No abstract available
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Τετάρτη 31 Ιανουαρίου 2018
Intestinal-type adenocarcinoma of the sinonasal tract: an update
Purpose of review Intestinal-type adenocarcinoma (ITAC) is one of the most frequent sinonasal tumors, especially in European countries. The purpose of this article is to review the most recent literature, with special emphasis on biological and genetic profile and treatment guidelines. Recent findings Results on large series support transnasal endoscopic surgery as the technique of choice in the large majority of patients with ITAC. Adjuvant radiotherapy is recommended in advanced-stage and high-grade lesions. More robust data are required to confirm that early-stage, low-grade lesions can be treated with exclusive surgery. The efficacy of new chemotherapy and biotherapy regimens and the added value of heavy particle radiotherapy are currently under evaluation. With a 5-year overall survival ranging between 53 and 83%, which is mainly impacted by local recurrences, ITAC requires a more detailed understanding of its biology. Genetic and biological studies have identified alterations in the molecular pathways of EGFR, MET, and H-RAS which might be considered as potential targets for biotherapy. Summary Surgery still plays a key role in the treatment of ITAC, but multidisciplinary management is mandatory. Although further validation is needed, the role of nonsurgical treatment strategies is rising, in agreement with the progresses made in the biological profiling of the disease. Correspondence to Piero Nicolai, MD, Unit of Otorhinolaryngology, Spedali Civili of Brescia, University of Brescia, Piazza Spedali Civili, 1, 25123 Brescia, Italy. Tel: +39 0303995319; fax: +39 030395212; e-mail: pieronicolai@virgilio.it Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Outcomes of Donation After Cardiac Death Liver Grafts from Donors ≥ 50 years of Age: A Multi-center Analysis
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Utility of Radionuclide Bone Scintigraphy in Complex Regional Pain Syndrome
Abstract
Purpose of Review
To describe the current understanding of the role of three-phase bone scintigraphy (TPBS) in the diagnosis and management of complex regional pain syndrome (CRPS), discuss its advantages and limitations, and present three examples of TPBS patterns typically seen in CRPS patients.
Recent Findings
CRPS is a debilitating disorder frequently presenting with pain to ordinarily non-painful stimuli, redness, swelling, following fractures, stroke, myocardial infarction, surgery, or even minor trauma, and its diagnosis, based on clinical criteria and supportive imaging findings, is difficult. Of the available adjunctive diagnostic imaging modalities, radionuclide bone scintigraphy using a TPBS protocol is the most sensitive and specific for detecting abnormalities commonly seen with this condition—classically, increased periarticular uptake on delayed phase of TPBS, with variable increased uptake on perfusion phases, depending on chronicity. Recent studies have (1) demonstrated a more heterogeneous correlation of TPBS findings with CRPS diagnosis using the current Budapest criteria than in studies using older criteria, (2) pointed to the utility of novel quantitative scintigraphic techniques, and (3) highlighted the value of the early perfusion phases of TPBS in predicting treatment response.
Summary
TPBS remains a valuable imaging adjunct to clinical diagnosis of CRPS. In combination with a multi-modal analgesic approach, TPBS can be used to follow disease course and potentially treatment response, although prospective trials are needed to further delineate its role.
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Medical Cannabis for Neuropathic Pain
Abstract
Purpose of Review
Many cultures throughout history have used cannabis to treat a variety of painful ailments. Neuropathic pain is a complicated condition that is challenging to treat with our current medications. Recent scientific discovery has elucidated the intricate role of the endocannabinoid system in the pathophysiology of neuropathic pain. As societal perceptions change, and legislation on medical cannabis relaxes, there is growing interest in the use of medical cannabis for neuropathic pain.
Recent Findings
We examined current basic scientific research and data from recent randomized controlled trials (RCTs) evaluating medical cannabis for the treatment of neuropathic pain. These studies involved patients with diverse etiologies of neuropathic pain and included medical cannabis with different THC concentrations and routes of administration. Multiple RCTs demonstrated efficacy of medical cannabis for treating neuropathic pain, with number needed to treat (NNT) values similar to current pharmacotherapies.
Summary
Although limited by small sample sizes and short duration of study, the evidence appears to support the safety and efficacy of short-term, low-dose cannabis vaporization and oral mucosal delivery for the treatment of neuropathic pain. The results suggest medical cannabis may be as tolerable and effective as current neuropathic agents; however, more studies are needed to determine the long-term effects of medical cannabis use. Furthermore, continued research to optimize dosing, cannabinoid ratios, and alternate routes of administration may help to refine the therapeutic role of medical cannabis for neuropathic pain.
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Making Sports Accessible to Student Athletes with Hearing Loss
Time Out! I Didn't Hear You, was published in 1996 as a resource to support the participation of student athletes with hearing loss in high school athletics. This article describes a project to update the resource for all stakeholders involved in making college level athletics accessible to students with hearing loss. 
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Cross-Generalization Profile to Orosensory Stimuli of Rats Conditioned to Avoid A High Fat/High Sugar Diet
Abstract
The orosensory characteristics of a diet play a role in its acceptance and rejection. The current study was designed to investigate the gustatory components that contribute to the intake of a palatable, high-energy diet (HE; 45% calories from fat, 17% calories from sucrose). Here, rats were conditioned to avoid HE diet by pairings with i.p. injections of LiCl to induce visceral malaise. Subsequently, the degree of generalization was tested to an array of taste compounds using a brief-access lick procedure (10-s trials, 30-min sessions). Compared to NaCl-injected controls, LiCl-injected rats suppressed licking response to 100% linoleic acid and 20% intralipid, and to a lesser extent 17% sucrose. There was more variability in the lick responses to sucrose among the LiCl-injected rats. Rats that tended to suppress licking responses to sucrose generalized this response to glucose, fructose and Na-saccharin but not to Polycose. In contrast, LiCl-injected rats did not significantly suppress lick responses to water, NaCl, citric acid or quinine compared to controls rats. The brief access feature of this procedure, allows for behavioral measures when postingestive factors are minimized. These findings support a role for gustatory cues in the detection of high fat/high sugar diets. Furthermore, it appears that the fat component is a more salient orosensory feature of the HE diet.http://ift.tt/2rZqJUA
Olfactory Adaptation is Dependent on Route of Delivery
Abstract
Odorants are perceived orthonasally (nostrils) or retronasally (oral cavity). Prior research indicates route of delivery impacts odorant perception, pleasantness, and directed behaviors thus suggesting differential processing of olfactory information. Adaptation is a form of neural processing resulting in decreased perceived intensity of a stimulus following prolonged and continuous exposure. The present study objective was to determine whether route of delivery differentially impacts olfactory adaptation and whether cross-adaptation occurs between orthonasal and retronasal pathways. Linalool (12%) or vanillin (25%) were delivered orthonasally (6 liters/min [LPM]) and retronasally (8 LPM) in air phase through a custom built olfactometer. Perceived odorant intensity was collected every 5 mins over 10-mins exposure. Immediately following the exposure period, cross-adaptation was assessed by shunting the delivery of the odorant from the nostrils to the oral cavity, or vice versa. A control study was also completed in which subjects underwent the orthonasal adaptation protocol using stimulus concentrations matched to the intensity of restronasal stimuli (e.g. 1.5% linalool and 6.25% vanillin). Following orthonasal delivery of both high and low vanillin concentrations, results showed perceived intensity decreased significantly at 5- and 10-mins. High concentrations of orthonasal linalool similarly decreased significantly whereas lower concentrations decreased but did not reach statistical significance. Linalool and vanillin delivered retronasally did not adapt as perceived intensity actually increased significantly following a 10-min exposure. In addition, evidence of cross-adaptation was not obvious following extended odorant exposure from either delivery pathway. This study suggests that olfactory processing may be affected by the route of odorant delivery.http://ift.tt/2GCtgYj
Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro
Abstract
Objective
To analyze the influence of an oral bisphosphonate and compare the potency to intravenous bisphosphonates on various cell types as regards the rarity of bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) caused by oral bisphosphonate.
Materials and methods
A viability assay (MTT), a migration assay (Boyden chamber), and an apoptosis assay (Caspase-Glo® 3/7) were performed to analyze the effect of bisphosphonates on human fibroblasts, umbilical vein endothelial cells (HUVEC), and osteoblasts.
Results
Alendronate and intravenous bisphosphonates suppressed cell viability and migration, and induced apoptosis in all tested cell types. Alendronate had a greater impact than ibandronate on the characteristics in fibroblasts and osteoblasts but not as strong as zoledronate.
Conclusions
The incidence of BP-ONJ in oral bisphosphonate treatment is reported to be much lower than that in intravenous bisphosphonates. However, the influences of alendronate on human cells were at least as strong as ibandronate, although it was lower than zoledronate.
Clinical relevance
Alendronate showed strong enough effects to suppress human somatic cells and was comparable to certain intravenous bisphosphonates in potency. This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies.
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Assessment of condylar morphology and position using MSCT in an Asian population
Abstract
Objectives
The purpose of the present study was to investigate the volume, surface, morphometric index (MI), and position of the condyle in a normal population by applying Mimics 17.0 software. Then, the difference between left and right sides, sex, and age can be explored, which will contribute to establish the reference value of condylar morphology and position in normal individuals, and help us to study characteristics of condylar morphology and position in abnormal individuals.
Materials and methods
Three-hundred subjects were enrolled in our study from the radiology department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital. They were divided into three groups according to the age: group 1 (18–24 years old), group 2 (25–34 years old), and group 3 (35–44 years old). Each group included 100 subjects (with 50 males and 50 females). They were examined using multislice computed tomography (MSCT) after that. All images of condyle were reconstructed by Mimics 17.0 software, so as to measure the volume, surface, and MI of condyle, and to analyze the position of condyle in the articular fossa by means of joint spaces.
Results
The differences of condylar volume, surface, and MI between left and right sides were not obvious (P > 0.05). The condylar volume and surface were greater in males than females (P < 0.05), while their condylar MI existed no difference (P > 0.05). No statistical differences were found in volume and surface among three age groups. However, the MI of group 1 was statistically lower than that of group 3 (P < 0.05). On the other hand, no significant differences were found between left and right condylar position (P > 0.05). Nevertheless, there were significant differences of condylar position regarding the gender and age (P < 0.05).
Conclusions
This study showed no significant differences in condylar morphology and position between left and right sides, but factors of gender and age were proven to have a certain influence on the morphology and position of the condyle. This information can be clinically useful in establishing the diagnostic criteria for condylar morphology and position in the normal Asian population.
Clinical relevance
Examination of condylar morphology and position is important for evaluating the abnormalities and bony changes that affect the temporomandibular joint (TMJ). So, this will be conducive to the diagnosis and the evaluation of therapeutic effect of temporomandibular joint diseases. Also, it is important to evaluate these indexes prior to commencing orthodontic treatment, because TMJ abnormalities play a critical role in orthodontic treatment planning.
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Use of balloon catheter dilation vs. traditional endoscopic sinus surgery in management of light and severe chronic rhinosinusitis of the frontal sinus: a multicenter prospective randomized study
OBJECTIVE: Chronic rhinosinusitis (CRS) of the frontal sinus is a complex pathological condition and many surgical techniques were described to treat this area endoscopically, like traditional endoscopic sinus surgery (ESS) and balloon catheter dilation (BCD).
PATIENTS AND METHODS: We designed a multicenter prospective randomized study to assess the validity and safety of BCD vs. ESS in symptomatological chronic rhinosinusitis of the frontal sinus enrolling a population of 102 adult patients (64 men and 38 women; overall 148 frontal sinuses studied) with non-polypoid CRS. For a better evaluation of the disease, in our study we decided to analyze both radiological (Lund-McKay CT scoring modified by Zinreich) and symptomatological results (SNOT-20 questionnaire). We divided the population affected in two groups, one with light/mild frontal CRS and the other with moderate/severe frontal CRS, basing on radiological findings at Lund-MacKay modified by Zinreich score. Every group was divided in two subgroups, in one we used BCD and in the other we used traditional ESS.
RESULTS: The current literature does not support the suggestion that indications for BCD and ESS are identical, and additional research is needed to determine the role for BCD in specific patient populations. The results showed a not statistically significative difference between BCD and conventional ESS of the frontal sinus in patients with light/mild CRS and in patients with moderate/severe CRS at Lund-Mackay modified by Zinreich score. The same not statistically significative difference was observed comparing the results of SNOT-20 questionnaire in the group of light/mild frontal chronic rhinosinusitis. However, we noticed a statistically significant better outcome of SNOT-20 score in patients with moderate/severe chronic rhinosinusitis that underwent BCD of frontal sinus compared to ESS.
CONCLUSIONS: BCD and ESS are two alternative weapons in the baggage of every endoscopic surgeon, even because they present similar outcomes, safeness and effectiveness both in light/mild and moderate/severe chronic rhinosinusitis of the frontal sinus. An interesting result of our study was the statistically significant better outcome of SNOT-20 score in patients that underwent BCD of frontal sinus for a moderate/severe CRS, compared to those that underwent a traditional ESS.
L'articolo Use of balloon catheter dilation vs. traditional endoscopic sinus surgery in management of light and severe chronic rhinosinusitis of the frontal sinus: a multicenter prospective randomized study sembra essere il primo su European Review.
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The Effect of Light Exposure on Insomnia anssd Nocturnal Movement in Parkinson’s Disease:An Open Label, Retrospective, Longitudinal Study
Source:Sleep Medicine
Author(s): Jessica T. Martino, Christopher B. Freelance, Gregory L. Willis
Insomnia, hypersomnia and REM Sleep Behavior Disorder (RSBD) during sleep are major problems for patients suffering from Parkinson's disease (PD) but they are also used to predict its onset. While these secondary symptoms detract from the quality of life in PD patients, few treatment options are available due to limited efficacy or risk of complicating the treatment regimen. Light therapy (LT) has been suggested as a strategy for sleep disorders but it has only been implemented recently for use in PD. An open label, retrospective study was undertaken where PD patients had been undergoing LT, using polychromatic light, for four months to 15 years prior. It was found that one hr. exposure to light, just prior to retiring, significantly improved insomnia and reduced RSBD in as little as one month after commencing LT. In addition, the improvement was maintained as long as LT was continued over a four to six year period. The efficacy of LT in alleviating these sleep related conditions was not compromised by time since diagnosis or age of the patient. These results intimate the value of long term application of non-invasive techniques such as LT for treating sleep disorders in PD and justify further controlled trials on the long term efficacy of LT.
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Prevalence of restless legs syndrome in Parkinson’s disease: a systematic review and meta-analysis of observational studies
Source:Sleep Medicine
Author(s): Xinglong Yang, Bin Liu, Hao Shen, Shimei Li, Quanzhen Zhao, Ran An, Fayun Hu, Hui Ren, Yanming Xu, Zhong Xu
ObjectiveRestless legs syndrome (RLS) and Parkinson's disease (PD) are common neurological disorders that respond to dopaminergic therapy. RLS prevalence among people with PD varies widely (0-38%) in the literature, complicating efforts to understand whether the two diseases might be associated.MethodThe databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for observational and case-control studies of RLS prevalence in PD. Eligible studies were meta-analyzed using Stata 12.0.ResultsPooled RLS prevalence in PD among various patient populations was 14%, and prevalence in Asia (12%) was slightly lower than outside Asia (16%). Prevalence was higher among patients who had previously received PD treatment (15%) than among drug-naïve patients (11%). Prevalence of RLS was higher in female PD patients (13%) than in male patients (11%). RLS prevalence was much higher among PD patients than among healthy controls (OR 2.86, 95% CI 2.10-3.90; p<0.001).ConclusionThis meta-analysis may provide the first reliable pooled estimate of RLS prevalence in PD, and strong evidence that RLS risk is higher among PD patients than among healthy individuals.
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Factors Associated with Insomnia and Complementary Medicine Use in Children: Results of a National Survey
Source:Sleep Medicine
Author(s): Ezra M. Cohen, Michelle L. Dossett, Darshan H. Mehta, Roger B. Davis, Yvonne C. Lee
ObjectivesSleep difficulties are a serious health problem in children, and interest in using complementary and alternative medicine (CAM) therapies to treat sleep is growing. We aimed to identify: a) the prevalence of sleep difficulties in children, and b) the prevalence and patterns of CAM use among children with trouble sleeping.MethodsWe used the 2012 National Health Interview Survey (NHIS) dataset to estimate the prevalence of sleep difficulties and CAM use in children ages 6 to 17 years. Prevalence estimates were weighted to reflect the survey's sampling design. We used logistic regression to explore associations between sleep difficulties, psychosocial factors, comorbidities and CAM use.Results6.4% of children in the 2012 NHIS dataset reported regular difficulty sleeping in the last year, corresponding to an estimated 1.5 million children in the US. Older age, poorer health status, more school days missed, and multiple comorbidities were all associated with sleep difficulties (p ≤ 0.001). Among children with sleep difficulties, 29% used at least one CAM therapy. Of the CAM therapies surveyed, non-vitamin, non-mineral supplements were the most commonly used (14.6%), followed by manipulation therapies (9.2%) and mind-body techniques (8.8%). Parental education and CAM use were most strongly associated with child CAM use (p ≤ 0.001).ConclusionsCAM therapies, particularly non-vitamin, non-mineral supplements, are commonly used among children with sleeping problems. More research is needed to characterize the safety and efficacy of CAM therapies for sleep in this population.
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Restless legs syndrome: A rarity in the Nigerian pregnant population?
Source:Sleep Medicine
Author(s): Michael B. Fawale, Ismaila I. Alani, Abubakar A. Kullima, Morenikeji A. Komolafe, Omotade A. Ijarotimi, Samuel Anu Olowookere, Rotimi Oluyombo, Tewogbade Adeoye Adedeji
ObjectivesThe prevalence of RLS in pregnancy is higher when compared with the general population however it remains unknown among indigenous black Africans. Available data indicate that RLS is uncommon in sub-Saharan Africa. We embarked on this study to determine the prevalence and characteristics of RLS in an antenatal clinic sample of Nigerian pregnant women compared with a primary care sample of non-pregnant women.MethodsA total of 310 pregnant women and non-pregnant women filled out a questionnaire which incorporated the 2014 minimal criteria of the International Restless Legs Syndrome Study Group. Demographic and clinical data, including sleep duration and samples for blood hemoglobin concentration and urinalysis were obtained.ResultsThe mean ages of the pregnant and non-pregnant women were 24.9 ± 5.6 years and 23.6 + 5.4 years, respectively (p = 0.003). There was no case of RLS found among pregnant women while five (1.6%) of the non-pregnant women fulfilled the criteria for RLS. Overall, the prevalence report of RLS symptoms was associated with lower mean habitual nocturnal sleep duration (p < 0.05) coffee (p = 0.013) and kola nut (0.023) consumption, report of leg cramps (p < 0.001) and proteinuria (p = 0.047), Report of leg cramps and proteinuria were independently associated with RLS.ConclusionThe prevalence of restless legs syndrome is low among women of child-bearing age in the Nigerian population and may be lower in pregnancy. Report of leg cramps and proteinuria are independently associated with RLS.
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RBD: a red flag for cognitive impairment in Parkinson’s disease?
Source:Sleep Medicine
Author(s): Yiqi Lin, Shengdi Chen
The increasing evidence indicates that there is a strong association between rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease - cognitive impairment (PD-CI). Numerous longitudinal and cross-sectional studies have shown that RBD may be an important risk factor and predictor of Parkinson's disease – mild cognitive impairment (PD-MCI) and Parkinson's disease dementia (PDD), which may be explained by association of mechanisms between RBD and PD-CI including neurotransmitter alterations, genetic mutation, neuroinflammation, alpha-synuclein inclusion, abnormal cerebral metabolism and slowing of cortical activity. Understanding the role of RBD in cognition of PD, we may predict and prevent the presence of PD-CI. The purpose of this comprehensive narrative review was to investigate the role of RBD in cognition of PD patients and its possible mechanism with lights from clinical epidemiological evidence, neuroimaging and electrophysiology studies.
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Joint effects of OSA and self-reported sleepiness on incident CHD and stroke
Source:Sleep Medicine
Author(s): Rachel P. Ogilvie, Kamakshi Lakshminarayan, Conrad Iber, Sanjay R. Patel, Pamela L. Lutsey
BackgroundAlthough excessive daytime sleepiness (EDS) is a common symptom of obstructive sleep apnea (OSA), and both EDS and OSA have separately been associated with increased risk of cardiovascular disease (CVD), their joint association with CVD risk is unknown.MethodsAmong 3,874 Sleep Heart Health Study (SHHS) participants without prevalent CVD, moderate to severe OSA was defined by an apnea hypopnea index (AHI) ≥ 15 on an in-home polysomnography. EDS was defined as an Epworth Sleepiness Scale score ≥ 11. Incident CVD events included total CVD events (coronary heart disease (CHD) and stroke), as well as CHD and stroke separately. Cox proportional hazards models adjusted for age, sex, alcohol, smoking, and body mass index.ResultsCompared to those with AHI <15, the hazard ratios (95% CI) for the association of moderate-severe OSA (AHI ≥15) were as follows: CVD 1.06 (0.85-1.33); CHD 1.08 (0.85-1.33); and stroke 1.18 (0.75-1.84). Weak associations between EDS and CVD risk = [1.22 (1.01-1.47)] and CHD risk [1.25 (1.02-1.53)] were present, however there were none for stroke risk [1.10 (0.75-1.63)]. When modeled jointly, both AHI ≥15 and EDS (compared with having AHI <15 and no EDS) was associated with HRs of 1.26 (0.91-1.73) for CVD, 1.24 (0.87-1.75) for CHD and 1.49 (0.78-2.86) for stroke. There were no statistically significant interactions between daytime sleepiness and OSA on the multiplicative or additive scales.ConclusionsHaving both EDS and moderate-severe OSA was not associated with an increased risk of CVD in the SHHS data.FundingThe Sleep Heart Health Study was obtained from the National Sleep Research Resource, funded by NIH (R24HL114473). In addition, support for R. Ogilvie was provided by NIH grants T32HL007779 and T32HL082610.
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Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort
Source:Sleep Medicine
Author(s): Simon M. Collin, Tom Norris, Paul Gringras, Peter S. Blair, Kate Tilling, Esther Crawley
Objective/Background: Sleep abnormalities are characteristic of chronic fatigue syndrome (CFS, also known as 'ME'), but it is not known whether sleep might be a causal risk factor for CFS/ME.Patients/MethodsWe analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. We describe sleep patterns from age 6 months to 11 years in children who were subsequently classified as having (or not having) 'chronic disabling fatigue' (CDF, a proxy for CFS/ME) between ages 13-18 years, and investigate associations of sleep duration at age 9 with CDF at age 13, and sleep duration at age 11 with CDF at age 16 years.ResultsChildren who had CDF during adolescence had shorter nighttime sleep duration from age 6 months to age 11 years, and there was strong evidence that difficulties in going to sleep were more common in children who subsequently developed CDF. The odds of CDF at age 13 were 39% lower (odds ratio (OR) = 0.61, 95% CI 0.43, 0.88) for each additional hour of nighttime sleep at age 9 years, and the odds of CDF at age 16 were 51% lower (OR = 0.49, 95% CI 0.34, 0.70) for each additional hour of nighttime sleep at age 11. Mean nighttime sleep duration at age 9 was 13.9 (95% CI 3.75, 24.0) minutes shorter among children who developed CDF at age 13, and sleep duration at age 11 was 18.7 (95% CI 9.08, 28.4) minutes shorter among children who developed CDF at age 16 (compared with children who did not develop CDF at 13 and 16, respectively).ConclusionsChildren who develop chronic disabling fatigue in adolescence have shorter nighttime sleep duration throughout early childhood, suggesting that sleep abnormalities may have a causal role in CFS/ME or that sleep abnormalities and CFS/ME are related to a common pathophysiological cause.
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Use of balloon catheter dilation vs. traditional endoscopic sinus surgery in management of light and severe chronic rhinosinusitis of the frontal sinus: a multicenter prospective randomized study
OBJECTIVE: Chronic rhinosinusitis (CRS) of the frontal sinus is a complex pathological condition and many surgical techniques were described to treat this area endoscopically, like traditional endoscopic sinus surgery (ESS) and balloon catheter dilation (BCD).
PATIENTS AND METHODS: We designed a multicenter prospective randomized study to assess the validity and safety of BCD vs. ESS in symptomatological chronic rhinosinusitis of the frontal sinus enrolling a population of 102 adult patients (64 men and 38 women; overall 148 frontal sinuses studied) with non-polypoid CRS. For a better evaluation of the disease, in our study we decided to analyze both radiological (Lund-McKay CT scoring modified by Zinreich) and symptomatological results (SNOT-20 questionnaire). We divided the population affected in two groups, one with light/mild frontal CRS and the other with moderate/severe frontal CRS, basing on radiological findings at Lund-MacKay modified by Zinreich score. Every group was divided in two subgroups, in one we used BCD and in the other we used traditional ESS.
RESULTS: The current literature does not support the suggestion that indications for BCD and ESS are identical, and additional research is needed to determine the role for BCD in specific patient populations. The results showed a not statistically significative difference between BCD and conventional ESS of the frontal sinus in patients with light/mild CRS and in patients with moderate/severe CRS at Lund-Mackay modified by Zinreich score. The same not statistically significative difference was observed comparing the results of SNOT-20 questionnaire in the group of light/mild frontal chronic rhinosinusitis. However, we noticed a statistically significant better outcome of SNOT-20 score in patients with moderate/severe chronic rhinosinusitis that underwent BCD of frontal sinus compared to ESS.
CONCLUSIONS: BCD and ESS are two alternative weapons in the baggage of every endoscopic surgeon, even because they present similar outcomes, safeness and effectiveness both in light/mild and moderate/severe chronic rhinosinusitis of the frontal sinus. An interesting result of our study was the statistically significant better outcome of SNOT-20 score in patients that underwent BCD of frontal sinus for a moderate/severe CRS, compared to those that underwent a traditional ESS.
L'articolo Use of balloon catheter dilation vs. traditional endoscopic sinus surgery in management of light and severe chronic rhinosinusitis of the frontal sinus: a multicenter prospective randomized study sembra essere il primo su European Review.
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Photochemical transformation of dimethyl phthalate (DMP) with N(III)(H2ONO+/HONO/NO2-) in the atmospheric aqueous environment
Photochem. Photobiol. Sci., 2017, Advance Article
DOI: 10.1039/C7PP00283A, Paper
DOI: 10.1039/C7PP00283A, Paper
Yu Lei, Chengzhu Zhu, Jun Lu, Rong Chen, Jun Xiao, Shuchuan Peng
The primary step of photochemical transformation of dimethyl phthalate (DMP) with N(III) is [radical dot]OH-addition on the aromatic ring of DMP to form a DMP-OH adduct, followed by several decay channels and corresponding rate constants are determined.
To cite this article before page numbers are assigned, use the DOI form of citation above.
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The primary step of photochemical transformation of dimethyl phthalate (DMP) with N(III) is [radical dot]OH-addition on the aromatic ring of DMP to form a DMP-OH adduct, followed by several decay channels and corresponding rate constants are determined.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
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The effects of rhBMP-2/7 heterodimer and RADA16 hydrogel scaffold on bone formation during rabbit mandibular distraction
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Ling-fei Ren, Geng-sheng Shi, Yong-qing Tong, Song-yao Jiang, Feng Zhang
PurposeThe effects of a rhBMP-2/7 heterodimer and a RADA16 (Ac-RADARADARADARADA-CONH2) hydrogel scaffold on bone formation during distraction osteogenesis were evaluated.MethodsForty New Zealand white rabbits, which underwent mandibular lengthening, were randomly divided into five groups. One group served as a control group. The others received 2 μg rhBMP-2 homodimer, 2 μg rhBMP-2/7 heterodimer, 100 μL RADA16 or 100 μl RADA16+2 μg rhBMP-2/7 heterodimer in the mandibular distraction gap at the beginning of distraction. [18F-] fluoride positron emission tomography (PET) was used to assess osteogenesis both after distraction and at the end of consolidation. Dual-energy X-ray absorptiometer (DEXA) examination and bone histology were also evaluated.ResultsAt the end of distraction, the radioactivity concentration in the distracted area was significantly higher in the RADA16+ rhBMP-2/7 heterodimer group than the other groups (p<0.01); differences between the other four groups were also statistically significant in the following order: rhBMP-2/7 heterodimer group > rhBMP-2 homodimer group > RADA16 group (or control group) (p<0.05). However, the radioactivity concentration of the RADA16 group was slightly higher than that of the control group with a non-significant difference (p>0.05). By the end of consolidation, activity in the control group, RADA16 group, rhBMP-2 homodimer group and rhBMP-2/7 heterodimer group had significantly diminished (p<0.05); however, the activity in the RADA16+ rhBMP-2/7 heterodimer group remained at the same level (p>0.05). DEXA results and bone histology findings indicated that more callus regeneration was noted in the RADA16+ rhBMP-2/7 heterodimer group than any other group.ConclusionRhBMP-2/7 heterodimer and RADA16 hydrogel scaffold significantly promote mandibular distraction osteogenesis.
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Custom-made titanium miniplates associated with a ultra-high molecular weight polyethylene graft in orthognathic surgery: an adjunct to maxillary advancement.
Source:Journal of Oral and Maxillofacial Surgery
Author(s): José Thiers Carneiro Júnior, Paulo Hemerson de Moraes, Douglas Voss de Oliveira, Nayara Cristina Monteiro Carneiro
Patients with considerable maxillomandibular anteroposterior discrepancies and maxillary hypoplasia, require corrective treatment through orthognathic surgery. However, in the treatment of severe maxillary retrognathism, it is necessary to reconstruct the areas of bone deficiency through grafting techniques in addition to maxillary advancement using only the Le Fort I osteotomy. Treatment in these patients is more challenging and requires high surgical predictability. Alloplastic materials have often been used for the reconstruction of poor bone contours. Ultrahigh molecular weight polyethylene (UHMWPE) is currently an excellent alternative as a filler material for poor bone regions and is a good substitute for autografts and other alloplastic materials for their unique properties, including high biocompatibility. The insertion of this material in the fixation system customized in orthognathic surgeries planned virtually is an innovative technique. This paper describes an association of UHMWPE inserted into the custom-made titanium miniplates manufactured by CAD-CAM (computer-aided desing/computer-aided manufacturing) technology in a surgery orthognathic of maxillary advancement and mandibular retrusion to treat a patient with Crouzon's syndrome with class III malocclusion and severe maxillary retrognathism.
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Long-Term Effects of Distraction Osteogenesis of the Mandible
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Zachary S. Peacock, Alfonso Salcines, Maria J. Troulis, Leonard B. Kaban
PurposeTo assess the fate of the permanent teeth in and adjacent to the regenerate in pediatric patients who underwent mandibular distraction osteogenesis (DO). Second, to compare the post-operative growth of the distracted mandible to age and gender matched controls.MethodsThis was a retrospective cohort study of children who underwent mandibular DO, during the primary or mixed dentition period and prior to completion of somatic growth (males ≤ 14 years old; females ≤12 years old), at Massachusetts General Hospital from 1996-2014. From the DO Registry, subjects were selected who had complete clinical and radiographic records and ≥1 year follow-up. Patients with disorders of dental development (e.g. ectodermal dysplasia) were excluded. Panoramic radiographs were used to assess changes in morphology, eruption and orientation of the the dentition. Standardized digital lateral cephalograms were used to assess the mandible (SNB, mandibular unit length, ramus height, body length) preoperatively(T0), at end-distraction(T1), 1 year post-device removal(T2) and longest follow-up(T3).ResultsA total of 118 patients in the registry had DO during the study period. For assessment of the effects on the dentition, 26 patients, who had 36 osteotomies and distraction wounds, met inclusion criteria. In this sample, 22/26 subjects (85%) experienced 52 adverse effects in 38/90 permanent teeth (42.2%) assessed. Cephalometric measurements at T3 indicated that there was net mandibular growth at longest follow-up, after a period of skeletal relapse during T1-T2; however, only 2/25 (8%) subjects regained a growth rate in the vector of DO that matched or exceeded normal age and gender matched controls.ConclusionDO commonly results in adverse effects on the dentition within and adjacent to the DO gap with only a minority resolving over time. Net growth of the mandible occurs after DO but at a slower rate and lesser magnitude than that of age and sex matched controls.
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Management of facial pyoderma gangrenosum using platelet-rich fibrin: a technical report
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Leonzio Fortunato, Selene Barone, Francesco Bennardo, Amerigo Giudice
This report describes a case of local pyoderma gangrenosum that was treated with short-term immunosuppressive therapy and the topical application of platelet-rich fibrin (PRF).Medical treatment included an oral corticosteroid therapy and a topical treatment with PRF in solid and liquid form. The previously mentioned therapy initially led to the reduction of the ulcer's size and an improvement of the symptoms, until the ulcer was completely healed after a few weeks. A relapse was treated only with the application of PRF to the affected tissue with an excellent recovery. The efficacy of PRF as a guide for wound healing is due to the continuous release of growth factors involved in tissue repair mechanisms. PRF has proved to be suitable for the management of facial pyoderma gangrenosum while allowing a reduction of systemic corticosteroids therapy. The ease of preparation, low cost, and outpatient use make PRF an optimal scaffold for tissue healing processes.
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The influential bony factors and vectors for predicting soft tissue responses after orthognathic surgery in mandibular prognathism
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Yoon-Sic Han, Ho Lee
PurposeTo identify hard tissue points and vectors that have the greatest effect on soft tissue movements after orthognathic surgery in patients with mandibular prognathism.Patient and MethodsThis retrospective study involved patients who underwent mandibular setback surgery with or without maxillary advancement. Multiple linear regression models were adapted to evaluate the association between the eight hard tissue landmark (predictor variables) changes and 11 soft tissue responses (outcome variables) based on the x and y coordinates assessed from superimposed pre- and postoperative three-dimensional computed tomography images.ResultsA total of 50 patients (42 patients underwent two-jaw surgery; eight patients underwent one-jaw surgery; mean age, 23 ± 4 years) were included in the present study. Our statistical models demonstrated that horizontal hard tissue changes had a greater influence on the soft tissue responses than the vertical changes did, and these changes were more notable in the lower facial area (lower lip contour and chin profile) than the midfacial area (nasal profile, upper lip contour, upper lip length, and nasolabial angle). In the horizontal soft tissue response model, the ratio of soft tissue A point to A point was 0.86 (95% CI, 0.674-1.049):1; the ratio of soft tissue B point to B point was almost 1 (95% CI, 0.919-1.071):1; and the ratio of the soft tissue pogonion to the pogonion was 0.88 (95% CI, 0.805-0.963):1.ConclusionsHorizontal or vertical bone tissue changes affected both the horizontal and vertical soft tissue changes in most areas. Our study demonstrated that the soft tissue response is not a linear change, but a more complicated and dynamic reaction.
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Clinical and radiographic performance of the rough surfaced implants placed in the atrophic posterior maxilla with sinus membrane elevation without bone graft: A prospective and preliminary study
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Suhyun Park, Hyun-Joong Yoon
PurposeThe aim of this prospective and preliminary study was to compare the clinical and radiographic outcomes of two types of rough surfaced implants after implant placement in the atrophic posterior maxilla with sinus membrane elevation without bone grafting using the crestal approach.Materials and MethodsAll clinical and radiographic records for 28 patients who received 40 implants were included in this study. The patients were recalled for radiographic and clinical examinations at 1, 3, and 6 months and every 6 months thereafter following implantation.CBCT images were taken to evaluate the amount of bone gain in the maxillary sinus. Standardized periapical digital radiographs were taken to evaluate changes in the crestal peri-implant bone level and peri-implant fixture radiolucency.ResultsThe Kaplan-Meier survival estimates demonstrated a 100% probability of survival to 24 months. There were no significant differences in cervical bone loss (CBL) and residual bone height (RBH) between the TS III CA group and the TS III SA group during the 2 years of follow up after implant placement. The CBL values according to gender, implant placement region, prosthesis type, and the time of implantation were not significantly different between the two groups.ConclusionThis preliminary study demonstrates that two types of rough surfaced implants placed in the atrophic posterior maxilla with sinus membrane elevation without a bone graft have good clinical and radiographic outcomes.
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Does the medical comorbidity profile of OSA patients treated with maxillomandibular advancement differ from that of OSA patients managed nonsurgically?
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Richard Ngo, Elaina Pullano, Zachary S. Peacock, Edward T. Lahey, Meredith August
PurposeObstructive sleep apnea (OSA) patients with retrognathia and measurable anatomic airway determinants may represent a subset of OSA patients and have distinct comorbidity profiles. Our aim is to compare the medical comorbidities of OSA patients managed surgically with maxillomandibular advancement (MMA) to those of non-surgical patients.Patients and MethodsThis is a cross-sectional retrospective study. Subjects for both cohorts were identified through the Massachusetts General Hospital Oral and Maxillofacial Surgery(OMS) data registry and the MGH Research Patient Data Registry(RPDR). Inclusion criteria consisted of clinical records documenting BMI, apnea-hypopnea index(AHI), respiratory disturbance index(RDI), and/or O2 nadir. The primary predictor variable was the treatment modality chosen: surgical(MMA) or nonsurgical. Demographic information and OSA parameters were evaluated. The primary outcome variable was the number of documented comorbidities in each group. Two-sample t-tests were used for continuous variables. Chi-square or Fisher's exact tests were used for categorical variables.ResultsThe non-surgical cohort consisted of 71 subjects(67.6% male) and the surgical cohort of 51 subjects(84.3% male). Comparison of descriptive characteristics showed that the nonsurgical cohort had a higher average age(49±9.4) than the surgical cohort(41±10.7; P< .001). A higher average BMI was also present among the nonsurgical group(42.3±11.9 nonsurgical vs. 29.7±5.5 surgical; P<.001). Polysomnogram parameters were comparable with exception of a higher Epworth Sleepiness Scale (ESS) in the surgical cohort(15.5±5.30 surgical vs. 9.90±6.80 nonsurgical; P=.005). The non-surgical cohort had a higher total number of comorbidities(7± 4 nonsurgical vs. 4± 3 surgical; P<0.001). Hypertension, cardiovascular disease, hyperlipidemia, pulmonary hypertension, obstructive pulmonary disease, and type 2 diabetes mellitus (DM) had higher prevalence within the non-surgical group.ConclusionThe results of this study suggest that non-surgically managed OSA patients tend to have more complex medical comorbidity profiles than those managed surgically. Obesity (BMI>30) was more prevalent in the nonsurgical cohort, which may be contributory. The additive contribution of OSA needs to be further elucidated.
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Unilateral congenital hearing loss in children: challenges and potentials
Source:Hearing Research
Author(s): Astrid van Wieringen, An Boudewyns, Anouk Sangen, Jan Wouters, Christian Desloovere
The estimated incidence of sensorineural hearing impairment (> 40 dB HL) at birth is 1.86 per 1000 newborns in developed countries and 30-40% of these are unilateral. Profound sensorineural unilateral hearing impairment or single sided deafness (SSD) can be treated with a cochlear implant. However, this treatment is costly and invasive and unnecessary in the eyes of many. Very young children with SSD often do not exhibit language and cognitive delays and it is hard to imagine that neurocognitive skills will present difficulties with one good ear. In the current paper we review the most recent evidence on the consequences of unilateral hearing impairment for auditory and neurocognitive factors. While data of both adults and children are discussed, we focus on developmental factors, congenital deafness and a window of opportunity for intervention. We discuss which etiologies qualify for a cochlear implant and present our multi-center prospective study on cochlear implants in infants with one deaf ear. The large, state-of-the art body of research allows for evidence-based decisions regarding management of unilateral hearing loss in children.
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Subcortical pathways: towards a better understanding of auditory disorders
Source:Hearing Research
Author(s): Richard A. Felix, Boris Gourévitch, Christine V. Portfors
Hearing loss is a significant problem that affects at least 15% of the population. This percentage, however, is likely significantly higher because of a variety of auditory disorders that are not identifiable through traditional tests of peripheral hearing ability. In these disorders, individuals have difficulty understanding speech, particularly in noisy environments, even though the sounds are loud enough to hear. The underlying mechanisms leading to such deficits are not well understood. To enable the development of suitable treatments to alleviate or prevent such disorders, the affected processing pathways must be identified. Historically, mechanisms underlying speech processing have been thought to be a property of the auditory cortex and thus the study of auditory disorders has largely focused on cortical impairments and/or cognitive processes. As we review here, however, there is strong evidence to suggest that, in fact, deficits in subcortical pathways play a significant role in auditory disorders. In this review, we highlight the role of the auditory brainstem and midbrain in processing complex sounds and discuss how deficits in these regions may contribute to auditory dysfunction. We discuss current research with animal models of human hearing and then consider human studies that implicate impairments in subcortical processing that may contribute to auditory disorders.
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The relation between flocculus volume and tinnitus after cerebellopontine angle tumor surgery
Source:Hearing Research
Author(s): Lilian M. Mennink, J. Marc C. Van Dijk, Bernard F.A.M. Van Der Laan, Jan D.M. Metzemaekers, Peter Jan Van Laar, Pim Van Dijk
PurposeChronic tinnitus is a common symptom after cerebellopontine angle (CPA) tumor removal. Sometimes, the tinnitus is gaze-modulated. In that case, patients can change the loudness or pitch of their tinnitus by ocular movements. During tumor removal by a retrosigmoid craniotomy, the cerebellar flocculus is manipulated by the surgical approach to access the tumor. The flocculus has been associated with tinnitus in rats, and is involved in eye-gaze control. This suggests that the flocculus may have a role in gaze-modulated tinnitus after CPA tumor removal. In order to investigate this hypothesis, the relation between the flocculus volume and the characteristics of postoperative tinnitus was studied.ResultsA single-center cohort of 51 patients completed a questionnaire after CPA tumor removal. The questionnaire asked for the effect of eye movements on tinnitus and included the Tinnitus Functional Index (TFI). Tinnitus was present in 36 patients (71% of 51), of which 29 (81% of 36) described gaze-modulation. The median TFI was 22 (range 0-85). A postoperative MRI-scan of sufficient quality was available in 34 cases. The volumes of the (para)flocculi ipsilateral and contralateral to the surgery, and the ratio of these volumes were similar between patients with and without tinnitus. The TFI correlated with the volume of both ipsi- and contralateral (para)flocculus (rs(23) = .516, p = .008 and rs(23) = .430, p = .032). The ipsilateral-to-contralateral volume ratio of the (para)flocculi volumes was significantly lower in patients that could modulate the loudness of their tinnitus by eye gaze, compared to patients that could not (t(23) = 3.337, p = .003).ConclusionsThe lack of a relation between flocculus volumes and the presence of tinnitus, combined with the significant correlation between tinnitus severity and flocculus volumes, suggests that the flocculus may not be the primary source of tinnitus, but is likely to mediate tinnitus severity. The reduced ipsi-to-contralateral volume ratio in patients with gaze-modulated tinnitus suggests that atrophy of the flocculus on the surgery side triggers cross-modal interactions leading to modulation of tinnitus.
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Direct bone conduction stimulation: ipsilateral effect of different transducer attachments in active transcutaneous devices
Source:Hearing Research
Author(s): Cristina Rigato, Sabine Reinfeldt, Bo Håkansson, Karl-Johan Fredén Jansson, Erik Renvall, Måns Eeg-Olofsson
Active transcutaneous bone conduction devices, where the transducer is implanted, are used for rehabilitation of hearing impaired patients by directly stimulating the skull bone. The transducer and the way it is attached to the bone play a central role in the design of such devices. The actual effect of varying the contact to bone has not been addressed yet. The aim of this study is therefore to compare how different attachment methods of the transducer to the bone for direct stimulation affect the ear canal sound pressure and vibration transmission to the ipsilateral cochlea.Three different attachments to the bone were tested: (A) via a flat small-sized surface, (B) via a flat wide surface and (C) via two separated screws. Measurements were done on four human heads on both sides. The attachments were compared in terms of induced cochlear promontory velocity, measured by a laser Doppler vibrometer, and ear canal sound pressure, measured by a low noise microphone. A swept sine stimulus was used in the frequency range 0.1-10 kHz.On an average level, the attachment method seems to affect the transmission mainly at frequencies above 5 kHz. Furthermore, the results suggest that a smaller contact surface might perform better in terms of transmission of vibrations at mid and high frequencies. However, when considering the whole frequency range, average results from the different attachment techniques are comparable.
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Role of Otoacoustic Emissions in Hearing Assessment of Neonates: A Prospective Observational Study
Abstract
Hearing plays an important role for children in learning speech and language, socialization and cognitive development. The child learns to speak based on what is heard (Rundjan et al. in Sari Pediatr 6(4):149–154, 2005). The aim of the study was to find out the percentage of hearing loss by OAE among low risk and high risk neonates. All the neonates (Low and High risk) born in a tertiary care center were screened by OAE before their discharge from the hospital and after stabilizing high risk neonates. The referred neonates were followed after two weeks. Total 722 neonates were screened of which 130 were high risk and 592 were low risk. Neonates with Serum bilirubin > 20 mg/dl or requiring exchange transfusion were excluded as OAE will be unreliable in them and they should be subjected to BERA directly. Percentage of bilateral hearing loss came to be 4.2%, 4 participants were lost to follow up and percentage of hearing loss on subsequent OAE came to be 11.6%. Low birth weight was an important risk factor for hearing loss (p value significant on initial and follow-up). Percentage of hearing loss with low birth weight, hyperbilirubenemia, low apgar score and prematurity to be 16%. Mechanical ventilation contributed 13% of total hearing loss followed by ototoxicity. Neonates with family history of childhood SNHL, in utero infection, craniofacial anomaly and bacterial meningitis contributed 3% of total hearing loss. On subsequent follow-up, one neonate was low-risk and the other 25 were high risk, of which 3 high risks showed sustained OAE refer. However the low risk neonate had normal outer hair cell function i.e. OAE pass. This study clearly demonstrates importance of Universal Neonatal Hearing Screening Programme so that hearing loss can be detected as early as possible and possible intervention can be taken at the earliest.
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Role of Otoacoustic Emissions in Hearing Assessment of Neonates: A Prospective Observational Study
Abstract
Hearing plays an important role for children in learning speech and language, socialization and cognitive development. The child learns to speak based on what is heard (Rundjan et al. in Sari Pediatr 6(4):149–154, 2005). The aim of the study was to find out the percentage of hearing loss by OAE among low risk and high risk neonates. All the neonates (Low and High risk) born in a tertiary care center were screened by OAE before their discharge from the hospital and after stabilizing high risk neonates. The referred neonates were followed after two weeks. Total 722 neonates were screened of which 130 were high risk and 592 were low risk. Neonates with Serum bilirubin > 20 mg/dl or requiring exchange transfusion were excluded as OAE will be unreliable in them and they should be subjected to BERA directly. Percentage of bilateral hearing loss came to be 4.2%, 4 participants were lost to follow up and percentage of hearing loss on subsequent OAE came to be 11.6%. Low birth weight was an important risk factor for hearing loss (p value significant on initial and follow-up). Percentage of hearing loss with low birth weight, hyperbilirubenemia, low apgar score and prematurity to be 16%. Mechanical ventilation contributed 13% of total hearing loss followed by ototoxicity. Neonates with family history of childhood SNHL, in utero infection, craniofacial anomaly and bacterial meningitis contributed 3% of total hearing loss. On subsequent follow-up, one neonate was low-risk and the other 25 were high risk, of which 3 high risks showed sustained OAE refer. However the low risk neonate had normal outer hair cell function i.e. OAE pass. This study clearly demonstrates importance of Universal Neonatal Hearing Screening Programme so that hearing loss can be detected as early as possible and possible intervention can be taken at the earliest.
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UCSF & iHEARu Calling on HEARos to Help Map Noise Levels in Bay Area
Seeking a quiet cafe to discuss business or chat with a friend? The new iHEARu mobile app can help.
The iHEARu mobile app uses crowd-sourcing to help individuals find locations with noise levels that suit your needs. Whether seeking a quiet eatery or lively bar with loud music, the iHEARu GPS will help you find it. By combining decibel data gathered from smartphone users in real-life environments, iHEARu provides the data to change the world…one ear-friendly place at a time.
Founded and inspired by world-renowned neuroscientists and audiologists from the University of Washington Dr. Kelly Tremblay and Dr. Charles Limb of the University of California, San Francisco (UCSF), the iHEARu app helps people collect decibel data in public spaces. The iHEARu team has partnered with the UCSF Sound and Music Perception Lab, headed by Dr. Limb, to help San Francisco's hearing-challenged community find ear-friendly places to visit. The team is calling on all citizen scientists to join the movement by downloading the free app and taking data readings across the city. For each data reading during Restaurant Week (January 22–31), the iHEARu team will make a contribution to the Hearing Loss Association of America and CHEFSGIVING.
Why create an ear-friendly movement? Consider:
- Over 20% of the U.S. population (48M) have some hearing loss
- Approximately 1 in 3 people older than 65 have disabling hearing loss.
- According to a 2010 census, this means that over 13.6% of San Francisco's population is suffering with disabling hearing loss!
- With over 17M visitors to the San Francisco area, that means over 3.5M will come to the city as hearing-challenged visitors.
The app can be downloaded for FREE via the App Store or Google Play. Learn more about iHearu from Dr. Tremblay's article .
Published: 1/31/2018 12:41:00 PM
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Narrow band imaging for head and neck malignancies: Lessons learned from mistakes
Abstract
Background
The accuracy of white light endoscopy in combination with narrow band imaging (WLE + NBI) for diagnosis of squamous cell carcinoma (SCC) does not reach 100%. We evaluated the characteristics of the false-negative and false-positive cases.
Methods
Five hundred thirty lesions of the upper airways were evaluated. The WLE was followed by NBI examination before performing a biopsy.
Results
The false-negative lesions (7.36%) were represented by submucosal and non-SCC tumors. Among the 25 non-SCC tumors, 72% did not show any suspicious vascular pattern under NBI. The false-positive lesions (6.04%) were mainly represented by postradiotherapy mucosal changes, ulcers, and infections. Regarding papillomas, NBI accuracy reached 95.32%, although cases with dysplasia were difficult to distinguish from SCC.
Conclusion
The WLE + NBI improved diagnostic accuracy, but not all lesions were ideally evaluated with current defined patterns. An accurate anamnesis is mandatory, because, in some cases, it may be more relevant than the NBI pattern.
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Head and neck lymphedema management: Evaluation of a therapy program
Abstract
Background
The purpose of this pilot study was to examine a therapeutic intervention for head and neck lymphedema. The 22-week intervention involved therapist-led care and participant self-management. Effectiveness was evaluated using a previously described lymphedema assessment tool, the Assessment of Lymphedema of the Head and Neck (ALOHA) to detect change over the course of the 22 weeks of treatment, and before and after a single treatment session.
Methods
A prospective observational pilot study was conducted with a cohort of 10 participants assessed. Measurements of size (tape measurements) and water content (tissue dielectric constant [TDC]) were used, per the ALOHA protocol. Participants received 13 lymphedema therapy treatments at reducing frequencies over 22 weeks and daily self-management.
Results
There was an overall significant reduction in lower neck circumference (F [2.15,19.35] = 7.11; P = .004), upper neck circumference (F [5,45] = 7.27; P < .001) and TDC (F (5,45) = 8.92; P < .001) over time. There were no significant differences over the course of treatment for mean ear-to-ear measurements or before and after a single session of treatment.
Conclusion
This pilot study found a reduction in head and neck lymphedema over the 22-week lymphedema treatment course. This intervention may be successful in reducing head and neck lymphedema; however, further studies are needed to investigate these findings in a larger sample with the use of a control group to negate improvements from healing over time.
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Extended endonasal approach versus maxillary swing approach to the parapharyngeal space
Abstract
Background
The nasopharyngeal and parapharyngeal spaces are difficult for surgeons to access. Of the various external routes described, the maxillary swing has emerged as the gold standard because of its simplicity. However, its morbidity has led to the development of less invasive techniques. The purpose of our study was to compare the surgical anatomy of the maxillary swing with that of the endoscopic endonasal approach.
Methods
Each procedure was performed on 10 anatomic specimens. The exposure and the limits obtained were evaluated. A CT scan analysis was performed.
Results
The endoscopic endonasal approach extended the limits, offering wider exposure. The endoscopic endonasal approach made possible better visualization of deep structures and precise dissection of the parapharyngeal spaces. However, the maxillary swing provided better access to the oropharynx and could be completed 3 times faster.
Conclusion
The endoscopic endonasal approach provides excellent exposure, a wide dissection range, and precise definition of anatomic structures, making it an alternative of choice rather than the maxillary swing approach.
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Modified combination of platelet count and neutrophil “to” lymphocyte ratio as a prognostic factor in patients with advanced head and neck cancer
Abstract
Background
We evaluated the prognostic potential of the combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) in patients with advanced head and neck cancer.
Methods
We proposed a modified COP-NLR scoring system defined as follows: score 0 (platelet count level <300 × 109/L and NLR <3); score 1 (platelet count level ≥300 × 109/L and NLR <3); and score 2 (NLR ≥3). We assessed whether the modified scoring system had better performance as an indicator of prognosis than the existing COP-NLR scoring system (original and 4-group scores).
Results
A total of 248 patients were enrolled. The Akaike Information Criterion value with the modified COP-NLR score was the smallest among the 3 models. The 3-year survival rates according to the modified COP-NLR scores of 0, 1, and 2 were 80.6%, 59.9%, and 23.8%, respectively.
Conclusion
The modified COP-NLR score is a useful prognostic marker in patients with advanced head and neck cancer.
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Intraoperative cardiac arrest etiologies in head and neck surgery: A comprehensive review
Abstract
Background
The etiologies of intraoperative cardiac arrest within otolaryngology are not well understood as they are rare events.
Methods
A comprehensive review of the etiologies and corresponding pathophysiologic neural mechanisms of intraoperative cardiac arrest in otolaryngologic surgery are examined.
Results
The occurrence of this rare complication has been described in a range of head and neck procedures, including but not limited to suspension laryngoscopy and oncologic resections in the neck, maxilla and thyroid. Three anatomically distinct pathways leading to intraoperative cardiac arrest are described: direct vagal stimulation, the trigeminocardiac reflex and the baroreceptor reflex. All three share the final common pathway of parasympathetic signaling to the sinoatrial node via the cardiac fibers of the vagus nerve.
Conclusion
With a firm understanding of the mechanistic underpinning of this rare phenomenon, otolaryngologic surgeons can be better prepared for its occurrence.
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Effects of excessive fibrin deposit and polylactide adhesion barrier on wound healing in thyroidectomy murine wound model
Abstract
Background
We hypothesize that excessive fibrin formation and inflammation induced by antiadhesive material, SurgiWrap (SW), would have an adverse effect on wound healing. It was evaluated by a thyroidectomy murine wound model.
Methods
Excessive fibrin formation was induced by isthmectomy without hemostasis. Rats were allocated into isthmectomy with SurgiWrap (I+SW+), I+SW-, I-SW+, I-SW-, and isthmectomy after electrocautery for hemostasis (I+C+SW-). The SWs were placed on the superficial and visceral layers for gross and microscopic evaluation.
Results
Microscopic examination showed collagen deposition occurred in the I-SW- sham group and at a higher level in I+C+SW-. The collagen deposition decreased in groups without SW with time but increased in groups with SW. Use of SW produced more inflammation and more collagen deposition. The I+SW + group developed the largest area of collagen deposition at 4 weeks and more collagen deposition than the I-SW + group.
Conclusion
The SW induced more collagen deposition increasing with time. The collagen deposition produced by SW was worsened by excessive fibrin formation and inflammation.
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Application of Sal classification to parotid gland fine-needle aspiration cytology: 10-year retrospective analysis of 312 patients
Abstract
Background
The accuracy of fine-needle aspiration biopsy (FNAB) is controversial in parotid tumors. We aimed to compare FNAB results with the final histopathological diagnosis and to apply the "Sal classification" to our data and discuss its results and its place in parotid gland cytology.
Methods
The FNAB cytological findings and final histological diagnosis were assessed retrospectively in 2 different scenarios based on the distribution of nondefinitive cytology, and we applied the Sal classification and determined malignancy rate, sensitivity, and specificity for each category.
Results
In 2 different scenarios FNAB sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were found to be 81%, 87%, 54.7%, and 96.1%; and 65.3%, 100%, 100%, and 96.1%, respectively. The malignancy rates and sensitivity and specificity were also calculated and discussed for each Sal category.
Conclusion
We believe that the Sal classification has a great potential to be a useful tool in classification of parotid gland cytology.
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Outcomes utilizing intensity-modulated radiotherapy in oropharyngeal cancers: Tonsils versus base of tongue
Abstract
Background
The purpose of this study was to present the outcomes of oropharyngeal cancers treated with intensity-modulated radiotherapy (IMRT) especially the differences between tonsillar and base of tongue (BOT) primaries.
Methods
Retrospective analysis of 124 patients with biopsy proven squamous cell carcinomas of the oropharynx, treated with IMRT.
Results
Human papillomavirus (HPV) association correlated with improvement in survivals in both tonsillar and BOT primaries. At the 2-year median follow-up, the cumulative incidences of locoregional recurrences were 8% in both the tonsil and BOT groups (P = .76) but the distant metastases were 8% in the tonsil group versus 26% in the BOT group (P = .009). Thirty percent of tonsil primaries has ≥N2c neck disease as compared to 54% of BOT. Incidence of distant metastases increases with advanced nodal classification, especially >N2c.
Conclusion
Even though the locoregional controls are excellent with IMRT and chemotherapy, these patients continue to fail distantly, particularly significant for the BOT group and for nodal stage >N2c.
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Role of Otoacoustic Emissions in Hearing Assessment of Neonates: A Prospective Observational Study
Abstract
Hearing plays an important role for children in learning speech and language, socialization and cognitive development. The child learns to speak based on what is heard (Rundjan et al. in Sari Pediatr 6(4):149–154, 2005). The aim of the study was to find out the percentage of hearing loss by OAE among low risk and high risk neonates. All the neonates (Low and High risk) born in a tertiary care center were screened by OAE before their discharge from the hospital and after stabilizing high risk neonates. The referred neonates were followed after two weeks. Total 722 neonates were screened of which 130 were high risk and 592 were low risk. Neonates with Serum bilirubin > 20 mg/dl or requiring exchange transfusion were excluded as OAE will be unreliable in them and they should be subjected to BERA directly. Percentage of bilateral hearing loss came to be 4.2%, 4 participants were lost to follow up and percentage of hearing loss on subsequent OAE came to be 11.6%. Low birth weight was an important risk factor for hearing loss (p value significant on initial and follow-up). Percentage of hearing loss with low birth weight, hyperbilirubenemia, low apgar score and prematurity to be 16%. Mechanical ventilation contributed 13% of total hearing loss followed by ototoxicity. Neonates with family history of childhood SNHL, in utero infection, craniofacial anomaly and bacterial meningitis contributed 3% of total hearing loss. On subsequent follow-up, one neonate was low-risk and the other 25 were high risk, of which 3 high risks showed sustained OAE refer. However the low risk neonate had normal outer hair cell function i.e. OAE pass. This study clearly demonstrates importance of Universal Neonatal Hearing Screening Programme so that hearing loss can be detected as early as possible and possible intervention can be taken at the earliest.
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Role of Otoacoustic Emissions in Hearing Assessment of Neonates: A Prospective Observational Study
Abstract
Hearing plays an important role for children in learning speech and language, socialization and cognitive development. The child learns to speak based on what is heard (Rundjan et al. in Sari Pediatr 6(4):149–154, 2005). The aim of the study was to find out the percentage of hearing loss by OAE among low risk and high risk neonates. All the neonates (Low and High risk) born in a tertiary care center were screened by OAE before their discharge from the hospital and after stabilizing high risk neonates. The referred neonates were followed after two weeks. Total 722 neonates were screened of which 130 were high risk and 592 were low risk. Neonates with Serum bilirubin > 20 mg/dl or requiring exchange transfusion were excluded as OAE will be unreliable in them and they should be subjected to BERA directly. Percentage of bilateral hearing loss came to be 4.2%, 4 participants were lost to follow up and percentage of hearing loss on subsequent OAE came to be 11.6%. Low birth weight was an important risk factor for hearing loss (p value significant on initial and follow-up). Percentage of hearing loss with low birth weight, hyperbilirubenemia, low apgar score and prematurity to be 16%. Mechanical ventilation contributed 13% of total hearing loss followed by ototoxicity. Neonates with family history of childhood SNHL, in utero infection, craniofacial anomaly and bacterial meningitis contributed 3% of total hearing loss. On subsequent follow-up, one neonate was low-risk and the other 25 were high risk, of which 3 high risks showed sustained OAE refer. However the low risk neonate had normal outer hair cell function i.e. OAE pass. This study clearly demonstrates importance of Universal Neonatal Hearing Screening Programme so that hearing loss can be detected as early as possible and possible intervention can be taken at the earliest.
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ANKRD1 regulates innate immune responses against herpes simplex virus 1: A potential role in eczema herpeticum
Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Lianghua Bin, Xiaozhao Li, Brittany Richers, Joanne E. Streib, Jack W. Hu, Patricia Taylor, Donald Y.M. Leung
BackgroundAtopic dermatitis (AD) is a common inflammatory skin disease. A subset of AD is susceptible to disseminated herpes simplex virus (HSV) infection, a complication termed as eczema herpeticum(ADEH+). The immune mechanisms causing ADEH+ remain elusive. Using RNA-sequencing, we recently found that ankyrin repeat domain 1 (ANKRD1) was significantly induced in human peripheral blood mononuclear cells (PBMCs) upon HSV-1 stimulation; and its induction in ADEH+ was significantly reduced as compared to AD patients without a history of EH (ADEH-).ObjectiveTo validate ANKRD1 gene expression in non-atopic (NA), ADEH- and ADEH+ subjects; to delineate the biological function of ANKRD1 and the signaling pathway(s) involved.MethodsPurification of human PBMCs, monocytes, B cells, dendritic cells, T cells and NK cells; RNA extraction and qRT-PCR; small interfering RNA technique; co-immunoprecipitation; and western-blot assays were used.ResultsANKRD1 was significantly reduced in PBMCs from ADEH+ patients after HSV-1 stimulation as compared to PBMCs from ADEH-. We found that the induction of ANKRD1 by HSV-1 and multiple pathogen pattern recognition receptor (PRR) agonists are mediated by inflammatory cytokines. Silencing ANKRD1 gene expression in APCs led to increased viral load and reduced IFNb1 and IL-29 production. Using co-immunoprecipitation methods, we demonstrated that ANKRD1 formed protein complexes with IRF3 and IRF7, which are important transcription factors regulating PRRs' signaling transduction. Over-expression of ANKRD1 enhanced the IRF3-mediated signaling pathways.ConclusionANKRD1 is involved in IRF3 mediated anti-viral innate immune signaling pathways. Its reduced expression in ADEH+ subjects may contribute to the pathogenesis of ADEH+.
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A comparative analysis of human bone marrow-resident and peripheral memory B cells
Source:Journal of Allergy and Clinical Immunology
Author(s): Sonya C. Becker, Martin Szyska, Angela Mensen, Katharina Hellwig, Raik Otto, Lisa Olfe, Hans-Dieter Volk, Thomas Dörner, Bernd Dörken, Carmen Scheibenbogen, Jörg Schröder, Andreas C. Hocke, Il-Kang Na
http://ift.tt/2Eudxtm
Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma
Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Steven F. Weinstein, Rohit Katial, Shyamalie Jayawardena, Gianluca Pirozzi, Heribert Staudinger, Laurent Eckert, Vijay N. Joish, Nikhil Amin, Jaman Maroni, Paul Rowe, Neil M.H. Graham, Ariel Teper
BackgroundDupilumab, an anti-IL-4Rα monoclonal antibody, inhibits IL-4/IL-13 signaling, key drivers of type 2/Th2 immune diseases (e.g. atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2-agonists.ObjectiveTo examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR).MethodsPost-hoc analysis reporting data from the phase 2b study for the 200 and 300 mg q2w doses under investigation in phase 3 (NCT02414854). PAR was defined at study entry as a specific response to typical perennial antigens (immunoglobulin E [IgE]≥0.35 Ku/L).ResultsOverall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w vs placebo significantly improved SNOT-22 total score (LS mean difference −5.98 [95% CI, −10.45, −1.51], P = 0.009) and all 4 AR-associated symptoms evaluated (nasal blockage: −0.60 [−0.96, −0.25]; runny nose: −0.67 [−1.04, −0.31]; sneezing: −0.55 [−0.89, −0.21]; post-nasal discharge: −0.49 [−0.83, −0.16]; all P < 0.01]. Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant decreases in SNOT-22 total score (−1.82 [−6.46, 2.83], P = 0.443 vs placebo] and in each AR-associated symptom. In non-PAR patients, no differences were observed for these measures vs placebo.ConclusionDupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.
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Intravenous immunoglobulin treatment abrogates transplacental autoantibody transfer in a murine pemphigus model
Source:Journal of Allergy and Clinical Immunology
Author(s): Sachiko Ono, Gyohei Egawa, Tetsuya Honda, Kenji Kabashima
http://ift.tt/2Etie6T
Intestinal IFN-γ-producing Tr1-cells co-express CCR5 and PD-1, and down-regulate IL-10 in the inflamed gut of IBD patients
Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Johanna Sophie Alfen, Paola Larghi, Federica Facciotti, Nicola Gagliani, Roberto Bosotti, Moira Paroni, Stefano Maglie, Paola Gruarin, Chiara Maria Vasco, Valeria Ranzani, Cristina Frusteri, Andrea Iseppon, Monica Moro, Maria Cristina Crosti, Stefano Gatti, Massimiliano Pagani, Flavio Caprioli, Sergio Abrignani, Richard A. Flavell, Jens Geginat
BackgroundIL-10 is an anti-inflammatory cytokine that is required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type-1 regulatory (Tr1-) cells, but is also produced by CD25+ Tregs.ObjectiveWe aimed to identify and characterize human intestinal Tr1-cells, and to investigate if they are a relevant cellular source of IL-10 in inflammatory bowel diseases (IBDs).MethodsCD4+T-cells isolated from the intestinal lamina propria of humans and mice were analyzed for phenotype, cytokine production and suppressive capacities. Intracellular IL-10 expression by CD4+T-cell subsets in the inflamed gut of IBD patients with Crohn's Disease or Ulcerative Colitis was compared to non-inflamed controls. Finally, the effects of pro-inflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1P εξπρεσσiον ανδ IL-23 responsiveness were assessed.ResultsIntestinal Tr1-cells could be identified by the co-expression of CCR5 and PD-1 in humans and mice. CCR5+PD-1+Tr1-cells expressed IFN-γ ανδ ΙL-10 and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-γ+Tr1-cells, but neither IL-7R+ helper T-cells nor CD25+Tregs, showed lower IL-10 expression in patients with IBDs. Tr1-cells were responsive to IL-23, and IFN-γ+Tr1-cells down-regulated IL-10 with IL-1β and IL-23. Conversely, CD25+Tregs expressed higher levels of IL-1R, but showed nevertheless stable IL-10 expression.ConclusionsWe provide the first ex vivo characterization of human intestinal Tr1-cells. The selective down-regulation of IL-10 by IFN-γ+Tr1-cells in response to pro-inflammatory cytokines is likely to drive excessive intestinal inflammation in IBDs.
Graphical abstract
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Short term ibrutinib therapy suppresses skin test responses and eliminates IgE-mediated basophil activation in adults with peanut or tree nut allergy
Source:Journal of Allergy and Clinical Immunology
Author(s): Melanie C. Dispenza, Jacqueline A. Pongracic, Anne Marie Singh, Bruce S. Bochner
Teaser
Two doses of ibrutinib significantly reduced skin prick test area and anti-IgE-induced basophil activation responses in peanut and tree nut allergic adults. Ibrutinib or other BTK inhibitors could potentially be used to prevent anaphylaxis.http://ift.tt/2ErcNp5
The Obese-Asthma Phenotype in Children: An Exacerbating Situation?
Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Cristina Longo, Gillian Bartlett, Tibor Schuster, Francine M. Ducharme, Brenda MacGibbon, Tracie A. Barnett
BackgroundCurrent evidence regarding the relationship between childhood obesity, decreased response to inhaled corticosteroids (ICS), and poor asthma control is conflicting.ObjectivesWe assessed if obesity: i) is associated with time-to-first exacerbation among children with asthma initiating Step-3 maintenance therapies; ii) modifies the effectiveness of Step-3 therapies.MethodsA retrospective cohort study was conducted from clinical data linked to health and drug administrative databases. The cohort consisted of children aged 2-18 years with specialist-confirmed asthma, who initiated medium/high-dose ICS monotherapy or low/medium-dose ICS with LTRA/LABA (combination therapy) at the Montreal Children's Hospital Asthma Center from 2000 to 2007. Children were classified as exposed to Step-3 therapies when they were dispensed a corresponding drug claim during follow-up, while those without claims were classified as non-adherers. Marginal structural Cox models were used to estimate the effect of obesity (BMI>97th percentile) and treatment on time-to-exacerbation, defined as any emergency department visit, hospitalization, or use of oral corticosteroids for asthma.ResultsOf the 4621 cohort patients, 231 initiated ICS monotherapy and 97 initiated combination therapy. The HR for obesity was 1.67 (95%CI 1.41-1.98). Compared to non-obese non-adherers, the HR for obese non-adherers was 1.54 (95%CI 0.97-2.45); the HR for ICS monotherapy in obese and non-obese children was 0.85 (95%CI 0.47-1.52) and 0.58 (95%CI 0.37-0.91), respectively; and the HR for combination therapy in obese and non-obese children was 0.50 (95%CI 0.13-1.89) and 0.46 (95%CI 0.23-0.92), respectively.ConclusionObesity may be a determinant of shorter exacerbation-free time in children with asthma; however, we could not rule out a differential response to Step-3 therapies by obesity status potentially due to a lack of precision.
Graphical abstract
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The role of local CpG DNA methylation in mediating the 17q21 asthma-susceptibility GSDMB/ORMDL3 expression quantitative trait locus
Source:Journal of Allergy and Clinical Immunology
Author(s): Parul H. Kothari, Weiliang Qiu, Damien C. Croteau-Chonka, Fernando D. Martinez, Andrew H. Liu, Robert F. Lemanske, Carole Ober, Jerry A. Krishnan, Dan L. Nicolae, Kathleen C. Barnes, Stephanie J. London, Albino Barraza-Villarreal, Steven R. White, Edward T. Naureckas, Joshua Millstein, W. James Gauderman, Frank D. Gilliland, Vincent J. Carey, Scott T. Weiss, Benjamin A. Raby
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Protein corona-mediated targeting of nano-carriers to B cells allows redirection of allergic immune responses
Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Limei Shen, Stefan Tenzer, Wiebke Storck, Dominika Hobernik, Verena Katharina Raker, Karl Fischer, Sandra Decker, Andrzej Dzionek, Susanne Krauthäuser, Mustafa Diken, Alexej Nikolaev, Joachim Maxeiner, Petra Schuster, Cinja Kappel, Admar Verschoor, Hansjörg Schild, Stephan Grabbe, Matthias Bros
BackgroundNanoparticle (NP) based vaccines are attractive immunotherapy tools due to their capability to co-deliver antigen and adjuvant to antigen presenting cells. Their cellular distribution and serum protein interaction ("protein corona") after systemic administration and its impact on functional properties of NP is poorly understood.ObjectivesWe analyzed the relevance of the protein corona on cell type-selective uptake of dextran (DEX)-coated NP and determined the outcome of vaccination with NP that codeliver antigen and adjuvant in disease models of allergy.MethodsThe role of protein corona constituents for cellular binding/uptake of DEX-NP was analyzed in vitro and in vivo. DEX-NP conjugated with the model antigen ovalbumin (OVA), and immunostimulatory CpG-rich oligonucleotides (ODN) were administered to monitor the induction of cellular and humoral immune responses. Therapeutic effects of this DEX-NP vaccine in mouse models of OVA-induced anaphylaxis and allergic asthma were assessed.ResultsDEX-NP triggered lectin-induced complement activation yielding deposition of activated complement C3 on the DEX-NP surface. In spleen, DEX-NP predominantly targeted B cells via their complement receptor CR1/2. The DEX-NP vaccine elicited much stronger OVA-specific IgG2a production than co-administered soluble OVA plus CpG ODN. B cell binding of the DEX-NP vaccine was critical for IgG2a production. Treatment of OVA-sensitized mice with the DEX-NP vaccine prevented the induction of anaphylactic shock and allergic asthma, accompanied by IgE inhibition.ConclusionsOpsonization of lectin-coated NP by activated complement components results in selective B cell targeting. The intrinsic B cell targeting property of lectin-coated NP can be exploited for the treatment of allergic immune responses.
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Benralizumab attenuates airway eosinophilia in prednisone-dependent asthma
Source:Journal of Allergy and Clinical Immunology
Author(s): Roma Sehmi, Hui Fang Lim, Manali Mukherjee, Chynna Huang, Katherine Radford, Paul Newbold, Louis-Philippe Boulet, Delbert Dorscheid, James G. Martin, Parameswaran Nair
http://ift.tt/2EtfxT1
T cell gene therapy for perforin deficiency corrects cytotoxicity defects and prevents Haemophagocytic Lymphohistiocytosis manifestations
Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Sujal Ghosh, Marlene Carmo, Miguel Calero-Garcia, Ida Ricciardelli, Juan Carlos Bustamante Ogando, Michael P. Blundell, Axel Schambach, Philip G. Ashton-Rickardt, Claire Booth, Stephan Ehl, Kai Lehmberg, Adrian J. Thrasher, H Bobby Gaspar
BackgroundMutations in the PRF1 gene account for up to 58% of familial haemophagocytic lymphohistiocytosis (FHL) syndromes. The resulting defects in effector cell cytotoxicity lead to hypercytokinaemia and hyperactivation with inflammation in various organs.ObjectiveTo determine whether autologous gene corrected T cells can restore cytotoxic function, reduce disease activity and prevent haemophagocytic lymphohistiocytosis (HLH) symptoms in in vivo models.MethodsWe developed a gammaretroviral vector to transduce murine CD8-T cells in the prf-/- mouse model. To verify functional correction of prf-/- CD8-T cells in vivo, we used a lymphocytic choriomeningitis virus (LCMV) epitope transfected murine lung carcinoma cell tumour model. Further, we challenged gene corrected and uncorrected mice with LCMV. One patient sample was transduced with a PRF1 encoding lentiviral vector to study restoration of cytotoxicity in human cells.ResultsWe demonstrated efficient engraftment and functional reconstitution of cytotoxicity after intravenous administration of gene corrected prf-/- CD8-T cells into prf-/- mice. In the tumour model, infusion of prf-/- gene corrected CD8-T cells eliminated the tumour as efficiently as the transplant of wild type CD8-T cells. Similarly, mice reconstituted with gene corrected prf-/- CD8-T cells, displayed complete protection from the HLH phenotype after infection with LCMV. Patient cells showed correction of cytotoxicity in human CD8-T cells after transduction.ConclusionThese data demonstrate the potential application of T cell gene therapy in reconstituting cytotoxic function and protection against HLH in perforin deficiency.
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Umbilical cord blood transplantation without in vivo T-cell depletion for children with MHC class II deficiency
Source:Journal of Allergy and Clinical Immunology
Author(s): Reem A. Elfeky, Juliana M. Furtado-Silva, Robert Chiesa, Kanchan Rao, Giovanna Lucchini, Persis Amrolia, Austen Worth, Bobby Gaspar, Waseem Qasim, Paul Veys
http://ift.tt/2Esa8eV
ADA2 deficiency: clonal lymphoproliferation in a subset of patients
Source:Journal of Allergy and Clinical Immunology
Author(s): Luca Trotta, Timi Martelius, Timo Siitonen, Timo Hautala, Sari Hämäläinen, Hanna Juntti, Mervi Taskinen, Mette Ilander, Emma Irene Andersson, Andrey Zavialov, Meri Kaustio, Riikka Keski-Filppula, Michael Hershfield, Satu Mustjoki, Terhi Tapiainen, Mikko Seppänen, Janna Saarela
http://ift.tt/2DRtDMz
Increased GATA-3 and T-bet expression in eosinophilic esophagitis vs gastroesophageal reflux disease
Source:Journal of Allergy and Clinical Immunology
Author(s): Benjamin L. Wright, Nathalie Nguyen, Kelly P. Shim, Joanne C. Masterson, Elizabeth A. Jacobsen, Sergei I. Ochkur, James J. Lee, Glenn T. Furuta
http://ift.tt/2Esa1Qx
Asthma, COPD and overlap in a national cohort: ACO on a gradient
Source:Journal of Allergy and Clinical Immunology
Author(s): Arnaud Bourdin, Carey M. Suehs, Gregory Marin, Isabelle Vachier, Eric Matzner-Lober, Pascal Chanez, Nicolas Molinari
http://ift.tt/2DRtyZh
Abnormal differentiation of B cells and megakaryocytes in Roifman syndrome
Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Jessica Heremans, Josselyn E. Garcia-Perez, Ernest Turro, Susan M. Schlenner, Ingele Casteels, Roxanne Collin, Francis de Zegher, Daniel Greene, Stephanie Humblet-Baron, Sylvie Lesage, Patrick Matthys, Christopher J. Penkett, Karen Put, Kathleen Stirrups, Chantal Thys, Chris Van Geet, Erika Van Nieuwenhove, Carine Wouters, Isabelle Meyts, Kathleen Freson, Adrian Liston
BackgroundRoifman syndrome is a rare inherited disorder characterized by spondyloepiphyseal dysplasia, growth retardation, cognitive delay, hypogammaglobulinemia and, in some patients, thrombocytopenia. Compound heterozygous variants in small nuclear RNA gene RNU4ATAC, necessary for U12-type intron splicing, were recently identified to drive Roifman syndrome.ObjectiveWe studied three patients from two unrelated kindreds harboring compound heterozygous or homozygous stem II variants in RNU4ATAC to gain insights in the mechanisms behind this disorder.MethodsWe systematically profiled the immunological and hematological compartments of the three Roifman patients and performed RNA sequencing to unravel important splicing defects in both cell lineages.ResultsThe patients exhibited a dramatic reduction in B cells, with differentiation halted at the transitional B cell stage. Despite abundant BAFF availability, development past this BAFF-dependent stage was crippled, with disturbed minor splicing of the critical MAPK1 signaling component. In the hematological compartment, Roifman patients demonstrated defects in megakaryocyte differentiation, with inadequate generation of proplatelets. Roifman platelets were rounder, with elevated tubulin and actin levels, and contained increased alpha and dense granule markers. Significant minor intron retention in 354 megakaryocyte genes was observed, including DIAPH1 and HPS1, genes known to regulate platelet and dense granule formation, respectively.ConclusionTogether, our results provide novel molecular and cellular data towards understanding the immunological and hematological features of Roifman syndrome.
Graphical abstract
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Single cell profiling of peanut-responsive T cells in peanut allergic subjects reveals heterogeneous effector Th2 subsets
Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): David Chiang, Xintong Chen, Stacie M. Jones, Robert A. Wood, Scott H. Sicherer, A. Wesley Burks, Donald Y.M. Leung, Charuta Agashe, Alexander Grishin, Peter Dawson, Wendy F. Davidson, Leah Newman, Robert Sebra, Miriam Merad, Hugh A. Sampson, Bojan Losic, M. Cecilia Berin
BackgroundThe contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood.ObjectivesOur objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of individuals with and without peanut allergy (PA).MethodsWe obtained samples from PA individuals, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (CoFAR6). Subjects were confirmed as PA, or if they passed a 1 g peanut challenge they were termed high-threshold (HT). Healthy controls (HC) were also recruited. Peanut-responsive T cells were identified by CD154 expression after 6-18h of stimulation with peanut extract. Cells were analyzed by flow cytometry and single cell RNA sequencing.ResultsPA individuals had tissue and follicle-homing peanut-responsive CD4+ T cells with a heterogeneous pattern of Th2 differentiation, while controls had undetectable T cell responses to peanut. The PA group had a delayed and IL-2-dependent upregulation of CD154 on cells expressing Treg markers, which was absent in HC or HT individuals. Depletion of Tregs in vitro enhanced cytokine production in HC and PA subjects, but cytokines associated with highly differentiated Th2 cells were more resistant to Treg suppression in PA subjects. Analysis of gene expression by single cell RNAseq identified T cells with highly correlated expression of IL4, IL5, IL9, IL13 and the IL-25 receptor IL17RB.ConclusionsThese results demonstrate the presence of highly differentiated Th2 cells producing Th2-associated cytokines with functions beyond IgE-class switch in peanut allergy. A multi-functional Th2 response was more evident than a Treg deficit among peanut-responsive T cells.
Graphical abstract
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