Complex regional pain syndrome type 1 predictors — Epidemiological perspective from a national database analysis

Complex regional pain syndrome type 1 is a disabling pain disorder with unclear etiology. It is usually triggered by an injury to a limb with or without specific nerve injury. The objective of this study is to explore the risk factors and predictors for this disease utilizing a large national database.

http://ift.tt/2njkC9p

Mom….Stop stressing me out!! Parental presence and its effect on cortisol levels in children

Parental presence during induction of anesthesia (PPIA) has been a long standing debate among pediatric anesthesiologists. In 1985, the British Medical Journal published a report of an ophthalmologist who was extremely dissatisfied when his request to be present at his 3year old child's induction was vehemently denied. His daughter awoke later that day screaming that she recalled the experience of the mask forcefully being held over her face [1]. It was this letter that triggered the pediatric anesthesia community to consider PPIA.

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Role of sugammadex in accelerating postoperative discharge: A meta-analysis

Sugammadex has been introduced for reversal of neuromuscular blockade (NMB) induced by rocuronium (or vecuronium). Although its efficacy and safety have been established, data are conflicting as to whether it accelerates discharge to the surgical ward compared with neostigmine, which is traditionally used for reversing NMB. The object of this systematic review and meta-analysis was to review the research comparing sugammadex and neostigmine in the context of patient discharge after general anesthesia.

http://ift.tt/2niUYRY

Three patients presenting with severe macrosomia and congenital hypertrophic cardiomyopathy: a case series

Macrosomia and hypertrophic cardiomyopathy are two features often associated in neonates of diabetic mothers. We report the cases of three patients with severe macrosomia and critical hypertrophic cardiomyopat...

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Tumor lysis syndrome in an extraskeletal osteosarcoma: a case report and review of the literature

This case report describes a spontaneous tumor lysis syndrome due to a rare solid tumor.

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Epstein–Barr Virus Lytic Reactivation Activates B Cells Polyclonally and Induces Activation-Induced Cytidine Deaminase Expression: A Mechanism Underlying Autoimmunity and Its Contribution to Graves' Disease

Viral Immunology , Vol. 0, No. 0.


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Transpalatal wiring for the management of sagittal fracture of the maxilla/palate

Sagittal fractures of the maxilla or palate, either in the midline or paramedian region, are usually associated with Le Fort fractures1,2, resulting in oronasal communication. Early stabilization of these fractures prevents the functional impairments and life-threatening situations, such as continuous haemorrhage from the traumatized nasal mucosa and nasal regurgitation of food leading to the risk of aspiration.

http://ift.tt/2mWNJM8

Newly developed method for mouse olfactory behavior tests using an automatic video tracking system

The mouse is the most popular animal model in olfactory research. Behavior tests with odorants are essential for determining olfactory phenotype. To the best of our knowledge, the mouse olfactory behavior test has not been standardized, making the results vulnerable to inter-observer variation. We sought to develop a new mouse olfactory behavior test assessed by an automatic video tracking system with minimal inter-observer variation.

http://ift.tt/2mWGqnF

Assessing eosinophilic cationic protein as a biomarker for monitoring patients with eosinophilic esophagitis treated with specific exclusion diets

Eosinophilic esophagitis (EoE) is a complex pathology. Attempts have been made in order to relate EoE with the intake of certain food. The problem is to establish which foods are really involved in the pathoph...

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Challenging hierarchy in healthcare teams – ways to flatten gradients to improve teamwork and patient care

In healthcare, mistakes that are potentially harmful or fatal to patients are often the result of poor communication between members of a team. This is particularly important in high-risk areas such as operating theatres or during any intervention, and the ability to challenge colleagues who are in authority when something does not seem right or is clearly wrong, is crucial. Colleagues in oral and maxillofacial surgery recognised the importance of this as early as 2004, and it is now well known that failure or reluctance to challenge others who might be wrong can severely compromise a patient's safety.

http://ift.tt/2mxOhNb

Three-dimensional facial changes correlated with sagittal jaw movements in patients with class III skeletal deformities

The aim of this prospective study was to correlate the postoperative 3-dimensional facial changes in skeletal class III deformity with sagittal jaw movements in 84 patients who had been treated by one piece Le Fort I maxillary advancement only (n=18), mandibular setback only (n=38), or both procedures (n=28). At the times of evaluation before and six months after operation all patients had fixed orthodontic appliances. Soft tissue changes were evaluated on optical 3-dimensional scans, while lateral cephalograms were superimposed to assess sagittal jaw movements.

http://ift.tt/2n05Hyh

Safer alternative for extraction of impacted supernumerary teeth of a patient in the mixed dentition stage with the aid of an image-guided operating system

Supernumerary teeth can exist throughout the mouth and are more common in the maxilla than in the mandible.1,2 During the mixed dentition stage, impacted supernumerary teeth that could block the eruption of permanent teeth, or interfere with the establishment of occlusal relations, should be extracted immediately. There is a risk of injury to the permanent tooth germs or of removing the wrong teeth in mixed dentition, because of the difficulty of locating the permanent tooth germs and the impacted teeth precisely from routine radiographs.

http://ift.tt/2mxQZCx

Rhabdomyosarcoma of the maxillofacial region in children and adolescents: Report of 9 cases and literature review

To review clinical presentation, histology, treatment and survival for pediatric maxillofacial rhabdomyosarcoma (RMS) and evaluate the role of surgical treatment.

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Validation of questionnaire-reported hearing with medical records: A report from the Swiss Childhood Cancer Survivor Study

by Annette Weiss, Grit Sommer, Rahel Kuonen, Katrin Scheinemann, Michael Grotzer, Martin Kompis, Claudia E. Kuehni, on behalf of the Swiss Paediatric Oncology Group (SPOG)

Background

Hearing loss is a potential late effect after childhood cancer. Questionnaires are often used to assess hearing in large cohorts of childhood cancer survivors and it is important to know if they can provide valid measures of hearing loss. We therefore assessed agreement and validity of questionnaire-reported hearing in childhood cancer survivors using medical records as reference.

Procedure

In this validation study, we studied 361 survivors of childhood cancer from the Swiss Childhood Cancer Survivor Study (SCCSS) who had been diagnosed after 1989 and had been exposed to ototoxic cancer treatment. Questionnaire-reported hearing was compared to the information in medical records. Hearing loss was defined as ≥ grade 1 according to the SIOP Boston Ototoxicity Scale. We assessed agreement and validity of questionnaire-reported hearing overall and stratified by questionnaire respondents (survivor or parent), sociodemographic characteristics, time between follow-up and questionnaire and severity of hearing loss.

Results

Questionnaire reports agreed with medical records in 85% of respondents (kappa 0.62), normal hearing was correctly assessed in 92% of those with normal hearing (n = 249), and hearing loss was correctly assessed in 69% of those with hearing loss (n = 112). Sensitivity of the questionnaires was 92%, 74%, and 39% for assessment of severe, moderate and mild bilateral hearing loss; and 50%, 33% and 10% for severe, moderate and mild unilateral hearing loss, respectively. Results did not differ by sociodemographic characteristics of the respondents, and survivor- and parent-reports were equally valid.

Conclusions

Questionnaires are a useful tool to assess hearing in large cohorts of childhood cancer survivors, but underestimate mild and unilateral hearing loss. Further research should investigate whether the addition of questions with higher sensitivity for mild degrees of hearing loss could improve the results.

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Editorial Board/ Publication Information

Publication date: April 2017
Source:Molecular Immunology, Volume 84





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Regulation and function of anaphylatoxins and their receptors in allergic asthma

Publication date: April 2017
Source:Molecular Immunology, Volume 84
Author(s): Yves Laumonnier, Anna V. Wiese, Julia Figge, Christian Karsten
Allergic asthma is a disease of the airways driven by maladaptive T helper 2 (Th2) and Th17 immune response against harmless, airborne substances. The hallmarks of this disease are airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Distinct dendric cell (DC) subsets together with airway epithelial and pulmonary vascular endothelial cells play critical roles in allergen sensing and in driving T cell differentiation towards Th2 and Th17 effector or regulatory T cells (Treg). Previous studies suggested already a pivotal role for the anaphylatoxins (C5a, C3a) in the pathogenesis of allergic asthma. During sensitization for example it is described, that C3a promotes, whereas C5a protects from the development of maladaptive immunity during allergen sensitization. Here we will discuss the role of the anaphylatoxins (C3a, C5a) and their receptors during the pathogenesis of allergic asthma, and specifically in lung DC biology. We will also have a look on canonical and non-canonical complement activation and we will discuss novel concepts on how the adaptive immune system can regulate the function of ATRs also in the context of allergic asthma.



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Regulation of airway inflammation and remodeling in asthmatic mice by TLR3/TRIF signal pathway

Publication date: May 2017
Source:Molecular Immunology, Volume 85
Author(s): Mei Yang, Hao-Ying Wang, Jian-Chang Chen, Jing Zhao
This paper aims to investigate the effect of Toll-like receptors 3 (TLR3)/TIR-domain-containing adapter-inducing interferon-β (TRIF) signal pathway on the airway inflammation and remodeling in asthmatic mice. C57BL/6 and TLR3^−/− mice were randomly divided into three groups (10 mice per group), including Control group (mice inhaled phosphate buffer saline (PBS)), Asthma group (mice inhaled ovalbumin (OVA)) and polyriboinosinic-ribocytidylic acid (poly (I: C)) group (asthmatic mice were injected intraperitoneally with TLR3 agonist poly (I: C)). Hematoxylin-eosin (HE) staining, Wright-Giemsa staining, Enzyme-linked immunosorbent assay (ELISA), Immunohistochemistry, Hydroxyproline assay, quantitative real time polymerase chain reaction (qRT-PCR) and Western blot were used to assess for the indices of airway inflammation and remodeling. In terms of WT mice, all asthma groups with or without the addition of poly (I: C) showed exaggerated inflammation and remodeling in the airways as compared to Control group, which were more seriously in poly (I: C) group than Asthma group. Furthermore, we observed the significant inhibition of airway inflammation and remodeling in the TLR3^−/− mice in both Asthma no matter with or without addition of poly (I: C) than the WT mice. TLR3 knockout could obviously relieve the airway inflammation and remodeling in asthma through inhibiting TLR3/TRIF signaling pathway.



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Preface to the special issue

Publication date: April 2017
Source:Molecular Immunology, Volume 84
Author(s): Mohamed Daha, Claudia Kemper




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PDL-1 Targeting in Resectable Oesophageal Cancer: a Phase II Feasibility Study of Atezolizumab and Chemoradiation

Conditions:   Esophageal Cancer, Stage II;   Esophageal Cancer Stage III
Interventions:   Drug: Atezolizumab;   Drug: Carboplatin;   Drug: Paclitaxel;   Radiation: Radiotherapy 23 x 1.8 Gy
Sponsors:   Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA);   UMC Utrecht
Not yet recruiting - verified March 2017

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Biomarker-based Study in R/M SCCHN

Condition:   Carcinoma, Squamous Cell of Head and Neck
Interventions:   Drug: Afatinib;   Drug: Palbociclib;   Drug: IPH2201;   Drug: standard of care
Sponsor:   European Organisation for Research and Treatment of Cancer - EORTC
Not yet recruiting - verified March 2017

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Editorial Board

Publication date: March–April 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 2





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Table of Contents

Publication date: March–April 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 2





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Guidelines for Contributing Authors

Publication date: March–April 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 2





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Delayed Otolith Development Does Not Impair Vestibular Circuit Formation in Zebrafish

Abstract

What is the role of normally patterned sensory signaling in development of vestibular circuits? For technical reasons, including the difficulty in depriving animals of vestibular inputs, this has been a challenging question to address. Here we take advantage of a vestibular-deficient zebrafish mutant, rock solo ^AN66 , in order to examine whether normal sensory input is required for formation of vestibular-driven postural circuitry. We show that the rock solo ^AN66 mutant is a splice site mutation in the secreted glycoprotein otogelin (otog), which we confirm through both whole genome sequencing and complementation with an otog early termination mutant. Using confocal microscopy, we find that elements of postural circuits are anatomically normal in rock solo ^AN66 mutants, including hair cells, vestibular ganglion neurons, and vestibulospinal neurons. Surprisingly, the balance and postural deficits that are readily apparent in younger larvae disappear around 2 weeks of age. We demonstrate that this behavioral recovery follows the delayed development of the anterior (utricular) otolith, which appears around 14 days post-fertilization (dpf), compared to 1 dpf in WT. These findings indicate that utricular signaling is not required for normal structural development of the inner ear and vestibular nucleus neurons. Furthermore, despite the otolith's developmental delay until well after postural behaviors normally appear, downstream circuits can drive righting reflexes within ∼1–2 days of its arrival, indicating that vestibular circuit wiring is not impaired by a delay in patterned activity. The functional recovery of postural behaviors may shed light on why humans with mutations in otog exhibit only subclinical vestibular deficits.

http://ift.tt/2nVb6rs

Photobiomodulation with LED and laser in repair of mandibular socket rabbit: clinical evaluation, histological, and histomorphometric

Abstract

Purpose

The aim of this study was to evaluate the effects of LED and low-intensity laser on the healing of rabbit dental alveoli.

Methods

A total of 18 rabbits were divided into three groups of six; all rabbits underwent surgical extraction of the first lower right premolar. Following surgery, group 1 received LED irradiation, group 2 received laser irradiation, and group 3 were untreated controls. The initial applications of LED and laser began 48 h after tooth extraction and were given perpendicularly to the dental alveoli. The three groups were clinically evaluated for 18 days in the postoperative period. At 90 days, the rabbits were euthanized and the mandibular fragments containing the healing alveoli were collected. These fragments initially underwent computed tomography scans and bone density was measured in Hounsfield units. Following this, the fragments were processed and stained with hematoxylin and eosin for histological and histomorphometric analysis.

Results

The results were compatible between the clinical, histological, and histomorphometric parameters evaluated. There were no statistical differences between the LED and laser groups. However, the difference of the average bone density between laser and control group was not statistically significant.

Conclusions

It was found that photobiomodulation with LASER and LED presented effects. However, only the LED demonstrated a beneficial effect on the process of bone repair in the dental alveoli of rabbits.

http://ift.tt/2nbhYkw

Lower face cephalometry based on quadrilateral analysis with cone-beam computed tomography: a clinical pilot study

Abstract

Objective

As most orthognathic surgeries focus on the lower face, the aim of this study was to transfer previously developed two-dimensional cephalometry—which is useful for surgeons in the orthognathic surgery of the lower face—to three-dimensional (3D) cephalometry by using cone-beam computed tomography (CBCT). We selected the quadrilateral lower face analysis developed by the surgeon Di Paolo, who focused only for the lower face and mentioned that data in millimeters are more easy to use than angles for surgeons. Additionally, we wanted to create a 3D lower face analysis approach based on quadrilateral analysis and establish a reference table for surgical planning.

Study design

Three investigators assigned 16 landmarks on CBCT images from 30 patients with normocclusion. Intra-class correlation coefficients (ICCs) and standard deviations (SDs) were calculated according to each landmark. The maxillary and mandibular lengths and widths and the anterior and posterior lower facial heights (ALFH and PLFH) are presented as means and SDs. The asymmetry of the face was calculated with paired t test, and the coherence of the lower face was assessed with correlation coefficients (r) and regression models.

Results

The ICCs were ≥0.90, and the SDs of the landmarks were lower than 1.00 mm, except for the J-point, which was located at the junction of the anterior border of the ramus and the corpus of the mandible. The SDs of linear measurements were 3.06–5.20 mm, and there was no significant facial asymmetry. The r among the structures was greater than 0.3 in 13 of 15 assessments. Based on these values, we could establish a floating norm of the lower face using the following five regressions: one linear regression for the mandibular length, two quadratic models for the ALFH and PLFH, and two multivariate regressions for the posterior widths of the maxillae and mandible.

Conclusion

The adaptation of quadrilateral analysis can provide accurate 3D characterization of the morphology of the lower face and the floating norm based on millimeter values, which is practical for surgeons. As the 3D extension of quadrilateral analysis could provide references of the lower face, which might be an accurate 3D approach for presurgical planning, the further investigation in bigger sample would be relevant in the practice.

http://ift.tt/2nh4Sni

Hearing Loss in Patients With an Enlarged Vestibular Aqueduct

This retrospective medical record review of 54 patients and 74 affected ears examines the association between vestibular aqueduct size and repeated measures of hearing loss.

http://ift.tt/2ns32Aq

Adjuvant Human Papillomavirus Vaccination for Secondary Prevention

This systematic review evaluates literature regarding human papillomavirus vaccination for secondary disease prevention after treatment of virus-related clinical disease.

http://ift.tt/2mYQP3i

Long-term Surveillance Following Intralesional Steroid Injection for Benign Vocal Fold Lesions

This cohort study reports the findings of a long-term surveillance following intralesional steroid injection for benign vocal fold lesions.

http://ift.tt/2nse4G6

Polymorphisms in chronic rhinosinusitis with nasal polyps – a systematic review

Publication date: Available online 23 March 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Vanessa Ramos Pires Dinarte, Anemari Ramos Dinarte dos Santos, Luiza Ferreira de Araújo, Mariah Guieiro Alves dos Reis, Edwin Tamashiro, Fabiana Cardoso Pereira Valera, Wilson Araújo da Silva Júnior, Wilma Terezinha Anselmo-Lima
IntroductionChronic rhinosinusitis with nasal polyps is a multifactorial disease with a complex pathophysiology involving multiple genetic and environmental factors.ObjectiveThe purpose of this work review is to focus on the importance of genetic studies in chronic rhinosinusitis with nasal polyps besides the several barriers that exists for its understanding.MethodsA systematic review on studies of association between single nucleotide polymorphisms and chronic rhinosinusitis with nasal polyps based on a PubMed/Medline and Periódicos CAPES search of all articles published between January 2005 and January 2015 was made. The search was guided on studies containing the terms polymorphisms, rhinosinusitis, and polyps.ResultsTwo studies found an association of MMP-9 and MMP-2 polymorphisms and chronic rhinosinusitis with nasal polyps, but not in patients with recurrent nasal polyps. Other studies found an association of nasal polyps with MMP-9 polymorphisms, but not with MMP-2 ones. There is evidence of an association of LTC4S, NOS2A, PTGDR, MET, COX-2, OSF-2, and LF polymorphisms and the risk of developing nasal polyps, especially when combined with chronic allergic rhinitis and asthma.ConclusionGenetic studies on chronic rhinosinusitis with nasal polyps are promising and may offer insights into its pathophysiology, which is likely affected by multiple genetic factors.



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Editorial Board

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Table of Contents

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Guidelines for Contributing Authors

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Inflammatory and Autoimmune Manifestations in X-linked carriers of Chronic Granulomatous Disease in the United Kingdom

Publication date: Available online 23 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Alexandra C. Battersby, Helen Braggins, Mark S. Pearce, Catherine M. Cale, Siobhan O. Burns, Scott Hackett, Stephen Hughes, Dawn Barge, David Goldblatt, Andrew R. Gennery

Teaser

Capsule summary: It has been recognized that X-linked carriers may have skin


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αS1-casein Elucidate Major T Cell Responses in Cow’s Milk Allergy

Publication date: Available online 23 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): L. Diego Archila, Fatima S. Khan, Nupur Bhatnagar, David Robinson, Mary L. Farrington, William W. Kwok
Cow's milk allergy (CMA) is increasing in prevalence, affecting approximately 4% of children. Cow's milk (CM) is a common cause of fatal/ near fatal anaphylactic reactions. Understanding of CM-specific CD4+ T-cells responses to milk allergens should help elucidate the pathological mechanisms of persistent CMA. Milk allergen epitopes specific T-cells were examined in CMA subjects. Frequencies and phenotypes of these T-cells were found to be different between older and younger subjects.



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Receptor-interacting Protein Kinase 3 Controls Keratinocyte Activation in a Necroptosis-independent Manner and Promotes Psoriatic Dermatitis in Mice

Publication date: Available online 23 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Tetsuya Honda, Osamu Yamamoto, Yu Sawada, Gyohei Egawa, Akihiko Kitoh, Atsushi Otsuka, Teruki Dainichi, Saeko Nakajima, Yoshiki Miyachi, Kenji Kabashima

Teaser

RIPK3 in keratinocytes facilitates psoriatic inflammation by promoting cytokine and chemokine production, independent of the induction of necroptosis. Control of RIPK3 activation may be a novel therapeutic target for psoriasis.


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Thunderstorm Related Asthma Attacks

Publication date: Available online 23 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Gennaro D'Amato, Isabella Annesi Maesano, Molino Antonio, Carolina Vitale, Maria D'Amato




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Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses

Publication date: Available online 23 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): David J. Dowling, Evan A. Scott, Annette Scheid, Ilana Bergelson, Sweta Joshi, Carlo Pietrasanta, Spencer Brightman, Guzman Sanchez-Schmitz, Simon D. Van Haren, Jana Ninković, Dina Kats, Cristiana Guiducci, Alexandre de Titta, Daniel K. Bonner, Sachiko Hirosue, Melody A. Swartz, Jeffrey A. Hubbell, Ofer Levy
BackgroundNewborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization.ObjectiveSmall-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form. We used rational engineering and age- and species-specific modeling to construct and characterize polymer nanocarriers encapsulating a TLR8 agonist, allowing direct intracellular release after selective uptake by DCs.MethodsChemically similar but morphologically distinct nanocarriers comprised of amphiphilic block copolymers were engineered for targeted uptake by murine DCs in vivo, and a range of TLR8 agonist–encapsulating polymersome formulations were then synthesized. Novel 96-well in vitro assays using neonatal human monocyte-derived DCs and humanized TLR8 mouse bone marrow–derived DCs enabled benchmarking of the TLR8 agonist–encapsulating polymersome formulations against conventional adjuvants and licensed vaccines, including live attenuated BCG vaccine. Immunogenicity of the TLR8 agonist adjuvanted antigen 85B (Ag85B)/peptide 25–loaded BCG-mimicking nanoparticle formulation was evaluated in vivo by using humanized TLR8 neonatal mice.ResultsAlthough alum-adjuvanted vaccines induced modest costimulatory molecule expression, limited TH-polarizing cytokine production, and significant cell death, BCG induced a robust adult-like maturation profile of neonatal DCs. Remarkably, TLR8 agonist polymersomes induced not only newborn DC maturation profiles similar to those induced by BCG but also stronger IL-12p70 production. On subcutaneous injection to neonatal mice, the TLR8 agonist–adjuvanted Ag85B peptide 25 formulation was comparable with BCG in inducing Ag85B-specific CD4⁺ T-cell numbers.ConclusionTLR8 agonist–encapsulating polymersomes hold substantial potential for early-life immunization against intracellular pathogens. Overall, our study represents a novel approach for rational design of early-life vaccines.

Graphical abstract

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REDD1 links stress with IL-1β-mediated familial Mediterranean fever attack through autophagy-driven neutrophil extracellular traps

Publication date: Available online 23 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Panagiotis Skendros, Akrivi Chrysanthopoulou, François Rousset, Konstantinos Kambas, Athanasios Arampatzioglou, Alexandros Mitsios, Veronique Bocly, Theocharis Konstantinidis, Philippe Pellet, Iliana Angelidou, Eirini Apostolidou, Dimitrios Ritis, Victoria Tsironidou, Sotiris Galtsidis, Charalampos Papagoras, Dimitrios Stakos, Georgios Kouklakis, Vasiliki Dalla, Maria Koffa, Ioannis Mitroulis, Ioannis Theodorou, Konstantinos Ritis
BackgroundFamilial Mediterranean fever (FMF) is an IL-1β-dependent autoinflammatory disease caused by mutations of MEFV encoding pyrin, and characterised by inflammatory attacks, induced by physical or psychological stress.ObjectiveWe investigate the underlying mechanism that links stress-induced inflammatory attacks with neutrophil activation and release of IL-1β-bearing neutrophil extracellular traps (NETs) in FMF.MethodsRNA-seq was performed in peripheral neutrophils from 3 FMF patients, isolated both during attack and remission, 8 patients in remission and 8 healthy individuals. NET formation and proteins were analysed by confocal immunofluorescence microscopy, immunobloting, MPO-DNA complex ELISA and flow cytometry. Samples from patients suffering from Still's disease and bacterial infections were also used.ResultsStress-related protein REDD1 is significantly over-expressed during FMF attacks. Neutrophils from FMF patients during remission are resistant to autophagy-mediated NET release, which can be overcome via REDD1 induction. Stress-related mediators (e.g. epinephrine) lower this threshold leading to autophagy-driven NET release, while the synchronous inflammatory environment of FMF attack leads to intracellular production of IL-1β and its release through NETs. REDD1 in autolysosomes co-localizes with pyrin and NALP3. Mutated pyrin prohibits this co-localization, leading to higher IL-1β levels on NETs.ConclusionsThis study provides a link between stress and initiation of inflammatory attacks in FMF. REDD1 emerges as an upstream to pyrin regulator of neutrophil function, is involved in NET release, regulation of IL-1β and, may constitute an important piece in the IL-1β-mediated inflammation puzzle.

Graphical abstract

Teaser

Stress-induced protein REDD1 is identified as a novel mediator in the pathogenesis of IL-1β-driven inflammation, through regulation of autophagy-mediated release of NETs. This study links environmental stress with inflammation in FMF attack as well as, with other IL-1β-associated autoinflammatory disorders.


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Basophils, high-affinity IgE receptors and CCL2 in human anaphylaxis

Publication date: Available online 22 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Peter Korosec, Paul J. Turner, Mira Silar, Peter Kopac, Mitja Kosnik, Bernhard F. Gibbs, Mohamed H. Shamji, Adnan Custovic, Matija Rijavec
BackgroundThe role of basophils in anaphylaxis is unclear.ObjectiveTo investigate whether basophils have an important role in human anaphylaxis.MethodsIn an emergency department study, we recruited 31 patients with acute anaphylaxis, predominantly to hymenoptera venom. We measured expression of basophil activation markers (CD63, CD203c), the absolute number of circulating basophils, whole-blood FcεRI, CPA3 and HDC gene expression, and serum markers (CCL2, CCL5, CCL11, IL-3, TSLP) at three time points (during the anaphylactic episode, and in convalescent samples 7 and 30 days later). We recruited 134 hymenoptera-allergic and 76 healthy controls for comparison. We then investigated whether the changes observed during venom-related anaphylaxis also occur during allergic reactions to food in 22 peanut-allergic individuals undergoing double-blind placebo-controlled food challenge to peanut (DBPCFC).ResultsThe number of circulating basophils was significantly lower during anaphylaxis (median 3.5 cells/μl) than 7 and 30 days later (17.5 and 24.7 cells/μl, P<0.0001), and compared to venom-allergic and healthy controls (21 and 23.4 cells/μl, P<0.0001). FcεRI expression during anaphylaxis was also significantly lower than in convalescent samples (P≤0.002) and venom-allergic controls (P<0.0001). CCL2 (but not other serum markers) was significantly higher during anaphylaxis (median 658 pg/ml) than in convalescent samples (314 and 311 pg/ml, 7 and 30 days, P<0.001). Peanut-induced allergic reactions resulted in a significant decrease in circulating basophils compared to pre-challenge samples (P=0.016), a decrease in FcεRI expression (P=0.007), and an increase in CCL2 (P=0.003).ConclusionsOur findings imply an important and specific role for basophils in the pathophysiology of human anaphylaxis.

Teaser

We demonstrate a substantial reduction in circulating basophils and whole blood FcεRI gene expression during acute anaphylaxis. There was an increase in the major basophil chemotactic factor CCL2, which correlated with a decrease in basophils.


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The Cellular Immune System Comes of Age

Publication date: Available online 22 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): René A.W. van Lier, Taco W. Kuijpers




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Peanut oleosins associated with severe peanut allergy - Importance of lipophilic allergens for comprehensive allergy diagnostics

Publication date: Available online 22 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Christian Schwager, Skadi Kull, Jochen Behrends, Niels Röckendorf, Frauke Schocker, Andreas Frey, Arne Homann, Wolf-Meinhard Becker, Uta Jappe
BackgroundPeanut allergy is one of the most common and most severe food allergies in Western countries and its accurate diagnosis to prevent potential life-threatening allergic reactions is crucial. However, aqueous extracts used for routine diagnostic measurements are devoid of lipophilic allergens such as oleosins. We have recently succeeded in the isolation and purification of these unique proteins, and the current study evaluates their allergenic potential and clinical relevance.ObjectiveWe sought to assess allergenicity and sensitization prevalence of oleosins obtained from both raw and in-shell roasted peanuts. Additionally, we tested the utilization of natural and recombinant oleosins for allergy diagnostic purposes.MethodsOleosin sensitization, prevalence, and impact of thermal processing were analyzed by immunoblot with sera from 52 peanut-allergic individuals displaying different clinical phenotypes. The application of natural and recombinant oleosins for allergy diagnostics was investigated by basophil activation test (BAT). IgE-binding epitopes were identified by oligopeptide microarray.ResultsSensitization to oleosins was observed exclusively in peanut-allergic subjects suffering from severe systemic reactions. IgE-binding capacity of oleosins derived from in-shell roasted peanuts was increased as shown by immunoblot analysis and BAT. Both natural and recombinant molecules can be used to identify oleosin-sensitized patients by BAT. A linear epitope of Ara h 15 was determined which displays high similarity to other seed-derived oleosins.ConclusionOleosins are clinically relevant peanut allergens and most likely associated with severe allergic symptoms. In-shell roasting increases their allergenicity, which is consistent with the observation that most allergic reactions are in connection with roasted peanuts.

Teaser

Peanut oleosins are novel lipophilic allergens associated with severe allergic reactions. Their IgE-binding capacity is increased in roasted peanuts. Application of either purified natural or recombinant oleosins now closes a diagnostic gap.


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Blood eosinophils predict therapeutic effects of a GATA3-specific DNAzyme in asthma patients

Publication date: Available online 22 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Norbert Krug, Jens M. Hohlfeld, Roland Buhl, Jonas Renz, Holger Garn, Harald Renz

Teaser

The effect of the GATA3-mRNA-specific DNAzyme SB010 treatment on EAR and LAR responses continuously increased with higher relative levels of blood eosinophils making them a suitable biomarker to stratify asthma patients for inhaled SB010 treatment.


http://ift.tt/2mYI0X9

Intestinal dendritic cell licensing through TLR4 is required for oral tolerance in allergic contact dermatitis

Publication date: Available online 22 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Feriel Hacini-Rachinel, Mercedes Gomez de Agüero, Reem Kanjarawi, Ludovic Moro-Sibilot, Jean-Benoit Le Luduec, Claire Macari, Gilles Boschetti, Emilie Bardel, Philippe Langella, Bertrand Dubois, Dominique Kaiserlian
BackgroundInduction of oral tolerance to haptens is an efficient way to prevent allergic contact dermatitis (ACD) in mice. Toll-like receptor (TLRs)-mediated sensing of the microbiota contributes to gut homeostasis, yet whether it contributes to induction of oral tolerance has not been documented.ObjectiveWe examined whether oral tolerance to the contact sensitizer DNFB depends on microbiota/TLRs and evaluated the role of TLR4 on the tolerogenic function of intestinal dendritic cells (DCs).MethodsOral tolerance was induced by DNFB gavage in germ-free (GF) and several TLR-deficient mice. Tolerance was assessed by suppression of contact hypersensitivity and of hapten-specific IFNγ-producing effector T cells. The tolerogenic function of intestinal DCs was tested by adoptive transfer experiments, ex vivo hapten-presentation and Foxp3 regulatory T cell conversion.ResultsOral tolerance induced by DNFB gavage was impaired in GF mice and in TLR4-deficient mice. Bone marrow chimeras revealed that TLR4 expression on hematopoietic cells was necessary for oral tolerance induction. TLR4 appeared to be essential for the ability of intestinal dendritic cells from DNFB-fed mice to inhibit ACD upon adoptive transfer. Indeed, TLR4 conditioned the in vivo mobilization to mesenteric lymph nodes of intestinal migratory CD103⁺ DCs carrying oral DNFB, especially the CD103⁺CD11b⁺ DC subset expressing the vitamin A-converting enzyme RALDH⁺ and specialized in Foxp3⁺Treg conversion.ConclusionsOur data demonstrate that TLR4 conditions induction of oral tolerance to DNFB via licensing tolerogenic gut DCs. Oral biotherapy with TLR4 ligands might be usefull to potentiate oral tolerance to haptens and alleviate ACD in humans.

Teaser

The commensal flora and expression of TLR4 on hematopoietic cells are essential for oral tolerance and suppression of DNFB-induced contact hypersensitivity. TLR4 conditions the mobilization of tolerogenic intestinal CD103⁺CD11b⁺ DCs carrying the allergen to MLNs.


http://ift.tt/2mwTdlt

Granulocyte transfusions in patients with chronic granulomatous disease and refractory infections: the NIH experience

Publication date: Available online 22 March 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Beatriz E. Marciano, Elisabeth S. Allen, Cathy C. Cantilena, Ervand Kristosturyan, Harvey G. Klein, Thomas A. Fleisher, Steven M. Holland, Harry L. Malech, Sergio D. Rosenzweig
Granulocyte transfusions are a relatively safe adjunctive therapeutic option for patients with chronic granulomatous disease and severe/refractory bacterial or fungal infections. Early initiation, high frequency and sustained therapy is associated with significantly better outcomes.



http://ift.tt/2mYJbWB

Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start?

Abstract

It is well recognised that a state of autoimmunity, in which immunological tolerance is broken, precedes the development of symptoms in the majority of patients with rheumatoid arthritis (RA). For individuals who will later develop seropositive disease, this manifests as autoantibodies directed against proteins that have undergone specific post-translational modifications. There is evidence that the induction of this autoantibody response occurs at peripheral extra-articular mucosal sites, such as the periodontium and lung. In addition to their utility as diagnostic markers, these autoantibodies may have a pathogenic role that helps localise disease to the synovium. Alongside the development of autoantibodies, other factors contributing to pre-symptomatic autoimmunity may include dysbiosis of the gastrointestinal tract, abnormal development of lymphoid tissue, and dysregulated autonomic and lipid-mediated anti-inflammatory signalling. These factors combine to skew the balance between pro-inflammatory and anti-inflammatory signalling in a manner that is permissive for the development of clinical arthritis. We present data to support the concept that the transitions from at-risk states to systemic autoimmunity and then to classifiable RA depend on multiple "switches". However, further prospective studies are necessary to define the molecular basis of these switches and the specific features of pre-symptomatic autoimmunity, so that preventative treatments can be targeted to individuals at high risk for RA. In this review, we analyse mechanisms that may contribute to the development of autoimmunity in at-risk individuals and discuss the relationship between this pre-symptomatic state and subsequent development of RA.

http://ift.tt/2mwCq1T

Increase in sensory sensitivity around, but not in the central part of, the hyperkeratotic papule in lichen amyloidosis

Abstract

Lichen amyloidosis (LA) is an itchy skin disorder characterized by amyloid deposits in the superficial dermis. Pruritus is the presenting symptom in 90% of LA patients.¹ However, the underlying mechanisms and mediators of pruritus in LA remain unclear.

One LA patient complained of severe pruritus in the hyperkeratotic papules, especially around the papule.

This article is protected by copyright. All rights reserved.

http://ift.tt/2nbCzoF

Burden of respiratory comorbidities in patients with atopic dermatitis and psoriasis

Abstract

Atopic dermatitis (AD), a skin disease with an estimated lifetime prevalence of up to 20%, represents a major global healthcare burden.¹ Patients with AD have a propensity to develop asthma due to a combination of genetic, immunological and environmental factors, yet descriptive studies on the impact of respiratory diseases in adults with AD are scarce.² In contrast, psoriasis, another chronic inflammatory skin disease, has been associated with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD)³, asthma⁴ and obstructive sleep apnea (OSA).

This article is protected by copyright. All rights reserved.

http://ift.tt/2ngYn3Y

Photobiomodulation with LED and laser in repair of mandibular socket rabbit: clinical evaluation, histological, and histomorphometric

Abstract

Purpose

The aim of this study was to evaluate the effects of LED and low-intensity laser on the healing of rabbit dental alveoli.

Methods

A total of 18 rabbits were divided into three groups of six; all rabbits underwent surgical extraction of the first lower right premolar. Following surgery, group 1 received LED irradiation, group 2 received laser irradiation, and group 3 were untreated controls. The initial applications of LED and laser began 48 h after tooth extraction and were given perpendicularly to the dental alveoli. The three groups were clinically evaluated for 18 days in the postoperative period. At 90 days, the rabbits were euthanized and the mandibular fragments containing the healing alveoli were collected. These fragments initially underwent computed tomography scans and bone density was measured in Hounsfield units. Following this, the fragments were processed and stained with hematoxylin and eosin for histological and histomorphometric analysis.

Results

The results were compatible between the clinical, histological, and histomorphometric parameters evaluated. There were no statistical differences between the LED and laser groups. However, the difference of the average bone density between laser and control group was not statistically significant.

Conclusions

It was found that photobiomodulation with LASER and LED presented effects. However, only the LED demonstrated a beneficial effect on the process of bone repair in the dental alveoli of rabbits.

http://ift.tt/2nbhYkw

Lower face cephalometry based on quadrilateral analysis with cone-beam computed tomography: a clinical pilot study

Abstract

Objective

As most orthognathic surgeries focus on the lower face, the aim of this study was to transfer previously developed two-dimensional cephalometry—which is useful for surgeons in the orthognathic surgery of the lower face—to three-dimensional (3D) cephalometry by using cone-beam computed tomography (CBCT). We selected the quadrilateral lower face analysis developed by the surgeon Di Paolo, who focused only for the lower face and mentioned that data in millimeters are more easy to use than angles for surgeons. Additionally, we wanted to create a 3D lower face analysis approach based on quadrilateral analysis and establish a reference table for surgical planning.

Study design

Three investigators assigned 16 landmarks on CBCT images from 30 patients with normocclusion. Intra-class correlation coefficients (ICCs) and standard deviations (SDs) were calculated according to each landmark. The maxillary and mandibular lengths and widths and the anterior and posterior lower facial heights (ALFH and PLFH) are presented as means and SDs. The asymmetry of the face was calculated with paired t test, and the coherence of the lower face was assessed with correlation coefficients (r) and regression models.

Results

The ICCs were ≥0.90, and the SDs of the landmarks were lower than 1.00 mm, except for the J-point, which was located at the junction of the anterior border of the ramus and the corpus of the mandible. The SDs of linear measurements were 3.06–5.20 mm, and there was no significant facial asymmetry. The r among the structures was greater than 0.3 in 13 of 15 assessments. Based on these values, we could establish a floating norm of the lower face using the following five regressions: one linear regression for the mandibular length, two quadratic models for the ALFH and PLFH, and two multivariate regressions for the posterior widths of the maxillae and mandible.

Conclusion

The adaptation of quadrilateral analysis can provide accurate 3D characterization of the morphology of the lower face and the floating norm based on millimeter values, which is practical for surgeons. As the 3D extension of quadrilateral analysis could provide references of the lower face, which might be an accurate 3D approach for presurgical planning, the further investigation in bigger sample would be relevant in the practice.

http://ift.tt/2nh4Sni

Head and Neck Round Cell Sarcomas: A Comparative Clinicopathologic Analysis of 2 Molecular Subsets: Ewing and CIC -Rearranged Sarcomas

Abstract

CIC-rearranged sarcoma (CRS) is a relatively new entity defined by its pathognomonic genetic signature and undifferentiated round cell phenotype, initially grouped together with the 'Ewing sarcoma-like tumors'. However, increasing data suggest that these tumors should be regarded as a stand-alone pathologic entity. We conducted a clinicopathologic analysis on molecularly conformed Ewing sarcoma (ES) and CRS arising in the head and neck (HN) and compared to a well characterized cohort of ES and CRS from other locations. A total of 41 HN round cell sarcoma patients were selected from our institutional and consultation files, including 25 ES (median 20 years) and 16 CRS (median 29 years). Clinical follow-up information was available for all ES patients, ranging from 4 to 436 months (median 70 months), while for CRS, follow-up information was available in 11 patients (69%), ranging from 1 to 269 months (median 27 months). The most common location for ES was the facial and jaw bones (56%), while CRS occurred exclusively in the soft tissue, commonly in the neck. CRS showed variable CD99 staining in 75% of cases and diffuse WT1 (6/6) reactivity, while all ES expressed diffuse membranous staining for CD99 but none for WT1 (0/6). The 2-year overall survival (OS) rate for HN-CRS patients was 78%, while for HN-ES it was 100%. The OS of ES and CRS showed a trend toward a favorable outcome for HN-round cell sarcomas compared to other sites. Our findings suggest that HN-CRS have different clinical presentation and pathologic features compared to ES and should be classified as a stand-alone pathologic entity.

http://ift.tt/2nr7yz6

Use of nanofractional radiofrequency for the treatment of acne scars in Indian skin

Summary

Background

Pitted acne scars of all types remain notoriously challenging to treat with no satisfactory treatment modality, particularly true for darker Fitzpatrick skin types such as Indian skin.

Aim

Nanofractional radiofrequency has been shown to be an effective treatment modality for the cosmetic improvement of acne scars.

Methods

Twenty healthy male and female Indian patients aged 16–60 years with Fitzpatrick skin types IV-V and moderate-to-severe acne scar lesions received 1–3 treatments with a nanofractional radiofrequency device (Venus Viva) at baseline and at 3- to 6 week intervals and were evaluated with photographs at each treatment visit and up to 6 months after the final treatment session. Patients reported on their satisfaction with the treatment. The safety of treatments was evaluated by the frequency, severity, and type of adverse events.

Results

The majority of study patients achieved improvement in the appearance of their acne scar lesions. There was less improvement on ice pick scar compared to box and rolling type scars, with less impact on ice pick scar type. Overall patient satisfaction from treatment at the 6-month follow-up visit was very high. Adverse events were mild but transient in nature.

Conclusion

The data and results presented here support the efficacy of nanofractional radiofrequency used for the cosmetic improvement of acne scar lesions in facial skin. Moreover, the favorable adverse event profile witnessed in this trial underscores the safety of this technology for cosmetic facial treatments such as facial acne scar lesion therapy in darker Fitzpatrick skin types.

http://ift.tt/2ngMCKT

Delayed Otolith Development Does Not Impair Vestibular Circuit Formation in Zebrafish

Abstract

What is the role of normally patterned sensory signaling in development of vestibular circuits? For technical reasons, including the difficulty in depriving animals of vestibular inputs, this has been a challenging question to address. Here we take advantage of a vestibular-deficient zebrafish mutant, rock solo ^AN66 , in order to examine whether normal sensory input is required for formation of vestibular-driven postural circuitry. We show that the rock solo ^AN66 mutant is a splice site mutation in the secreted glycoprotein otogelin (otog), which we confirm through both whole genome sequencing and complementation with an otog early termination mutant. Using confocal microscopy, we find that elements of postural circuits are anatomically normal in rock solo ^AN66 mutants, including hair cells, vestibular ganglion neurons, and vestibulospinal neurons. Surprisingly, the balance and postural deficits that are readily apparent in younger larvae disappear around 2 weeks of age. We demonstrate that this behavioral recovery follows the delayed development of the anterior (utricular) otolith, which appears around 14 days post-fertilization (dpf), compared to 1 dpf in WT. These findings indicate that utricular signaling is not required for normal structural development of the inner ear and vestibular nucleus neurons. Furthermore, despite the otolith's developmental delay until well after postural behaviors normally appear, downstream circuits can drive righting reflexes within ∼1–2 days of its arrival, indicating that vestibular circuit wiring is not impaired by a delay in patterned activity. The functional recovery of postural behaviors may shed light on why humans with mutations in otog exhibit only subclinical vestibular deficits.

http://ift.tt/2nVb6rs

Head and Neck Round Cell Sarcomas: A Comparative Clinicopathologic Analysis of 2 Molecular Subsets: Ewing and CIC -Rearranged Sarcomas

Abstract

CIC-rearranged sarcoma (CRS) is a relatively new entity defined by its pathognomonic genetic signature and undifferentiated round cell phenotype, initially grouped together with the 'Ewing sarcoma-like tumors'. However, increasing data suggest that these tumors should be regarded as a stand-alone pathologic entity. We conducted a clinicopathologic analysis on molecularly conformed Ewing sarcoma (ES) and CRS arising in the head and neck (HN) and compared to a well characterized cohort of ES and CRS from other locations. A total of 41 HN round cell sarcoma patients were selected from our institutional and consultation files, including 25 ES (median 20 years) and 16 CRS (median 29 years). Clinical follow-up information was available for all ES patients, ranging from 4 to 436 months (median 70 months), while for CRS, follow-up information was available in 11 patients (69%), ranging from 1 to 269 months (median 27 months). The most common location for ES was the facial and jaw bones (56%), while CRS occurred exclusively in the soft tissue, commonly in the neck. CRS showed variable CD99 staining in 75% of cases and diffuse WT1 (6/6) reactivity, while all ES expressed diffuse membranous staining for CD99 but none for WT1 (0/6). The 2-year overall survival (OS) rate for HN-CRS patients was 78%, while for HN-ES it was 100%. The OS of ES and CRS showed a trend toward a favorable outcome for HN-round cell sarcomas compared to other sites. Our findings suggest that HN-CRS have different clinical presentation and pathologic features compared to ES and should be classified as a stand-alone pathologic entity.

http://ift.tt/2nr7yz6

Economics of Chronic Rhinosinusitis

Abstract

Purpose of Review

The objective of this article is to provide an updated review of the economic burden of chronic rhinosinusitis (CRS) and discuss how both medical and surgical interventions impact direct and indirect costs related to CRS. By understanding the economics of CRS, clinicians may improve the patient-centeredness of their care and help distinguish between low and high value interventions.

Recent Findings

Direct costs related to CRS are primarily driven by outpatient physician visits, prescription medical therapy, and endoscopic sinus surgery (ESS). CRS produces large indirect costs and these costs often vary based on the severity of the patients CRS-specific QoL impairment. The overall direct cost related to CRS is estimated to range between $10 and $13 billion per year in the USA. The overall indirect cost related to CRS-related losses in work productivity is estimated to be in excess of $20 billion per year.

Summary

In the appropriate patients with refractory CRS, ESS provides significant reductions in both direct and indirect costs; however, continued medical therapy alone may be a high value intervention in select patients who have lower severity in their baseline QoL and work productivity.

http://ift.tt/2ng4ENl

Mechanisms Driving Gender Differences in Asthma

Abstract

Purpose of Review

Many phenotypes of asthma exist, ranging from mild asthma with onset during childhood to severe asthma with later onset, making asthma a broad disease with different pathologies. A gender disparity exists in asthma prevalence. As adults, women have an increased asthma prevalence compared to men. Further, women are more likely to have severe asthma and a later onset of asthma compared to men. Here, we review clinical and animal studies that have defined the role of sex hormones in airway inflammation, smooth muscle contraction, mucus production, and airway mechanics associated with asthma pathogenesis.

Recent Findings

Clinical evidence shows that increased asthma symptoms occur in females starting at puberty compared to those in boys. However, after puberty, the role for sex hormones in regulating asthma symptoms during menstruation, pregnancy, and menopause is not as clear. Animal studies have shown that estrogen increases and testosterone decreases Th2-mediated airway inflammation, and that females have increased IL-17A-mediated airway inflammation compared to males. Further, females had increased DC and Mϕ function compared to males. However, the mechanisms driving the types of allergic inflammation are not fully elucidated.

Summary

Overall, ovarian hormones increased and testosterone decreased airway inflammation in asthma, but the mechanisms remain unclear. Delineating these pathways using animal models as well as women and men with various phenotypes of asthma will help determine if women with asthma should take (or avoid) hormonal contraceptives as well as predict changes in asthma symptoms during life phases, including pregnancy and menopause, when sex hormones are dramatically changing.

http://ift.tt/2nasUyI

Prevalence of obstructive sleep apnea syndrome following oropharyngeal cancer treatment: a Prospective cohort study

Abstract

Objectives

To evaluate the prevalence of obstructive sleep apnea syndrome (OSAS) in a population of patients treated for an advanced cancer of the oropharynx (AJCC Stage III or IV), depending on treatment strategy and to evaluate its impact on quality of life.

Design

Prospective cohort study.

Setting

University Teaching Hospital of La Conception, Marseille, France.

Participants

ifty-one disease free patients were included. Forty-one patients received a combined chemoradiotherapy while 10 patients have been treated by surgery followed by (chemo)radiotherapy.

Main outcome measures

Every patient underwent a formal sleep consultation and was asked to complete the Epworth sleepiness scale and EORTC QLQ C-30 and the EORTC H&N 35 questionnaires. A home overnight respiratory polygraphy was performed in every subject.

Results

The mean time between the end of cancer treatment and OSAS analysis was 54.04 months [20; 84]. An OSAS was found in 25.49% of our patients. There was no significant difference between patients treated with surgery (30%) or CRT (24.39%), p=0.79. The EORTC QLQ C-30 questionnaire showed a significant difference between positive and negative OSAS groups about the Global Health Status Scale (50.64 vs. 67.11, p = 0.02) and on the fatigue item (35.04 vs. 17.25, p = 0.03).

Conclusions

Our population with advanced oropharyngeal cancer, whatever treatment strategy, was at risk of developing OSAS with negative impact on quality of life. A routine screening and treatment of OSAS seems necessary to improve the quality of life of patients treated for advanced cancer of the oropharynx.

This article is protected by copyright. All rights reserved.

http://ift.tt/2ngqH6z

Head and Neck Round Cell Sarcomas: A Comparative Clinicopathologic Analysis of 2 Molecular Subsets: Ewing and CIC -Rearranged Sarcomas

Abstract

CIC-rearranged sarcoma (CRS) is a relatively new entity defined by its pathognomonic genetic signature and undifferentiated round cell phenotype, initially grouped together with the 'Ewing sarcoma-like tumors'. However, increasing data suggest that these tumors should be regarded as a stand-alone pathologic entity. We conducted a clinicopathologic analysis on molecularly conformed Ewing sarcoma (ES) and CRS arising in the head and neck (HN) and compared to a well characterized cohort of ES and CRS from other locations. A total of 41 HN round cell sarcoma patients were selected from our institutional and consultation files, including 25 ES (median 20 years) and 16 CRS (median 29 years). Clinical follow-up information was available for all ES patients, ranging from 4 to 436 months (median 70 months), while for CRS, follow-up information was available in 11 patients (69%), ranging from 1 to 269 months (median 27 months). The most common location for ES was the facial and jaw bones (56%), while CRS occurred exclusively in the soft tissue, commonly in the neck. CRS showed variable CD99 staining in 75% of cases and diffuse WT1 (6/6) reactivity, while all ES expressed diffuse membranous staining for CD99 but none for WT1 (0/6). The 2-year overall survival (OS) rate for HN-CRS patients was 78%, while for HN-ES it was 100%. The OS of ES and CRS showed a trend toward a favorable outcome for HN-round cell sarcomas compared to other sites. Our findings suggest that HN-CRS have different clinical presentation and pathologic features compared to ES and should be classified as a stand-alone pathologic entity.

http://ift.tt/2nr7yz6

Case 9-2017: A 27-Year-Old Woman with Nausea, Vomiting, Confusion, and Hyponatremia

Presentation of Case. Dr. Meaghan E. Colling (Medicine): A 27-year-old woman was admitted to this hospital because of nausea, vomiting, confusion, and hyponatremia. The patient had been well until 1 week before admission, when she had nausea and nonbloody, nonbilious emesis. She did not seek…

http://ift.tt/2nFOH3Y

Keratoacanthoma en plaque/nodule: A brief report of the clinicopathological features of five cases

Abstract

Keratoacanthoma (KA) is characterized by exoendophytic growth with a central keratin-filled crater, representing the crateriform architecture. We herein report five rare cases of KA without a central keratin-filled crater. These KA cases histopathologically showed that one or a few infundibular structures/isthmic lobules had their own open keratotic pores on the surface without a common merged keratotic plug/horn, clinically representing verrucous (keratotic) plaque/nodule, namely, "KA en plaque/nodule". KA rarely but on occasion does show verrucous plaque (or nodular) lesions without a central keratin-filled crater, as the notion that KA invariably shows crateriform architecture is nonsensical.

http://ift.tt/2nqX8jg

Translucent basal cell carcinoma with a single cyst of the upper eyelid

http://ift.tt/2o86b5N

Tongue Necrosis Secondary to Giant Cell Arteritis: A Case Report and Literature Review

Giant cell arteritis is a form of vasculitis involving the medium- and large-sized arteries that chiefly affects older people. Clinical findings are headache, jaw claudication, fever, pain, and thickening of the temporal artery. The most feared complication is visual loss due to impairment of the ophthalmic artery and posterior ciliary arteries. This a case report of an 85-year-old male presenting with headache and jaw pain, who was admitted with tongue necrosis as an initial manifestation of giant cell arteritis. The necrotic area detached spontaneously after two weeks of therapy with corticosteroids and methotrexate. Reviewing the literature, our patient presented with clinical symptoms consistent with most reports, except for the fact of being male. Although unusual as an initial manifestation, tongue necrosis is an important alert for diagnosing giant cell arteritis. Early diagnosis and treatment of this atypical manifestation may reduce morbidity.

http://ift.tt/2nfRwrn

A Case of Xanthogranulomatous Pyelonephritis Associated with Renoduodenal Fistula

Xanthogranulomatous pyelonephritis (XGP) is a rare form of pyelonephritis associated with repeated infection, chronic inflammation, and obstruction. Various fistulas, including those to the intestine, are a known association with XGP. Here, a 55-year-old woman with a history of multiple previous renal calculi presented with dysuria and back pain. Contrast-enhanced computed tomography (CT) revealed a soft tissue density in her renal pelvis and perirenal space consistent with XGP along with a tract connecting the upper pole of her right kidney to the second portion of the duodenum. This finding was subsequently confirmed during percutaneous nephrostomy placement, stent placement, a small bowel follow-through study, and upper endoscopy. She was diagnosed with XGP with associated renoduodenal fistula, eventually treated by open nephrectomy with fistula takedown. Histopathologic analysis was consistent with the diagnosis of XGP with no malignant or infectious cause of the fistula. XGP should be considered in the diagnosis of patients with dysuria and back pain, especially when a history of obstruction or chronic inflammation. Associated fistulas should also be considered prior to surgical management to prevent complications.

http://ift.tt/2o7HJRQ

Economics of Chronic Rhinosinusitis

Abstract

Purpose of Review

The objective of this article is to provide an updated review of the economic burden of chronic rhinosinusitis (CRS) and discuss how both medical and surgical interventions impact direct and indirect costs related to CRS. By understanding the economics of CRS, clinicians may improve the patient-centeredness of their care and help distinguish between low and high value interventions.

Recent Findings

Direct costs related to CRS are primarily driven by outpatient physician visits, prescription medical therapy, and endoscopic sinus surgery (ESS). CRS produces large indirect costs and these costs often vary based on the severity of the patients CRS-specific QoL impairment. The overall direct cost related to CRS is estimated to range between $10 and $13 billion per year in the USA. The overall indirect cost related to CRS-related losses in work productivity is estimated to be in excess of $20 billion per year.

Summary

In the appropriate patients with refractory CRS, ESS provides significant reductions in both direct and indirect costs; however, continued medical therapy alone may be a high value intervention in select patients who have lower severity in their baseline QoL and work productivity.

http://ift.tt/2ng4ENl

Mechanisms Driving Gender Differences in Asthma

Abstract

Purpose of Review

Many phenotypes of asthma exist, ranging from mild asthma with onset during childhood to severe asthma with later onset, making asthma a broad disease with different pathologies. A gender disparity exists in asthma prevalence. As adults, women have an increased asthma prevalence compared to men. Further, women are more likely to have severe asthma and a later onset of asthma compared to men. Here, we review clinical and animal studies that have defined the role of sex hormones in airway inflammation, smooth muscle contraction, mucus production, and airway mechanics associated with asthma pathogenesis.

Recent Findings

Clinical evidence shows that increased asthma symptoms occur in females starting at puberty compared to those in boys. However, after puberty, the role for sex hormones in regulating asthma symptoms during menstruation, pregnancy, and menopause is not as clear. Animal studies have shown that estrogen increases and testosterone decreases Th2-mediated airway inflammation, and that females have increased IL-17A-mediated airway inflammation compared to males. Further, females had increased DC and Mϕ function compared to males. However, the mechanisms driving the types of allergic inflammation are not fully elucidated.

Summary

Overall, ovarian hormones increased and testosterone decreased airway inflammation in asthma, but the mechanisms remain unclear. Delineating these pathways using animal models as well as women and men with various phenotypes of asthma will help determine if women with asthma should take (or avoid) hormonal contraceptives as well as predict changes in asthma symptoms during life phases, including pregnancy and menopause, when sex hormones are dramatically changing.

http://ift.tt/2nasUyI

Pigmented onychomatricoma: Four cases

Abstract

Onychomatricoma (OM) presenting as a longitudinal melanonychia is a very uncommon clinical presentation with very few cases in the literature. Our aim in this article is to report four cases of pigmented OM, and describe their clinical and dermoscopic findings and the importance of the differential diagnoses, especially with melanoma.

http://ift.tt/2ng1qt8

High serum vitamin D level correlates with better prognostic indicators in primary melanoma: A pilot study

Abstract

Background/Objectives

Sunlight is a major risk factor for cutaneous melanoma. However, its interaction with melanoma is complex. In particular, vitamin D is a UVB-derived hormone that has been shown to have anti-cancer effects. In this retrospective pilot study we sought to determine an association between the clinicopathological features of melanoma and the patients' corresponding serum vitamin D level.

Methods

In total, 109 primary melanomas diagnosed between 2001 and 2013 were retrospectively identified from our institutional database with a corresponding 25-hydroxyvitamin D3 level estimated within 6 months of diagnosis. Tumour, clinical (age, sex, tumour location) and pathological (thickness, mitosis, ulceration, Clark level, subtype, metastatic status) parameters were correlated with vitamin D. For statistical analysis, an unpaired Student's t-test and anova was used for categorical variables, and Spearman's correlation for continuous variables.

Results

Vitamin D level was inversely associated with Breslow thickness as a dichotomous, categorical and continuous variable. The association remained significant when controlled for patient's age and sex (P = 0.026). Vitamin D was higher in non-ulcerated tumours compared with ulcerated tumours (P = 0.006) and in tumours with mitotic rate <1/mm² compared with ≥1/mm² (P = 0.036). A significant association was found between vitamin D level and tumour histological subtype (P = 0.019). On subgroup analysis, significant associations were found between superficial spreading melanoma (SSM) and nodular melanoma (P = 0.026), and SSM and acral lentiginous melanoma (P = 0.007).

Conclusion

A high vitamin D status may benefit prognosis in patients diagnosed with primary melanoma. A prospective cohort analysis with a large sample and controlled for other vitamin D confounders would validate these findings.

http://ift.tt/2nao0S8

Skin cancer history, sun-related attitudes, behaviour and sunburn among renal transplant recipients versus general population

Abstract

Background/Objectives

Renal transplant recipients (RTR) have both an excessive skin cancer incidence and a high mortality rate. In Australia RTR receive extensive public education on skin cancer and many undergo further education pre/post-transplant. This study examines whether RTR have sufficiently rigorous sun protection behaviour compared with the general population.

Methods

Altogether 179 RTR from two large Melbourne hospitals involving skin clinic teams in patient care were recruited to undergo cross-sectional telephone interviews. Comparisons were made with residents (25–69 years) surveyed using equivalent measures and methods in adjacent summers (2006–2007, n = 904; 2010–2011, n = 942) for regular population monitoring surveys. Multivariate analyses of weekend behaviour were adjusted for related ambient temperature records.

Results

RTR were more compliant with sun protection behaviour on the weekend prior to interview than the residents surveyed. For example, for 2006–2007 and 2010–2011, the odds ratio and confidence intervals (CI 95%) were respectively: used sunscreen: 2.0 (1.1–3.8) and 2.8 (1.4–5.3); wore a long-sleeved top: 4.5 (2.4–8.5) and 3.6 (1.9–7.0). RTR sunburn prevalence (5%) appeared similar to that of residents (odds ratios comparing 2006–2007 and 2010–2011 0.6 [95% CI, 0.2–1.6] and 0.7 [95% CI, 0.3–1.9]). Despite generally good sun protection behaviour, many RTR (47%) had skin cancers treated.

Conclusion

The intensive education of RTR may have contributed to their better sun protection. Some RTR with excessive exposure to UV radiation introduction of may benefit from implementation of further photoprotection strategies. These findings may be particularly relevant to other RTR groups receiving education about sun protection.

http://ift.tt/2ng4qG4

Efficacy and safety of luliconazole 5% nail solution for the treatment of onychomycosis: A multicenter, double-blind, randomized phase III study

Abstract

Onychomycosis is a highly prevalent and intractable disease. The first-line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double-blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20–50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end-point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.

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Association of sleep disordered breathing symptoms with early postoperative analgesic requirement in pediatric ambulatory surgical patients

Publication date: May 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 96
Author(s): Kamie Yang, Anne Baetzel, Wilson T. Chimbira, Yuliya Yermolina, Paul I. Reynolds, Olubukola O. Nafiu
IntroductionSleep disordered breathing (SDB) symptoms are associated with increased rates of opioid-induced respiratory depression as well as enhanced nociception. Consequently, practitioners often withhold or administer lower intraoperative doses of opioids out of concern for postoperative respiratory depression. Therefore, SDB may be a critical determinant of analgesic requirement in the post-anesthesia care unit (PACU). We investigated whether preoperative SDB classification was independently associated with need for PACU analgesic intervention in a cross-sectional sample of 985 children who underwent elective, painful ambulatory surgical procedures.MethodsUsing prospectively collected data, children aged 4–17yr were grouped into two categories based on whether or not they had symptoms of SDB. Perioperative variables were compared between the exposed and control groups using Chi-squared test for categorical or t-test for continuous variables. Logistic regression analysis was used to assess the association between SDB and the odds of requiring PACU IV opioids.ResultsChildren with preoperative SDB symptoms (N = 325) compared with the reference group of children who did not have these symptoms had higher rates of PACU analgesic intervention (47.1% vs. 37.4%; p = 0.004) and higher mean arousal pain scores (3.7 ± 3.5 vs.1.9 ± 2.9; p < 0.001). In our primary multivariable logistic regression model adjusted for a number of variables, preoperative SDB symptoms was associated with a two-fold increased odds of receiving PACU intravenous opioid (OR = 2.01, 95%CI, 1.29–3.12; p = 0.002).ConclusionThese results suggest that preoperative SDB symptoms in children undergoing ambulatory surgery, exerts a significant influence on PACU pain behavior and analgesic requirement. Mechanisms underlying this enhanced pain experience deserve further elucidation.



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Protective role of misoprostol in prevention of gentamicin ototoxicity

Publication date: May 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 96
Author(s): Murat Dogan, Halil Polat, Mehmet Yasar, Ali Bayram, Duran Karatas, İbrahim Hira, Ahmet Kale, Fatma Senel, İbrahim Özcan
ObjectivesTo demonstrate potential protective effect of misoprostol on cochlear toxicity caused by gentamicin with electrophysiological tests and histopathological studies.Materials and methodsThe study included 80 ears of 40 rats with normal hearing threshold and DPOAE value in both ears. Animals were assigned into 4 groups. The rats were randomized into 4 groups. Group I (n = 10): Gentamicin, Group II (n = 10): Gentamicin plus misoprostol, Group III (n = 10): Saline; Group IV (n = 10): Misoprostol. All drugs used in the study were given once daily for 15 days. DPOAE and ABR measurements were repeated after drug administration. Subsequently, the rats' cochleae were examined histopathologically. Baseline DPOAE and ABR values were compared to those obtained after drug exposure and cochlear toxicity was evaluated in electrophysiological manner.ResultsWhen At baseline, there were no significant differences in DPOAE responses at frequencies of 1001, 1501, 2002, 3003, 4004, 6006 and 7996 Hz among groups. However In DPOAE test, statistically significant difference was observed between the pre-study basal values and post-study results in groups other than gentamicin + misoprostol group. Additionally, It was found that there was a significant difference in DPOAE response at frequency of 4004 Hz obtained at baseline and after drug exposure according to measurements of epithelial vacuolization in stria vascularis. While ABR threshold values were compared at baseline, there were no significant difference in ABR threshold values of left and right ear between groups. Histopathologically it was also found that there were significant differences measurements of epithelial vacuolization in stria vascularis and inflammation among groups (p < 0.05).ConclusionBy these results, misoprostol, a potent antioxidant, has protective effect against cochlear damage, and that may be a safe alternative.



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Atypische Mykobakterien

Zusammenfassung

Dermatologisch relevante atypische Mykobakterien sind insbesondere Mycobacterium (M.) marinum und M. ulcerans sowie verschiedene schnell wachsende Mykobakterien. Letztere sind in der Umwelt weit verbreitet und fakultativ pathogen. Der diagnostische Nachweis atypischer Mykobakterien stellt oft eine Herausforderung dar. Immunkompetente Patienten zeigen meist nur lokale Infektionen. Immunsupprimierte Patienten können jedoch schwere, disseminierte Verläufe entwickeln. In diesen Fällen sind frühzeitige Therapien wichtig. Auch Infektionen mit dem aggressiveren Erreger M. ulcerans sollten frühzeitig therapiert werden. In der Regel ist eine antibiotische Therapie mit mindestens 2 Antibiotika indiziert, da die Gefahr der Entwicklung von Wirkstoffresistenzen besteht. Eine chirurgische Intervention ist ebenso in Betracht zu ziehen. In diesem Beitrag werden Klinik, Diagnostik und insbesondere die antibiotische Therapie dermatologisch relevanter atypischer Mykobakteriosen diskutiert.

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