Head and Neck Medicine by Alexandros G.Sfakianakis

Association of Gel-Forming Mucins and Aquaporin Gene Expression With Hearing Loss, Effusion Viscosity, and Inflammation in Otitis Media With Effusion.

JAMA Otolaryngol Head Neck Surg. 2017 Jun 08;:

Authors: Samuels TL, Yan JC, Khampang P, Dettmar PW, MacKinnon A, Hong W, Johnston N, Papsin BC, Chun RH, McCormick ME, Kerschner JE

Abstract
Importance: Persistent, viscous middle ear effusion in pediatric otitis media (OM) contributes to increased likelihood of anesthesia and surgery, conductive hearing loss, and subsequent developmental delays. Biomarkers of effusion viscosity and hearing loss have not yet been identified despite the potential that such markers hold for targeted therapy and screening.
Objective: To investigate the association of gel-forming mucins and aquaporin 5 (AQP5) gene expression with inflammation, effusion viscosity, and hearing loss in pediatric OM with effusion (OME).
Design, Setting, and Participants: Case-control study of 31 pediatric patients (aged 6 months to 12 years) with OME undergoing tympanostomy tube placement and control individuals (aged 1 to 10 years) undergoing surgery for cochlear implantation from February 1, 2013, through November 30, 2014. Those with 1 or more episodes of OM in the previous 12 months, immunologic abnormality, anatomical or physiologic ear defect, OM-associated syndrome (ie, Down syndrome, cleft palate), chronic mastoiditis, or history of cholesteatoma were excluded from the study. All patients with OME and 1 control were recruited from Children's Hospital of Wisconsin, Milwaukee. The remainder of the controls were recruited from Sick Kids Hospital in Toronto, Ontario, Canada.
Main Outcomes and Measures: Two to 3 middle ear biopsy specimens, effusions, and preoperative audiometric data (obtained <3 weeks before surgery) were collected from patients; only biopsy specimens were collected from controls. Expression of the mucin 2 (MUC2), mucin 5AC (MUC5AC), mucin 5B (MUC5B), and AQP5 genes were assayed in middle ear biopsy specimens by quantitative polymerase chain reaction. One middle ear biopsy specimen was sectioned for histopathologic analysis. Reduced specific viscosity of effusions was assayed using rheometry.
Results: Of the 31 study participants, 24 patients had OME (mean [SD] age, 50.4 [31.9] months; 15 [62.5%] male; 16 [66.7%] white) and 7 acted as controls (mean [SD] age, 32.6 [24.4] months; 2 [26.6%] male; 6 [85.7%] white). Mucins and AQP5 gene expression were significantly higher in patients with OME relative to controls (MUC2: ratio, 127.6 [95% CI, 33.7-482.7]; MUC5AC: ratio, 3748.8 [95% CI, 558.1-25 178.4]; MUC5B: ratio, 471.1 [95% CI, 130.7-1697.4]; AQP5: ratio, 2.4 [95% CI, 1.1-5.6]). A 2-fold increase in MUC5B correlated with increased hearing loss (air-bone gap: 7.45 dB [95% CI, 2.65-12.24 dB]; sound field: 6.66 dB [95% CI, 6.63-6.69 dB]), effusion viscosity (2.75 mL/mg; 95% CI, 0.89-4.62 mL/mg), middle ear epithelial thickness (3.5 μm; 95% CI, 1.96-5.13 μm), and neutrophil infiltration (odds ratio, 1.7; 95% CI, 1.07-2.72). A 2-fold increase in AQP5 correlated with increased effusion viscosity (1.94 mL/mg; 95% CI, 0.08-3.80 mL/mg).
Conclusions and Relevance: Further exploration of the role of MUC5B in the pathophysiology of OME holds promise for development of novel, targeted therapies to reduce effusion viscosity, facilitation of effusion clearance, and prevention of disease chronicity and hearing loss in patients with OME.

PMID: 28594978 [PubMed - as supplied by publisher]

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Patient-Reported Outcome Measures in Upper Airway-Related Dyspnea: A Systematic Review.

Patient-Reported Outcome Measures in Upper Airway-Related Dyspnea: A Systematic Review.

JAMA Otolaryngol Head Neck Surg. 2017 Jun 08;:

Authors: Noud M, Hovis K, Gelbard A, Sathe NA, Penson DF, Feurer ID, McPheeters ML, Francis DO

Abstract
Importance: Patient-reported outcome (PRO) measures address the need for patient-centered data and are now used in diverse clinical, research, and policy pursuits. They are important in conditions causing upper airway-related dyspnea in which the patient's reported experience and physiological data can be discrepant.
Objectives: To perform a systematic review of the literature on upper airway dyspnea-related PRO measures and to rigorously evaluate each measure's developmental properties, validation, and applicability.
Evidence Review: This study strictly adhered to Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. MEDLINE via the PubMed interface, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Health and Psychosocial Instruments (HaPI) database were searched using relevant vocabulary terms and key terms related to PRO measures and upper airway-related dyspnea. Three investigators performed abstract review, and 2 investigators independently performed full-text review by applying an established checklist to evaluate the conceptual model, content validity, reliability, construct validity, scoring and interpretability, and respondent burden and presentation of each identified instrument. The initial literature search was conducted in November 2014 and was updated in April 2016.
Findings: Of 1269 studies reviewed, 3 upper airway-related dyspnea PRO measures met criteria for inclusion. One PRO measure was designed de novo to assess upper airway-related dyspnea symptoms and monitor treatment outcomes, while 2 were adapted from established instruments designed for lower airway disease. Measurement properties and psychometric characteristics differed, and none met all checklist criteria. Two met a criterion in each of 7 domains evaluated. Two demonstrated test-retest and internal consistency reliability, and 2 showed that their scores were responsive to change. Thematic deficiencies in current upper airway-related dyspnea PRO measures are lack of patient involvement in item development (content validity), plan for interpretation, and literacy level assessments.
Conclusions and Relevance: PRO measures are critical in the assessment of patients with upper airway-related dyspnea. Three instruments with disparate developmental rigor have been designed or adapted to assess this construct. Care must be taken to understand the measurement characteristics and contextual relevance before applying these PRO measures for clinical, research, or quality initiatives.

PMID: 28594976 [PubMed - as supplied by publisher]

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Disseminated papular lesions as a unique manifestation heralding bacille Calmette–Guérin infection in a patient with T-B+NK− severe combined immunodeficiency

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An unusual clinical presentation of lupus erythematosus tumidus localized on the thigh

Summary

A 44-year-old woman with seronegative polyarthritis presented with a 2-year history of a solitary, bluish-red, oedematous, nonscaly, annular and partially reticulated macule on her right thigh. Histopathological findings revealed perivascular and periadnexal lymphocytic infiltrate in the dermis. Alcian blue and colloidal iron stains highlighted mucinous deposit in the upper and mid dermis. Direct immunofluorescence showed a linear deposit of IgG and C3 along the basement membrane zone. Antinuclear antibody was positive at a titre of 1 : 80, with homogenous and speckled patterns. Except for its unusual localization and lack of photosensitivity, our case had the clinical and histopathological features of lupus erythematosus tumidus. These characteristics were also reminiscent of reticular erythematous mucinosis and erythema annulare centrifugum, both of which are considered to be associated with cutaneous lupus erythematosus (CLE). Hydroxychloroquine 200 mg daily led to improvement of the skin lesion. The unusual clinical presentation of our case emphasizes the heterogeneity of clinical manifestations of CLE.

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Systemic ALA-PDT effectively blocks the development of psoriasis-like lesions and alleviates leucocyte infiltration in the K14-VEGF transgenic mouse

Summary

Background

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders. In spite of significant advances in the treatment of psoriasis, more effective and safer therapeutic strategies are still needed. Photodynamic therapy (PDT) is a method of light treatment that is being used increasingly in the treatment of dermatological diseases.

Aim

To evaluate the therapeutic effects of systemic 5-aminolaevulinic acid (ALA)-PDT on psoriasis and to explore its potential mechanism of action.

Methods

We investigated the therapeutic effects of systemic ALA-PDT in K14-vascular endothelial growth factor (VEGF) transgenic homozygous mice, an animal model of psoriasis, which has many clinical and histopathological characteristics similar to those of human psoriasis. Using haematoxylin and eosin staining, immunohistochemistry and real-time quantitative PCR respectively, we assessed the changes in psoriasis-like lesions, cellular infiltration of T cells, dendritic cells (DCs) and neutrophils, and the mRNA expression of the inflammatory cytokines interleukin (IL)-17 and interferon (IFN)-γ in the lesions.

Results

Systemic ALA-PDT blocked the development of psoriasis-like lesions and moderately attenuated the histopathological changes in K14-VEGF transgenic mice. Furthermore, systemic ALA-PDT produced an obvious reduction in infiltration of T cells, CD11c+ DCs and neutrophils in psoriasis-like lesions. In addition, systemic ALA-PDT also significantly decreased the mRNA expression of IL-17 and IFN-γ.

Conclusions

We suggest that the mechanism of systemic ALA-PDT in this psoriasis-like model might be associated with selective damage to abnormal T helper (Th)1 and Th17 cells, and reduction of the inflammatory cytokines IL-17 and IFN-γ. These observations partly explain the potential mechanism of systemic ALA-PDT in psoriasis and other inflammatory skin diseases.

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Onset of Kaposi sarcoma and Merkel cell carcinoma during low-dose steroid therapy for rheumatic polymyalgia

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