessment of voice including acoustic analysis of voice (AAV) and electroglottography (EGG) provide objective data of voice production and voice disorders.

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Aerodynamic Patterns in Patients With Voice Disorders: A Retrospective Study

A recently published retrospective chart review of aerodynamic profiles of women with primary muscle tension dysphonia by Gillespie et al (2013) identified various relationships between mean airflow rate (MFR) and estimated subglottal pressure (est-Psub). The current retrospective study expanded the diagnostic categories to include all voice disorders referred for voice therapy. Three research questions were proposed: (1) Are there differences in the MFR and the est-Psub compared with the normal control group? (2) Within the disordered population, are there different variations in the pairing of MFR and est-Psub? (3) If these variations exist, are they diagnosis specific?

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Long-term outcomes of central neck dissection for cN0 papillary thyroid carcinoma

Objective.The risk-benefit ratio of central neck dissection (CND) in patients affected by papillary thyroid carcinoma (PTC) without clinical or ultrasonographic (US) evidence of neck lymph node metastasis (cN0) is currently debated. The aim of this study was to evaluate long-term outcome of CND on locoregional recurrence, distant metastasis, survival, and postoperative complications in a large series of patients with cN0-PTC.Study Design.Observational retrospective controlled study.

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The effects of fibroblast growth factor-2 delivered via a Gelfoam patch on the regeneration of myringosclerotic traumatic eardrum perforations lying close to the malleus

We evaluated the effects of fibroblast growth factor-2 (FGF-2) delivered via a Gelfoam patch on the regeneration of myringosclerotic traumatic tympanic membrane perforations (TMPs) lying close to the malleus.

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Scar Management After Surgical Repair of Lateral Facial Clefts

Abstract

The prevention of scar contracture after surgery is an important aspect of lateral facial cleft repair. Maintaining adequate mouth opening is essential for speech, expression, chewing, oral hygiene and psychosocial well-being. Although there have been extensive reviews of non-surgical microstomia management in patients with oral electrical burns, there have been no reports on the use of oral commissure splints to manage the surgical scar in patients with lateral facial clefts. The case study presented here will demonstrate the clinical use of cheek retractors to provide physical resistance to scar contracture. We recommend early rehabilitation with cheek retractors to minimize scar contracture and the negative sequelae of scarred tissues on the dentition after lateral facial cleft repair.



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Clinical Analysis of MatrixMANDIBLE Preformed Reconstruction Plate Design

The MatrixMANDIBLE Preformed Reconstruction Plates (MMPRPs) were developed to overcome the laborious bending procedures of conventional reconstruction plates. Besides reducing operating time, the biomechanical stress on the plate, known to promote fatigue fracturing, could be avoided. Furthermore, morphometric shape analysis of the anterolateral mandible in various ethnic populations resulted in a preshaped, load-bearing, osteosynthesis system designed to address the typical complications of reconstruction plates, such as screw and plate loosening, and exposure of the plate with subsequent intra-oral or orocutaneous fistula formation (Gellrich et al., 2004; Klotch et al., 1999; Martola et al., 2007; Metzger et al., 2011).

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“Cold-Steel” Phonosurgery of Reinke Edema Evaluated by the Multidimensional Voice Program

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Publication date: Available online 5 June 2017
Source:Journal of Voice
Author(s): Ylva Margareta Schyberg, Kristian Hveysel Bork, Martin Kryspin Sørensen, Niels Rasmussen
Objectives“Cold-steel” phonosurgery (PS) of Reinke edema is challenging, as the delicate structures of the vocal folds are difficult to preserve. This study aimed to evaluate the results of PS using the Multidimensional Voice Program (MDVP) .Materials and MethodsFrom 2003 to 2007, 76 consecutive patients with Reinke edema were treated with PS for the first time. Reliable MDVP data were available in 37 female patients with both pre- and postoperative values in 14 patients. Voice quality and outcome after PS were evaluated by jitter, shimmer, soft phonation index, and fundamental frequency (f0) using MDVP, videostroboscopy, and a five-step voice outcome score.ResultsIn the 14 patients, the mean f0 increased from 172 to 222 (P = 0.01), and jitter decreased from 2.03 to 1.17 (P = 0.04) 3 months postoperatively. Vocal fold grading based on videostroboscopy correlated significantly with jitter (P = 0.01). Patients with high preoperative values of jitter, shimmer, or soft phonation index had larger reductions than those with normal values. All had a postoperative reduction of the edemas. The mean voice outcome score increased postoperatively. None of the 37 patients reported complications, but seven patients were reoperated. Preoperatively, 95% of the 37 patients were smokers and only 9 (24%) changed smoking habits. Pre- or postoperative voice therapy was used in 23 (62%) patients.Conclusionsf0 and jitter by MDVP adequately reflected the postoperative voice improvement and reduction of the edema. Removal of large amounts of edematous tissue, many years of vocal abuse, and unchanged smoking habits may prevent optimal results.



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Acoustic Analysis of Voice and Electroglottography in Patients With Laryngopharyngeal Reflux

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Publication date: Available online 5 June 2017
Source:Journal of Voice
Author(s): Daphne Anahit Morales Ramírez, Víctor Manuel Valadez Jiménez, Xochiquetzal Hernández López, Pablo Antonio Ysunza
BackgroundLaryngopharyngeal reflux (LPR) refers to the flow of gastric acid content into the laryngopharynx. It has been reported that 10% of the patients consulting an otolaryngologist present with this condition. Signs of LPR can be identified during flexible or rigid laryngoscopy. The Voice Handicap Index (VHI) is a reliable tool for detecting the impact of voice disorders, and acoustic assessment of voice including acoustic analysis of voice (AAV) and electroglottography (EGG) provide objective data of voice production and voice disorders.ObjectiveThis study aimed to describe changes in AAV, EGG, and VHI in patients who present with LPR compared with a matched control group of healthy subjects.Materials and MethodsSeventeen patients with LPR were studied. A group of healthy subjects matched by age and gender without any history of voice disorder, LPR, or gastroesophageal reflux disease was assembled. Both groups of patients were studied by VHI, flexible laryngoscopy, AAV, and EGG.ResultsAll patients with LPR demonstrated abnormal VHI values. Shimmer, jitter, open quotient, and irregularity were significantly increased in the patients with LPR. Nonsignificant correlations were found between VHI scores and abnormal acoustic parameters in patients with LPR.ConclusionsAlthough abnormal acoustic parameters of patients with LPR were not predictive of the overall VHI score, the abnormal acoustic parameters of patients with LPR suggest a decrease in adequate laryngeal control during phonation.



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Menstrual Cycle, Vocal Performance, and Laryngeal Vascular Appearance: An Observational Study on 17 Subjects

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Publication date: Available online 5 June 2017
Source:Journal of Voice
Author(s): Hagit Shoffel-Havakuk, Narin N. Carmel-Neiderman, Doron Halperin, Yael Shapira Galitz, Dan Levin, Yaara Haimovich, Oded Cohen, Jean Abitbol, Yonatan Lahav
ObjectiveTo assess the anatomical and functional features of the vocal folds during different phases of the female menstrual cycle.MethodsAn observational study of 17 healthy fertile female volunteers not using hormonal contraception was carried out. Each volunteer underwent two examinations: first, during the early days of the menstrual cycle when progesterone levels are low (p-depletion), and second, during premenstruation when progesterone levels are high (p-peak). The workup included blood hormone levels, Voice Handicap Index, acoustic analysis, rigid telescopy, stroboscopy, and narrow band imaging. The videos were evaluated by blinded observers.ResultsThe participants' mean age was 31.7 ± 5.6 (range 23–43). Progesterone levels were 13- to 45-fold higher in p-peak relative to p-depletion. No significant differences were detected in Voice Handicap Index scores, stroboscopic reports, or acoustic analysis between p-peak and p-depletion examinations. Analyzing the rigid telescopy and narrow band imaging videos, the observers tended to estimate the different laryngeal subsites more vascularized during the p-peak examination. Moreover, this tendency was significantly correlated with blood progesterone levels during the p-depletion examinations; the lower the blood progesterone levels were during p-depletion, the higher the probability for the observers to estimate the p-peak examinations more vascularized (P value = 0.024).ConclusionsAlterations in laryngeal vascular characteristics are evident throughout the menstrual cycle and may suggest increased congestion during premenstrual days. Variations in progesterone levels during the menstrual cycle correlate with laryngeal vascular changes. Hormone-related alterations in vocal folds' vascularity may have a role in the variability of vocal performance in certain women.



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Endoscopic rescue treatment in a pregnant ulcerative colitis patient with a severe colonic stricture: a conservative approach to bring the pregnancy to term



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Preventing Tuberculosis in a Low Incidence Setting: Evaluation of a Multi-lingual, Online, Educational Video on Latent Tuberculosis

Abstract

Treating latent tuberculosis infection (LTBI) in those at risk is an important yet challenging cornerstone of TB elimination. We evaluated a culturally-tailored, multi-lingual, 4.5-min, health promotional video on LTBI. Mixed methods study assessed use of the video with web-analytics, acceptability of content through interviews and survey questions, and compared knowledge scores in viewers and non-viewers using a survey. The video was viewed 6999 times in six languages over 1 year. Of 1598 survey respondents, 193 viewers had a mean knowledge score of 59%, compared to 38% in non-viewers. Eighty-four percent of viewers rated the video as helpful. When controlling for other factors, viewing the video was associated with a 1.04 (95% CI 0.85–1.26) or a 21% increase in a knowledge score. Qualitative data suggested the video was acceptable and may facilitate behavior change. This online, educational video shows promise as a tool to supplement clinical care.



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Health of International Marriage Immigrant Women in South Korea: A Systematic Review

Abstract

International marriage migration is now one of the most prominent forms of migration in Asia, and the number of women migrating to South Korea for marriage has increased dramatically in the last two decades. In this article, we provide a systematic review regarding the health status and health-related issues of international marriage immigrant women. The literature search identified 620 articles, of which 53 studies are presented in the article. Three overarching categories including six subcategories were identified according to the research focus; 'Environmental factors of health' including social support and barriers, 'Health status' including physical, psychological and social health, and quality of life as 'Outcome of health'. Overall women immigrants by marriage showed relatively poor health outcomes. Social support was an important factor affecting the health status and quality of life in this population. We offer recommendations to develop and implement culturally and linguistically appropriate health promoting programs for international marriage immigrant women in South Korea.



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Qualitative Study of Latino Cancer Patient Perspectives on Care Access and Continuity in a Rural, U.S.-Mexico Border Region

Abstract

Access to quality cancer care for cancer patients living in the rural U.S.-Mexico border region is complex due to common binational health care-seeking behaviors and regional socio-economic and cultural characteristics. But little is known about the challenges border dwelling residents face when navigating their cancer care systems. In-depth interviews were conducted with 22 cancer patients in Southern California. Thematic analysis was applied to identify patterns of meaning in the data. Emerging themes were: (1) delays in cancer care coordination: (a) poor coordination of cancer care (b) U.S. and cross-border discordance in cancer diagnosis; (2) regional shortage of cancer specialists; and (3) financial hardship. Findings revealed that care needs distinctly involved care coordination in/outside of the patient's community and bi-national care coordination. In addition to local solutions to improve cancer coordination through community-based partnerships, efforts to bridge care in a two-nation context are also imperative.



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Curcumin Protects Against Acoustic Trauma in the Rat Cochlea

Publication date: Available online 5 June 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Harun Soyalıç, Fikret Gevrek, Serhat Karaman
ObjectivesIn this study we evaluated the therapeutic utility of curcumin in a rodent model of acoustic trauma using histopathology, immunohistochemical, and distortion product otoacoustic emission (DPOAEs) measurements.Methods28 Wistar albino rats were included in the study and randomly assigned to 4 treatment groups. The first group (group 1) served as the control and was exposed to acoustic trauma alone. Group 2 was the curcumin group. Group 3 was the curcumin plus acoustic trauma group. Group 4 was the saline plus acoustic trauma group. Otoacoustic emission measurements were collected at the end of the experiment and all animals were sacrificed. Cochlea were collected and prepared for TUNEL (TdT-mediated deoxyuridinetriphosphate nick end-labelling) staining assay.ResultsGroup 3 maintained baseline DPOAEs values at 3000 Hz, 4000Hz and 8000Hz on the 3rd and 5th day of the experiment. DPOAEs results were correlated with the immunohistochemical and histopathological findings in all groups. In comparison to the histopathologic control group, Group 1 exhibited a statistically significant increase in apoptotic indices in the organ of Corti, inner hair cell, and outer hair cell areas (p<0.05). Relative to the control group, rats in Group 3 showed little increase in inner hair cell and outer hair cell apoptotic indices.ConclusionsOur results support the conclusion that curcumin may protect the cochlear tissues from acoustic trauma in rats. Curcumin injection prior to or after an acoustic trauma reduces cochlear hair cell damage and may protect against hearing loss.



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Clinical role of electrocochleography in children with auditory neuropathy spectrum disorder

Publication date: Available online 5 June 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Tatyana E. Fontenot, Christopher K. Giardina, Holly F. Teagle, Lisa R. Park, Oliver F. Adunka, Craig A. Buchman, Kevin D. Brown, Douglas C. Fitzpatrick
ObjectivesTo assess electrocochleography (ECochG) to tones as an instrument to account for CI speech perception outcomes in children with auditory neuropathy spectrum disorder (ANSD).Materials & methodsChildren (<18 years) receiving CIs for ANSD (n=30) and non-ANSD (n=74) etiologies of hearing loss were evaluated with ECochG using tone bursts (0.25-4 kHz). The total response (TR) is the sum of spectral peaks of responses across frequencies. The compound action potential (CAP) and the auditory nerve neurophonic (ANN) in ECochG waveforms were used to estimate nerve activity and calculate nerve score. Performance on open-set monosyllabic word tests was the outcome measure. Standard statistical methods were applied.ResultsOn average, TR was larger in ANSD than in non-ANSD subjects. Most ANSD (73.3%) and non-ANSD (87.8%) subjects achieved open-set speech perception; TR accounted for 33% and 20% of variability in the outcomes, respectively. In the ANSD group, the PTA accounted for 69.3% of the variability, but there was no relationship with outcomes in the non-ANSD group.In both populations, nerve score was sensitive in identifying subjects at risk for not acquiring open-set speech perception, while the CAP and the ANN were more specific.ConclusionIn both subject groups, the TRs correlated with outcomes but these measures were notably larger in the ANSD group. There was also strong correlation between PTA and speech perception outcome in ANSD group. In both subject populations, weaker evidence of neural activity was related to failure to achieve open-set speech perception.



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Factors influencing hearing outcomes in pediatric patients undergoing ossicular chain reconstruction

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Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Nandini Govil, Thomas M. Kaffenberger, Amber D. Shaffer, David H. Chi
ObjectiveOssicular chain disruption in children leads to conductive hearing loss. Few studies have focused on factors influencing successful results in pediatric ossicular chain reconstruction (OCR). We aim to determine whether demographic or surgical factors affect hearing outcomes in pediatric OCR.MethodsWe conducted a retrospective chart review of 120 patients undergoing OCR at our institution, a tertiary care hospital, between 2003 and 2014, with median length of follow-up of 2.2 years (range 0.1–9.3 years). Pediatric patients (<18 years old at time of surgical procedure) who had current procedural terminology (CPT) codes of OCR, and available pre- and post-operative audiograms were included in the study. Demographic information, surgical details, and pre- and post-operative pure-tone averages (PTA), speech reception thresholds (SRT), and air-bone gaps (ABG) were recorded from clinic notes, audiograms and operative reports. Differences between PTA, SRT and ABG pre- and post-operatively, as well as demographic and surgical factors, were evaluated using Wilcoxon rank-sum tests. Factors influencing revision were evaluated using Log-rank tests.ResultsA total of 120 patients (123 ears) were included. 35.8% of cases were revised, most commonly due to displaced prostheses. 28.5% of surgeries resulted in normal hearing (PTA ≤25 dB) post-operatively. Post-operative SRT and ABG were significantly better in patients with partial ossicular replacement prosthesis (PORP) compared with those with total ossicular replacement prosthesis (TORP) (p = 0.016, 0.027). Titanium prostheses resulted in better post-operative PTA and larger changes in PTA compared with all other materials (p = 0.034, p = 0.038).ConclusionsIn our experience, children with titanium prostheses had better hearing outcomes than those with other materials, and children with PORP had better hearing outcomes than those with TORP.



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Evaluation of speech in noise abilities in school children

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Publication date: August 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 99
Author(s): Nádia Giulian de Carvalho, Carolina Verônica Lino Novelli, Maria Francisca Colella-Santos
This study aimed to analyze the perception of speech in noise in children with poor school performance and to compare them with children with good school performance, considering gender, age and ear side as variables.The intelligibility of speech was evaluated in school children utilizing the Brazilian Hearing in Noise Test (HINT) in the situations of quiet (Q), Left ear competitive noise (NL), Right Ear Competitive Noise (NR), as well as the global average of other hearing situations, denominated Noise Composite (NC). Ninety seven school children between the ages of 8 and 10 were recruited in five schools of São Paulo-Brazil; the control group (CG) consisted of 54 students (23 male/ 31 female) without language and/or speech difficulties and good school performance, and the study group (SG) consisted of 43 students (28 male/ 15 female) identified by their teachers as having poor school performance.The variables gender and ear side did not interfere in speech perception. The age variable influenced only the CG. The SG had worse performance than the CG in the Q, NF and NC conditions. NF was the most difficult for both groups.The perception of speech in noise was the worst in children with poor school performance. The variables gender and ear side did not interfere in speech perception. The age group variable influenced the performance of the group of children with good school performance, demonstrating a better ability in older children. The speech perception in noise ability is more difficult for both groups when the noise affects both ears.



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Comparison between selective and routine intensive care unit admission post-supraglottoplasty

Publication date: Available online 5 June 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Timothy Cooper, Bree Harris, Ahmed Mourad, Daniel Garros, Hamdy El-Hakim
ObjectiveTo compare major post-operative respiratory complications, post-operative disposition and duration of hospital admission before and after adopting a selective intensive care unit (ICU) admission care plan following supraglottoplasty (SGP).MethodsRetrospective case series set in a tertiary pediatric referral center. Eligible patients undergoing SGP between October 2003 and July 2015 were identified through a prospectively kept surgical database. Historical cohorts with routine admission to ICU and selective admission to ICU were identified based on a shift in surgeon practice. The cohorts were compared with respect to demographics, presenting features, endoscopic findings, baseline sleep and swallowing study results, major respiratory complications (including repeat or unplanned ICU admission or intubation) and length of post-operative hospital admission.Results141 eligible patients were identified with 35 children in the routine ICU admission cohort and 106 in the selective ICU admission cohort. There were no significant differences between cohorts regarding major respiratory complications with only one patient in the selective ICU admission cohort requiring an unplanned admission to ICU (P=1.00, Fisher’s exact test). This gives a number needed to harm of 78 step-down unit admissions for 1 unplanned ICU admission. The rate of ICU admission was reduced from 71% to 26% with adoption of a selective ICU admission care plan (p<0.01, χ2). Mean duration of post-operative hospitalization was reduced from 5.1 ± 3.5 days to 1.9 ± 2.3 days (P<0.01, Student’s t-test).ConclusionsSelective post-operative ICU admission following SGP significantly reduces ICU utilization and may reduce length of hospital stay without compromising safety and care. This has significant cost benefit implications.



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Clinical and bacteriological differences of deep neck infection in pediatric and adult patients: review of 123 cases

Publication date: Available online 5 June 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Yuichi Shimizu, Hiroshi Hidaka, Daiki Ozawa, Risako Kakuta, Kazuhiro Nomura, Hisakazu Yano, Ken-ichi Watanabe, Yukio Katori
ObjectivesDeep neck infections (DNIs) can lead to life-threatening disease. However, the detailed pathophysiology remains unclear due to its rarity and only a few reports have directly compared DNIs in children and adults. This study aimed to reveal the clinical differences between DNIs in children and adults.MethodsWe retrospectively reviewed 123 patients who suffered from DNIs at Tohoku University Hospital from August 2005 to July 2015. We extracted data on patient sex, age, antecedent illness, extension of infections, operative procedures, and bacteriology results. The patients were categorized into pediatric (≤18 years) and adult (>18 years) groups. Fisher’s exact test was performed to determine significant differences between the two groups.ResultsFifteen children (6 males and 9 females) and 108 adults (71 males and 37 females) were identified. The most common antecedent illness in pediatric patients was lymphadenitis, which was the least common in adult patients (73% vs 7%, p < 0.0001). The incidence of DNIs extending below the hyoid bone was significantly lower in pediatric patients than in adult patients (20% vs 53%, p < 0.05). Regarding bacterial culture analysis, Staphylococcus species was the most common pathogen in children (60%), whereas only 9% of adults were positive for Staphylococcus (p < 0.001). Streptococcus species were significantly less common in children than in adults (27% vs 56%, p = 0.05). Anaerobes were also significantly less common in children than in adults (13% vs 45%, p < 0.01). Concerning surgical intervention, 53% of pediatric patients underwent external incision compared with 70% of adults. Specifically, tracheostomy was significantly less frequently performed in children than in adults (7% vs 54%, p < 0.01).ConclusionDNIs in children feature different characteristics from those in adults regarding severity, antecedent illness, bacteriology, and clinical management.



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Binding object features to locations: Does the “spatial congruency bias” update with object movement?

Abstract

One of the fundamental challenges of visual cognition is how our visual systems combine information about an object’s features with its spatial location. A recent phenomenon related to object–location binding, the “spatial congruency bias,” revealed that two objects are more likely to be perceived as having the same identity or features if they appear in the same spatial location, versus if the second object appears in a different location. The spatial congruency bias suggests that irrelevant location information is automatically encoded with and bound to other object properties, biasing perceptual judgments. Here we further explored this new phenomenon and its role in object–location binding by asking what happens when an object moves to a new location: Is the spatial congruency bias sensitive to spatiotemporal contiguity cues, or does it remain linked to the original object location? Across four experiments, we found that the spatial congruency bias remained strongly linked to the original object location. However, under certain circumstances—for instance, when the first object paused and remained visible for a brief time after the movement—the congruency bias was found at both the original location and the updated location. These data suggest that the spatial congruency bias is based more on low-level visual information than on spatiotemporal contiguity cues, and reflects a type of object–location binding that is primarily tied to the original object location and that may only update to the object’s new location if there is time for the features to be re-encoded and rebound following the movement.



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Natural scenes can be identified as rapidly as individual features

Abstract

Can observers determine the gist of a natural scene in a purely feedforward manner, or does this process require deliberation and feedback? Observers can recognise images that are presented for very brief periods of time before being masked. It is unclear whether this recognition process occurs in a purely feedforward manner or whether feedback from higher cortical areas to lower cortical areas is necessary. The current study revealed that the minimum presentation time required to identify or to determine the gist of a natural scene was no different from that required to determine the orientation or colour of an isolated line. Conversely, a visual task that would be expected to necessitate feedback (determining whether an image contained exactly six lines) required a significantly greater minimum presentation time. Assuming that the orientation or colour of an isolated line can be determined in a purely feedforward manner, these results indicate that the identification and the determination of the gist of a natural scene can also be performed in a purely feedforward manner. These results challenge a number of theories of visual recognition that require feedback.



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Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects [INNATE IMMUNITY AND INFLAMMATION]

During sepsis, excessive activation of the complement system with generation of the anaphylatoxin C5a results in profound disturbances in crucial neutrophil functions. Moreover, because neutrophil activity is highly dependent on intracellular pH (pHi), we propose a direct mechanistic link between complement activation and neutrophil pHi. In this article, we demonstrate that in vitro exposure of human neutrophils to C5a significantly increased pHi by selective activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated intracellular alkalinization was dependent on C5aR1, intracellular calcium, protein kinase C, and calmodulin, and downstream signaling regulated the release of antibacterial myeloperoxidase and lactoferrin. Notably, the pH shift caused by C5a increased the glucose uptake and activated glycolytic flux in neutrophils, resulting in a significant release of lactate. Furthermore, C5a induced acidification of the extracellular micromilieu. In experimental murine sepsis, pHi of blood neutrophils was analogously alkalinized, which could be normalized by C5aR1 inhibition. In the clinical setting of sepsis, neutrophils from patients with septic shock likewise exhibited a significantly increased pHi. These data suggest a novel role for the anaphylatoxin C5a as a master switch of the delicate pHi balance in neutrophils resulting in profound inflammatory and metabolic changes that contribute to hyperlactatemia during sepsis.



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