Pharyngolaryngeal ulcers associated with the improper use of alendronate

Publication date: Available online 10 December 2016
Source:Auris Nasus Larynx
Author(s): Hiroshi Sakaida, Hiroto Yuasa, Kazuo Fukutome, Kazuhiko Takeuchi
Bisphosphonates can cause mucosal irritation. Although esophageal ulceration is a well-recognized adverse effect of bisphosphonates, pharyngolaryngeal ulcers associated with the improper use of oral bisphosphonates have rarely been described. A previously healthy 78-year-old woman presented with refractory pharyngolaryngeal ulcers. Extensive evaluation, including biopsy, bacterial culture, and blood tests did not identify any findings that indicated a specific disease diagnosis. Antibiotics and oral prednisolone were ineffective. Ultimately, it was found that the patient regularly took a tablet of alendronate, a type of bisphosphonate, by dissolving it in the oral cavity. Within 2 weeks after withdrawal of the use of the medication, her symptoms were eliminated, and the lesions were completely healed. This case illustrates the importance of correct administration of bisphosphonates. Given the widespread use of bisphosphonates, physicians need to be aware that their improper use can cause pharyngolaryngeal ulcers.



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Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease

Publication date: Available online 10 December 2016
Source:Auris Nasus Larynx
Author(s): Kenichi Takano, Motohisa Yamamoto, Hiroki Takahashi, Tetsuo Himi
IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders. Systemic corticosteroids are generally effective in inducing IgG4-RD remission; however, recurrent or refractory cases are common. In addition, although the pathogenic mechanisms of IgG4-RD remain unclear, an antigen-driven inflammatory condition is believed to be involved. Recent studies have indicated the important pathogenic role of B cell/T cell collaboration and innate immunity in this disease. Nevertheless, additional research and discussions are needed to resolve many remaining questions. In this review, we provide an overview of the recent insights on the history, clinical features, diagnosis, and treatment of IgG4-RD in the head and neck region. Furthermore, we have also addressed the pathogenesis of this disease.



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Transoral robotic surgery (TORS) for excision of a retropharyngeal intramuscular lipoma

Publication date: Available online 10 December 2016
Source:Auris Nasus Larynx
Author(s): Chase M. Heaton, Saqib R. Ahmed, William R. Ryan
ObjectiveTo describe the feasibility, effectiveness, and improved morbidity profile of transoral robotic surgery (TORS) for the excision of a retropharyngeal intramuscular lipoma.MethodsCase report of a robot-assisted transoral resection of a retropharyngeal intramuscular lipoma.ResultsA 62-year-old woman presented with tongue pain and globus with dysphagia for six months. Transoral exam revealed a pharyngeal submucosal mass, and MRI demonstrated a prevertebral lipomatous lesion with protrusion into the airway. The patient elected for robot-assisted transoral surgical treatment. The patient tolerated the procedure well, experienced no complications, and was discharged on post-operative day one. At six months post-operatively, the patient was without dysphagia and was disease free on imaging.ConclusionsTORS is an effective, safe, feasible, and likely more efficient way to excise a retropharyngeal intramuscular lipoma or other retropharyngeal masses.



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High Frequency Tympanometry (1000Hz) in Young Infants and Its Comparison With Otoacoustic Emissions, Otomicroscopy and 226Hz Tympanometry

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Eduardo A. Mena-Domínguez, José I. Benito-Orejas, Beatriz Ramírez-Cano, Darío Morais-Pérez, M. Fe Muñoz-Moreno
Introduction and objectiveIn the first 6 months of life, 226Hz tympanometry is considered an ineffective procedure for the diagnosis of otitis media with effusion. With the introduction of universal hearing screening, the use of high frequency 1000Hz (1kHz) tympanometry has been recommended. To optimise the diagnosis of neonatal hearing loss, we present this comparison, from the clinical point of view, of the results of 226Hz and 1kHz tympanometry in infants.Materials and methodsWe designed a prospective study of 100 children under 9 months of age proceeding from our hearing screening programme. We compare the result of tympanometry with binocular microscopy and transient evoked otoacoustic emissions.ResultsThe application of transient otoacoustic emissions, otomicroscopy and 226Hz and 1kHz tympanometry has shown its usefulness in the management of otitis media with effusion of young infants, with a similar effectiveness between the 4 tests.ConclusionThe joint use of otomicroscopy, transient otoacoustic emissions and 226Hz and 1kHz tympanometry, has allowed us to diagnose otitis media with effusion in young infants more accurately than each test separately. We recommend initial use of 1kHz tympanometry, at least in children younger than 7 months, but in the presence of hearing loss or an unclear result, 226Hz tympanometry is a good diagnostic complement.



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Change in Tinnitus After Acoustic Neuroma Removal Using a Translabyrinthine Approach. A Prospective Study

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Leire Alvarez, Ane Ugarte, Miren Goiburu, Iratxe Urreta Barallobre, Xabier Altuna
IntroductionTinnitus is one of the primary symptoms of vestibular schwannoma (VS) and the effect of surgery is unpredictable.Materials and methodsWe conducted a prospective study of the patients who underwent a translabyrinthine approach for the treatment of their VS (2009–2013) at our Hospital. Patients answered the Tinnitus Handicap Inventory (THI) questionnaire pre- and postoperatively. The clinical charts provided data such as age, gender, tumour size, preoperative audiometry and postoperative facial function.ResultsThe study included 39 patients. Of these, 71.8% suffered from tinnitus: 50% grade I, 17.9% grade II, 10.7% grade III, 21.4% grade IV and 0% grade V. We found no statistical association between tinnitus and the different variables measured preoperatively. Postoperatively, 48.7% of the patients suffered from tinnitus: 31.6% grade I, 36.8% grade II, 10.5% grade III, 15.8% grade IV and 5.3% grade V. The difference between mean pre- and postoperative THI was statistically significant (P=.011); this difference was greater in younger patients. We have found a significant negative correlation (r=−0.335; P=.037) between preoperative audiometry and postoperative THI.ConclusionsWe did not find any significant association between tinnitus and age, gender, tumour size and postoperative facial function. Translabyrinthine surgical removal of VS in these patients led to better THI results, with the younger patients having better outcomes. The patients with poorest preoperative audition were the ones that had the best results in the postoperative THI questionnaire.



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Delayed Diagnosis of Childhood Deafness: The Value of False Negatives in the Programme for Early Detection of Neonatal Hearing Loss

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): María C. Martínez-Pacheco, Luis Ferrán de la Cierva, Francisco J. García-Purriños
IntroductionDespite its importance, the existence of false negatives (patients who are told they hear well, but they have some degree of hipacusia) is rarely evaluated in programmes for early detection of hearing loss. The aim of this study is to determine the variables that can lead to a delayed diagnosis, especially the existence of false negatives and the lack of registration of risk factors.MethodsA retrospective study of prevalence has been carried out, in which the medical records of children diagnosed with sensorineural hearing loss born within 2005 and 2012 in the health centres of study have been analysed.ResultsOf the 32 children with sensorineural hearing loss, 16 passed the OAE, 12 did not passed the OAE, and in four they were not carried out. Of the children who passed the OAE, 57% have severe hearing loss. 66% of children with hearing loss presented a risk factor for hearing loss at birth, being the most frecuent family history of hearing loss, but only 7% of those with family history of hearing loss were included in the risk group.ConclusionsThe results of the study indicate that the late diagnosis of hearing loss is related to the presence of false negatives to the OAE and the non-registration of risk factors.



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Cicatricial Posterior Glottic Stenosis. Our Experience

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Ana Maeso-Plaza, María Dablanca-Blanco, Consuelo Ortega-Fernandez, Primitivo Ortega-del Álamo
Introduction and objectivesPresentation of the results obtained in the treatment of cicatricial posterior glottic stenosis.MethodsA retrospective study of 34 patients diagnosed and treated for cicatricial posterior glottic stenosis in our ENT department.ResultsIn our series, 85.36% of our patients were decannulated. Of these, 80% of the patients with glottic stenosis were decannulated, while 92.9% of the patients with other associated laryngotracheal stenosis were paradoxically decannulated.Of all the patients, 70% required more than 1 surgical procedure, although most of these interventions were to resolve minor issues following our protocol.The number of subsequent interventions was determined by the location of the stenosis, with there being more interventions when the posterior glottic stenosis was associated with another type of laryngotracheal stenosis (P=.001).ConclusionsThe surgical results for treating cicatricial posterior glottic stenosis are quite positive. However, unlike other types of posterior glottic stenosis (such as neurogenic abductor paralysis), it requires a greater number of interventions to achieve definitive decannulation. Endoscopic procedures play an important role and represent our main tool.



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Using low level laser therapy to reduce early postoperative airway obstruction following modified Hogan's flap

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Abdelrahman E. Ezzat, Hanna M. EL-Shenawy, Marwa M. El-Begermy, Mustafa I. Eid, Ayman Y. Abbas
Introduction and objectiveThe most common postoperative complications of velopharyngeal insufficiency surgery are postoperative bleeding and airway obstruction or obstructive sleep apnoea. Consequently, the aim of this study was to evaluate the effect of low level laser therapy (LLLT) during the first postoperative days in children undergoing superiorly based pharyngeal flap (SBF) surgery.Materials and methodsA randomized double blind clinical study on 30 children divided on two groups 15 patients each, who underwent SBF. LLLT was used in a group and the other was a control group. The study was conducted in academic tertiary care medical centres between 2013 and 2015. The degree of edema, oxygen saturation, occurrence of obstructive sleep apnoea (OSA) and steroid administration were recorded.ResultsThe mean of the average oxygen saturation was significantly less in the control group in the 1st and 2nd day as compared to the laser group. The need for oxygen and the incidence of OSA in the first 3 days were significantly higher in the control group as compared to the laser group. The degree of edema showed no significant difference in the first day but was significantly higher in the control group in the 2nd and 3rd days. Hence, the need of steroids was significantly higher in the control group in the first 3 days.ConclusionsPreliminary results showed that low level laser therapy is effective in reducing the incidence of early postoperative airway obstruction after SBF operations.



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Practical Management of Periprosthetic Leakage in Patients Rehabilitated With a Provox® 2 Voice Prosthesis After Total Laryngectomy

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Eviatar Friedlander, Paloma Pinacho Martínez, Daniel Poletti Serafini, Carlos Martín-Oviedo, Tomás Martínez Guirado, Bartolomé Scola Yurrita
Introduction and objectivesPeriprosthetic leakage of liquids is a common complication in patients rehabilitated with voice prostheses. Our objective was to describe and review the results of procedures for treating periprosthetic leakage.Materials and methodsThis was a retrospective analysis of 41 patients rehabilitated with Provox® 2 voice prostheses between 1997 and 2015. We describe 3 techniques: periprosthetic silicon collar placement, injection of hyaluronic acid into the tracheoesophageal wall and the combination of the 2 techniques. We present a method to reduce the diameter of the tracheoesophageal fistula by removing the voice prosthesis and placing a nasogastric tube through the fistula.ResultsIn the 3 groups treated with silicone collar (n=5, 13 procedures), hyaluronic acid injection (n=5, 9 procedures) and the combination of both techniques (n=3, 5 procedures), we observed an increase in prosthesis lifespan of an average of 56 days (range 7–118 days), 32 days (range 3–55 days) and 63 days (range 28–136 days), respectively. The tracheoesophageal fistula diameter reduction was performed in 100% (n=6) of patients.ConclusionsThe use of silicone collars, injection of hyaluronic acid into the tracheoesophageal wall and the combination of both techniques for the treatment of periprosthesis leakage increase the lifespan of the prosthesis. Temporary prosthesis removal and placement of nasogastric tube has also been shown effective in our experience. These techniques are simple, inexpensive and reproducible, thereby reducing healthcare costs.



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Nasal closure for the treatment of epistaxis secondary to hereditary hemorrhagic telangiectasia

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Sara Sena Esteves, Carla Cardoso, Ana Silva, José Abrunhosa, Cecília Almeida e Sousa
Hereditary hemorrhagic telangiectasia (HHT), also known by the eponym Osler-Weber-Rendu syndrome, is an autosomal dominant disorder characterised by the presence of multiple arteriovenous malformations (AVMs) affecting multiple organs. Many procedures have been used for epistaxis control in patients with this disorder.The objective of this study was to report the treatment of severe HHT-related epistaxiswith the modified Young's procedure.Materials and methodsWe describe the treatment of 4 patients with severe blood-transfusion-dependent epistaxis who underwent a modified Young's procedure in a tertiary hospital.The nasal closure was bilateral and complete in all cases. All patients were followed for 12 months or longer.ResultsThe procedure was well tolerated and complete cessation of bleeding was achieved in all the patients.ConclusionYoung's technique is a safe surgical procedure, well tolerated by patients with severe epistaxis and HHT.



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Palinacousis Secondary to Brain Damage From Methotrexate

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Ana Sánchez-Martínez, José I. Benito-Orejas, Dulce M. Campos-Blanco, Darío Morais-Pérez




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Paediatric Mucoepidermoid Carcinoma

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Estefanía Hernández-García, Rosario García-Monescillo, Laura Castillo-Fernández, Guillermo Plaza




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Osteoblastoma of the Thyroid Cartilage

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Francisco Javier García Callejo, Jaume Redondo Martínez, Verónica Andrade Gamarra, Tomás Pérez Carbonell




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Mucocutaneous Leishmaniasis

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Vania Novoa Juiz, Raquel Redondo Luciañez




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Giant Pleomorphic Adenoma of the Parotid Gland

Publication date: November–December 2016
Source:Acta Otorrinolaringologica (English Edition), Volume 67, Issue 6
Author(s): Christian E. Calvo-Henriquez, Andrea Telmo-Mella, Cristina Dios-Loureiro, Carlos Martín-Martín




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Epigenetic Changes During Food-Specific Immunotherapy

Abstract

Purpose of Review

The prevalence and severity of IgE-mediated food allergy has increased dramatically over the last 15 years and is becoming a global health problem. Multiple lines of evidence suggest that epigenetic modifications of the genome resulting from gene-environment interactions have a key role in the increased prevalence of atopic disease. In this review, we describe the recent evidence suggesting how epigenetic changes mediate susceptibility to food allergies, and discuss how immunotherapy (IT) may reverse these effects. We discuss the areas of the epigenome as yet unexplored in terms of food allergy and IT such as histone modification and chromatin accessibility, and new techniques that may be utilized in future studies.

Recent Findings

Recent findings provide strong evidence that DNA methylation of certain promoter regions such as Forkhead box protein 3 is associated with clinical reactivity, and further, can be changed during IT treatment. Reports on other epigenetic changes are limited but also show evidence of significant change based on both disease status and treatment.

Summary

In comparison to epigenetic studies focusing on asthma and allergic rhinitis, food allergy remains understudied. However, within the next decade, it is likely that epigenetic modifications may be used as biomarkers to aid in diagnosis and treatment of food-allergic patients. DNA methylation at specific loci has shown associations between food challenge outcomes, successful desensitization treatment, and overall phenotype compared to healthy controls.

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Laryngeal pacing for bilateral vocal fold paralysis: Voice and respiratory aspects

Objective

To evaluate the effects of neurostimulation with the laryngeal pacemaker (LP) system in patients with bilateral vocal fold paralysis (BVFP) in terms of voice quality and respiratory function.

Study Design

Feasibility study, first-in-human, single-arm, open-label, prospective, multicenter study with group-sequential design and 6-month follow-up period, as described in details in our previous publication.

Methods

Nine symptomatic BVFP subjects were unilaterally implanted with the LP system at three study sites in Germany and Austria. Subjective and objective voice function, spirometric parameters other than peak expiratory/inspiratory flow (PEF/PIF), and PEF-meter self-assessment were evaluated pre- and 6 months postimplantation.

Results

In general, the LP system did not considerably change the voice quality of the implanted patients. Only the sound pressure level range improved significantly 6 months postimplantation (P = 0.018). The LP system implantation did not affect the glottal closure configuration, the duration of the closed phase, and the mucosal wave of the implanted side. The evaluated spirometric parameters were not significantly affected by laryngeal pacing, whereas PEF meter self-assessment showed a stable and significant (P = 0.028) improvement of the PEF within a week upon activation of the LP system.

Conclusion

Neurostimulation with the LP system results in an immediate and stable PEF improvement, without negative effects on the voice quality. The PEF meter self-assessment confirmed the spirometry results of the PEF. The stimulated abduction did not affect the glottal closure during phonation. These results should be confirmed in larger and more homogenous patient cohorts.

Level of Evidence

2b Laryngoscope, 2016

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The relation of innate and adaptive immunity with viral-induced acute asthma attacks: Focusing on IP-10 and cathelicidin

Publication date: Available online 9 December 2016
Source:Allergologia et Immunopathologia
Author(s): T. Arikoglu, E. Akyilmaz, D.D. Yildirim, S.B. Batmaz, S.T. Ulger, G. Aslan, S. Kuyucu
BackgroundDespite growing evidence suggesting potential association between innate and adaptive immunity in viral-induced acute asthma, there is paucity of data in this area.ObjectiveThis study aimed to investigate the association of innate and adaptive immunity with acute asthma attacks by analysing the role of IFN-γ-inducible protein 10 (IP-10), TLR2, cathelicidin, vitamin D and cytokines.Material and methodsThis prospective study included 33 patients with viral-induced acute asthma and 30 children with controlled asthma. Nasopharyngeal swab samples were collected for virus identification and asthma attack scores assessed in acute asthma group. Blood sampling for IP-10, TLR2, cathelicidin, vitamin D levels, and spirometric indices were employed.ResultsSerum IP-10 and cathelicidin levels of acute asthma group were significantly higher and vitamin D levels were lower than controlled asthma group (IP-10; p=0.006, cathelicidin; p=0.002, vitamin D; p<0.001). Serum IP-10 levels showed a significant negative correlation with age (p=0.009), TLR2 (p=0.05) and spirometric indices (p=0.002) in all asthmatics and a significant positive correlation with parameters of asthma attack severity (p=0.03) in acute asthma group. Higher cathelicidin values showed significant positive relation to IP-10 (beta coefficient: 33, p=0.02). Serum IP-10 levels higher than 38.9pg/ml (sensitivity: 85%, specificity: 47%, p=0.002) were predictive of virus-induced asthma. Serum IP-10 and vitamin D levels were found to be significantly related to viral-asthma attacks (IP-10; aOR: 8.93, p=0.03 and vitamin D; aOR: 0.82, p=0.001).ConclusionsInnate immunity biomarkers such as serum IP-10 and cathelicidin can be used to predict viral-induced acute asthma. These biomarkers may provide potential new treatment targets for acute asthma.



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Personality traits inventory in patients with vocal nodules

Abstract

The objective of the study was to analyze temperament and character in females with vocal nodules (VN) compared to a vocally healthy control population. 61 females were examined over a 17-month period for dysphonia with VN (mean age 46 years, duration of vocal complaints from 2 months to 6 years). 71 control females were recruited in their environment (mean age 34 years). The validated French Version of the Temperament and Character Inventory (TCI) was used. Patients with VN had significantly (p < 0,05) greater scores for Persistence and Novelty Seeking, particularly for the subscales exploratory excitability and extravagance. They had lower scores for Harm Avoidance, in particular fear of uncertainty, shyness and fatigability. Scores on Reward Dependence were not significantly different except for the subscale dependence, which were significantly lower in patients. No significant difference was found with regard to scores on Self-directedness, except for scores on the subscale self-acceptance, which were significantly lower in patients. Scores on Cooperativeness were not significantly different, except for the subscale helpfulness, which were significantly higher in patients. Patients had significant greater scores for Self-transcendence overall and specifically on the subscales self-forgetfulness and spiritual acceptance. Our findings suggested that women with VN are likely to have a passionate temperament, which might constitute an indirect predisposition to elevated vocal loading and greater risk for phonotrauma. The risk for developing or maintaining VN could be decreased by attending to those personality-specific maladaptive behaviors. A possible personalized approach to voice therapy could be organized on the basis of the TCI findings.

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JAK3 deficiency caused by a homozygous synonymous exonic mutation that creates a dominant splice site

Publication date: Available online 10 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Craig D. Platt, Michel J. Massaad, Brittany Cangemi, Birgitta Schmidt, Hasan Aldhekri, Raif S. Geha

Teaser

Two siblings were found to have JAK3 deficiency due to a synonymous exonic mutation. The mutation does not change the predicted JAK3 amino acid sequence, though it is pathogenic as it creates a new donor splice site that disrupts protein expression.


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Involvement of high mobility group box-1 in imiquimod-induced psoriasis-like mice model

Abstract

In the previous work, we have indicated that HMGB1, a pro-inflammatory cytokine, is closely associated with the pathogenesis of psoriasis. To further clarify the role of HMGB1 in the pathogenesis of psoriasis, we investigated the direct function of HMGB1 application and HMGB1 blockade in imiquimod (IMQ)-induced psoriatic mouse model in this study. Mice were treated with imiquimod (IMQ) to induce psoriasis-like inflammation, and consecutively injected with recombinant HMGB1 or phosphate-buffered saline (PBS) i.d. Abundant cytoplasmic expression of HMGB1 was observed in lesional skin from IMQ-treated skin. The injection of HMGB1 into the IMQ-treated skin further aggravated the psoriasis-like disease, enhanced the infiltration of CD3⁺ T cells, myeloperoxidase⁺ neutrophils and CD11c⁺ dendritic cells, increased the number of γδ T cells, and upregulated the mRNA expression of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IL-17 compared with the PBS injection. Finally, by using anti-HMGB1 monoclonal antibody or HMGB1 inhibitor glycyrrhizin, we indicated that HMGB1 blockade reduced the number of γδ T cells, suppressed the mRNA expression of IL-6, TNF-α, IFN-γ and IL-17, and moderated clinical and histological evolvement in the IMQ-treated skin. Our data suggest that HMGB1 may act as a pro-inflammatory cytokine, and contribute to the development of IMQ-induced psoriasis-like inflammation. HMGB1 blockade may represent a new direction in the suppression of psoriasis.

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Malignant melanoma with bone marrow involvement diagnosed from hypercalcemia: Development of a neural cell adhesion molecule stain

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Clinical features of Birt–Hogg–Dubé syndrome: A Japanese case with pulmonary cysts, fibrofolliculomas and renal cell carcinoma

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Efficacy, safety and drug survival of conventional agents in pediatric psoriasis: A multicenter, cohort study

Abstract

The data on long-term efficacy, safety and drug survival rates of conventional systemic therapeutics in pediatric psoriasis is lacking. The primary aim of this study is to investigate acitretin, methotrexate, cyclosporin efficacy, safety and drug survival rates in pediatric patients as well as predictors of drug survival. This is a multicenter study including 289 pediatric cases being treated with acitretin, methotrexate and cyclosporin in four academic referral centers. Efficacy, adverse events, reasons for discontinuation, 1, 2- and 3-year drug survival rates, and determinants of drug survival were analyzed. A 75% reduction of Psoriasis Area and Severity Index score or better response rate was obtained in 47.5%, 34.1% and 40% of the patients who were treated with acitretin, methotrexate and cyclosporin, respectively. One-year drug survival rates for acitretin, methotrexate and cyclosporin were 36.3%, 21.1% and 15.1%, respectively. The most significant determinant of drug survival, which diminished over time, was treatment response whereas arthritis, body mass index and sex had no influence. Although all three medications are effective and relatively safe in children, drug survival rates are low due to safety concerns at this age group. Effective disease control through their rational use can be expected to improve survival rates.

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Case of thymoma-associated multi-organ autoimmunity following herpes zoster

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Diaphragm-Sparing Nerve Blocks for Shoulder Surgery.

Shoulder surgery can result in significant postoperative pain. Interscalene brachial plexus blocks (ISBs) constitute the current criterion standard for analgesia but may be contraindicated in patients with pulmonary pathology due to the inherent risk of phrenic nerve block and symptomatic hemidiaphragmatic paralysis. Although ultrasound-guided ISB with small volumes (5 mL), dilute local anesthetic (LA) concentrations, and LA injection 4 mm lateral to the brachial plexus have been shown to reduce the risk of phrenic nerve block, no single intervention can decrease its incidence below 20%. Ultrasound-guided supraclavicular blocks with LA injection posterolateral to the brachial plexus may anesthetize the shoulder without incidental diaphragmatic dysfunction, but further confirmatory trials are required. Ultrasound-guided C7 root blocks also seem to offer an attractive, diaphragm-sparing alternative to ISB. However, additional large-scale studies are needed to confirm their efficacy and to quantify the risk of periforaminal vascular breach. Combined axillary-suprascapular nerve blocks may provide adequate postoperative analgesia for minor shoulder surgery but do not compare favorably to ISB for major surgical procedures. One intriguing solution lies in the combined use of infraclavicular brachial plexus blocks and suprascapular nerve blocks. Theoretically, the infraclavicular approach targets the posterior and lateral cords, thus anesthetizing the axillary nerve (which supplies the anterior and posterior shoulder joint), as well as the subscapular and lateral pectoral nerves (both of which supply the anterior shoulder joint), whereas the suprascapular nerve block anesthetizes the posterior shoulder. Future randomized trials are required to validate the efficacy of combined infraclavicular-suprascapular blocks for shoulder surgery. Copyright (C) 2016 by American Society of Regional Anesthesia and Pain Medicine.

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Predictions of the Contribution of HCN Half-Maximal Activation Potential Heterogeneity to Variability in Intrinsic Adaptation of Spiral Ganglion Neurons

Abstract

Spiral ganglion neurons (SGNs) exhibit a wide range in their strength of intrinsic adaptation on a timescale of 10s to 100s of milliseconds in response to electrical stimulation from a cochlear implant (CI). The purpose of this study was to determine how much of that variability could be caused by the heterogeneity in half-maximal activation potentials of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, which are known to produce intrinsic adaptation. In this study, a computational membrane model of cat type I SGN was developed based on the Hodgkin-Huxley model plus HCN and low-threshold potassium (KLT) conductances in which the half-maximal activation potential of the HCN channel was varied and the response of the SGN to pulse train and paired-pulse stimulation was simulated. Physiologically plausible variation of HCN half-maximal activation potentials could indeed determine the range of adaptation on the timescale of 10s to 100s of milliseconds and recovery from adaptation seen in the physiological data while maintaining refractoriness within physiological bounds. This computational model demonstrates that HCN channels may play an important role in regulating the degree of adaptation in response to pulse train stimulation and therefore contribute to variable constraints on acoustic information coding by CIs. This finding has broad implications for CI stimulation paradigms in that cell-to-cell variation of HCN channel properties are likely to significantly alter SGN excitability and therefore auditory perception.

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Machine-Learning Algorithms Predict Graft Failure Following Liver Transplantation.

Background: Ability to predict graft failure or primary nonfunction at liver transplant decision time assists utilization of scarce resource of donor livers, while ensuring that patients who are urgently requiring a liver transplant are prioritized. An index that is derived to predict graft failure using donor and recipient factors, based on local datasets, will be more beneficial in the Australian context. Methods: Liver transplant data from the Austin Hospital, Melbourne, Australia, from 2010-2013 has been included in the study. The top 15 donor, recipient and transplant factors influencing the outcome of graft failure within 30 days, were selected using a machine learning methodology. An algorithm predicting the outcome of interest was developed using those factors. Results: Donor Risk Index (DRI) predicts the outcome with an area under the receiver operating characteristic curve (AUC-ROC) value of 0.680 (95% CI 0.669-0.690). The combination of the factors used in DRI with the model for end-stage liver disease (MELD) score yields an AUC-ROC of 0.764 (95% CI 0.756-0.771), whereas Survival outcomes following liver transplantation (SOFT) score obtains an AUC-ROC of 0.638 (95% CI 0.632- 0.645). The top 15 donor and recipient characteristics within random forests results in an AUC-ROC of 0.818 (95% CI 0.812-0.824). Conclusions: Using donor, transplant and recipient characteristics known at the decision time of a transplant, high accuracy in matching donors and recipients can be achieved, potentially providing assistance with clinical decision making. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Vascularized Composite Allograft Preservation: Ubi Sumus?.

No abstract available

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Long-Term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

Background: Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Methods: Intestinal samples were taken from 4 isolated intestine (ITx) and 3 multivisceral (MvTx) transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor- or recipient-specific HLA marker to analyze chimerism. Results: Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be Lymphoid tissue inducer (LTi) cells among donor ILCs was far higher than that among recipient ILCs. Conclusions: Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human LTi cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Role of Circulating microRNAs in the Immunopathogenesis of Rejection Following Pediatric Lung Transplantation.

BACKGROUND: Acute rejection (AR) and development of chronic rejection, bronchiolitis obliterans syndrome (BOS), remain major limiting factors for lung transplantation (LTx). This retrospective study is to identify differentially expressed circulating microRNAs (miRNAs) that associate with development of AR and BOS in pediatric lung transplant recipients (LTxR). METHODS: We determined the circulating levels of 7 selected candidate miRNAs in 14 LTxR with AR, 7 with BOS, and compared them against 13 stable pediatric LTxR at 1, 6, and 12 months following LTx. In addition, 6 AR, 7 BOS and 8 stable pediatric LTxR, 16 AR, 17 BOS and 16 stable adult LTxR were included for validation. RESULTS: MiR-10a, -195, -133b were significantly lower in AR and miR-144, -142-5p, -155 were higher in AR compared to stable (p

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Immune reconstitution following HCV clearance with direct antiviral agents: potential consequences for patients with HCC?.

Recent introduction of all-oral direct acting antiviral treatment has revolutionized care of patients with chronic hepatitis C virus infection. Since patients with different liver disease stages have been treated with great success including those awaiting liver transplantation, therapy has been extended to patients with hepatocellular carcinoma as well. From observational studies among compensated cirrhotic hepatitis C patients treated with interferon-containing regimens, it would have been expected that the rate of hepatocellular carcinoma occurrence is markedly decreased after a sustained virological response. However, recently two studies have been published reporting markedly increased rates of tumor recurrence and occurrence after viral clearance with direct acting antiviral agents. Over the last decades it has been established that chronic antigen stimulation during persistent infection with hepatitis C virus is associated with continuous activation and impaired function of several immune cell populations such as natural killer cells and virus-specific CD8 T cells. This review therefore focuses on recent studies evaluating the restoration of adaptive and innate immune cell populations after direct acting antiviral therapy in patients with chronic hepatitis C virus infection in the context of the immune responses in hepatocarcinogenesis. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Kidney fibrosis: origins and interventions.

All causes of renal allograft injury, when severe and/or sustained, can result in chronic histological damage of which interstitial fibrosis and tubular atrophy (IF/TA) are dominant features. Unless a specific disease process can be identified, what drives IF/TA progression in individual patients is often unclear. In general, clinicopathological factors known to predict and drive allograft fibrosis include graft quality, inflammation (whether 'nonspecific' or related to a specific diagnosis), infections such as polyomavirus-associated nephropathy, calcineurin inhibitors and genetic factors. The incidence and severity of chronic histological damage have decreased substantially over the last 3 decades, but it is difficult to disentangle what effects individual innovations (eg, better matching and preservation techniques, lower calcineurin inhibitor dosing, BK viremia screening) may have had. There is little evidence that CNI-sparing/minimization strategies, steroid minimization or renin-angiotensin-aldosterone system blockade result in better preservation of intermediate-term histology. Treatment of subclinical rejections has only proven beneficial to histological and functional outcome in studies in which the rate of subclinical rejection in the first 3 months was > 10-15%. Potential novel antifibrotic strategies include antagonists of transforming growth factor-[beta], connective tissue growth factor (CTGF), several tyrosine kinase ligands (EGF, PDGF, VEGF), endothelin and inhibitors of chemotaxis. Although many of these drugs are mainly being developed and marketed for oncological indications and diseases such as idiopathic pulmonary fibrosis, a number may hold promise in the treatment of diabetic nephropathy, which could eventually lead to applications in renal transplantation. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Mortality and Graft Loss Attributable to Readmission following Kidney Transplantation: Immediate and Long-Term Risk.

Background: Following kidney transplantation, early readmission is independently associated with graft loss and mortality. The mechanism of this association is poorly understood. Understanding the timeline of risk, ie, during the readmission hospitalization versus time periods postreadmission, will provide additional insights. Methods: We used national registry data to study 56,076 adult Medicare-primary first-time kidney transplant recipients from December 1999-October 2011. Piecewise Cox proportional hazard models were used to estimate the association between graft loss, mortality, and readmission for two time periods: readmission hospitalization and postreadmission. Results: During the readmission hospitalization, graft loss was substantially higher (deceased donor (DDKT) without delayed graft function (DGF) hazard ratio: 24.634.447.9, p

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Conformational variants of HLA-I antigens on Luminex Single Antigen Beads.

No abstract available

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MyD88 inhibitors and the continuing challenge of TLR antagonism.

No abstract available

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Activation of Fibrinolysis, But Not Coagulation, During End-ischemic Ex Situ Normothermic Machine Perfusion of Human Donor Livers.

Background: Ex situ normothermic machine perfusion (NMP) can be performed after traditional static cold preservation to assess graft function and viability prior to transplantation. It is unknown whether this results in activation of coagulation and fibrinolysis, as may occur upon graft reperfusion in vivo. Methods: Twelve donor livers declined for transplantation underwent 6 hours of end-ischemic NMP using a heparinized plasma-based perfusion fluid. Concentration of prothrombin fragment F1+2 (marker of coagulation activation), D-dimer, PAP complex, tPA and PAI-1 (markers for fibrinolysis) and alanine aminotransferase (ALT; marker of ischemia/reperfusion [I/R] injury) were measured in perfusion fluid at regular intervals. Liver biopsies were examined for the presence of fibrin, using light microscopy after MSB staining. Results: No significant increase in prothrombin F1+2 was noted during NMP. D-dimer and PAP complex levels increased soon after start of NMP and D-dimer concentrations correlated significantly with levels of tPA. In livers displaying good function during NMP, perfusate levels of ALT and D-dimers were low (3,500 ng/mL) were in found in livers with poor graft function. Activation of fibrinolysis correlated significantly with the degree of I/R injury, as reflected by ALT levels. Conclusion: End-ischemic ex situ NMP results in activation of fibrinolysis, but not of coagulation. Markers of fibrinolysis activation correlate significantly with markers of I/R injury. High concentrations of D-dimer early after start of NMP can be considered a marker of severe I/R injury and a predictor of poor liver graft function. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Low measured hepatic artery flow increases rate of biliary strictures in deceased donor liver transplantation: An age dependent phenomenon.

Background: This study was conducted to determine effect of lower measured hepatic arterial (HA) flow (=400 mL/min; N = 1099) HA flow groups. Incidence of biliary complications and graft survival were analyzed. Results: HA flows 50 years was associated with increased rate of biliary strictures (HR 1.67 (1.14-2.45), p = 0.0085) and graft failure (HR 1.68 (1.35-2.1), p

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Report of the 22nd Annual Congress of the International Liver Transplantation Society.

The 2016 Annual Congress of the International Liver Transplantation Society was held in Seoul, South Korea in May. The 22nd Congress marked the largest multidisciplinary liver transplantation meeting in Asia since 2010. The principal themes were living donation, allocation, immunosuppression, machine preservation, novel treatment of hepatitis C, and expansion of the deceased-donor allograft pool. This report presents select abstracts from the scientific sessions within the context of the published literature to serve as a quick reference. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Financial Burden Borne by Laparoscopic Living Kidney Donors.

Introduction: Living kidney donors have donation-related, out-of-pocket costs (direct costs) and/or ongoing daily expenses while losing income (indirect costs) associated with donation. Yet there is little information about how much of a subjective burden these constitute for the donors. Methods: From 12/2003-1/2015, we surveyed donors 6 months postdonation to determine financial burden related to donation (on a scale of 1-10) and what resources were used to cover expenses. Results: Of 1136 surveyed, 796 (70%) responded. Among respondents, mean age at donation was 43.6+/-10.6 years, 64% were female, 96% white, and 53% related by blood to their recipient. Overall, 26% scored their financial burden as >=5; 8% scored it as >=8. Increased expenses were associated with a higher reported burden; however, significant burden was reported by some with no out-of-pocket expenses (presumably due to lost wages and continuing expenses). The burden was scored as >=5 by 27% of those employed outside the home (n=660), 15% homemakers, 13% retirees, 40% students; 28% unemployed; and by 26% whose occupation was unknown. Over half (51%) of those receiving a local or (means-tested) national grant still reported moderate to severe burden. Besides grants, donors used a variety of sources to help offset expenses: dipped into savings, borrowed from friends or family, took out a loan, and/or had a fundraiser. Those with the highest burden reported using the most additional sources. Conclusions: Donors should not have to incur costs or a financial burden to donate; the transplant community should strive to make donation financially neutral. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Live donors of the initial observational study of uterus transplantation-Psychological and medical follow up until 1 year after surgery in the 9 cases.

Background: The first prospective observational study of uterus transplantation was initiated in 2013 with live donation to 9 women with absolute uterine factor infertility. We explored the medical complications and psychosocial wellbeing of the donors during the first postoperative year. Methods: Complications were registered and graded according to the Clavien-Dindo (C-D) classification. Symptoms related to the surgery were registered. Data on length of hospital stay, sick leave, socioeconomic parameters and life events were obtained. Psychological evaluations (PGWB, DAS, HADS, SF-36) questionnaires focusing on quality-of-life, mood, and relationship, were conducted at inclusion and at 3, 6 and 12 months after uterus donation. Results: One major surgical complication (C-D IIIb) occurred. A ureteric-vaginal fistula developed 2 weeks after uterus procurement. The fistula was surgically repaired. Two self-reported and transient complications (C-D I) were noted (nocturia, meralgia paresthetica). Hospital stays of all donors were 6 days and median sick leave was 56 days (range 14-132). At inclusion, median scores exceeded the normative values of the Swedish population in PGWB and DAS. Anxiety (HADS-A) was detected preoperatively in 1 donor. Two donors exceeded 10-point declines in SF-36 summary scores and increased their HADS scores by 6 points during the observation period. All donors returned to their predonation levels of physical health. Conclusions: The results support that it is feasible to retrieve a uterus safely from a live donor. Further studies are needed to better evaluate the method. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Cost-Effectiveness of Direct-Acting Anti-viral Treatment in Hepatitis C-infected Liver Transplant Candidates with Compensated Cirrhosis and Hepatocellular Carcinoma.

Background: HCV(+) donors represent an effective strategy to increase liver donor availability to HCV-infected recipients. However, many HCV(+) transplant candidates are now receiving treatment with direct acting anti-virals (DAA) that lower the risk of posttransplant HCV recurrence but could make the patient ineligible for HCV(+) livers. Methods: We compared pretransplant DAA treatment versus deferred DAA treatment using a cost-effectiveness decision analysis model to estimate incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted life year [QALY] gained) from the societal perspective across a range of HCV(+) liver availability rates. For practical considerations, the population modelled was restricted to well-compensated HCV(+) cirrhotics listed for liver transplantation with HCC MELD exception points. Results: Under base case conditions, the deferred DAA treatment strategy was found to be the "dominant" strategy. That is, it provided superior health outcomes at cost savings compared to the pretransplant DAA treatment strategy. The pretransplant DAA treatment strategy trended towards cost-effectiveness as HCV(+) donor liver availability declined. However, only in 1 scenario that was highly optimized for favorable outcomes in the pretransplant DAA treatment arm (low availability of HCV(+) organs, low cost of DAA treatment, high cost of HCV recurrence) was the ICER associated with HCV DAA treatment before transplant

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Active Nanorheology with Plasmonics

Jeong, H-H; Mark, AG; Lee, T-C; Alarcón-Correa, M; Eslami, S; Qiu, T; Gibbs, JG; Jeong, H-H; Mark, AG; Lee, T-C; Alarcón-Correa, M; Eslami, S; Qiu, T; Gibbs, JG; Fischer, P; - view fewer (2016) Active Nanorheology with Plasmonics. Nano Letters , 16 (8) pp. 4887-4894. 10.1021/acs.nanolett.6b01404 .

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Overcoming the challenges of low-cost inertial navigation

Martin, HFS; (2016) Overcoming the challenges of low-cost inertial navigation. Doctoral thesis, UCL (University College London). Green open access

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Being Critical? Multimodal Engagement with English Literary Text in Senior Cycle Irish Classrooms

Malone, A; (2016) Being Critical? Multimodal Engagement with English Literary Text in Senior Cycle Irish Classrooms. Doctoral thesis, UCL (University College London).

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Tone processing and the acquisition of tone in Mandarin- and English-speaking typically developing children and children with Autism Spectrum Disorder

Lu, Y-F; (2016) Tone processing and the acquisition of tone in Mandarin- and English-speaking typically developing children and children with Autism Spectrum Disorder. Doctoral thesis, UCL (University College London). Green open access

http://ift.tt/2h8Afhb

Creating Interactions between Tissue-Engineered Skeletal Muscle and the Peripheral Nervous System.

Smith, AS; Passey, SL; Martin, NR; Player, DJ; Mudera, V; Greensmith, L; Lewis, MP; (2016) Creating Interactions between Tissue-Engineered Skeletal Muscle and the Peripheral Nervous System. Cells Tissues Organs , 202 (3-4) pp. 143-158. 10.1159/000443634 . Green open access

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Monoamine influences in cerebellar memory consolidation

Longley, M; (2016) Monoamine influences in cerebellar memory consolidation. Doctoral thesis, UCL (University College London). Green open access

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Tungsten Oxide and Tungsten Oxide Based Heterogeneous Nanostructure thin films: Synthesis via AACVD, Characterisation, Growth Mechanism, and Application in Photocatalysis

Ling, M; (2016) Tungsten Oxide and Tungsten Oxide Based Heterogeneous Nanostructure thin films: Synthesis via AACVD, Characterisation, Growth Mechanism, and Application in Photocatalysis. Doctoral thesis, UCL (University College London).

http://ift.tt/2hwqhTI

Selection platforms for directed evolution in synthetic biology

Tizei, PA; Csibra, E; Torres, L; Pinheiro, VB; (2016) Selection platforms for directed evolution in synthetic biology. Biochemical Society Transactions , 44 (4) pp. 1165-1175. 10.1042/BST20160076 . Green open access

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Why marine phytoplankton calcify

Monteiro, FM; Bach, LT; Brownlee, C; Bown, P; Rickaby, REM; Poulton, AJ; Tyrrell, T; Monteiro, FM; Bach, LT; Brownlee, C; Bown, P; Rickaby, REM; Poulton, AJ; Tyrrell, T; Beaufort, L; Dutkiewicz, S; Gibbs, S; Gutowska, MA; Lee, R; Riebesell, U; Young, J; Ridgwell, A; - view fewer (2016) Why marine phytoplankton calcify. Science Advances , 2 (7) , Article e1501822. 10.1126/sciadv.1501822 . Green open access

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Cognitive Processes during Acute Psychosis: The Role of Heightened Responsibility and Catastrophic Misinterpretations

Luzón, O; Harrop, C; Nolan, F; (2009) Cognitive Processes during Acute Psychosis: The Role of Heightened Responsibility and Catastrophic Misinterpretations. Behavioural and Cognitive Psychotherapy , 37 (4) p. 357. 10.1017/S1352465809990191 .

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Low-oxygen waters limited habitable space for early animals

Tostevin, R; Wood, RA; Shields, GA; Poulton, SW; Guilbaud, R; Bowyer, F; Penny, AM; Tostevin, R; Wood, RA; Shields, GA; Poulton, SW; Guilbaud, R; Bowyer, F; Penny, AM; He, T; Curtis, A; Hoffmann, KH; Clarkson, MO; - view fewer (2016) Low-oxygen waters limited habitable space for early animals. Nature Communications , 7 , Article 12818. 10.1038/ncomms12818 . (In press). Green open access

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Through the Past Darkly: A Review of the British Ability Scales Second Edition

Hill, V; (2005) Through the Past Darkly: A Review of the British Ability Scales Second Edition. Child and Adolescent Mental Health , 10 (2) pp. 87-98. 10.1111/j.1475-3588.2004.00123.x .

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Facial swelling in a child on chronic hemodialysis: Answers.

Sawan, ZA; El-Desoky, SM; Shalaby, MA; Bockenhauer, D; Kari, JA; (2016) Facial swelling in a child on chronic hemodialysis: Answers. Pediatr Nephrol 10.1007/s00467-016-3525-z . (In press).

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