Social Factors in the Development of Chronic Rhinosinusitis: a Systematic Review

Abstract

Purpose of Review

In an era where prevention is paramount, understanding social factors for chronic rhinosinusitis (CRS) may facilitate preventive interventions that mitigate risk factors associated with the initiation or progression of the disease.

Recent Findings

Both passive and active smoking are clearly and unequivocally associated with both the incidence and the severity of rhinosinusitis, while there an increasing body of evidence linking social deprivation and low socioeconomic status with rhinosinusitis and its complications. However, overall, only a handful of studies were longitudinal, while the available studies suffer from lack of standardized definitions of rhinosinusitis.

Summary

In this systematic review, we assessed the available evidence linking CRS with social factors, such as socioeconomic status and class, educational status, family status, living and working location and conditions, and use of toxins or recreational drugs as well as exercise and diet. Thirty studies from 1995 onwards fulfilled our inclusion criteria and were used for this review. Social deprivation and low socioeconomic level seem to be directly associated with rhinosinusitis, as there are pollutants in living or working environment. A clear and direct association between smoking (both active and passive) and rhinosinusitis was also shown. However, the link between rhinosinusitis and education level, and exercise and diet, if any, seems to be more complex.

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Systematic Reviews and Meta-analysis in Rhinosinusitis: a Critical Review of the Reviews

Abstract

Purpose of Review

There has been an explosion in the number of published systematic reviews on chronic rhinosinusitis in the last decade.

Recent Findings

While the aim of these reviews in facilitating evidence-based practice is laudable, poor quality reviews may contain significant bias that can mislead a non-discerning reader.

Summary

Attention therefore must be given to review methodology before implanting findings. Organisations such as the Cochrane Collaboration promote high-quality reviews, but are limited in chronic sinus disease by heterogeneous outcomes and a paucity of randomised trials.

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Neurotrophins in Asthma

Abstract

Purpose of Review

Asthma is a chronic airway disease that affects more than 300 million people worldwide. Current treatment focuses on symptomatic relief by temporally dampening inflammation and relaxing the airway. Novel combative strategies against asthma and hopefully a cure are yet to be developed. The goal of this review is to summarize recent literature on neurotrophins (NTs) in experimental models and clinical settings of asthma research.

Recent Findings

We highlight studies of early phases of asthma that collectively reveal a profound impact of elevated NT levels following initial detrimental insults on long-term airway dysfunction.

Summary

We hope this review will foster insights into the complex interaction between NTs, nerves, immune cells, and airway structural cells during a critical time window of development and disease susceptibility. Future studies are required to better understand the role of NTs in asthma pathophysiology and to evaluate whether NTs and their receptors may serve as new drug targets.

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Modified Allergens for Immunotherapy

Abstract

Purpose of Review

During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT.

Recent Findings

In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens.

Summary

The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT.

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Occupational Animal Allergy

Abstract

Purpose of Review

This review explores animal allergen exposure in research laboratories and other work settings, focusing on causes and prevention.

Recent Findings

(1) Consistent with the hygiene hypothesis, there is new evidence that early childhood exposure to pets produces changes in the gut microbiome that likely lead to a lower risk of allergy. (2) Anaphylaxis from laboratory animal bites occurs more frequently than suggested by prior literature. (3) Animal allergens represent an occupational hazard in a wide variety of work settings ranging from fields that work with animals to public settings like schools and public transportation where allergens are brought into or are present in the workplace.

Summary

Exposure to animal allergens can result in allergy, asthma, and anaphylaxis. Animal allergy has been most studied in the research laboratory setting, where exposure reduction can prevent the development of allergy. Similar prevention approaches need to be considered for other animal work environments and in all settings where animal allergens are present.

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Optimizing the induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal Carcinoma: A big-data intelligence platform-based analysis

Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Hao Peng, Ling-Long Tang, Bin-Bin Chen, Lei Chen, Wen-Fei Li, Yan-Ping Mao, Xu Liu, Yuan Zhang, Li-Zhi Liu, Li Tian, Ying Guo, Ying Sun, Jun Ma
ObjectivesThis study aimed at identifying the optimal induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy.Materials and methodsWe identified eligible patients with newly-diagnosed stage III-IVA NPC (excluding T3N0) between September 2009 and May 2015. Survival outcomes and grade 3–4 toxicities were compared between different IC regimen groups.ResultsIn total, 3738 patients were eligible for this study, with 1572 (42.1%), 1085 (29.0%) and 1081 (28.9%) receiving TPF, PF and TP, respectively. In the whole population, multivariate analysis found that TPF seems to be better than PF and TP. Howerver, subgroup analysis revealed TPF and TP had same effectiveness in patients receiving a cumulative cisplatin dose (CCD) ≥200mg/m² in concurrent chemotherapy, while TPF shows relatively better survival benefit in patients receiving CCD<200mg/m². Grade 3–4 toxicities were similar between TPF and TP groups, but were relatively higher than that in PF group.ConclusionsOur study concluded that induction TP regimen may be enough for patients receiving a CCD≥200mg/m², while TPF may be superior to TP and PF for patients receiving a CCD<200mg/m², although grade 3–4 toxic events were more common but tolerable. Further studies are needed to validate our findings.



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Aquagenic pruritus successfully treated with omalizumab

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Association of clinicopathological features of melanoma with total naevus count and a history of dysplastic naevi: a cross-sectional retrospective study within an academic centre

Summary

Background

High naevus count (HNC) (≥ 50 naevi) and presence of dysplastic naevi (DN) are risk factors for malignant melanoma (MM); however, MMs also occur in patients with low naevus count (LNC) (< 50 naevi) and in patients without DN. Little is known about differences between MMs in these groups.

Aim

To characterize the clinicopathological differences between MMs in patients with HNC and those in patients with LNC, with or without biopsy-proven DN.

Methods

This was a cross-sectional retrospective chart review of 281 patients with MM seen between April 2013 and March 2014 at an academic pigmented lesion clinic (Boston, MA, USA).

Results

Patients with LNC MMs were diagnosed at an older age (51 vs. 41 years, P < 0.001, OR = 0.95, 95% CI 0.93–0.97), with more aggressive MM features, including greater Breslow thickness (1.1 vs. 0.8 mm, P = 0.01), more mitoses (2 vs. 1 mitoses/mm², P < 0.001), lower rate of superficial spreading subtype (58 vs. 78%, P < 0.01, OR = 2.57, 95% CI 1.31–5.03) and higher MM stage (P < 0.001), compared to patients with HNC. Patients with DN had similar trends as those in patients with HNC described above, and in addition, were more likely to have a truncal MM (55 vs. 39%, P < 0.01, OR = 1.97, 95% CI 1.22–3.18) with less ulceration (13 vs. 29%, P < 0.01, OR = 0.36, 95% CI 0.19–0.71). Patients without DN were more likely to have a history of a non-MM skin cancer (32 vs. 19%, P = 0.01, OR = 0.49, 95% CI 0.28–0.85) and an amelanotic MM (33 vs 21%, P = 0.03, OR = 0.55, 95% CI 0.31–0.96).

Conclusions

Patients with LNC may develop MMs with more aggressive features at an older age than patients with HNC. A history of biopsy-proven DN reveals distinct MM differences compared to patients without DN.

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Preoperative Clinical and Sonographic Predictors for Lateral Cervical Lymph Node Metastases in Sporadic Medullary Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.


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Diagnostik von AVWS bei Erstklässlern: Welche Tests trennen auffällige von unauffälligen Kindern?

Laryngo-Rhino-Otol
DOI: 10.1055/s-0044-101836

Hintergrund Im kontrollierten Gruppenvergleich wurde für 2., 3. und 4.-Klässler gezeigt, dass eine Trennung von Kindern mit auditiven Verarbeitungs- und Wahrnehmungsstörungen (AVWS) von solchen ohne (Non-AVWS) durch 3 bzw. 4 Untersuchungsinstrumente möglich ist mit einer Zuordnungsrichtigkeit von 93,6 % bzw. 97,5 % 1, 2. Die vorliegende Studie erfolgte mit der Fragestellung, ob auch für Erstklässler eine Trennung der Gruppen gelingt. Material und Methoden Leistungen von 77 Kindern (n = 40 mit AVWS, mittl. Alter: 6,93, SD 0,53 Jahre; n = 37 Non-AVWS, mittl. Alter: 6,90, SD 0,52 Jahre) im 1. Regelgrundschuljahr wurden in 8 spezifisch auditiven Tests einer eklektischen AVWS-Testbatterie miteinander verglichen: Uttenweiler-Test zum Dichotischen Wortverstehen; Subtests Lautdifferenzierung u. Kinästhetik (Heidelberger Lautdifferenzierungstest- HLAD); Göttinger Sprachaudiometrie II im Störgeräusch; Hannoverscher Binauraler Summationstest; Zahlenfolgen-Gedächtnis u. Laute Verbinden (Psycholinguistischer Entwicklungstest); Mottier-Test. Ergebnisse Kinder mit AVWS wurden von unauffälligen Kindern (Non-AVWS) der gleichen Schuljahrgangsstufe in 94,8 % aller Fälle (kreuzvalidiert: in 92,2 %) statistisch signifikant durch vier Testvariablen getrennt: (1) PET-Zahlenfolgen-Gedächtnis; (2) HLAD-Lautdifferenzierung; (3) Mottier-Test; (4) Sprachaudiometrie im Störgeräusch. Schlussfolgerungen Die Qualität der diagnostischen A-Priori-Gruppierung mittels einer multivariaten Statistik konnte für das 1. Regelgrundschuljahr bestätigt werden.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Transcriptional and epigenetic regulation of innate-like T lymphocyte development

Mihalis Verykokakis | Barbara L Kee

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Chemical sensing in development and function of intestinal lymphocytes

Luisa Cervantes-Barragan | Marco Colonna

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Dysphagia and Pharyngeal Obstruction in a Nonsmoker

A man in his 60s presented with a 6-month history of dysphagia and a 3-month history of a 5-pound weight loss and a right neck mass; physical examination, including flexible nasolaryngoscopy, was notable for a large smooth nonulcerated right base of tongue mass. What is your diagnosis?

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February 2018 Issue Highlights

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Granulomatosis With Polyangiitis

This Viewpoint examines the continued use of the name Wegner granulomatosis despite the 2011 consensus to change the name of the disease to granulomatosis with polyangiitis.

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Addition to Funding/Support

In the Original Investigation titled "Association of Oral Cavity and Oropharyngeal Cancer Biomarkers in Surgical Drain Fluid With Patient Outcomes," published online April 13, 2017, and in the July 2017 print issue, a funding source and grant information were missing from the Funding/Support section. University of Minnesota Cancer Center (grant P30CA077598) was added. This article has been corrected online.

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First-Generation Deescalation Trials in HPV-Positive Oropharyngeal Cancer

This Viewpoint discusses the limitations of precision medicine in patients with human papillomavirus–positive oropharyngeal cancer.

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Sensory Changes and the Hearing Loss–Cognition Link

The UK National Institute of Health and Care Excellence (NICE) and the US National Institutes of Health (NIH) identified peripheral age-related hearing loss (ARHL) and social isolation as potentially modifiable dementia risk factors. A growing body of evidence suggested that ARHL and cognition in older age are interrelated and that midlife ARHL may be a risk factor for the development of Alzheimer disease (AD) and dementia in older adults. In a recent meta-analysis of only 3 selected studies with follow-up periods of 9 to 17 years, Livingstone and colleagues found that peripheral ARHL was a significant risk factor for incident dementia, calculating a pooled risk ratio of 1.94. At early stage of ARHL, part of the hearing problems are not related to the peripheral deficit of the auditory system but also to the central auditory processing (CAP) dysfunction, with considerable difficulty in understanding speech in presence of a background noise. Both peripheral and central auditory dysfunctions are therefore relevant to assess a possible influence of ARHL on late-life cognitive disorders.

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Association of Hearing Loss and Otologic Outcomes With Fibrous Dysplasia

This study characterizes audiologic and otologic manifestations in a cohort of individuals with fibrous dysplasia and/or McCune-Albright syndrome and investigated potential mechanisms of hearing loss.

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Hypercoagulability and Severe Obstructive Sleep Apnea

To the Editor I read with interest the study by Hong et al, which assessed the association between hypercoagulability and severe obstructive sleep apnea (OSA). The authors measured several coagulation tests, including platelet count, bleeding time, prothrombin time (PT) in seconds and as international normalized ratio, and activated partial thromboplastin time and their association with severity of OSA. They found that patients with moderate to severe OSA had elevated blood coagulability markers compared with healthy individuals.

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Association of Lymph Node Density With Survival in Papillary Thyroid Cancer

This cohort study assesses the association of lymph node density—the ratio of the number of positive lymph nodes to the total number of nodes excised—with survival in patients with papillary thyroid cancer.

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Missing Acknowledgment

In the article titled "Asymptomatic Septal Mass," an acknowledgement that was omitted has been added to thank Jonathan B. McHugh, MD, for his consultation on the case presented. The article was corrected online.

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Age-Related Hearing Loss, Cognitive Function, and Dementia

This meta-analysis examines the association between age-related hearing loss and cognitive function, cognitive impairment, and dementia in epidemiologic studies from 12 countries.

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Prevalence of Laryngeal Cleft in Patients With Esophageal Atresia

This study uses data from the Esophageal and Airway Treatment Center at Boston Children's Hospital to assess the prevalence of laryngeal cleft in pediatric patients with esophageal atresia with or without tracheoesophageal fistula.

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Association of Sudden Sensorineural Hearing Loss With Cardiocerebrovascular Disease

This cohort study uses Korea National Health Insurance Service data to investigate the association between sudden sensorineural hearing loss and cardiocerebrovascular disease.

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Asymptomatic Septal Mass

A woman in her 40s presented with a 2-month history of an enlarging asymptomatic anterior septal mass; she denied a history of localized trauma, and examination revealed an 8-mm pink-red, soft fleshy growth posterior to the membranous septum near the nostril apex. What is your diagnosis?

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Traumatic Tympanic Membrane Perforations Diagnosed in Emergency Departments

This cross-sectional analysis of cases from a national survey system reports the mechanism of injury for traumatic tympanic membrane perforation among patients who presented to the emergency department.

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Cerebrospinal Fluid Rhinorrhea and a Lytic-Appearing Lesion

A man with a recent history of meningitis presented with a 1-month history of intermittent clear drainage from his left naris during activity; temporal bone computed tomography demonstrated a lytic-appearing lesion of the posterior fossa and partial opacification of the mastoid air cells. What is your diagnosis?

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Association of GERD With Cancer of the Upper Aerodigestive Tract in Elderly Patients

This case-control study uses a database of population-based tumor registries to investigate the association of gastroesophageal reflux disease with the risk of malignancy in the upper aerodigestive tract in elderly patients.

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Hypercoagulability and Severe Obstructive Sleep Apnea—Reply

In Reply We appreciate the interest of Dr Ghadami in our recently published study titled "Association Between Hypercoagulability and Severe Obstructive Sleep Apnea." The comments raised by the reader can be summarized as follows: The frequent arousals in sleep might be one of the reasons for elevated coagulability markers in patients with obstructive sleep apnea (OSA).

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Outcomes Following Cordotomy by Coblation for Bilateral Vocal Fold Immobility

This case series of 19 patients examines outcomes of coblation in cordotomy for treatment of patients with bilateral vocal fold immobility.

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Errors in Figures 1, 2, and 3

In the Original Investigation titled "Association of Age-Related Hearing Loss With Cognitive Function, Cognitive Impairment, and Dementia: A Systematic Review and Meta-analysis," published online December 7, 2017, in Figure 1, the total number of studies included in quantitative synthesis (meta-analysis) should have been 36 instead of 40; in Figure 2, the r value for reasoning should have been −0.18 instead of −0.17; and in Figure 3, the numbers of participants and events for all categories were incorrect. This article has been corrected online.

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Erratum: Frontal Fibrosing Alopecia and Cutaneous Comorbidities: A Potential Relationship with Rosacea

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Sensing Danger after Kidney Transplantation

No abstract available

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3D Endoscopic Donor Nephrectomy Versus Robot-Assisted Donor Nephrectomy: a Detailed Comparison of 2 Prospective Cohorts

AbstractBackgroundThere are 2 endoscopic surgical techniques that implement 3D vision to overcome visual misperception: 3D endoscopy and the da Vinci surgical system. 3D endoscopy has several advantages, such as the presence of tactile feedback and easy implementation, at lower costs. We aimed to assess whether 3D endoscopy could be an alternative to the robot during living donor nephrectomy (LDN).MethodsBetween April 2015 and April 2016 we prospectively collected data on 40 patients undergoing 3D endoscopic LDNs in 1 center, performed by a da Vinci certified surgeon. Data on donors' perioperative results and recipient and graft survival were collected. These data were compared to 40 robot-assisted donor nephrectomies (RADNs) performed in the same center (between January 2012 and May 2014).ResultsBaseline characteristics for both groups were comparable. Intraoperative results showed a significantly shorter median skin-to-skin time (STS-time) of 138.5 min. (125.8-163.8) versus 169.0 (141.5-209.8) min. in favour of the 3D group (P=0.001). Warm ischemia time ([WI-time], P=0.003) and hilar phase for both single- (1 artery and vein) and multiple anatomies (≥1 artery and/or vein [P=0.002 and P=0.010, respectively]) were also significantly reduced in favour of the 3D group, with a flat learning curve. Follow-up demonstrated no readmissions, nor significant differences for donors, recipients and graft survival.Conclusions3D endoscopy may be a good alternative to RADN, since morbidity, graft and recipient survival were comparable, with a significantly shorter median STS-time, WI-time and hilar dissection phase. Furthermore, implementation was easy and at lower costs, whilst tactile feedback was preserved. Background There are 2 endoscopic surgical techniques that implement 3D vision to overcome visual misperception: 3D endoscopy and the da Vinci surgical system. 3D endoscopy has several advantages, such as the presence of tactile feedback and easy implementation, at lower costs. We aimed to assess whether 3D endoscopy could be an alternative to the robot during living donor nephrectomy (LDN). Methods Between April 2015 and April 2016 we prospectively collected data on 40 patients undergoing 3D endoscopic LDNs in 1 center, performed by a da Vinci certified surgeon. Data on donors' perioperative results and recipient and graft survival were collected. These data were compared to 40 robot-assisted donor nephrectomies (RADNs) performed in the same center (between January 2012 and May 2014). Results Baseline characteristics for both groups were comparable. Intraoperative results showed a significantly shorter median skin-to-skin time (STS-time) of 138.5 min. (125.8-163.8) versus 169.0 (141.5-209.8) min. in favour of the 3D group (P=0.001). Warm ischemia time ([WI-time], P=0.003) and hilar phase for both single- (1 artery and vein) and multiple anatomies (≥1 artery and/or vein [P=0.002 and P=0.010, respectively]) were also significantly reduced in favour of the 3D group, with a flat learning curve. Follow-up demonstrated no readmissions, nor significant differences for donors, recipients and graft survival. Conclusions 3D endoscopy may be a good alternative to RADN, since morbidity, graft and recipient survival were comparable, with a significantly shorter median STS-time, WI-time and hilar dissection phase. Furthermore, implementation was easy and at lower costs, whilst tactile feedback was preserved. Corresponding author: T.C.K. Tran, MD, Erasmus MC, Department of Surgery's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Email: t.tran@erasmusmc.nl. Tel. number: 00317031810. Fax number: 00317032396 Authorship Page Participated in research design: Mulder, Janki, Terkivatan, Klop, IJzermans, Tran Participated in the writing of the paper: Mulder, Janki, Tran Participated in the performance of the research: Mulder, Janki, Terkivatan, Klop, IJzermans, Tran Participated in data analysis: Mulder, Janki, Klop, IJzermans, Tran Critical revision: Mulder, Janki, Terkivatan, Klop, IJzermans, Tran Disclosure The study was supported by Olympus Netherlands B.V., who provided all necessary equipment for free, and the Erasmus MC Efficiency Research grant. E.E.A.P. Mulder, S. Janki, T. Terkivatan, K.W.J. Klop, J.N.M. IJzermans and T.C.K. Tran declare no conflicts of interest or financial ties; neither the investigators nor subjects received compensation for the performance of the study, and the investigators had control of the presentation of the data. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Ganja, No Barrier for Liver Transplantation?

No abstract available

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Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in response to TLR9 and CD40 activation

Abstract

Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. B-cells and T-cells were obtained from the peripheral blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the International Workshop on Chronic Lymphocytic Leukemia. Co-culture assays were used to examine the ability of CLL cells to suppress autologous T-cell immune responses. IL-10 potency of CLL cells was assessed following stimulation with activators of the toll-like receptor 9 (TLR9) or CD40 and was correlated with the inhibitory activity of the cells. TLR9-activated CLL cells were found to increase the frequency of CD4⁺CD25^hiFOXp3⁺ regulatory T-cells (Tregs) and to inhibit autologous CD4⁺ T-cell proliferation. This signaling cascade proved to control IL-10 generation in CLL cells, which in turn promoted the inhibition of T-cell proliferation by CLL cells. However, CD40 activation of CLL cells, while exhibiting a similar ability to augment Treg frequency, did not either affect IL-10 generation or T-cell proliferation. In conclusion, CLL cells demonstrate a unique clonal quality of adopting Breg properties which promote modulation of T-cell characteristics. TLR9 appears to be a potent activator of regulatory abilities in CLL cells, possibly contributing to preferential immune escape of TLR9-responsive cells.

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Laugier–Hunziker Syndrome Presenting with Metachronous Melanoacanthomas

Abstract

Laugier–Hunziker syndrome (LHS, also termed idiopathic lenticular mucocutaneous hyperpigmentation) is an unusual condition characterized by progressive pigmentation of the mucous membranes. LHS displays a benign course and is not associated with malignancy. Here we present a case of LHS with a 7-year follow-up. We document metachronous oral melanoacanthomas in this individual. In addition, we found that the oral melanotic macules in this patient waxed and waned in a cyclical manner. To our knowledge, this is the first report of these findings in the context of LHS. Finally, we provide an overview of other conditions that can present with mucosal hyperpigmentation. It is critical to distinguish LHS from other conditions characterized by mucosal pigmentation in order to facilitate optimal patient care.

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Vestibulo-ocular reflex gain values in the suppression head impulse test of healthy subjects

Objective

To assess whether there are differences in vestibulo-ocular reflex (VOR) gain for suppression head impulse (SHIMP) and head impulse (HIMP) video head impulse test paradigms, and if so, what are their causes.

Methods

Prospective multicenter observational double-blind nonrandomized clinical study was performed by collecting 80 healthy subjects from four reference hospitals. SHIMP data was postprocessed to eliminate impulses in which early SHIMP saccades were detected. Differences between HIMP and SHIMP VOR gain values were statistically evaluated. Head impulse maximum velocity, gender, age, direction of impulse, and hospital center were considered as possible influential factors.

Results

A small significant statistical difference between HIMP and SHIMP VOR gain values was found on repeated measures analysis of variance (−0.05 ± 0.006, P < 0.001). Optimized linear model showed a significant influence of age variable on the observed differences for HIMP and SHIMP gain values and did not find influence between gain values differences and maximum head impulse velocity. Both HIMP and SHIMP VOR gain values were significant lower (−0.09, P < 0.001) when the impulses were performed to the left side.

Conclusion

We had observed a difference in SHIMP and HIMP gain values not adequately explained by known gain modification factors. The persistence of this slight but significant difference indicates that there are more factors causing lower SHIMP VOR gain values. This difference must to be considered in further studies as well as in the clinical SHIMP testing protocols. We hypothesized that VOR phasic response inhibition could be the underlying cause of this difference.

Level of Evidence

IIb. Laryngoscope, 2018

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Indicators for imaging in periorbital cellulitis secondary to rhinosinusitis

Abstract

Purpose

Our objective was to identify the clinical indicators for subperiosteal orbital abscess (SPOA) among patients who present with periorbital cellulitis secondary to rhinosinusitis, and to evaluate the need for performing a computerized tomography (CT) scan.

Methods

A retrospective cohort study of all patients admitted to our tertiary care emergency department between 2006 and 2014 was conducted. Included were healthy patients with acute periorbital cellulitis secondary to rhinosinusitis. Variables analyzed included age, gender, duration of symptoms, previous antibiotic therapy, highest recorded temperature, physical examination findings, ophthalmologist's examination results, laboratory results, and interpretation of imaging studies, when performed.

Results

Of the 123 identified patients, 78 (63%) were males, with a mean age of 4 years (range 1–70). 68 patients were categorized as Chandler's 1 disease, 2 as Chandler's 2, and 53 as Chandler's 3. 68 patients underwent a CT scan, of those 53 had SPOA. Proptosis and ophthalmoplegia were strongly associated with the presence of an abscess (P < 0.001). However, 14 patients with no ophthalmoplegia or proptosis who underwent a CT scan were older (mean age, 10 years; P < 0.028), and had higher neutrophil count of 78 versus 59% (P = 0.01). This group of patients had a clinically rapidly progressive disease, receiving wider broad-spectrum antibiotics or had their antibiotic treatment replaced to broader spectrum antibiotics through their course of treatment (48.2% compared to only 6.1%).

Conclusions

We confirmed that patients with proptosis and/or limitation of extraocular movements are at high risk for developing SPOA, yet many do not have these predictors. Other features can identify patients who do not have proptosis and/or limitation of extraocular movements but do have significant risk of SPOA, and in these cases performing an imaging study is strongly suggested.

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AAD 2018

Read clinically focused news coverage of key developments from AAD 2018.
Medscape Dermatology

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Grommet and adenoid pain evaluation (GRAPE) study

Publication date: Available online 15 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Lammens F, Boons J, Michiels E, Beckers K, Laureyns G, Indesteege J, Indesteege F, Lemmens W, Lemkens N, Jans F, Jorissen M, Lemkens P
In the GRAPE study an analysis is made of postoperative pain sensation in children between 6 months and 6 years after adenotomy and placement of ear grommets. Intraoperative treatment with paracetamol versus placebo shows no statistically significant difference in pain between both groups indicating that this type of surgery causes little discomfort and does not require specific intraoperative analgesic treatment.



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Management of complex pediatric laryngotracheal stenosis with skin graft reconstruction

Publication date: Available online 15 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Sarah N. Bowe, Carissa J. Wentland, G.S. Sandhu, Christopher J. Hartnick
ObjectivesFor pediatric patients with laryngotracheal stenosis, the ultimate goal is creation of a safe, functional airway. Unfortunately, wound healing in a hollow structure can complicate repair attempts, leading to restenosis. Herein, we present our experience using skin-grafting techniques in a series of two complex pediatric laryngotracheal stenosis cases, leading to successful decannulation or speech production.MethodsA chart review was performed examining the evaluation and management of two pediatric patients with laryngotracheal stenosis despite prior reconstructive attempts. Patient history, bronchoscopic evaluation, intra-operative technique, post-operative management, treatment outcomes, and complications were noted. Harvesting and preparation of the split-thickness skin grafts (STSG) proceeded in a similar manner for each case. Stenting material varied based on the clinical scenario.ResultsUsing this technique, a patient with Type 3 glottic web achieved substantial improvement in exercise tolerance, as well as vocal strength and quality. Furthermore, both nearly aphonic patients could vocalize for the first time since their laryngotracheal injures.ConclusionsTemporary endoluminal stenting with skin graft lining can reproduce epithelial continuity and provide "biological inhibition" to enhance the wound healing process. When previous reconstructive efforts have failed, use of STSG can be considered in the management of complex pediatric laryngotracheal stenosis.



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Genetic mutations in non-syndromic deafness patients in Hainan Province have a different mutational spectrum compared to patients from Mainland China

Publication date: Available online 15 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Bangqing Huang, Mingyu Han, Guojian Wang, ShaSha Huang, Jialing Zeng, Yongyi Yuan, Pu Dai
ObjectivesTo provide appropriate genetic testing and counseling for non-syndromic hearing impairment patients in Hainan Province, an island in the South China Sea.Methods299 unrelated students with non-syndromic hearing loss who attended a special education school in Hainan Province were enrolled in this study. Three prominent deafness-related genes (GJB2, SLC26A4, and mtDNA 12S rRNA) were analyzed using Sanger sequencing.ResultsGJB2 mutations were detected in 32.78% (98/299) of the entire cohort; however, only 5.69% (17/299) had two confirmed pathogenic mutations. The most common mutation observed in this population was c.109G > A in the GJB2 gene, with an allelic frequency of 15.05% (90/598), which is significantly higher than that reported in previous cohorts. A total of 16 patients had two confirmed pathogenic SLC26A4 gene mutations, and 16 patients had one. The IVS7-2A > G mutation was the most commonly observed, with an allelic frequency of 3.51% (21/598). Three patients had a m.1555A > G mutation in the mtDNA 12S rRNA gene.ConclusionsThese results reveal that genetic etiology occurred in 11.71% (35/299) of patients, suggesting that Hainan province have a different mutational spectrum compare to Mainland China in non-syndromic deafness patients, which provide useful information to genetic counseling in Hainan province.



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Evaluation of the outcome of CT and MR imaging in pediatric patients with bilateral sensorineural hearing loss

Publication date: Available online 15 February 2018
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): E.A. van Beeck Calkoen, P. Merkus, S.T. Goverts, J.M. van de Kamp, M.F. Mulder, E. Sanchez Aliaga, E.F. Hensen
ObjectiveTo evaluate the clinically relevant abnormalities as visualized on CT and MR imaging in children with symmetric and asymmetric bilateral sensorineural hearing loss (SNHL), in relation to age and the severity of hearing loss.Study designRetrospective cohort study.SettingTertiary referral otology and audiology center.Patients and diagnostic interventionsFrom January 2006 until January 2016, a total of 207 children diagnosed with symmetric and asymmetric bilateral SNHL were included. They underwent CT and/or MR imaging for the evaluation of the etiology of their hearing loss.Main outcome measuresRadiologic abnormalities associated with SNHL.Results302 scans were performed in 207 children (median age of 0.8 years old) with bilateral SNHL. The most frequently identified cause of bilateral SNHL was a malformation of the labyrinth. The combined diagnostic yield of CT and MR imaging was 32%. The diagnostic yield of MR (34%) was considerably higher than that of CT (20%). We found a higher rate of abnormalities in children with profound hearing loss (41%) compared to milder hearing loss (8–29%), and in asymmetric SNHL (52%) compared to symmetric SNHL (30%).ConclusionImaging is essential in the etiologic evaluation of children with bilateral SNHL. The highest diagnostic yield is found in children with bilateral asymmetric SNHL or profound SNHL. Based on our findings, MR is the primary imaging modality of choice in the etiological evaluation of children with bilateral SNHL because of its high diagnostic yield.



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Mucinous cystic neoplasm of the liver with extrahepatic growth presenting with ascending cholangitis diagnosed by endoscopic ultrasound features: a case report

Mucinous cystic neoplasm of the liver with extrahepatic growth is a rare benign epithelial neoplasm of the biliary system that presents with a mass effect or is incidentally found on imaging. The tumor affects...

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Association of Metabolic Syndrome With Sudden Sensorineural Hearing Loss

This medical record review evaluates the association of the metabolic syndrome with the rate of recovery among adult patients with sudden sensorineural hearing loss.

http://ift.tt/2EtBFj6

Otorhinolaryngological Hazards Related to Diving—Part 1: Compressed Gas Scuba Diving

This review provides an overview of otorhinolaryngological complications during scuba diving.

http://ift.tt/2CneT6J

Postadenotonsillectomy Blood Pressure Changes in Children With Obstructive Sleep Apnea

This case series investigates disparities in blood pressure changes after adenotonsillectomy in hypertensive and nonhypertensive children with obstructive sleep apnea.

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Hard Swelling on Inner Cheek

A man had a hard swelling of the left inner cheek, with increasing spontaneous pain and swelling; examination revealed an erythematous lesion of the buccal mucosa, adjacent to the maxillary first molar, which produced a small amount of bleeding with palpation. What is your diagnosis?

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Otorhinolaryngological Fitness for Compressed Gas Scuba Diving—Part 2

This review aims to provide a comprehensive overview of existing otorhinolaryngological fitness guidelines for diving recreationally.

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Dimensions of the medial wall of the prelacrimal recess

Background

Addressing anterior maxillary sinus pathology endoscopically that is inaccessible with an endoscopic modified medial maxillectomy requires either a prelacrimal approach (PLA) or an endoscopic Denker's approach (EDA). The PLA involves removing the medial wall of the prelacrimal recess (PLR), which is the bone between the pyriform aperture (PA) and nasolacrimal duct (NLD), from nasal floor to orbital floor. The PLA preserves the inferior turbinate and NLD, whereas both are sacrificed during an EDA. The purpose of this computed tomography (CT)-based study was to determine the anteroposterior and superoinferior dimensions of the medial wall of the PLR.

Methods

One hundred thirty-one triplanar sinus CT scans of patients with various rhinologic diseases, but with intact bony PLR walls, were reviewed to assess dimensions of the medial wall of the PLR. The anteroposterior distances from the PA to the inferior-most, middle, and superior-most aspects of the NLD were measured. The height from the nasal floor to orbital floor was also measured. Combining left and right sides, there were 262 measurements.

Results

The anteroposterior distances between the PA and the NLD were as follows: inferior: mean, 8.4 mm (standard error [SE], 0.2; range, 1.9–14.2); middle: mean, 7.6 mm (SE, 0.2; range, 0–13.6); and superior: mean, 5.5 mm (SE, 2.5; range, 0–11.9). The mean height of the medial wall of the PLR was 26.5 mm (SE, 0.2; range, 18.5–39.9).

Conclusion

The anteroposterior and superoinferior dimensions of the medial wall of the PLR are variable, with the anteroposterior dimension being widest inferiorly. Its dimensions should be evaluated preoperatively when considering endoscopic approaches to or through the anterior maxillary sinus.

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Mast Cells Signal their Importance in Health and Disease

Publication date: Available online 15 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Ana Olivera, Michael A. Beaven, Dean D. Metcalfe
FcεRI is the primary receptor in mast cells that mediate allergic reactions by inducing rapid release of mediators, an adaptive immune response that may have evolved as a host defense against parasites and venoms. Yet, it is apparent that mast cells are also activated via non-IgE receptors whose significance is just beginning to be understood. This includes the Mas-related GPCRs (MRGPRX2) that may contribute to reactions to diverse antimicrobials and polybasic compounds, and ADGRE2, an adhesion GPCR which is activated by mechanical vibration and whose variants are associated with familial vibratory urticaria. Mast cells similarly have long been recognized as the main repository for histamine, heparin and proteases. Recent evidence also points to new functions, modes of delivery and mechanisms of action of mast cell proteases that add new dimensions to the roles of mast cells in human biology. In addition, exposure of mast cells to environmental cues can quantitatively and qualitatively modulate their responses and thus their impact on allergic inflammation. Illustrating this paradigm, we summarize a number of recent studies implicating the injury/tissue damage cytokine IL-33 as a modulator of allergen-induced mast cell responses. We also discuss the discovery of markers associated with transformed mast cells and new potential directions in suppressing mast cell activity.



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Long term clinical effects of early thymectomy: associations with autoimmune diseases, cancer, infections and atopic diseases

Publication date: Available online 14 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Judith Gudmundsdottir, Jonas Söderling, Håkan Berggren, Sólveig Óskarsdóttir, Martin Neovius, Olof Stephansson, Olov Ekwall




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Identification and analysis of peanut-specific T effector and T regulatory cells in children allergic and tolerant to peanut

Publication date: Available online 15 February 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Katherine A. Weissler, Marjohn Rasooly, Tom DiMaggio, Hyejeong Bolan, Daly Cantave, David Martino, Melanie R. Neeland, Mimi LK. Tang, Thanh D. Dang, Katrina J. Allen, Pamela A. Frischmeyer-Guerrerio
BackgroundPeanut allergy is potentially life-threatening and generally persists lifelong. Recent data suggests the skin may be an important route of initial sensitization to peanut, while early oral exposure to peanut is protective. In mice, T regulatory cells (Tregs) are central to development of tolerance to food, but their contribution to the pathogenesis of food allergy in humans is less clear.ObjectiveWe sought to quantify and phenotype peanut-specific CD4+ T effector (ps-Teff) and ps-Tregs in children with and without peanut allergy or sensitization.MethodsPs-Teffs and ps-Tregs were identified from peripheral blood of peanut allergic, peanut sensitized, and non-sensitized/non-allergic school-aged children and one year old infants based on upregulation of CD154 or CD137, respectively, following stimulation with peanut extract. Expression of cytokines and homing receptors were evaluated using flow cytometry. Methylation at the FOXP3 locus was measured as a marker of Treg stability.ResultsDifferential upregulation of CD154 and CD137 efficiently distinguished ps-Teffs and ps-Tregs. A greater percentage of ps-Teffs from peanut allergic and sensitized infants expressed the skin homing molecule CLA, suggesting activation following exposure through the skin, compared to non-allergic infants. While ps-Teffs in both school-aged and infant peanut-allergic children produced primarily Th2 cytokines, a Th1-skewed anti-peanut response was only seen in non-allergic school-aged children. The frequency, homing receptor expression, and stability of ps-Tregs in infant and school-aged children were similar regardless of allergic status.ConclusionsExposure to peanut through the skin may prime the development of Th2 ps-Teffs that promote sensitization to peanut, despite the presence of normal numbers of ps-Tregs.

Graphical abstract

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Population Viability Analysis of the Endangered Roan Antelope in Ruma National Park, Kenya, and Implications for Management

Population viability analysis (PVA) was used to (1) establish causes of roan population decline for the past 30 years in Ruma National Park (RNP), the only park where wild roans remain in Kenya, and (2) predict the probability of roan persistence under existing and alternative management options. PVA was done using long-term data based on population dynamics, life history, climatic conditions, and expert knowledge. Poaching was identified as the main cause of roan decline in RNP. Several antipoaching and prioritized habitat management interventions to promote population recovery and sustainable conservation of roans are described. PVA predictions indicated that, without these interventions, the roan population cannot persist more than 3 decades. Furthermore, ensuring sustainable conservation of roans in RNP will boost tourism in Western Kenyan and thus alleviate poverty in this part of the country. Improved income from tourism will reduce the possible pressures from hunting and give greater incentives for local people to be actively engaged in roan conservation.

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Regarding the Use of the Term “Cementum” in Fibro-Osseous Lesions of the Craniofacial Skeleton

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Szent-Györgyi Prize to honor NCI’s Douglas R. Lowy and John T. Schiller

Dr. Douglas R. Lowy and Dr. John T. Schiller of the National Cancer Institute will receive the 2018 Szent-Gyorgyi Prize for Progress in Cancer Research for the development of HPV vaccines.

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Fungal liver abscess in an immunocompetent patient who underwent repeated ERCPs and subtotal cholecystectomy

We report a case of a previously healthy female patient who initially presented with fever, jaundice and right upper quadrant pain three days after dilatation and stenting of a stricture of the common bile duct (CBD). During an earlier admission, the patient had undergone endoscopic retrograde cholangiopancreatography (ERCP) having presented with fevers and biliary dilatation on ultrasound. The ERCP features were more consistent with Mirizzi's Syndrome. The patient subsequently underwent subtotal cholecystectomy and later developed a CBD stricture, requiring repeat ERCP and stent insertion. At presentation, she had moderately deranged liver function tests and significantly elevated inflammatory markers and was found on cross-sectional imaging to have developed a liver abscess. Aspiration of the lesion cultured Candida albicans. She was treated with intravenous antifungals, broad-spectrum antibiotics and further aspiration of abscess, which contributed towards her successful recovery. Fungal liver abscess should be suspected in immunocompetent patients who undergo ERCP and or cholecystectomy.

http://ift.tt/2F44Lmg

Clinical trials in allergen immunotherapy: current concepts and future needs

Abstract

Allergen immunotherapy (AIT) is a safe, effective treatment for allergic rhinoconjunctivitis and allergic asthma. However, AIT's clinical effect is still contested - primarily due to heterogeneity in clinical trial designs, study populations, therapeutic formulations and efficacy criteria. After discussing current concepts and unmet needs, an international panel of experts made several recommendations: (i) explore and validate definitions for [clinical] responders in AIT-trials; (ii) use of well-documented, standardized provocation tests prior to inclusion of subjects with relevant diseases in AIT trials; (iii) monitoring neo-sensitizations and occurrence of new allergy in extended AIT trials, and exclusion of polyallergic participants; (iv) validation of allergen exposure chambers with regard to natural exposure; (v) in studies of seasonal allergies, focus on peak exposure but also consider organising two parallel, geographically distinct but otherwise identical trials; (vi) discuss adaptive trial designs with the regulatory authorities; (vii) use e-health and m-health technologies to capture more information on individual exposure to allergens; (viii) initiate research on potential psychological, biochemical, immune, neural and even genomic markers of the placebo response; (ix) identify trial designs and primary endpoints that will give children with allergies easier, faster access to AIT formulations; and (x) promote and apply standardized methods for reporting systemic and local adverse events. The latest technologies and trial designs may provide novel, ethical ways of reducing bias and heterogeneity in AIT clinical trials. There is scope for physicians, patient organizations, companies and regulators to improve clinical trials in AIT and, ultimately, to provide patients with better treatments.

This article is protected by copyright. All rights reserved.

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Implementation of an Outcomes-Based Curriculum for Dermatology Clerkships and Initial Positive Perceptions from Faculty and Students

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JAK/STAT inhibitors and other small molecule cytokine antagonists for the treatment of allergic disease

To provide an overview of janus kinase (JAK), chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders.

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Rituximab as a therapeutic consideration for refractory eosinophilic fasciitis

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Case 5-2018: A 63-Year-Old Man with Confusion after Stem-Cell Transplantation

Presentation of Case. Dr. Joshua A. Cohen (Medicine): A 63-year-old man was admitted to this hospital with confusion and weakness 5 months after he had undergone allogeneic stem-cell transplantation for chronic lymphocytic leukemia (CLL). The patient had been generally well until 2 years before…

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Alpinia Essential Oils and Their Major Components against Rhodnius nasutus, a Vector of Chagas Disease

Species of the genus Alpinia are widely used by the population and have many described biological activities, including activity against insects. In this paper, we describe the bioactivity of the essential oil of two species of Alpinia genus, A. zerumbet and A. vittata, against Rhodnius nasutus, a vector of Chagas disease. The essential oils of these two species were obtained by hydrodistillation and analyzed by GC-MS. The main constituent of A. zerumbet essential oil (OLALPZER) was terpinen-4-ol, which represented 19.7% of the total components identified. In the essential oil of A. vittata (OLALPVIT) the monoterpene β-pinene (35.3%) was the main constituent. The essential oils and their main constituents were topically applied on R. nasutus fifth-instar nymphs. In the first 10 min of application, OLALPVIT and OLALPZER at 125 μg/mL provoked 73.3% and 83.3% of mortality, respectively. Terpinen-4-ol at 25 μg/mL and β-pinene at 44 μg/mL provoked 100% of mortality. The monitoring of resistant insects showed that both essential oils exhibited antifeedant activity. These results suggest the potential use of A. zerumbet and A. vittata essential oils and their major constituents to control R. nasutus population.

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Olfactory function in systemic lupus erythematosus and systemic sclerosis. A longitudinal study and review of the literature

Publication date: Available online 11 February 2018
Source:Autoimmunity Reviews
Author(s): Mariana Freschi Bombini, Fernando Augusto Peres, Aline Tamires Lapa, Nailú Angélica Sinicato, Beatriz Ricato Quental, Ágatha de Souza Melo Pincelli, Tiago Nardi Amaral, Caroline Cristina Gomes, Ana Paula del Rio, João Francisco Marques-Neto, Lilian T.L. Costallat, Paula Teixeira Fernandes, Fernando Cendes, Leticia Rittner, Simone Appenzeller
Background/PurposeTo evaluate olfactory function in systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and healthy controls over a 2-year period, and to determine the association of olfactory dysfunction with age, disease activity, disease damage, treatment, anxiety and depression symptoms and limbic structures volumes.MethodsConsecutive SLE and SSc patients were enrolled in this study. Clinical, laboratory disease activity and damage were assessed according to diseases specific guidelines. Olfactory functions were evaluated using the Sniffin' Sticks test (TDI). Volumetric magnetic resonance imaging (MRI) were obtained in a 3T Phillips scanner. Amygdalae and hippocampi volumes were analyzed using FreeSurfer® software.ResultsWe included 143 SLE, 57 SSc and 166 healthy volunteers. Olfactory dysfunction was observed in 78 (54.5%) SLE, 35 (59.3%) SSc patients and in 24 (14.45%) controls (p<0.001) at study entry. SLE and SSc patients had significantly lower mean in all three phases (TDI) of the olfactory assessment when compared with healthy volunteers. In SLE, the presence of olfactory dysfunction was associated with older age, disease activity, higher anxiety and depression symptoms score, smaller left hippocampus volume, smaller left and right amygdalae volume and the presence of anti-ribosomal P (anti-P) antibodies. In SSc the presence of olfactory impairment was associated with older age, disease activity, smaller left and right hippocampi volumes and smaller right amygdala volume. Olfactory function was repeated after a 2-year period in 90 SLE, 35 SSc and 62 controls and was stable in all three groups.ConclusionBoth SLE and SSc patients with longstanding disease had significant reduction in all stages of TDI that maintained stable over a 2-year period. Olfactory dysfunction was associated with age, inflammation and hippocampi and amygdalae volumes. In SLE, additional association with anti-P, anxiety and depression symptoms was observed.



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The imprint of salivary secretion in autoimmune disorders and related pathological conditions

Publication date: Available online 9 February 2018
Source:Autoimmunity Reviews
Author(s): Kashi Raj Bhattarai, Raghupatil Junjappa, Mallikarjun Handigund, Hyung-Ryong Kim, Han-Jung Chae
Xerostomia is a state of oral dryness associated with salivary gland dysfunction and is induced by stress, radiation and chemical therapy, various systemic and autoimmune diseases, and specific medications. Fluid secretion is interrupted by the stimulation of neurotransmitter-induced increase in cytosolic calcium ([Ca²⁺] i) in salivary gland acinar cells, prompting the mobilization of ion channels and their transporters. Salivary fluid and protein secretion are principally dependent on parasympathetic and sympathetic nerves. Various inflammatory cytokines allied with lymphocytic infiltration cause glandular damage and Sjogren's syndrome, an autoimmune exocrinopathy associated with hyposalivation. A defect in IP3Rs, a major calcium release channel, prompts inadequate agonist-induced [Ca²⁺]i in acinar cells and deters salivary flow. The store-operated calcium entry-mediated Ca²⁺ movement into the acini activates K⁺ and Cl^- channels, which further opens a water channel protein, aquaporin-5, and triggers the release of fluid secretion from the salivary glands. The cellular mechanism of salivary gland dysfunction and hyposalivation has not yet been elucidated. In this review, we focused mainly on the proteins responsible for deficient saliva, the correlation between inflammation and salivation, autoimmune disorders and other ailments or complications associated with hyposalivation.



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TCRαβ+CD3+CD4−CD8− (double negative) T cells in autoimmunity

Publication date: Available online 9 February 2018
Source:Autoimmunity Reviews
Author(s): D. Brandt, C.M. Hedrich
TCRαβ⁺CD3⁺CD4⁻CD8⁻ "double negative" (DN) T cells comprise a small subset of mature peripheral T cells. The origin and function of DN T cells are somewhat unclear and discussed controversially. While DN T cells resemble a rare and heterogeneous T cell subpopulation in healthy individuals, numbers of TCRαβ⁺ DN T cells are expanded in several inflammatory conditions, where they also exhibit distinct effector phenotypes and infiltrate inflamed tissues. Thus, DN T cells may be involved in systemic inflammation and tissue damage in autoimmune/inflammatory conditions, including SLE, Sjögren's syndrome, and psoriasis. Here, the current understanding of the origin and phenotype of DN T cells, and their role in the instruction of immune responses, autoimmunity and inflammation will be discussed in health and disease.



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Cellular immune regulation in the pathogenesis of ANCA-associated vasculitides

Publication date: Available online 9 February 2018
Source:Autoimmunity Reviews
Author(s): Anouk von Borstel, Jan Stephan Sanders, Abraham Rutgers, Coen A. Stegeman, Peter Heeringa, Wayel H. Abdulahad
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are systemic autoimmune diseases characterized by necrotizing inflammation of small- to medium-sized blood vessels, affecting primarily the lungs and kidneys. Both animal and human studies show that the balance between inflammatory- and regulatory T- and B cells determines the AAV disease pathogenesis. Recent evidence shows malfunctioning of the regulatory lymphocyte compartment in AAV. In this review we summarize the immune regulatory properties of both T- and B cells in patients with AAV and discuss how aberrations herein might contribute to the disease pathogenesis.



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Oxidized low density lipoproteins: The bridge between atherosclerosis and autoimmunity. Possible implications in accelerated atherosclerosis and for immune intervention in autoimmune rheumatic disorders

Publication date: Available online 7 February 2018
Source:Autoimmunity Reviews
Author(s): Claudia Floriana Suciu, Marcella Prete, Piero Ruscitti, Elvira Favoino, Roberto Giacomelli, Federico Perosa
Atherosclerotic vasculopathy is a multifactorial process causing vessels damage and cardiovascular diseases, the leading causes of death worldwide. Atherosclerotic plaque is the asymptomatic primary, elementary, lesion of atherosclerotic vasculopathy. Accumulation of the oxidized low-density lipoprotein (oxLDL) at sub endothelial sites is now recognized as one of the major trigger events in plaque formation. The concomitant presence at the plaque site of cells belonging to either natural or adaptive immunity, the detection of autoantibodies to oxLDL, the cross-reactivity of oxLDL with anti-phospholipid antibodies, in addition to the clinical evidence of increased rates of cardiovascular events in several rheumatic diseases, has stimulated intensive research to define interconnections between the immune system and traditional risk factors at the molecular levels in order to explain accelerated atherosclerosis. Here, we critically review the results of previous and recent studies, which have disclosed molecules of both either innate or adaptive immunity involved in atherosclerosis, focusing primarily on B cells and autoantibodies, where data are more consolidated. Particular attention has also been paid to molecules that may be predictive markers of atherosclerosis progression and can be potential target for immune intervention to delay the atherosclerotic process. The latter include CD20 antigen, molecules involved in the BAFF-BAFFR axis, inflammatory molecules and modified LDL. The successful results of a recent randomized controlled clinical trial targeting inflammasome with anti-IL1β monoclonal antibody in non-autoimmune conditions, prove that specific immunotherapy can be a promising and effective strategy to control atherosclerosis in rheumatic diseases as well.



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The effect of non anti TNF targeting biologics and small molecules on insulin resistance in inflammatory arthritis

Publication date: Available online 13 February 2018
Source:Autoimmunity Reviews
Author(s): Francesco Ursini, Emilio Russo, Piero Ruscitti, Roberto Giacomelli, Giovambattista De Sarro
Inflammatory arthritides are chronic diseases characterised by an increase in cardiovascular risk, largely attributable to the synergy between high-grade systemic inflammation and an elevated prevalence of traditional cardiovascular risk factors. Amongst the latter, insulin resistance and type 2 diabetes (T2D) play a key position. Previous studies demonstrated a potential insulin-sensiting effect of anti-TNF biologic medications. For converse, less is known about the role of newer biologics or small molecules. For this reason, we performed a systematic review of the literature in order to identify the available data on the effect on insulin resistance of non-TNF targeting biologics and small molecules approved for the treatment of inflammatory arthritides. The search strategy initially retrieved 486 records of which only 10 articles were selected for inclusion in the final review. According to the available evidence, some of the newest molecules, in particular tocilizumab and abatacept, may have a role in improving insulin sensitivity; for converse, anakinra-mediated effect on glucose metabolism may exploit different facets of T2D pathophysiology, such as the preservation of beta-cell function. However, the data available on this issue are largely inconsistent and future, adequately designed studies are still needed to clarify the differential impact of novel therapeutics on individual pathophysiological features of T2D and other emerging cardiovascular risk factors.



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Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: Clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis)

Publication date: Available online 7 February 2018
Source:Autoimmunity Reviews
Author(s): Pierre Grumet, Laurent Kodjikian, Audrey de Parisot, Marie-Hélène Errera, Neila Sedira, Emmanuel Heron, Laurent Pérard, Pierre-Loïc Cornut, Christelle Schneider, Sophie Rivière, Priscille Ollé, Grégory Pugnet, Pascal Cathébras, Pierre Manoli, Bahram Bodaghi, David Saadoun, Stéphanie Baillif, Nathalie Tieulie, Marc Andre, Frédéric Chiambaretta, Nicolas Bonin, Philip Bielefeld, Alain Bron, Frédéric Mouriaux, Boris Bienvenu, Stéphanie Vicente, Sylvie Bin, Marc Labetoulle, Christiane Broussolle, Yvan Jamilloux, Evelyne Decullier, Pascal Sève
PurposeULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance.MethodsULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not.ResultsAmong the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first step's systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second step's most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon® (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed.ConclusionOnly a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations.



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IgE in lupus pathogenesis: Friends or foes?

Publication date: Available online 7 February 2018
Source:Autoimmunity Reviews
Author(s): Jean-François Augusto, Marie-Elise Truchetet, Nicolas Charles, Patrick Blanco, Christophe Richez
Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple immunological pathways. Recently, several studies have suggested an implication of Immunoglobulin E (IgE) in the pathophysiology of SLE. In the Lyn^−/− and FcγIIB^−/−.Yaa lupus mouse models, autoreactive IgE activate basophils, and promote a Th2 environment with, subsequently, production of autoantibodies by plasma cells. Autoreactive IgE has been also shown to play a role in the activation of human plasmacytoid dendritic cells (pDCs), in synergy with IgG, which results in an increase of interferon-alpha (IFN-α) production. In contrast, a protective effect of total non-autoreactive IgE has also been suggested, through a decreased ability of FcεRI-triggered pDCs to secrete IFN-α. This review summarizes in a comprehensive manner the emerging recent literature in the field, and propose new concepts to reconcile the observations.



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Large-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients

Publication date: Available online 7 February 2018
Source:Autoimmunity Reviews
Author(s): Hubert de Boysson, Aurélie Daumas, Mathieu Vautier, Jean-Jacques Parienti, Eric Liozon, Marc Lambert, Maxime Samson, Mikael Ebbo, Anael Dumont, Audrey Sultan, Bernard Bonnotte, Alain Manrique, Boris Bienvenu, David Saadoun, Achille Aouba
ObjectivesLarge-vessel involvement (LVI) can occur in giant-cell arteritis (GCA) and may represent a distinct disease subgroup with a higher risk for aortic dilation. This study aimed to better characterize the presentation and evolution of LVI in patients with GCA.Patients and methodsA retrospective multicenter study enrolled 248 GCA patients with LVI and 301 GCA patients without LVI on imaging. Factors associated with aortic dilation were identified in a multivariable model.ResultsThe patients with LVI were younger (p<0.0001), more likely to be women (p=0.01), and showed fewer cephalic symptoms (p<0.0001) and polymyalgia rheumatica (p=0.001) but more extracranial vascular symptoms (p=0.05) than the patients without LVI. Glucocorticoids (GC) management did not differ between the two groups, but the GC discontinuation rate was lower in the patients with LVI (p=0.0003). Repeated aortic imaging procedures were performed at 19months [range: 5–162months] and 17months [range: 6–168months] after diagnosis in 154 patients with LVI and 123 patients without LVI, respectively, of whom 21% and 7%, respectively, presented new aortic dilations (p=0.0008). In the patients with LVI, aortic dilation occurred on an aorta segment shown to be inflammatory on previous imaging in 94% of patients. In the multivariate analysis, LVI was the strongest predictor of aortic dilation (hazard ratio: 3.16 [range: 1.34–7.48], p=0.009).ConclusionsLVI represents a distinct disease pattern of GCA with an increased risk of aortic dilation. Control of the aortic morphology during follow-up is required.



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A case of Kaposi varicelliform eruption progressing to herpes simplex virus hepatitis in an immunocompetent patient

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An audit of compliance with tuberculosis screening prior to treatment with biologics in psoriasis

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The effect of magnolol on Ca2+ homeostasis and its related physiology in human oral cancer cells

Publication date: Available online 14 February 2018
Source:Archives of Oral Biology
Author(s): Shu-Feng Hsieh, Chiang-Ting Chou, Wei-Zhe Liang, Chun-Chi Kuo, Jue-Long Wang, Lyh-Jyh Hao, Chung-Ren Jan
ObjectiveMagnolol, a polyphenol compound from herbal medicines, was shown to alter physiology in various cell models. However, the effect of magnolol on Ca²⁺ homeostasis and its related physiology in oral cancer cells is unclear. This study examined whether magnolol altered Ca²⁺ signaling and cell viability in OC2 human oral cancer cells.MethodsCytosolic Ca²⁺ concentrations ([Ca²⁺]i) in suspended cells were measured by using the fluorescent Ca²⁺-sensitive dye fura-2. Cell viability was examined by 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1) assay.ResultsMagnolol at concentrations of 20–100 μM induced [Ca²⁺]i rises. Ca²⁺ removal reduced the signal by approximately 50%. Magnolol (100 μM) induced Mn²⁺ influx suggesting of Ca²⁺ entry. Magnolol-induced Ca²⁺ entry was partially suppressed by protein kinase C (PKC) regulators, and inhibitors of store-operated Ca²⁺ channels. In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished magnolol-evoked [Ca²⁺]i rises. Conversely, treatment with magnolol abolished BHQ-evoked [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 partially inhibited magnolol-induced [Ca²⁺]i rises. Magnolol at 20–100 μM decreased cell viability, which was not reversed by pretreatment with the Ca²⁺ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM).ConclusionsTogether, in OC2 cells, magnolol induced [Ca²⁺]i rises by evoking partially PLC-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ entry via PKC-sensitive store-operated Ca²⁺ entry. Magnolol also caused Ca²⁺-independent cell death. Therefore, magnolol-induced cytotoxicity may not be involved in activation mechanisms associated with intracellular Ca²⁺ mobilization in oral cancer cells.



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Effects of Molecular Weight of Hyaluronic Acid on its Viscosity and Enzymatic Activities of Lysozyme and Peroxidase

Publication date: Available online 14 February 2018
Source:Archives of Oral Biology
Author(s): Jihoon Kim, Ji-Youn Chang, Yoon-Young Kim, Moon-Jong Kim, Hong-Seop Kho
ObjectivesTo investigate the effects of the molecular weight of hyaluronic acid on its viscosity and enzymatic activities of lysozyme and peroxidase in solution and on the hydroxyapatite surface.DesignHyaluronic acids of four different molecular weights (10 kDa, 100 kDa, 1 MDa, and 2 MDa), hen egg-white lysozyme, bovine lactoperoxidase, and human whole saliva were used. Viscosity values of hyaluronic acids were measured using a cone-and-plate viscometer at six different concentrations (0.1-5.0 mg/mL). Enzymatic activities of lysozyme and peroxidase were examined by hydrolysis of fluorescein-labeled Micrococcus lysodeikticus and oxidation of fluorogenic 2′,7′-dichlorofluorescein to fluorescing 2′,7′-dichlorofluorescein, respectively.ResultsIn solution assays, only 2 MDa-hyaluronic acid significantly inhibited lysozyme activities in saliva. In surface assays, hyaluronic acids inhibited lysozyme and peroxidase activities; the inhibitory activities were more apparent with high-molecular-weight ones in saliva than in purified enzymes. The 100 kDa-hyaluronic acid at 5.0 mg/mL, 1 MDa-one at 0.5 mg/mL, and 2 MDa-one at 0.2 mg/mL showed viscosity values similar to those of human whole saliva at a shear rate range required for normal oral functions. The differences among the influences of the three conditions on the enzymatic activities were not statistically significant.ConclusionsHigh-molecular-weight hyaluronic acids at low concentration and low-molecular-weight ones at high concentration showed viscosity values similar to those of human whole saliva. Inhibitory effects of hyaluronic acids on lysozyme and peroxidase activities were more significant with high-molecular-weight ones on the surface and in saliva compared with in solution and on purified enzymes.



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Efficacy of different strategies to treat root dentin eroded by liquid or gaseous hydrochloric acid associated with brushing abrasion

Publication date: Available online 14 February 2018
Source:Archives of Oral Biology
Author(s): Juliana Jendiroba Faraoni, Carmen Victoria Torres Toro, Laís Lopes Machado de Matos, Regina Guenka Palma-Dibb
ObjectiveThis study aims to evaluate how casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) associated with Nd:YAG or Diode laser affects dentin exposed to hydrochloric acid (HCl) with or without tooth brushing.DesignOne hundred and sixty human root dentin blocks were selected after they were initially eroded with liquid HCl (pH 1.2) 3x for one day. The blocks were divided into the following groups: G1– liquid HCl (HCl-l), G2– HCl-l + brushing, G3– gaseous HCl (HCl-g), and G4– HCl-g + brushing. Each group was randomly assigned to the following treatments (n = 10): A) Control (no treatment), B) CPP-ACP, C) CPP-ACP associated with Nd:YAG laser (λ = 1064 nm) (40 mJ, 10 Hz, 0.4 W, 15 s), and D) CPP-ACP associated with Diode laser (λ = 980 nm) (0.5 W, 200 μs, 15 s). The treatment with CPP-ACP (G2, G3 and G4) was applied on the dentine surface for 5 min. Erosion (6x/day/20 s) and erosion (6x/day/20 s) with abrasion (2x/10 s) were performed for five days. Dentin volume loss was determined by 3D confocal laser microscopy. Data were analyzed with two-way ANOVA and Tukey's tests.ResultsG1 - CPP-ACP (10.77 ± 1.66) and CPP-ACP associated with Diode laser (9.98 ± 0.89) showed lower volume loss in relation Control group (12.86 ± 0.63) (p < 0.05). G2 - CPP-ACP associated with Diode laser (12.41 ± 1.08) elicited lower volume loss as compared to the Control (14.42 ± 1.24) (p < 0.05). As for G3 and G4, all treatments showed similar volume loss.ConclusionCPP-ACP and CPP-ACP associated with Diode laser could control dental tissue loss in dentin eroded by liquid HCl. Moreover, CPP-ACP associated with Diode laser could effectively decrease dental tissue loss in dentin exposed to liquid HCl and brushing.



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Opioid prescribing patterns among otolaryngologists: Crucial insights among the medicare population

Objectives/Hypothesis

There has been growing recognition of the roles prescription drug misuse and diversion play in facilitating the ongoing opioid epidemic. Our objective was to evaluate opioid prescription patterns among practicing otolaryngologists.

Study Design

Retrospective review of a CMS database.

Methods

Medicare Part D beneficiary data (2015) were accessed for a list of otolaryngologists. Opioid prescription rates, amount, and supply were calculated. Factors including board certification, experience, gender, and location were obtained for the 9,068 unique otolaryngologists represented in this dataset.

Results

In 2015, otolaryngologists wrote 133,779 opioid prescriptions for 922,806 days (6.9 days/per prescription). The majority was for hydrocodone-acetaminophen (64.0%). Most otolaryngologists (51.2%) prescribed ≤ 10 opioids; 6.1% offered > 50 opioid prescriptions. Men wrote more prescriptions on average. Opioid prescription rates were greatest in the Midwest (4.6%) and least in the Northeast (1.8%), and the highest/lowest rates were in Delaware (8.6%) and New York (1.3%). Midcareer (11 –20 years) otolaryngologists were most likely to write >50 prescriptions. The opioid prescription rate declined with greater experience.

Conclusions

Opioid prescriptions written by otolaryngologists may play a significant role in the availability of these agents, as otolaryngologists wrote nearly 1 million days worth of opioids to Medicare beneficiaries in 2015. Although the majority of otolaryngologists write fewer than 11 prescriptions annually, those writing more prescriptions also write lengthier courses. There is significant geographic variation in prescribing patterns, highlighting a lack of consensus, and midcareer otolaryngologists are more aggressive in offering opioids. These findings highlight an urgent need for strengthening educational resources aimed at minimizing unnecessary prescriptions.

Level of Evidence

NA. Laryngoscope, 2018

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Clinical criteria for CT scan evaluation of upper digestive tract fishbone

Objectives

To establish clinical criteria for performing computed tomography scan for suspected upper digestive tract fishbone.

Methods

This is a prospective study of all adult patients referred to the otolaryngology emergency department at our medical center for suspected fishbone in the upper digestive tract after no fishbone was seen on physical examination. The patients were divided into two groups: 1) The first was a high clinical suspicion group, which included patients with at least one of the following criteria: drooling, accumulation of saliva in the sinus piriformis, fever, referral 24 hours after the ingestion with worsening/continuing symptoms, and readmission. These patients underwent nonenhanced CT scan (NECT) of the neck. 2) The second was a low clinical suspicion group, which included patients discharged with no NECT performed. These patients were followed at 1 week and 3 months.

Results

One hundred and fourteen patients were included in the study; the median age was 41 years. Half of the patients arrived at the emergency department within 7 hours. There were no false negatives. The negative predictive value and sensitivity were 100%. Positive predictive value and specificity were 28.5% and 65%, respectively. Referral to the emergency department 24 hours after the ingestion with continuing symptoms had the highest false positive rate.

Conclusions

Our clinical criteria score for excluding foreign body fishbone in the upper aerodigestive tract was established. According to this score, a NECT can be spared in about 75% of all cases, thus reducing unnecessary ionizing radiation, stay at the emergency department, and costs with a very high NPV of almost 99%.

Level of Evidence

4. Laryngoscope, 2018

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Telemedicine in otolaryngology outpatient setting—single Center Head and Neck Surgery experience

Objectives/Hypothesis

We present our experience with telemedicine visits in an otolaryngology outpatient setting within our institution's Center for Head and Neck Surgery.

Study Design

Retrospective chart review.

Methods

A review of telemedicine outpatient encounters examining patient demographics, visit type, and wait times was conducted. Internet-based navigation applications were used to calculate travel distance and estimate commute time to our clinic. Patient survey responses were reviewed.

Results

Two hundred fifty telemedicine encounters were reviewed between December 2015 and June 2017. The average age of patients was 50 years (range, 4–87 years). Patients waited an average of 10 minutes for their telemedicine appointments and avoided an average estimated commute time of 78 minutes (64 miles). The majority of visits were postoperative encounters (70%). Clinical follow-up of recent results or nonpostoperative complaints accounted for the remaining 30% of visits. All patients were offered a post-telemedicine survey, and 78 (31%) completed the survey. Of the respondents, 95% of patients reported that they were satisfied with their visit. Among patients who were dissatisfied, wait time and technical issues were cited as reasons.

Conclusions

With appropriate patient selection, telemedicine is an effective way to safely conduct outpatient clinic visits while maintaining high patient satisfaction. It can be particularly useful for institutions with large catchment areas to minimize travel times and increase ease of communication.

Level of Evidence

4. Laryngoscope, 2018

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Uncultivated stromal vascular fraction is equivalent to adipose-derived stem and stromal cells on porous polyurethrane scaffolds forming adipose tissue in vivo

Objectives/Hypothesis

To find an alternative approach to contemporary techniques in tissue augmentation and reconstruction, tissue engineering strategies aim to involve adipose-derived stem and stromal cells (ASCs) harboring a strong differentiation potential into various tissue types such as bone, cartilage, and fat.

Study Design

Animal research.

Methods

The stromal vascular fraction (SVF) was used directly as a cell source to provide a potential alternative to contemporary ASC-based adipose tissue engineering. Seeded in TissuCol fibrin, we applied ASCs or SVF cells to porous, degradable polyurethane (PU) scaffolds.

Results

We successfully demonstrated the in vivo generation of volume-stable, well-vascularized PU-based constructs containing host-derived mature fat pads. Seeded human stem cells served as modulators of host-cell migration rather than differentiating themselves. We further demonstrated that preliminary culture of SVF cells was not necessary.

Conclusions

Our results bring adipose tissue engineering, together with automated processing devices, closer to clinical applicability. The time-consuming and cost-intensive culture and induction of the ASCs is not necessary.

Level of Evidence

NA. Laryngoscope, 2018

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JAK/STAT inhibitors and other small molecule cytokine antagonists for the treatment of allergic disease

Publication date: Available online 14 February 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Michael D. Howell, Carolyn Fitzsimons, Paul Smith
ObjectiveTo provide an overview of janus kinase (JAK), chemoattractant receptor-homologous molecule expressed on T-helper 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders.Data sourcesPubMed literature review.Study selectionsArticles included in this review discuss the emerging mechanism of action of small molecule inhibitors and their utilization in atopic dermatitis (AD), asthma, and allergic rhinitis (AR).ResultsAllergic diseases represent a spectrum of diseases including AD, asthma, and AR. For decades, these diseases have been primarily characterized by increased Th2 signaling and downstream inflammation. In recent years, additional research has identified disease phenotypes and subsets of patients with non-Th2 mediated inflammation. The increasing heterogeneity of disease has prompted investigators to move away from wide-ranging treatment approaches with immunosuppressive agents such as corticosteroids to consider more targeted immunomodulatory approaches focused on specific pathways. In the past decade, inhibitors targeting JAK signaling, PDE4, and CRTH2 have been explored for their potential activity in models of allergic disease and therapeutic benefit in clinical trials. Interestingly, while JAK inhibitors provide an opportunity to interfere with cytokine signaling and could be beneficial in a broad range of allergic diseases, current clinical trials are focused on the treatment of AD. Conversely, both PDE4 and CRTH2 inhibitors have been evaluated in a spectrum of allergic diseases. This review summarizes the varying degrees of success that these small molecules have demonstrated across allergic diseases.ConclusionEmerging therapies currently in development may provide more consistent benefit to patients with allergic diseases by specifically targeting inflammatory pathways important for disease pathogenesis.



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Cover Image

The cover image, by Vinidh Paleri et al., is based on the Original Article Transoral robotic surgery for residual and recurrent oropharyngeal cancers: Exploratory study of surgical innovation using the IDEAL framework for early-phase surgical studies, DOI: 10.1002/hed.25032

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Issue Information

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The role of TEVAR in the management of a recurrent aorto-gastric fistula

Abstract

An aorto-gastric fistula is a catastrophic and rare cause of an upper gastrointestinal bleed. The diagnosis requires a high index of suspicion and expedient management as any delay in each of these component, will be to the detriment of the patient. We report a case of a patient with two episodes of this rare event, with haemodynamic compromise, 15 years after having had a trans-hiatal oesophagectomy for an adenocarcinoma of the oesophagus who presented on both occasions. He had thoracic endo-vascular aortic repair (TEVAR) on both presentations and survived. This case exemplifies the fact that while TEVAR is a good bridging therapy for the management of an aorto-enteric fistula. It however should not be considered as the definitive management for patients who are operable or patients who do not have prohibitive surgical risk.

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Wilkie’s syndrome: a case report of favourable minimally invasive surgery

Abstract

Wilkie's syndrome, or superior mesenteric artery syndrome (SMAS), is a rare clinical entity caused by compression of the third portion of the duodenum between the abdominal aorta and superior mesenteric artery, leading to duodenal obstruction and severe malnutrition. The authors report a case of a female patient with years of chronic intestinal obstruction with abdominal pain, vomits and weight loss. Contrast intestinal series showed dilation of stomach and duodenum. Abdominal computed tomography study revealed findings compatible with SMAS. After initial nutritional support, she was successfully treated by laparoscopic duodenojejunostomy. Surgical treatment of SMAS may be necessary in most cases with chronic symptoms or conservative treatment failure. A minimally invasive approach can be considered a safe surgical option with favourable outcomes. Clinical details, diagnostic studies and treatment are discussed.

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Neurosurgical management of multiple intracranial Nocardia and Enterococcus abscesses in an immunocompetent patient

Abstract

Nocardia farcinica and Enterococcus faecium are both rare causes of cerebral abscess. The former is associated with high morbidity and mortality. We describe a neurosurgical approach to the management of multiple intracranial abscesses of dual microbial pathology in an immunocompetent patient to achieve a good outcome.

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