Treating multiple body parts for skin laxity and fat deposits using a novel focused radiofrequency device with an ultrasound component: Safety and efficacy study

Summary

Background and objectives

Growing demand for noninvasive skin tightening and reduction in fat results in an increasing pressure for devices with good clinical efficacy, consistency of results, and high patient comfort. The objective was to validate clinical efficacy and versatility of a novel device, which combines radiofrequency (RF) and ultrasound for treating skin laxity and fat deposits.

Methods

We treated 34 subjects with facial skin laxity and/or abundant body or arm fat deposits. Subjects were divided based on their indications. Ten subjects received treatments to the face, 7 subjects to arms, 8 subjects to thighs, and 9 subjects on abdomen. All patients received 4 treatments on a weekly basis. Photographs of patients were assessed by blinded evaluators to recognize the baseline images from the 3-month follow-up images. Patient comfort and satisfaction were evaluated using a 5-point Likert scale questionnaire. Any adverse events were recorded.

Results

Patient images were correctly recognized in >90% of cases in all study groups. Patient questionnaires showed overall satisfaction with the therapy course and results. On a scale of 1 to 5, the patients agreed (4.1) that they are satisfied with the results that the treatment is comfortable (4.1) and that they are satisfied with the treatment time (4.1). No adverse events were reported.

Conclusions

Consistent clinical efficacy was confirmed across all the treated areas, together with high patient comfort and satisfaction. We conclude the device is a highly versatile solution that can deliver results across body parts and different indications.

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Ventilation Defect Percent in Helium-3 MRI as a Biomarker of Severe Outcomes in Asthma

Publication date: Available online 10 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): David G. Mummy, Stanley J. Kruger, Wei Zha, Ronald L. Sorkness, Nizar N. Jarjour, Mark L. Schiebler, Loren C. Denlinger, Michael D. Evans, Sean B. Fain
Ventilation defect percent (VDP) measured in asthmatics with hyperpolarized helium-3 MRI was more strongly associated with ED visits and hospitalizations due to asthma exacerbation than were conventional biomarkers of lung function and inflammation.



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Identification of atopic dermatitis subgroups in children from two longitudinal birth cohorts

Publication date: Available online 10 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Lavinia Paternoster, Olga E.M. Savenije, Jon Heron, David M. Evans, Judith M. Vonk, Bert Brunekreef, Alet H. Wijga, A. John Henderson, Gerard H. Koppelman, Sara J. Brown
BackgroundAtopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups based on disease trajectories, which may represent different genetic and environmental pathomechanisms.ObjectiveTo investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in two independent cohorts.MethodsThe presence of AD was examined in two birth cohort studies including 9,894 children from the UK (ALSPAC) and 3,652 from the Netherlands (PIAMA). AD was defined by parental report of a typical itchy and/or flexural rash. Longitudinal latent class analysis was used to investigate patterns of AD from birth to the age of 11 to 16 years. We investigated associations with known AD risk factors, including FLG null mutations, 23 other established AD-genetic risk variants and atopic comorbidity.ResultsSix latent classes were identified, representing subphenotypes of AD, with remarkable consistency between the two cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male gender. Two classes of persistent disease were identified (early-onset-persistent and early-onset-late-resolving); these were most strongly associated with the AD-genetic risk score as well as personal and parental history of atopic disease. A yet unrecognised class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified.ConclusionSix classes based on temporal trajectories of rash were consistently identified in two population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.Clinical ImplicationsAtopic dermatitis ranges from a transient condition to lifelong morbidity. This study has identified distinct subphenotypes of atopic dermatitis in children, which could indicate the importance of a stratified approach to management of this complex disease.

Teaser

Longitudinal latent class analysis models the course of disease subsets over time. Atopic dermatitis in childhood shows diversity in risk factors, prognoses and comorbidities. This study demonstrates robust subphenotypes of AD in two population cohorts.


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EoE genetic susceptibility is mediated by synergistic interactions between EoE-specific and general atopic disease loci

Publication date: Available online 10 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): L.J. Martin, H. He, M.H. Collins, J.P. Abonia, J.M. Biagini Myers, M. Eby, H.E. Johansson, L.C. Kottyan, G.K. Khurana Hershey, M.E. Rothenberg
BackgroundEosinophilic esophagitis (EoE) is an esophageal inflammatory disease associated with atopic diseases. TSLP and CAPN14 genetic variation contribute to EoE, but how this relates to atopy is unclear. The purpose of this study was to explore the relationship between EoE, atopy and genetic risk.MethodsEoE-atopy enrichment was tested using 700 EoE cases and 801 community controls. Probing 372 SNPs in 63 atopy-genes, we evaluated EoE associations using 412 non-atopic and 868 atopic disease controls. Interaction and stratified analyses of EoE-specific and atopy SNPs were performed.ResultsAtopic disease was enriched in EoE (p < 0.0001). Comparing EoE and non-atopic controls, EoE associated strongly with IL4/KIF3A (p = 2.8×10^-6; odds ratio (OR) = 1.85), moderately with TSLP (p = 1.5×10^-4; OR = 1.43), and nominally with CAPN14 (p = 0.029; OR = 1.35). Comparing EoE to atopic disease controls, EoE associated strongly with ST2 (p = 3.5×10^-6; OR = 1.79) and nominally with IL4/KIF3A (p = 0.019, OR = 1.25); TSLP's association persisted (p = 4.7×10^-5; OR = 1.37), and CAPN14's association strengthened (p = 0.0001; OR = 1.71). Notably, there was gene-gene interaction between TSLP and IL4 SNPs (p = 0.0074). Children with risk alleles for both genes were at higher risk for EoE (p = 2.0×10^-10; OR = 3.67).ConclusionsEoE genetic susceptibility is mediated by EoE-specific and general atopic disease loci which may have synergistic effects. These results may aid in identifying potential therapeutics and predicting EoE susceptibility.Clinical Implications.EoE susceptibility is mediated by multiple genes, which have synergistic effects. These genes include both EoE-specific and general atopic disease loci. Identifying these effects may help customize treatments.

Teaser

TSLP is a susceptibility locus for EoE. We demonstrate that TSLP and IL4 variants interact, partially explaining the high degree of co-morbid atopy. These findings will improve risk prediction and may help identify novel therapeutics.


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The β and α2δ auxiliary subunits of Cav1 channels are required for Th2-lymphocyte function and acute allergic airway inflammation

Publication date: Available online 10 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Nicolas Rosa, Emily Triffaux, Virginie Robert, Marion Mars, Martin Klein, Gregory Bouchaud, Astrid Canivet, Antoine Magnan, Jean-Charles Guéry, Lucette Pelletier, Magali Savignac
BackgroundT-lymphocytes express not only the cell membrane calcium ORAI1 but also voltage-dependent Cav1 channels. In excitable cells, these channels are composed of the ion forming pore α1 and auxiliary subunits (β and α2δ) needed for proper trafficking and activation of the channel. We previously disclosed the role of Cav1.2 α1 in mouse and human Th2- but not Th1-cell functions and showed that knocking-down Cav1 α1 prevents experimental asthmaObjectiveWe investigated the role of β and α2δ auxiliary subunits on Cav1 α1 function in Th2 lymphocytes and on the development of acute allergic airway inflammation.MethodsWe used antisense oligonucleotides (CavβAS) to knockdown Cavβ and gabapentin, a drug that binds to and inhibits α2δ1 and α2δ2, to test their effects on Th2 functions and their capacity to reduce allergic airway inflammation.ResultsMouse and human Th2-cells express mainly Cavβ1, β3 and α2δ2 subunits. CavβAS reduces TCR-driven calcium responses and cytokine production by mouse and human Th2, with no effect on Th1-cells. Cavβ is mainly involved in restraining Cav1.2 α1 degradation through the proteasome as a proteasome inhibitor partially restores the α1 protein level. Gabapentin impairs TCR-driven calcium response and cytokine production associated with the loss of α2δ2 protein in Th2-cells.ConclusionsThese results stress the role of Cavβ and α2δ2 auxiliary subunits in the stability and activation of Cav1.2 channels in Th2 lymphocytes both in vitro and in vivo as demonstrated by the beneficial effect of CavβAS and gabapentin in allergic airway inflammation.Clinical implicationsThe demonstration that auxiliary subunits are involved in calcium signaling through Cav1 channels and function of mouse and human Th2-lymphocytes supports their potential beneficial effect on allergic asthma.

Teaser

This work demonstrates that Cavβ and α2δ auxiliary subunits of Cav1 calcium channels are required for proper calcium signaling in Th2 lymphocytes and their targeting is beneficial in allergic asthma.


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Hearing Preservation Cochlear Implantation: a Review of Audiologic Benefits, Surgical Success Rates, and Variables That Impact Success

Abstract

Purpose of Review

The objectives of this review are as follows: (1) examine the audiologic benefits of hearing preservation, (2) review rates of successful hearing preservation, and (3) analyze variables that impact hearing preservation success.

Recent Findings

Hearing preservation has been shown to confer the following audiologic benefits: better speech understanding in complex listening environments, superior sound localization, and improved music appreciation. There is a notable lack of standardized criteria for reporting of hearing preservation outcomes—this leads to considerable heterogeneity across studies. Rates of functional (i.e., aidable) hearing preservation generally range between 50 and 90%. Studies demonstrate higher preservation rates and more durable hearing outcomes with shorter, straight electrode arrays.

Summary

With advances in CI technology and surgical techniques, residual hearing can be preserved after CI surgery in the majority of patients. Cochlear implant recipients with preserved hearing demonstrate better speech understanding, sound localization, and improved music appreciation.

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Generating new evidence, improving clinical practice and developing research capacity: the benefits of recruiting to the U.K. Dermatology Clinical Trials Network's STOP GAP and BLISTER trials

Summary

Clinical trials may benefit clinical practice in three ways: firstly, clinicians may change their practice according to the new trial evidence; secondly, clinical processes can improve when working on a trial; and thirdly, research capacity is increased. We held a meeting to present and discuss the results of two large multicentre randomized controlled trials delivered through the U.K. Dermatology Clinical Trials Network. Investigators gave reflections on how the trials had changed their clinical practice. The STOP GAP trial showed that prednisolone and ciclosporin are equally effective as first-line systemic treatment for pyoderma gangrenosum. The final decision of which treatment to use should be based on the different adverse event profiles of the two drugs in relation to comorbidities, along with age, disease severity and patient preference. The BLISTER trial showed that starting people with pemphigoid on doxycycline produces acceptable short-term effectiveness and a superior safety profile to oral corticosteroids. Recruiting to these trials has led to the development of new specialist clinics with improved documentation. It has increased the profile of participating departments and embedded research in the department's activities. Helping to design and run these trials has also allowed trial staff to develop new skills in research design, which has been beneficial for career development. These and other benefits of recruiting to the trials are summarized here. We hope that these reflections will inspire wider involvement in clinical research.

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