Association between serum autotaxin or phosphatidylserine-specific phospholipase A1 levels and melanoma

Abstract

Autotaxin (ATX), a producing enzyme for lysophosphatidic acids, was first identified from the medium of a melanoma cell line and has been considered to be one of the candidate targets to treat melanoma; however, the association between serum ATX and melanoma in human subjects has not been elucidated. Along with ATX, phosphatidylserine-specific phospholipase A1 (PS-PLA₁) is a producing enzyme for lysophosphatidylserine, a similar glycero-lysophospholipid mediator to lysophosphatidic acids. In the present study, we aimed to investigate the association between serum ATX or PS-PLA₁ levels and melanoma. We measured the serum levels of ATX, ATX isoforms and PS-PLA₁ in subjects with melanoma (n = 57) and healthy subjects (n = 58). We further investigated the existence of trends according to the clinical stages of melanoma. We observed that serum total ATX and classical ATX levels were significant higher and serum novel ATX levels tended to be higher in male subjects with melanoma, while no significant difference was observed between the two groups in female subjects. The trend test revealed that the serum total ATX and ATX isoforms were significantly associated with the clinical stages of female subjects with melanoma. Regarding PS-PLA₁, serum PS-PLA₁ levels were significantly higher in the melanoma subjects and associated with the clinical stages. The present study is the first study which revealed the association between ATX or PS-PLA₁ and melanoma, suggesting the possible involvement of ATX/lysophosphatidic acids or PS-PLA₁/lysophosphatidylserine axis in the pathogenesis of melanoma.

http://ift.tt/2CUFCrG

Case of punctate palmoplantar keratoderma type I treated with combination of low-dose oral acitretin and topical salicylic acid and steroid

Abstract

Palmoplantar keratodermas (PPK) are heterogeneous disorders characterized by abnormal keratinization. Especially, punctate PPK (PPPK), one of the subtypes of hereditary PPK, is a rare punctate keratoderma characterized by tiny "raindrop" keratoses having a tendency to coalesce on the edge of soles, which are exposed to sustained pressure. If typical punctate lesions are confined to the palms and soles and the patient has a family history and late onset, it can be considered as PPPK type I (PPKP1), also called Buschke–Fisher–Brauer disease. The exact etiology of PPPK has not been fully understood. Furthermore, no standardized treatment for PPPK has been established and treatment options are limited. Above all, traditional systemic retinoids have been used in several cases, but dose-related adverse effects are common. Therefore, combination of low-dose systemic retinoids and adjuvant topical therapy can be an alternative treatment option for PPPK. Herein, we report a case of PPKP1 treated with combination of low-dose oral acitretin (10 mg/day) and topical salicylic acid and steroid. Despite low capacity, low-dose acitretin showed excellent regression of the lesions by combined use of topical ointments. The supplementary topical therapy may be useful in reducing the dose of systemic retinoids and preventing potential toxicity.

http://ift.tt/2FMOum4

Changes in salivary chromogranin A levels in adults with atopic dermatitis are correlated with changes in their condition

Abstract

Stress-induced scratching is an issue in patients with adult atopic dermatitis (AD). Symptoms of stress-induced AD are common in clinical practise. Salivary chromogranin A (CgA) level has research value as a possible index related to a patient's psychological stress. Using saliva, which is easily collectable, we compared two assessments of the severities of AD and stress with the levels of stress proteins in the saliva of 30 patients with AD in the Department of Dermatology of Shimane University between April 2015 and May 2017. The severities of AD and stress were assessed using the Scoring Atopic Dermatitis (SCORAD) score and State–Trait Anxiety Inventory score, respectively. Additionally, the assessments included those of personality using the Tokyo University Egogram (TEG)-II score and quality of life using the Dermatology Life Quality Index score. Simultaneously, we measured their salivary CgA levels. The change in salivary CgA per protein in patients with AD was correlated with their changes in SCORAD score (correlation coefficient, r = 0.596, P = 0.001) and objective SCORAD (r = 0.608, P < 0.001). The changes in CgA per protein correlated with those in TEG-II A (r = 0.370, P = 0.022), while the changes in SCORAD score correlated with those in DLQI (r = 0.309, P = 0.048). Our results suggest that changes in a patient's condition are reflective of the changes in the patient's stress. The changes in salivary CgA level in patients with AD correlated with the changes in their condition.

http://ift.tt/2CTTUsw

Cutaneous sarcoidosis in a patient with rheumatoid arthritis receiving tocilizumab

http://ift.tt/2FNrJhL

Splice site mutation in COL7A1 resulting in aberrant in-frame transcripts identified in a case of recessive dystrophic epidermolysis bullosa, pretibial

Abstract

Dystrophic epidermolysis bullosa (DEB), pretibial, a rare subtype of epidermolysis bullosa (EB), is characterized by recurrent blisters and erosions predominantly on the pretibial region. We report the case of a 60-year-old Japanese woman with persistent blistering eruptions and scar formation on the pretibial region and elbows. Mutational analysis revealed a previously reported c.5797C>T mutation in exon 70 (p.R1933X) and a novel c.6348+1G>A mutation in intron 76 of COL7A1. Reverse transcription polymerase chain reaction revealed that the c.6348+1G>A mutation resulted in the skipping of exon 76 (69 bp) and the retention of intron 76 (75 bp), and both transcripts were in-frame. From these results, we diagnosed the patient as having recessive DEB, pretibial. A review of previously reported mutations in DEB, pretibial, revealed that one-third of DEB, pretibial, cases showed a recessive inheritance pattern, and no case had a combination of premature termination codon (PTC)/PTC mutations. The DEB, pretibial, case described herein is the first reported case of a compound heterozygote with PTC/in-frame mutations. Although no special characteristic features of the mutations were identified, a high diversity of COL7A1 mutations was shown even in DEB, pretibial.

http://ift.tt/2FbCitV

Overexpression of PIK3CA in head and neck squamous cell carcinoma is associated with poor outcome and activation of the YAP pathway

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Ramón García-Escudero, Carmen Segrelles, Marta Dueñas, María Pombo, Claudio Ballestín, Marina Alonso-Riaño, Pablo Nenclares, Roberto Álvarez-Rodríguez, Gregorio Sánchez-Aniceto, Ana Ruíz-Alonso, José Luis López-Cedrún, Jesús M. Paramio, Corina Lorz
ObjectivesPhosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved.Material and methodsMutation and copy-number variation in PIK3CA, and whole-genome expression profiles, were analyzed in primary HNSCC tumors from The Cancer Genome Atlas (TCGA) cohort (n = 243). The results were validated in an independent cohort form the University Hospital of A Coruña (UHAC, n = 62). Expression of the PIK3CA gene protein product (PI3K p110α) and nuclear YAP were assessed in tissue microarrays in a cohort from the University Hospital 12 de Octubre (UH12O, n = 91).ResultsOnly high expression of the PIK3CA gene was associated with poor clinical outcome. The study of gene expression, transcription factor and protein signatures suggested that the activation of the Hippo-YAP pathway, involved in organ size, stem cell maintenance and tumorigenesis, could underlie tumor progression in PI3KCA overexpressing tumors. Tissue arrays showed that PI3K p110α levels correlated with YAP nuclear localization in HNSCC tumors.ConclusionsHigh expression of PIK3CA in HNSCC primary tumors identifies patients at high risk for recurrence. In these tumors, progression could rely on the Hippo-YAP pathway instead of the canonical Akt/mTOR pathway. This observation could have important implications in the therapeutic options for patients.

Graphical abstract

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La azatioprina reduce el riesgo de recaída audiométrica en hipoacusia inmunomediada

Publication date: Available online 2 March 2018
Source:Acta Otorrinolaringológica Española
Author(s): Nieves Mata-Castro, Javier Gavilanes-Plasencia, Rafael Ramírez-Camacho, Alfredo García-Fernández, José Ramón García-Berrocal
IntroducciónLos esquemas actuales de tratamiento de la hipoacusia inmunomediada con corticoides, a dosis baja y pauta corta, son insuficientes.MétodosPara determinar el papel de la azatioprina en el control del deterioro auditivo se ha llevado a cabo un estudio observacional descriptivo longitudinal con 20 pacientes tratados con azatioprina por vía oral (1,5-2,5mg/kg/día en dos dosis) durante 1año. Se consideró recaída la pérdida de 10dB en dos frecuencias consecutivas o de 15dB en una frecuencia aislada.ResultadosLa edad media de los pacientes fue de 52,50años (IC95%: 46,91-58,17), y la mitad fueron mujeres. La afectación bilateral fue del 65%. Un 75% presentaban enfermedad organoespecífica y un 25%, enfermedad autoinmune sistémica. La diferencia entre la PTA basal (46,49 dB; DE18,90) y la PTA a los 12meses (45,47dB; DE18,88) no alcanzó significación estadística (p=0,799). Existía una correlación positiva moderada entre sexo femenino y presencia de enfermedad sistémica (R=0,577). Aplicando t de Student para datos apareados se obtuvo una diferencia significativa (p=0,042) entre el descenso de la PTA en frecuencias hasta 1.000Hz (PTA125-1.000Hz). La tasa relativa de incidencia de recaída por año fue de 0,52 recaídas/año (IC95%: 0,19-1,14). El tiempo medio de supervivencia libre de recaída audiométrica fue de 9,70meses (DE1,03).ConclusionesLa azatioprina mantiene el umbral de audición, disminuye el riesgo de recaída y frena la velocidad con la que los pacientes recaen, alterando el curso de la enfermedad inmunomediada del oído interno.IntroductionCurrent schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient.MethodsTo determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5-2.5mg/kg/day into two doses) for 1year. The loss of 10dB on two consecutive frequencies or 15dB on an isolated frequency was considered as relapse.ResultsThe mean age of the patients was 52.50years (95%CI: 46.91-58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49dB; DS18.90) and PTA at 12months (45.47dB; DS18.88) did not reach statistical significance (P=.799). There was a moderate positive correlation between female sex and the presence of systemic disease (R=.577). By applying Student's t for paired data, a significant difference (P=.042) was obtained between the PTA in frequencies up to 1000 Hz (PTA125-1000Hz). The relative incidence rate of relapse per year was .52 relapses/year (95%CI: .19-1.14]). The median time to audiometric relapse-free was 9.70months (DS1.03).ConclusionsAzathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease.



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Discriminatory miRNAs for the Management of Papillary Thyroid Carcinoma and Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features

Thyroid , Vol. 0, No. 0.


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A mechanistic linkage between oral lichen planus and autoimmune thyroid disease

Abstract

Objective

To determine the levels of antithyroid antibodies and thyroid hormones in the sera of patients with oral lichen planus (OLP), and to quantify the expression of thyroid proteins in OLP lesions.

Subjects and methods

Venous blood samples were drawn from 110 patients with OLP who had no history of thyroid disease or levothyroxine supplementation (OLP+/LT₄-). A random population sample of 657 healthy subjects was used as the control group. Two additional groups were used as comparators. Immunohistochemical and qPCR analyses were performed on tissue specimens collected from the patients with OLP and thyroid disease and healthy subjects.

Results

No association was found between the presence of antithyroid antibodies and OLP. More patients in the OLP+/LT₄- group showed high levels of thyroid-stimulating hormone and low levels of free thyroxine than were seen in the control group. Thyroid-stimulating hormone receptor was more highly expressed in the OLP lesions of patients with thyroid disease than in the healthy oral mucosa.

Conclusions

A significant number of patients with OLP who are not previously diagnosed with thyroid disease have thyroid parameters that are compatible with hypothyroidism. The expression of thyroid-stimulating hormone receptor in OLP lesions suggests that mechanisms related to autoimmune thyroid disease are involved in the aetiology of OLP.

This article is protected by copyright. All rights reserved.

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Radial nerve injury following dry needling

Robin McManus<br />Jan 26, 2018; 2018:bcr-2017-221302-bcr-2017-221302<br />Case report

http://ift.tt/2oNOha7

Impact of different concentrations of an octenidine dihydrochloride mouthwash on salivary bacterial counts: a randomized, placebo-controlled cross-over trial

Abstract

Objectives

This bi-centric, placebo-controlled, randomized, evaluator-blinded, incomplete cross-over clinical phase II trial was initialized to identify the most appropriate concentration of octenidine dihydrochloride (OCT) in mouth rinses.

Materials and methods

Rinses of 0.10, 0.15, and 0.20% OCT were compared to a saline placebo rinse regarding the reduction of salivary bacterial counts (SBCs) in 90 gingivitis patients over 4 days. Changes in plaque (PI) and gingival index (GI), taste perception, and safety issues were evaluated.

Results

At baseline, the first OCT (0.10, 0.15, 0.20%) rinse resulted in a decrease of SBC (reduction by 3.63–5.44 log₁₀ colony forming units [CFU]) compared to placebo (p < 0.001). Differences between OCT concentrations were not verified. After 4 days, the last OCT rinse again resulted in a significant SBC decrease (3.69–4.22 log₁₀ CFU) compared to placebo (p < 0.001). Overall, SBC reduction between baseline and day 4 was significantly higher in OCT 0.15 and 0.20% groups compared to OCT 0.10% and placebo. Mean GI/PIs were significantly lower in OCT groups than in the placebo group (p < 0.001). Differences in GI/PI between OCT groups were not verified. Adverse effects increased with increasing OCT concentrations.

Conclusions

Considering antibacterial efficacy, frequency of adverse events, and user acceptance, 0.10% OCT was identified as the preferred concentration to be used in future clinical trials.

Clinical relevance

Due to its low toxicity and pronounced antibacterial properties, octenidine dihydrochloride (OCT) is a promising candidate for the use in antiseptic mouth rinses. OCT concentrations of 0.10% are recommended for future clinical trials evaluating the plaque-reducing properties of OCT mouth rinses.

(www.clinicaltrials.gov, NCT022138552)

http://ift.tt/2CVi4Ti

Uvulopalatopharyngoplasty vs CN XII stimulation for treatment of obstructive sleep apnea: A single institution experience

Hypoglossal nerve stimulation (HNS) therapy is an emerging surgical treatment for select patients with obstructive sleep apnea (OSA). This study aims to compare outcomes in patients with moderate to severe OSA who underwent HNS surgery (Inspire Medical Systems) and those who underwent traditional airway reconstructive surgery, specifically uvulopalatopharyngoplasty (UPPP).

http://ift.tt/2Febrkv

Partial parotidectomy under local anesthesia for benign parotid tumors - An experience of 50 cases

Benign parotid tumors are adequately treated with partial parotidectomy, which is often performed under general anesthesia (GA). We have reported our preliminary results on the feasibility to perform parotidectomy under local anesthesia (LA). We hereby present our accumulated experience of partial parotidectomy under LA to further consolidate its feasibility, efficacy and safety in a larger series.

http://ift.tt/2CVhrJq

Impact of Topical Fluorouracil Cream on Costs of Treating Keratinocyte Carcinoma (Nonmelanoma Skin Cancer) and Actinic Keratosis

It is unknown whether treatment costs of Keratinocyte Carcinoma (KC) and Actinic Keratosis (AK) can be lowered by spending more on chemoprevention.

http://ift.tt/2I0LiUv

Inflammatory response and cytokine levels induced by intralesional photodynamic therapy and 630nm laser in a case series of basal cell carcinoma

http://ift.tt/2HZaBX5

Modified purse-string closure: a lymphatic channel and tissue sparing technique for biopsy of suspicious pigmented lesions on extremities

http://ift.tt/2oLAsZV

Patients prioritize local recurrence risk over other attributes for surgical treatment of facial melanomas - results of a stated preference survey and choice-based conjoint analysis

Surgical treatment options for facial melanomas include conventional excision with postoperative margin assessment (CE-POMA), Mohs micrographic surgery with immunostains (MMS-I) or slow Mohs. Patient preferences for these surgical options have not been studied.

http://ift.tt/2oM6Coh

Comparison between burning mouth syndrome patients with and without psychological problems

The purpose of this study was to compare clinical and socio-demographic characteristics between burning mouth syndrome (BMS) patients with and without psychological problems. Of 644 patients with symptoms of oral burning, 224 with primary BMS were selected on the basis of laboratory testing, medical history, and psychometric tests: 39 with psychological problems (age 62.5±11.5years) and 185 without psychological problems (age 58.4±11.4years). Comprehensive clinical and socio-demographic characteristics, including psychological profiles and salivary flow rates, were compared between the two groups.

http://ift.tt/2tbC0lp

Retrobulbar abscess: rare complication after repair of an oroantral communication

We present the case of a retrobulbar abscess that developed secondary to the repair of an oroantral communication. Orbital abscesses have been described in relation to odontogenic infections, facial injury, sinusitis, and after dental extractions but, to the best of our knowledge, none has been reported in these circumstances. Retrobulbar abscess is a rare complication, but early clinical and radiological diagnosis, and urgent decompression are vital because it comes with considerable risk of irreversible visual impairment.

http://ift.tt/2GXm08G

Ophthalmological injuries associated with fractures of the orbitozygomaticomaxillary complex

Our aim was to evaluate ophthalmological injuries associated with fractures of the orbitozygomaticomaxillary complex that required operative treatment, and we collected data retrospectively over a period of five years (2012-2016 inclusive). Of the 190 patients, 162 were male with a median age of 31 (IQR 25 -39) years. Assault was the most common mechanism of injury (125/190, 66%). Minor ophthalmic injuries (those unlikely to cause permanent visual disturbance) and major ophthalmic injuries (those with the potential to cause permanent visual disturbance) were recorded.

http://ift.tt/2Fi0fDj

Haematinic deficiencies and patient clinical profiles in Polish patients with recurrent aphthous stomatitis (RAS)

Abstract

Background

RAS is a common ulcerative disorder of the oral mucosa, where the immune impairment may develop in genetically predisposed subjects exposed to certain environmental factors. The aim of the study was to investigate the frequency of anaemia, iron and vitamin B12 deficiency in RAS and to explore its impact on the clinical presentation of RAS.

Methods

A total of 141 adults including: 71 subjects with RAS and 70 controls were enrolled in the study. A detailed dental and haematological assessment, including full blood count, serum iron and vitamin B12 evaluation was performed in all study participants. The results were statistically analysed with Mann-Whitney, Kruskal-Wallis, χ2 and Fisher tests with p<0.05 designated as a significance level.

Results

RAS patients were found to suffer anaemia, iron and vitamin B12 deficiency more frequently than the controls. The mean serum iron levels were also significantly lower in RAS subjects than in controls, although still within the norm. The lowest mean serum iron levels were observed in patients with a mild course of RAS. No significant differences in mean serum iron and vitamin B12 levels were revealed as a function of stratification according to the number of lesions per single flare-up.

Conclusions

The results of our study indicate an association between iron and vitamin B12 deficiency and RAS in a Polish population. However, as the haematinic deficiencies did not significantly modify the course and clinical phenotype of the disease, further studies to explore their role in RAS aetiology are required.

This article is protected by copyright. All rights reserved.

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The significance of an algorithm for human papilloma virus detection in HNSCC

Abstract

We read with great interest the article titled "The role of human papillomavirus in p16-positive oral cancers" by Belobrov et al. [1]. We appreciate the author's efforts on their interesting contribution to the complex paradigm of Human papillomavirus (HPV) detection which has been prevalent in literature for a long time. We would like to further emphasize the importance of their findings with reference to two aspects.

This article is protected by copyright. All rights reserved.

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Using salivary glands to treat serious systemic diseases:sExamples of new roles for oral medicine in the health care team?

Abstract

It is necessary to begin this Commentary with a very significant disclaimer. I have extensively published on and extolled the merits of using gene transfer to salivary glands as a means for turning these critically important oral tissues into valuable in vivo bioreactors to make therapeutic proteins for systemic use (e.g., Voutetakis et al, 2004; Hai et al, 2009; Perez et al, 2010).

This article is protected by copyright. All rights reserved.

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Does audiovisual distraction reduce dental anxiety in children under local anesthesia? A systematic review and meta-analysis

Abstract

Objectives

To perform a systematic review and meta-analysis on the effects of audiovisual distraction on reducing dental anxiety in children during dental treatment under local anesthesia.

Methods

The authors identified eligible reports published through August 2017 by searching PubMed, EMBASE, and Cochrane Central Register of Controlled Trials. Clinical trials that reported the effects of audiovisual distraction on children's physiological measures, self-reports and behavior rating scales during dental treatment met the minimum inclusion requirements. The authors extracted data and performed a meta-analysis of appropriate articles.

Results

Nine eligible trials were included and qualitatively analyzed; some of these trials were also quantitatively analyzed. Among the physiological measures, heart rate or pulse rate was significantly lower (p=0.01) in children subjected to audiovisual distraction during dental treatment under local anesthesia than in those who were not; a significant difference in oxygen saturation was not observed. The majority of the studies using self-reports and behavior rating scales suggested that audiovisual distraction was beneficial in reducing anxiety perception and improving children's cooperation during dental treatment.

Conclusion

The audiovisual distraction approach effectively reduces dental anxiety among children. Therefore, we suggest the use of audiovisual distraction when children need dental treatment under local anesthesia.

This article is protected by copyright. All rights reserved.

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Salivary human beta defensins affected by oral Candida status in Chinese HIV/AIDS patients undergoing ART

Abstract

Objectives

To observe relationships between oral Candida status and salivary human beta defensin-2 and -3 (hBD-2 and hBD-3) levels in HIV/AIDS patients of Guangxi, China during the first year of antiretroviral therapy (ART) dynamically, and to understand the influence of ART on oral Candida status and salivary hBDs expressions.

Methods

A prospective self-controlled study was carried to observe the dynamic changes of CD4⁺ T cell counts, oral Candida carriages and salivary hBD-2,3 expressions in HIV/AIDS patients during the first year of ART. A total of 90 HIV/AIDS patients were enrolled, and were examined at the baseline, 3rd, 6th, 12th month of ART. Thirty healthy individuals were enrolled as control. Peripheral blood, oral rinse sample and unstimulated whole saliva were collected to test CD4⁺ T cell counts, oral Candida carriages and hBD-2,3 expressions.

Results

In the first year of ART, CD4⁺ T cell counts increased significantly. However, oral Candida carriages and oral candidiasis decreased significantly, and salivary hBD-2 expressions in HIV/AIDS patients decreased gradually, salivary hBD-3 levels were highly variable. Salivary hBD-2 concentrations were positively related to oral Candida carriages.

Conclusions

The incidence of oral candidiasis among HIV/AIDS patients gradually decreased due to the immune reconstruction of ART. Salivary defensins might play an important role in Candida-host interaction in HIV/AIDS patients.

This article is protected by copyright. All rights reserved.

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Loss of function NFKB1 variants are the most common monogenic cause of CVID in Europeans

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Paul Tuijnenburg, Hana Lango Allen, Siobhan O. Burns, Daniel Greene, Machiel H. Jansen, Emily Staples, Jonathan Stephens, Keren J. Carss, Daniele Biasci, Helen Baxendale, Moira Thomas, Anita Chandra, Sorena Kiani-Alikhan, Hilary J. Longhurst, Suranjith L. Seneviratne, Eric Oksenhendler, Ilenia Simeoni, Godelieve J. de Bree, Anton T.J. Tool, Ester M.M. van Leeuwen, Eduard H.T.M. Ebberink, Alexander B. Meijer, Salih Tuna, Deborah Whitehorn, Matthew Brown, Ernest Turro, Adrian J. Thrasher, Kenneth G.C. Smith, James E. Thaventhiran, Taco W. Kuijpers
BackgroundThe genetic etiology of primary immunodeficiency disease (PID) carries prognostic information.ObjectiveWe conducted a whole-genome sequencing study assessing a large proportion of the NIHR-BioResource – Rare Disease cohort.MethodsIn the predominantly European study population of principally sporadic unrelated PID cases (n=846), a novel Bayesian method identified NFKB1 as one most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n=390) in the cohort. Amino-acid substitutions predicted to be pathogenic were assessed by analysis of structural protein data. Immunophenotyping, immunoblotting and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype co-segregation analyses.ResultsBoth sporadic and familial cases demonstrated evidence of the non-infective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%) and autoimmune disease (48%), features prior studies correlate with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B lymphocyte differentiation. Detailed assessment of B lymphocyte numbers, phenotype and function identifies the presence of a raised CD21^low B cell population: combined with identification of the disease-causing variant, this distinguishes between healthy individuals, asymptomatic carriers and clinically affected cases.ConclusionWe show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID that results in a temporally progressive defect in the formation of immunoglobulin-producing B cells.

Graphical abstract

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Role of lipid mediators and control of lymphocyte responses in type 2 immunopathology

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Sachin K. Samuchiwal, Joshua A. Boyce
Type 2 immunopathology is a cardinal feature of allergic diseases, and involves cooperation between adaptive immunity and innate effector responses. Virtually all cell types relevant to this pathology generate leukotriene and/or prostaglandin mediators that derive from arachidonic acid, and/or express receptors for such mediators. Recent studies highlight prominent functions for these mediators in communication between innate and adaptive immune systems, as well as amplification or suppression of type 2 effector responses. This review focuses on recent advances and insights, and highlights existing and potential therapeutic applications of drugs that target these mediators or their receptors, with a special emphasis on their regulation of the innate and adaptive lymphocytes relevant to type 2 immunopathology.



http://ift.tt/2GWKNK2

Prevalence and clinical challenges among adult primary immunodeficiency patients with RAG deficiency

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Dylan Lawless, Christoph B. Geier, Jocelyn R. Farmer, Hana Allen Lango, Daniel Thwaites, Faranaz Atschekzei, Matthew Brown, David Buchbinder, Siobhan O. Burns, Manish J. Butte, Krisztian Csomos, Sri V.V. Deevi, William Egner, Stephan Ehl, Martha M. Eibl, Olajumoke Fadugba, Zsofia Foldvari, Deanna M. Green, Sarah E. Henrickson, Steven M. Holland, Tami John, Christian Klemann, Taco W. Kuijpers, Fernando Moreira, Alexander Piller, Paula Rayner-Matthews, Neil D. Romberg, Ravishankar Sargur, Reinhold E. Schmidt, Claudia Schröder, Catharina Schuetz, Svetlana O. Sharapova, Ken G.C. Smith, Georgios Sogkas, Carsten Speckmann, Kathleen Stirrups, Adrian J. Thrasher, Hermann M. Wolf, Luigi D. Notarangelo, Rashida Anwar, Joan Boyes, Boglarka Ujhazi, James Thaventhiran, Jolan E. Walter, Sinisa Savic




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Mast Cell-Derived PAI-1 Promotes Airway Inflammation and Remodeling in a Murine Model of Asthma

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ara Jo, Sun H. Lee, Dong-Young Kim, Seung-Jae Hong, Michael N. Teng, Narasaiah Kolliputi, Richard F. Lockey, Robert P. Schleimer, Seong H. Cho




http://ift.tt/2GWKBKO

Personalized and rapid test for food-related allergy

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Mikaël Frossard, Natalia Gasilova, Lionel Arlettaz, Eric Dayer, Hubert H. Girault




http://ift.tt/2FkOEmO

Innate lymphoid cells 3 induce psoriasis in xenotransplanted healthy human skin

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Aviad Keren, Avner Shemer, Alex Ginzburg, Yehuda Ullmann, Adam G. Schrum, Ralf Paus, Amos Gilhar




http://ift.tt/2GWK9MC

Epigenome analysis links gene regulatory elements in group 2 innate lymphocytes to asthma susceptibility

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ralph Stadhouders, Bobby W.S. Li, Marjolein J.W. de Bruijn, Antonio Gomez, Tata Nageswara Rao, Hans Jörg Fehling, Wilfred F.J. van IJcken, Ai Ing Lim, James P. Di Santo, Thomas Graf, Rudi W. Hendriks
BackgroundGroup 2 innate lymphoid cells (ILC2s) are major producers of cytokines driving allergic asthma and elevated numbers of ILC2s have been detected in blood and sputum of asthma patients. Asthma susceptibility has a strong genetic component, but the underlying mechanisms and whether asthma genetics impact ILC2 biology remains unclear.ObjectiveTo study the ILC2 transcriptome and epigenome during airway inflammation (AI) in order to couple these to genes and genetic variants associated with asthma pathogenesis.MethodsMice harboring a reporter for the key ILC2 transcription factor GATA3 were subjected to IL-33-driven AI and ILC2s were isolated from bronchoalveolar lavage fluid and mediastinal lymph nodes. Human ILC2s were purified from peripheral blood and activated in vitro. We employed RNA-Seq, genome-wide identification of histone-3 lysine-4 dimethylation (H3K4me2) marked chromatin and computational approaches to study the ILC2 transcriptome and epigenome.ResultsActivated ILC2s in mice displayed a tissue-specific gene expression signature that emerged from remarkably similar epigenomes. We identified superenhancers implicated in controlling ILC2 identity and asthma-associated genes. Over 300 asthma-associated genetic polymorphisms identified in genome-wide association studies localized to H3K4Me2⁺ gene regulatory elements in ILC2s. A refined set of candidate causal asthma-associated variants was uniquely enriched in ILC2 - but not Th2 cell - regulatory regions.ConclusionsILC2s in AI employ a flexible epigenome that couples adaptation to new microenvironments with functional plasticity. Importantly, we reveal strong correlations between gene regulatory mechanisms in ILC2s and the genetic basis of asthma, supporting a pathogenic role for ILC2s in allergic asthma.

Graphical abstract

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Pharmacological Inhibition of Caspase-8 Suppresses Inflammation-Induced Lymphangiogenesis and Allograft Rejection in the Cornea

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Wenru Su, Longhui Han, Xiaoqing Chen, Jianfeng Yu, Xiaokang Cheng, Jingwen Huang, Yichen Xiao, Yunzhe Tian, Nancy Olsen, Song Guo Zheng, Dan Liang




http://ift.tt/2GYn4Ju

Recurrent Wheezing in Children Following Human Metapneumovirus Infection

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Andrea M. Coverstone, Bradley S. Wilson, Dana Burgdorf, Kenneth B. Schechtman, Gregory A. Storch, Michael J. Holtzman, Mario Castro, Leonard B. Bacharier, Kaharu Sumino




http://ift.tt/2Fhe7NZ

inhaled Corticosteroids in Infants and Toddlers Attenuate Linear Growth

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Antti Saari, Lauri J. Virta, Leo Dunkel, Ulla Sankilampi




http://ift.tt/2GXoJik

New human combined immunodeficiency caused by interferon regulatory factor 4 (IRF4) deficiency inherited by uniparental isodisomy

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): María Bravo García-Morato, Francisco Javier Aracil Santos, Alejandro Contreras Briones, Alfonso Blázquez Moreno, Ángela del Pozo Maté, Ángeles Domínguez-Soto, María José Beato Merino, Lucía del Pino Molina, Juan Torres Canizales, Ana Victoria Marin, Elena Vallespín García, Marta Feito Rodríguez, Diego Plaza López Sabando, Anaïs Jiménez-Reinoso, Yasmina Mozo del Castillo, Francisco José Sanz Santaeufemia, Raúl de Lucas-Laguna, Paula P. Cárdenas, Laura Casamayor Polo, María Coronel Díaz, Mar Valés-Gómez, Ernesto Roldán Santiago, Antonio Ferreira Cerdán, Julián Nevado Blanco, Ángel L. Corbí, Hugh T. Reyburn, José Ramón Regueiro, Eduardo López-Granados, Rebeca Rodríguez Pena




http://ift.tt/2FfhEMW

A critical role of IL-18 in transformation and maturation of naïve eosinophils to pathogenic eosinophils

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Sathisha Upparahalli Venkateshaiah, Akanksha Mishra, Murli Manohar, Alok K. Verma, Priya Rajavelu, Rituraj Niranjan, Laurianne G. Wild, Nereida A. Parada, Uwe Blecker, Joseph A. Lasky, Anil Mishra.

Teaser

The current studies demonstrate a critical role of IL-18 in transforming IL-5 generated naïve eosinophils into the distinct inflammatory CD101⁺CD274⁺ expressing mature and activated tissue eosinophils that promote disease pathogenesis.


http://ift.tt/2F8ZXv0

Reply

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Masashi Akiyama




http://ift.tt/2FfqrP4

Hidradenitis suppurativa as an autoinflammatory keratinization disease

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Valerio De Vita, Dennis McGonagle




http://ift.tt/2F8Fdnk

CD40LG duplication-associated autoimmune disease is silenced by non-random X-chromosome inactivation

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Carole Le Coz, Melissa Trofa, Camille M. Syrett, Anna Martin, Harumi Jyonouchi, Soma Jyonouchi, Montserrat C. Anguera, Neil Romberg

Teaser

An inherited syndrome of autoimmunity associated with CD40LG duplication is silenced by non-random X-chromosome inactivation and is treatable with CD40L directed therapy.


http://ift.tt/2Ff1NxQ

Proximity to traffic and asthma among Mexican American children: Independent and interactive effects

Publication date: Available online 2 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Kamal Eldeirawi, Colin Kunzweiler, Natalya Rosenberg, Shannon Zenk, Elizabeth Tarlov, Jennifer Hebert-Beirne, Victoria Persky

Teaser

Our results show deleterious effects of living closer to traffic on respiratory outcomes among Mexican American children. Some of these effects are exacerbated in children with parental history of asthma or allergies.


http://ift.tt/2H0pZS2

SLAM family member 8 is involved in oncogenic KIT-mediated signaling in human mastocytosis

Abstract

The signaling lymphocytic activation molecule family member 8 (SLAMF8)/CD353 is a member of the CD2 family of proteins. Its ligand has not been identified. SLAMF8 is expressed by macrophages and suppresses cellular functions. No study has yet explored SLAMF8 expression or function in human mastocytosis, which features oncogenic KIT-mediated proliferation of human mast cells. SLAMF8 protein was expressed in human mastocytosis cells, immunohistochemically. SLAMF8 expression was also evident in the human mast cell lines, HMC1.2 (expressing oncogenic KIT) and LAD2 (expressing wild-type KIT) cells. SLAMF8-knockdown significantly reduced the KIT-mediated growth of HMC1.2 cells but not that of LAD2 cells. SLAMF8-knockdown HMC1.2 cells exhibited significant attenuation of SHP-2 activation and oncogenic KIT-mediated RAS–RAF–ERK signaling. An interaction between SLAMF8 and SHP-2 was confirmed in HMC1.2 cells and all pathological mastocytosis specimens examined (19 of 19 cases, 100%). Thus, SLAMF8 is involved in oncogenic KIT-mediated RAS–RAF–ERK signaling and the subsequent growth of human neoplastic mast cells mediated by SHP-2. SLAMF8 is a possible therapeutic target in human mastocytosis patients.

This article is protected by copyright. All rights reserved.

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IL-26 in allergic contact dermatitis: resource in a state of readiness

Abstract

In this study, we investigated the role of IL-26 in allergic contact dermatitis (ACD), highlighting its contribute in the cytotoxic mechanism responsible of the tissue injury. IL-26 is a signature Th17 cytokine, and immune cells are its predominant sources. Recently, it has shown that Th17 cell-derived-IL-26 functions like an antimicrobial peptide. Here, we hypothesized that IL-26 could be involved in cytotoxicity mechanism, that underlies ACD. Indeed, we have attributed a role to IL-26 in this context, through PBMC cytotoxicity assays versus Hacat. In order to demonstrate that IL-26 was effectively involved in this activity, we performed the assay using transfected ACD PBMCs by siRNA for IL-26. Indeed, we demonstrated that these cells were less able to kill keratinocytes compared to ACD PBMC (p<0.01). In conclusion, our findings support the idea that this emergent cytokine, IL-26, is implicated in the killing mechanisms of KC observed during ACD.

This article is protected by copyright. All rights reserved.

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Dermal fibroblasts can activate matrix metalloproteinase-1 independent of keratinocytes via plasmin in a 3D collagen model

Abstract

Photoaging of the skin is marked by obvious wrinkles and mainly depends on degradation of the extracellular matrix (ECM) in the dermis. Matrix metalloproteinase (MMP)-1 is one of the most important factors involved in degradation of the ECM, however, its mechanism of activation is not fully understood. It has been thought that MMP-1 is expressed by dermal fibroblasts as an inactive precursor protein that is activated by proteinases produced by keratinocytes in the epidermis. In this study, we constructed a 3D model of the dermis using collagen-embedded fibroblasts with or without ultraviolet (UV)-A exposure to mimic photoaging in the dermis. Collagen lattices embedded with UV-A irradiated fibroblasts miniaturized and collagen was degraded to a greater extent than collagen lattices embedded with non-irradiated fibroblasts. The results demonstrate that fibroblasts in this 3D model express activated-MMP-1 in the absence of keratinocytes. Moreover, the results confirm that activation of MMP-1 depends on increased plasmin activity in this model and lattice miniaturization was inhibited by the plasmin inhibitor tranexamic acid. Our results suggest that plasmin acts as an activator of MMP-1 and the inhibition of plasmin prevents collagen degradation.

This article is protected by copyright. All rights reserved.

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Innate immunity gene expression by epithelial cells of upper respiratory tract in children with adenoid hypertrophy

Publication date: Available online 2 March 2018
Source:Auris Nasus Larynx
Author(s): Lyudmila Viktorovna Gankovskaya, Valentina Pavlovna Bykova, Leila Seimurovna Namasova-Baranova, Alexander Viktorovich Karaulov, Irina Viktorovna Rahmanova, Viktor Anatolievich Gankovskii, Catherine Dmitrievna Merkushova, Oksana Anatolievna Svitich
BackgroundA major role of the innate immunity in the defence of mucosal tissue is well established. However, a balance between the main components of the immunity such as toll-like receptors (TLRs) and defensins in the pathology of upper respiratory tract in children has not been addressed yet. Our aim was to investigate the gene expression of some TLRs as well as alpha and beta-defensins in children suffered from adenoid hyperthrophy in comparison with healthy children.MethodsSamples (nasal epithelium and adenoids) from patients with hypertrophic adenoids (n = 77) and control group (n = 33) were investigated. Quantification of HBD-1 and 2 mRNA, alpha-defensin-HNP1 and toll-like receptors (TLR) 2, 4 and 9 mRNA expression was performed by real-time polymerase chain reaction (PCR). The detection of TLR4 and TLR9 was performed by immunohistochemistry.ResultsThe main finding of the study is a dramatic up-regulation of TLR2 and TLR4 expression (but down-regulation of TLR9) along with a significant reduction in the expression of the defensins in children with adenoid hyperthrophy.ConclusionThe data suggest that one of the mechanisms of mucosal involvement in the pathogenesis of upper respiratory tract infection might by a disbalance between TLRs and defensins revealed in our study.



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Uvulopalatopharyngoplasty vs CN XII stimulation for treatment of obstructive sleep apnea: A single institution experience

Publication date: Available online 2 March 2018
Source:American Journal of Otolaryngology
Author(s): Janki Shah, Jonathon O. Russell, Tina Waters, Alan H. Kominsky, Douglas Trask
ObjectivesHypoglossal nerve stimulation (HNS) therapy is an emerging surgical treatment for select patients with obstructive sleep apnea (OSA). This study aims to compare outcomes in patients with moderate to severe OSA who underwent HNS surgery (Inspire Medical Systems) and those who underwent traditional airway reconstructive surgery, specifically uvulopalatopharyngoplasty (UPPP).MethodsPatients who underwent HNS implantation (n = 20), all with moderate to severe OSA, inability to adhere to positive pressure therapy, and compliant with previously published inclusion criteria, were compared to a historical cohort that were intolerant of CPAP with similar inclusion criteria who all underwent UPPP (n = 20) with some also undergoing additional procedures such as septoplasty/turbinate reduction. Data including body mass index (BMI), pre- and post-implant apnea-hypopnea index (AHI) were assessed.ResultsFor patients who underwent HNS, mean preoperative BMI was 28.0. Mean AHI decreased significantly from 38.9 ± 12.5 to 4.5 ± 4.8. All patients achieved an AHI < 20 post implant with 65% (13/20) with an AHI ≤ 5. For patients who underwent traditional airway surgery, mean preoperative BMI was 27.5; mean AHI decreased from 40.3 ± 12.4 to 28.8 ± 25.4.ConclusionWhile both traditional surgery and HNS are effective treatments for patients with moderate to severe OSA with CPAP intolerance, our study demonstrates that HNS is "curative" in normalizing the AHI to <5 in the majority of patients. For select patients, HNS therapy provides excellent objective improvement in outcome measures.



http://ift.tt/2Fa5IIT

Transoral robotic surgery for the treatment of laryngeal chondrosarcoma: A case report

Publication date: Available online 1 March 2018
Source:American Journal of Otolaryngology
Author(s): Ashley J. Guthrie, Raymond L. Chai
ImportanceTransoral robotic surgery has revolutionized the practice of head and neck surgery over the past decade, with indications now expanding to include laryngeal pathology. Although laryngeal chondrosarcoma is a rare entity, trends in otolaryngology literature suggest that it can frequently be managed with conservative approaches. We hope to inspire other head and neck surgeons to consider transoral robotic surgery for the treatment of such tumors so that outcomes data can be collected and studied.ObservationAn 87-year-old male presented with a left-sided supraglottic mass that was found incidentally on imaging performed for an unrelated reason. Flexible fiberoptic laryngoscopy revealed a cystic-appearing supraglottic mass with near complete obstruction of the glottis airway. Internal review of the imaging demonstrated a 3.5 by 2.3 by 2.8 cm centrally hypodense lesion with a rim of calcification in the left paraglottic space, with resultant narrowing of the laryngeal airway.InterventionThe patient underwent awake tracheostomy and transoral robotic subtotal resection of the mass using the Da Vinci surgical system (Intuitive Surgical Inc., Sunnyvale, CA, USA). The vocal folds, ventricular mucosa, and arytenoid cartilage were grossly preserved. Final pathology revealed a low-grade cartilaginous neoplasm consistent with low-grade chondrosarcoma.Conclusions and relevanceChondrosarcoma of the larynx is a rare entity that accounts for roughly 1% of laryngeal neoplasms. Recent trends in otolaryngology literature and practice suggest that low-grade chondrosarcomas can be effectively treated with organ-preserving, conservative surgery. Transoral robotic surgery offers numerous advantages over both open and endoscopic approaches. To our knowledge, this is the first report in the literature describing the successful use of transoral robotic surgery for the resection of a laryngeal chondrosarcoma.



http://ift.tt/2FNvkwg

Partial parotidectomy under local anesthesia for benign parotid tumors - An experience of 50 cases

Publication date: Available online 2 March 2018
Source:American Journal of Otolaryngology
Author(s): Siu Hong Cheung, Wai Yin Wilson Kwan, Kwan Pok Tsui, Tam Lin Chow
PurposeBenign parotid tumors are adequately treated with partial parotidectomy, which is often performed under general anesthesia (GA). We have reported our preliminary results on the feasibility to perform parotidectomy under local anesthesia (LA). We hereby present our accumulated experience of partial parotidectomy under LA to further consolidate its feasibility, efficacy and safety in a larger series.Materials and methodsCase series review was carried out using our own center patients' database. 50 patients with parotid tumors were treated with partial parotidectomy under LA, using a retrograde nerve dissection approach from January 2006 to October 2016. The inclusion criteria encompassed mobile parotid nodules primarily operated after non-suspicious fine-needle aspiration cytology. Their demographics, complications and outcomes were evaluated.ResultsNo procedure required conversion to GA. There were 48 benign tumors and 2 lymphomas based on the histopathologic examination. The commonest pathologies were pleomorphic adenoma (40%), Warthin's tumor (38%) and cyst (8%). The mean tumor size was 2.68 ± 1.5 cm and the mean operative time was 91.5 ± 34.7 min. Forty-two operations were done as day cases. Ten (20%) patients suffered from transient ear lobe numbness and two (4%) patients had sialocele. Transient facial palsy occurred in 2(4%) patients while another patient (2%) had persistent House-Brackmann grade II facial palsy. No tumor recurrence was noted during follow-up period.ConclusionsPartial parotidectomy adopting a retrograde nerve dissection under LA is feasible and minimally invasive in treating benign parotid tumors. It can avoid the adverse effects of general anesthesia and promote day surgery or minimize hospital stay.



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Short dental implants in patients with oral lichen planus: a long-term follow-up

Publication date: Available online 2 March 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): E. Anitua, L. Piñas, V. Escuer-Artero, R.S. Fernández, M.H. Alkhraisat
Oral lichen planus is associated with the Koebner phenomenon, and trauma may exacerbate oral lesions. Short dental implants, as alternatives to bony augmentation, would reduce the number of interventions and their morbidity. However, we know of no studies that have analysed the long-term outcomes of short implants in patients with oral lichen planus. We have therefore designed a retrospective study of such patients treated with short implants (≤8.5mm long), with survival of implants as the main outcome. The secondary outcomes were marginal bone loss and the development of complications. We calculated the implants' survival and compared the outcomes statistically between erosive and reticular oral lichen planus. Sixty-six short implants were placed in 23 patients with a mean (SD) age of 58 (7) years. The mean (SD) peri-implant bone loss was 0.96 (0.89) mm mesially and 0.99 (1.1) mm distally. Sixty-five of the 66 implants survived with a mean (SD) follow-up of 68 (32) months, and there were no significant differences between erosive and reticular disease. Stable long-term outcomes can be expected for short implants placed in patients with oral lichen planus, and graftless rehabilitation of missing teeth could be possible in these patients if short implants were used.



http://ift.tt/2FKYQ5U

So-called “bad split” may not be “bad” when the split is on the buccal side: technical note

Publication date: Available online 2 March 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): K. Matsushita




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Conflicts of Interest in Clinical Guidelines: Lack of Authors and Disclosures in the AAOMS White Papers

Publication date: Available online 2 March 2018
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Yisi D. Ji, Edward T. Lahey
PurposeThe purpose of this study was to evaluate current state of authorship, financial disclosures, and conflicts of interest in position papers published by the American Association of Oral and Maxillofacial Surgeons (AAOMS).MethodsThis is a cross-sectional review of the position papers published by the AAOMS from 2013 to 2017. Primary outcome variables include the position papers published by the AAOMS. Secondary outcome variables include declaration of authorship and financial disclosures, and financial payments. The Open Payments Database for financial disclosures was reviewed for the year the position paper was published as well as the immediate preceding year.ResultsThe results of this study revealed there were 10 position papers published by the AAOMS from 2013 to 2017. Of the 10 papers, authorship was listed in 3, and none explicitly address the presence or absence of financial disclosures or conflicts of interest. Contributors to 3 of the 3 authored papers were found upon review of the Open Payments Database to have received industry funding in both the year the position paper was published and the immediate preceding year. The remuneration ranged from less than $1000 to $554,006.02.ConclusionPosition papers published by AAOMS lack standardization with regards to both authorship and statements on potential financial disclosure. The authors suggest full disclosures of authorship and their conflicts of interest should be made on all position papers to provide transparency to the process.



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A study on etiopathogenesis and clinical features of multi-headed (bifid and trifid) mandibular condyles and review of the literature

Publication date: Available online 1 March 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Orhan Güven
PurposeThe formations of second or more condylar heads are considered as rare anomalies. Fourteen multi-headed condyles (MHC) were presented; 13 of these were bifid mandibular condyles (BMC), whereas one exceptionally rare case was a trifid mandibular condyle (TMC). The TMC presented in this paper is the eighth case reported in the literature. In this paper, etiopathogenesis, types, and treatments are discussed.Materials and MethodsPatients were classified according to their status, etiologies, gender, functions of the mandible, interocclusal distances, pathological conditions, types, and treatment received.ResultsBMCs were classified into two groups: type I BMCs were nontraumatic, nonsymptomatic, mediolateral, presumably developmental, and characterized by shallow grooves. Type II BMCs were traumatic and may have two subgroups. The first group of type II BMCs were mediolateral and Y-shaped. The second group of type II BMCs were characterized by two separate and anteroposteriorly located condyles.ConclusionTreatment depended on patients' complaints. In this study, asymptomatic patients did not receive therapy, whereas patients with temporomandibular join internal derangement received medical treatment, and patients with ankylosis had surgical treatment.



http://ift.tt/2tdcQD3

SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry

Conditions:   Cancer, Metastatic;   Cancer;   Cancer of Pancreas;   Cancer of Liver;   Cancer of Stomach;   Cancer Liver;   Cancer of Rectum;   Cancer of Kidney;   Cancer of Esophagus;   Cancer of Cervix;   Cancer of Colon;   Cancer of Larynx;   Cancer, Lung;   Cancer, Breast;   Cancer, Advanced;   Cancer Prostate;   Cancer of Neck;   Cancer of Skin;   Neuroendocrine Tumors;   Carcinoma;   Mismatch Repair Deficiency;   BRCA Gene Rearrangement;   Non Hodgkin Lymphoma;   Leukemia;   Non Small Cell Lung Cancer;   Cholangiocarcinoma;   Glioblastoma;   Central Nervous System Tumor;   Melanoma;   Urothelial Carcinoma;   Bladder Cancer;   Ovarian Cancer;   Endometrial Cancer;   Testicular Cancer;   Breast Cancer
Intervention:   Other: Clinical Trial Matching
Sponsor:   Massive Bio, Inc.
Recruiting

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A Study of Atezolizumab (Anti−Pd-L1 Antibody) as Adjuvant Therapy After Definitive Local Therapy in Patients With High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Condition:   Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Interventions:   Drug: Atezolizumab;   Drug: Placebo
Sponsor:   Hoffmann-La Roche
Not yet recruiting

http://ift.tt/2F9bXAP

Activation of RhoA, Smad2, c-Src, PKC-βII/δ and JNK in atopic dermatitis

Abstract

Atopic dermatitis is a multifactorial skin disease characterised by chronic and relapsing inflammation whose pathogenesis is incompletely understood. We found that the expression of TGFβR1 and the activation of SMAD2, RhoA, JNK, PKC-βII/δ and c-Src were upregulated in the infiltrated inflammatory cells, fibroblasts and vasculatures in the dermis and epidermis. In addition, increases in the expression of TGFβR1 and phosphorylation levels of JNK and c-Src were positively correlated with the inflammatory progression of atopic dermatitis severity.

http://ift.tt/2FOuoYQ

Dental Follicle Mesenchymal Stem Cells Downregulate Th2 Mediated Immune Response in Asthmatic Patients Mononuclear Cells

Abstract

Background

Asthma is a chronic inflammatory disease in which inflammatory responses have the polarization of CD4⁺ T cells to Th2 cells. Dental follicle mesenchymal stem cells (DFSCs) have strong anti-inflammatory properties comparable to other mesenchymal stem cells.

Objective

We investigated the immunomodulatory effects of DFSCs on CD4⁺ T helper cell responses of asthmatic patients and compared the results with those obtained with asthmatic subjects on immunotherapy and with healthy individuals.

Method

Peripheral blood mononuclear cells (PBMC) were isolated from immunotherapy naïve asthmatics, asthmatics on subcutaneous Der p1 immunotherapy and from healthy individuals. PBMC were pre-conditioned with anti-CD3/anti-CD28 mAbs, Der p1 or IFN-γ in the presence and absence of DFSCs and analyzed for T cell viability and proliferation, CD4⁺CD25⁺FOXP3⁺ regulatory T cell frequencies, cytokine expression, and GATA3, T bet and FoxP3 expressions. Neutralization of TGF-β and blockade of IDO and PGE2 pathways were performed to determine suppressive signaling pathways of DFSCs.

Results

DFSCs suppressed proliferative responses of CD4⁺ T lymphocytes and increased the frequency of Treg cells. DFSCs decreased effector and effector memory CD4+ T cell phenotypes in favor of naïve T cell markers. DFSCs decreased IL-4 and GATA3 expression and increased IFN-γ, T-bet and IL-10 expression in asthmatics. Costimulatory molecules were suppressed in monocytes with DFSCs in the cocultures. DFSCs downregulated inflammatory responses via IDO and TGF-β pathways in asthmatic patients.

Conclusion

DFSCs suppressed allergen-induced Th2-cell polarization in favor of Th1 responses and attenuated antigen-presenting cell co-stimulatory activities. These studies suggest that DFSC-based cell therapy may provide pro-tolerogenic immunomodulation relevant to allergic diseases such as asthma.

This article is protected by copyright. All rights reserved.

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Evaluation of the chemopreventive effects of Ankaferd Bloodstopper in 7,12-dimethylbenz[a]anthracene-induced oral epithelial dysplasia

Abstract

Objectives

Ankaferd BloodStopper® (ABS) is an herbal extract which has been used historically as a hemostatic agent in traditional Turkish medicine. ABS comprises of standardized mixture of herbs Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. In addition to its hemostatic effects, the herb ABS contains some other biological effects including antioxidant and antitumoral properties. The aim of this study is to investigate the chemopreventive effects of ABS in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral epithelial dysplasia.

Materials and methods

A total of 40 Sprague Dawley rats were randomly divided into four groups. Group 1 animals received DMBA alone, and group 2 animals received both DMBA and Ankaferd. Group 3 animals received ABS alone while group 4 animals served as control group and received only liquid paraffine. All animals were sacrificed, and tissue samples were analyzed histologically at the end of the experimental period (14 weeks).

Results

Histological studies have shown that the buccal pouches of animals treated with DMBA alone revealed severe dysplasia while only mild or no dysplasia were noticed in DMBA + ABS group. Ankaferd were administered to animals and control group showed no dysplasia or other oral lesions.

Conclusion

The results suggest that Ankaferd Bloodstopper® has chemopreventive effect against DMBA-induced oral epithelial dysplasia.

Clinical relevance

Ankaferd Bloodstopper® could be used as a supportive treatment option of cancer in oral and maxillofacial surgery since it possesses chemopreventive effect.

http://ift.tt/2FeewAZ

Daratumumab augments alloreactive natural killer cell cytotoxicity towards CD38+ multiple myeloma cell lines in a biochemical context mimicking tumour microenvironment conditions

Abstract

Natural killer (NK) cell-based immunotherapy is a promising novel approach to treat cancer. However, NK cell function has been shown to be potentially diminished by factors common in the tumor microenvironment (TME). In this study, we assessed the synergistic potential of antibody-dependent cell-mediated cytotoxicity (ADCC) and killer immunoglobin-like receptor (KIR)-ligand mismatched NK cells to potentiate NK cell antitumor reactivity in multiple myeloma (MM). Hypoxia, lactate, prostaglandin E2 (PGE2) or combinations were selected to mimic the TME. To investigate this, NK cells from healthy donors were isolated and NK cell ADCC capacity in response to MM cells was assessed in flow cytometry-based cytotoxicity and degranulation (CD107a) assays in the presence of TME factors. Hypoxia, lactate and PGE2 reduced cytotoxicity of NK cells against myeloma target cells. The addition of daratumumab (anti-CD38 antibody) augmented NK-cell cytotoxicity against target cells expressing high CD38, but not against CD38 low or negative target cells also in the presence of TME. Co-staining for inhibitory KIRs and NKG2A demonstrated that daratumumab enhanced degranulation of all NK cell subsets. Nevertheless, KIR-ligand mismatched NK cells were slightly better effector cells than KIR-ligand matched NK cells. In summary, our study shows that combination therapy using strategies to maximize activating NK cell signaling by triggering ADCC in combination with an approach to minimize inhibitory signaling through a selection of KIR-ligand mismatched donors, can help to overcome the NK-suppressive TME. This can serve as a platform to improve the clinical efficacy of NK cells.

http://ift.tt/2tcIwbH

Clinical implications of CD4+ T cell subsets in adult atopic asthma patients

T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood.

http://ift.tt/2CUFXug

The Third Institute for Cancer Vaccines and Immunotherapy (ICVI) symposium on immunotherapy: May 12–13, 2017, Royal Society, London, UK

http://ift.tt/2FgLvEJ

Diagnostic and Management Tool for Monitoring Patients Implanted with a Shape-Changing Corneal Inlay

We report two cases that underwent corneal inlay implantation under a femtosecond flap. The first case had no complications during the postoperative period. Pentacam maps remained stable over time: corneal densitometry (CD) values had less than 2 units of change across visits up to 3 years. Axial/sagittal topography maps showed a stable K_max (∼47 D), i.e., less than 1 D change between visits. The second case developed haze at 8 months postoperatively. CD increased by more than 4 units from 3 to 8 M and K_max increased by 2.6 D. The patient was prescribed steroids and 1 month later the haze regressed, resulting in pre-haze CD and K_max values, similar to the ones at 3 months.
Case Rep Ophthalmol 2018;9:190–196

http://ift.tt/2ta0xHE

Amnwiotic Membrane Transplantation as a Treatment for Sterile Infiltration and Corneal Melting after Corneal Crosslinking for Keratoconus

We report a case of corneal melting through sterile infiltration presumably due to excessive use of nonsteroidal anti-inflammatory eye drops after corneal crosslinking (CXL). It was treated using steroids combined with amniotic membrane transplantation (AMT). A 33-year-old man with progressing keratoconus underwent left eye CXL. We prescribed betamethasone and levofloxacin eye drops 5 times daily and diclofenac sodium eye drops 3 times daily for 3 days. Three days after CXL, there was a persistent epithelial defect and the left corneal stroma was clouded. His visual acuity remained unchanged. We prescribed betamethasone hourly and 20 mg prednisolone daily. At 1 week after CXL, the corneal epithelial defect and infiltration were unchanged. He had not stopped using diclofenac at the prescribed time. On day 17, we performed AMT and his cornea and visual acuity improved. AMT may be effective against persistent epithelial defects and corneal melting after CXL.
Case Rep Ophthalmol 2018;9:185–189

http://ift.tt/2F6WAJa

Intraocular Lens Dislocation after Cataract Surgery in Tambolaka, Southwest Sumba, Indonesia: A Case Report

Intraocular lens (IOL) dislocation is a rare complication of cataract extraction requiring prompt surgery. This case report aims to raise awareness of such cases and the importance of post-surgery follow-up. A 58-year-old female patient was found with anterior IOL dislocation a week after phacoemulsification surgery in her right eye. Visual acuity of the right eye was 1/60 with ciliary injection and IOL dislocation to the anterior chamber of the right eye. The patient underwent surgery of the right eye and the IOL haptic was found to be broken. In this case report, the factors affecting IOL dislocation are axis length, broken IOL haptic, and patient activity that increased intraocular pressure. Cataract extraction surgery, although common, needs to be conducted carefully, and it is important for ophthalmologists and general practitioners to detect this condition, especially in rural areas where facilities are limited, as IOL dislocation could occur and requires immediate treatment to achieve a better result.
Case Rep Ophthalmol 2018;9:179–184

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One-Year Outcome of Aflibercept and Photodynamic Therapy in a Caucasian Patient with Polypoidal Choroidal Vasculopathy Refractory to Ranibizumab and Photodynamic Therapy

Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration characterised by an abnormal branching vascular network with aneurysmal polypoidal choroidal vascular lesions. PCV is more prevalent in Asian populations than in Caucasians, which may explain its underdiagnosis in Western countries. Evidence regarding the efficacy of different anti-vascular endothelial growth factor (anti-VEGF) agents on PCV is scarce, with most of these studies being conducted in Asian treatment-naïve patients. Ranibizumab was the first anti-VEGF agent to demonstrate the superiority of a combination of photodynamic therapy (PDT) and anti-VEGF over PDT or anti-VEGF monotherapy for inducing polyp regression in Asian patients with PCV. The efficacy of other anti-VEGF agents has been less studied. Resistance to ranibizumab has been described. Aflibercept offers another mechanism of targeting choroidal neovascular lesions. A 75-year-old Caucasian woman presenting to our office was diagnosed with PCV using indocyanine green angiography. Combination therapy with a loading dose of 0.5 mg intravitreal ranibizumab followed by PDT at standard fluence at month 4 and a fourth dose of ranibizumab at month 5 yielded no visual or anatomic outcomes. Treatment was switched to intravitreal aflibercept at month 6 (3 monthly loading doses of 2.0 mg) followed by half-fluence PDT (month 9). Optical coherence tomography revealed remission of the anatomic lesions. Right-eye visual acuity increased to 0.6. Aflibercept injections were administered bimonthly afterwards. Follow-up during 1 year has shown functional and anatomic stability.
Case Rep Ophthalmol 2018;9:172–178

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Posterior Wall Collapse in High Myopia following Cataract Surgery

Purpose: We report a case of posterior globe collapse of an eye after initial recovery from uncomplicated cataract surgery in a patient with high myopia and discuss the course of management involving recognition and emergent air injection with globe reformation. Case Report: A 64-year-old functionally monocular male with a history of high myopia presented for follow-up after uncomplicated cataract surgery. Uncorrected distance visual acuity (UCDVA) at postoperative day 1 was 20/150 with an intraocular pressure (IOP) of 19 mm Hg. At the week 1 visit, UCDVA had decreased to 20/200 with an IOP at 9 mm Hg. After preliminary exam, the keratome site suture was removed, after which the patient reported vision changes. A dilated fundus exam was performed revealing posterior scleral wall collapse. A clinical diagnosis of hypotony was made and a pars plana injection of 1 mL air was performed. This resulted in immediate subjective improvement of vision. Exam the next day revealed UCDVA 20/50 with pinhole improvement to 20/30 and IOP 15 mm Hg. Conclusion: This case demonstrates postoperative hypotony in a patient with pathologic myopia, following cataract surgery. Pathologically myopic eyes may have greater propensity to collapse in the setting of reduced IOP.
Case Rep Ophthalmol 2018;9:167–171

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Erratum

Case Rep Ophthalmol 2018;9:166

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Reconstruction of a chronically ruptured Achilles tendon using an internal brace: a case report

We reconstructed a chronically ruptured Achilles tendon and the associated scar tissue using braided polyblend polyethylene sutures (FiberWire; Arthrex Inc.; Naples, FL, USA) and anchors.

http://ift.tt/2oCOjCr

Voice Analysis in Post Tonsillectomy Patients

Abstract

The main aim of this study was to analyse the change in voice in terms of acoustic parameters and its perceptual impact in patients who have undergone tonsillectomy. A prospective study was conducted in our institution—JSS Hospital and JSS institute of speech and hearing, Mysore for a duration of 1 year (December 2015–December 2016). 50 post tonsillectomy cases were selected randomly and subjected to acoustic analysis. It was inferred that situation of vocal analysis and assessment for the vowels 'a', 'i' and 'u' under the categories hoarse, harsh and breathy remain more or less the same during preoperative stages, first preoperative follow up and the second post operative follow up. It was concluded that tonsillectomy did not appear to change the acoustic features of vowels remarkably. It was assumed that the subject may adjust the shape of the vocal tract to produce consistent speech sound after surgery using auditory feedback.

http://ift.tt/2oObAkr

Comparison of Endoscopic Turbinoplasty Versus Conventional Partial Inferior Turbinectomy in Chronic Hypertrophic Rhinitis

Abstract

To compare the benefits of endoscopic turbinoplasty and conventional partial inferior turbinectomyin terms of symptomatic relief of the post operative subjective and objective outcomes in patients with chronic hypertrophic rhinitis. A comparative longitudinal study was carried out over a period of 18 months. 60 cases were assigned randomly into two groups—group A (endoscopic turbinoplasty) and group B (conventional partial inferior turbinectomy) and post-operatively were followed up to 6 months to look for postoperative subjective and objective outcomes. Symptomatic improvement in nasal obstruction was found to be consistently better in group A patients at postoperative days 7 and 15, but both groups achieved comparable symptom relief at the third month. A statistically significant difference in SNOT 22 scores were observed between the two groups at all follow-ups. Relatively higher rates of post-operative morbidities were observed in group B at the 7th and 15th postoperative days. Endoscopic turbinoplasty may be better than conventional partial inferior turbinectomy in terms of improvement in nasal obstruction and decreased postoperative morbidity in the immediate postoperative period.

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Barosinusitis: Comprehensive review and proposed new classification system

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Evaluation of a new and simple classification for endoscopic sinus surgery

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The study of a possible correlation between serum levels of interleukin 17 and clinical severity in patients with allergic rhinitis

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Prenatal maternal depression related to allergic rhinoconjunctivitis in the first 5 years of life in children of the EDEN mother-child cohort study

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Characterization of T-cell subpopulations in patients with chronic rhinosinusitis with nasal polyposis

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A multicenter, prospective, noninterventional study in a Norwegian cohort of patients with moderate-to-severe allergic rhinitis treated with MP-AzeFlu

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Oral immunotherapy in children with IgE-mediated hen's egg allergy: Follow-ups at 2.5 and 7 years

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Long-term omalizumab use in the treatment of exercise-induced anaphylaxis

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Long-term follow-up of a patient with malignant transformation of inverted papilloma into sinonasal undifferentiated carcinoma

http://ift.tt/2FMItWM

Multiple doses of icatibant used during pregnancy

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Satisfaction rate of patients undergoing sleeve gastrectomy as day-case surgery compared to conventional hospitalization: a prospective non-randomized study

Abstract

Purpose

Day-case surgery (DCS) has boomed over recent years. However, day-case bariatric surgery remains controversial due to a lack of evaluation. The objective of this study was to compare the experiences and satisfaction with general anesthesia of patients undergoing sleeve gastrectomy (SG) as DCS compared to conventional hospitalization.

Methods

Between January 2015 and June 2016, all patients undergoing primary SG as day-case surgery or with conventional hospitalization were prospectively included in this non-randomized, non-inferiority study comparing the level of satisfaction of patients undergoing SG with conventional hospitalization (CH group, gold standard) versus SG as DCS (DCS group). The primary efficacy endpoint was comparison of the overall satisfaction rate using the EVAN-G questionnaire. The secondary endpoints were evaluation of the 6 dimensions of the EVAN-G questionnaire, discharge from hospital, adhesion with SG management and overall satisfaction with SG.

Results

One-hundred and twenty-four patients met the inclusion criteria (62 in both groups). The DCS group was younger with fewer comorbidities (p ≤ 0.01) and had a lower BMI (p ≤ 0.01). Overall, the mean EVAN-G questionnaire score was 66.4 (63.9–68.9) for the DCS group and 68.9 (65.9–71.8) for the CH group (non-inferiority of DCS group). In the DCS group, 19% of patients would have preferred to spend the night in hospital, while 82% of patients in the CH group would have preferred DCS and a total of 75% of patients reported a high level of satisfaction.

Conclusion

Overall satisfaction of patients undergoing SG as day-case surgery was not inferior to that of patients managed by conventional hospitalization.

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Helicobacter pylori and gastric cancer in Alaskan Natives: Time to stop studyingH. pylori and to eradicate it

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Impaired lymphocyte function in patients with hepatic malignancies after selective internal radiotherapy

Abstract

The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays. Absolute counts and percentages of leukocyte and lymphocyte subsets were determined by flow cytometry. The most prominent finding was an immediate and significant (p < 0.05) decrease of lymphocyte proliferation and interferon-γ production directly after therapy which lasted until day 28 and was stronger upon stimulation with microbial antigens than with mitogens. Moreover, lymphopenia was revealed, affecting all lymphocyte subsets (CD3+, CD4+, CD8+ T cells, CD4+ CD8+ T cells, B cells and NK cells). SIRT led to a reduction in the percentage of activated HLA-DR+ monocytes and of CD45R0+ memory T cells. Higher radiation activity, the presence of liver cirrhosis, chronic kidney disease, diabetes mellitus and metastases were unfavorable factors for immunocompetence, while a better Eastern Cooperative Oncology Group performance status was associated with stronger immunological reactions. In conclusion, SIRT leads to severe impairment of cellular in vitro immune responses. Further studies are needed to assess a potential clinical impact.

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An undergraduate Otolaryngology curriculum comparison in the United Kingdom using a curriculum evaluation framework

http://ift.tt/2oI9z92

Bile acids: a potential role in the pathogenesis of pharyngeal malignancy

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Single‐sided deafness affects language and auditory development – a case–control study

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Workload and costs of audiological assessment on tertiary settings: Data analysis and audit

http://ift.tt/2HWpwBt

Local extension staging of sinonasal tumours: retrospective comparison between CT/MRI assessment and pathological findings

http://ift.tt/2oKuIPV

Adaptation and validation of the Singing Voice Handicap Index into Polish

http://ift.tt/2HUwtD4

An evaluation of the quality of evidence available to inform current bone conducting hearing device national policy

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Effect on mortality of elective parathyroid surgery in one hundred and three patients with chronic kidney disease: our experience

http://ift.tt/2HWpnOv

The value of direct audiology access for magnetic resonance imaging: an audit of 40 cases

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Dura and sinus compression with a transcutaneous bone conduction device – hearing outcomes and safety in 38 patients

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Congenital anosmia: our experience of eleven patients with aplasia or hypoplasia of the olfactory tract

http://ift.tt/2oJrRHi

UK tertiary centre experience of outcomes from osseointegrated transcutaneous magnetic bone conduction hearing system implanted in twenty‐five patients using a linear incision technique

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Short‐term results from seventy‐six patients receiving a bone‐anchored hearing implant installed with a novel minimally invasive surgery technique

http://ift.tt/2oKuzfl

Squamous cell carcinoma associated with inverted papilloma of the maxillary sinus: our experience with 21 patients

http://ift.tt/2HWpRnJ

Functional magnetic resonance imaging in seven borderline cochlear implant candidates: a preliminary research study

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Balloon tuboplasty in patients with Eustachian tube dysfunction: a prospective study in 39 patients (55 ears)

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A retrospective analysis of seven patients with acquired immunodeficiency syndrome and pharyngeal and/or laryngeal Talaromyces marneffei infection

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The role of sentinel lymph node biopsy in the management of laryngeal carcinoma

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Insulin effect on hearing recovery in idiopathic sudden sensorineural hearing loss: Retrospective study of 145 patients

http://ift.tt/2HWkAN2