Outcome measures for use in trials of paediatric otorrhoea: A systematic review.

INTRODUCTION: Paediatric otorrhoea (PO) describes a middle ear infection that results in a perforation of the tympanic membrane and ear discharge, in children and young people (CYP). Prolonged infection may be associated with hearing loss and developmental delay. The current management of paediatric otorrhoea is variable, including non-invasive treatments (conservative, oral antibiotics, topical antibiotics) and surgery, reflecting the lack of a sufficiently strong evidence base. Outcome reporting is fundamental to producing reliable and meaningful evidence to inform best practice. OBJECTIVES: Primary objective: to determine which outcome measures are currently used to evaluate treatment success in studies of non-surgical treatments for paediatric otorrhoea. SECONDARY OBJECTIVES: to identify outcome measurement instruments used in the literature and assess their applicability for use in clinical trials of PO. METHODS: This systematic review was registered with PROSPERO (CRD42023407976). Database searches of EMBASE, MEDLINE and Cochrane was performed on June 6, 2023, covering from Jan 1995 to May 2023. Randomised controlled trials or study protocols involving CYP with PO were included following PRISMA guidelines. Risk of bias was assessed with Cochrane's tool. RESULTS: Of the 377 papers identified, six were included in the systematic review. The primary outcome of five of the studies related to otorrhoea cessation; both time to cessation and proportion recovered at various time points were used as measures. Two measurement instruments were identified: Otitis Media-6 Questionnaire and the Institute for Medical Technology Assessment Productivity Cost Questionnaire. Both were shown to be applicable measurement instruments when used in clinical trials of PO. CONCLUSIONS: To promote homogeneity and facilitate meaningful comparison and combination of studies, we propose that time to cessation of otorrhoea from onset of otorrhoea should be used as the primary outcome in future studies. Further research is needed to establish if this is the most important outcome to children and their caregivers.

Topical Delivery of Elastic Liposomal Vesicles for Treatment of Middle and Inner Ear Diseases.

We present a topical drug delivery mechanism through the ear canal to the middle and inner ear using liposomal nanoparticles without disrupting the integrity of the tympanic membrane. The current delivery method provides a noninvasive and safer alternative to transtympanic membrane injections, ear tubes followed by ear drops administration, and systemic drug formulations. We investigate the capability of liposomal NPs, particularly transfersomes (TLipo), used as drug delivery vesicles to penetrate the tympanic membrane (TM) and round window membrane (RWM) with high affinity, specificity, and retention time. The TLipo is applied to the ear canal and found to pass through the tympanic membrane quickly in 3 h post drug administration. They are identified in the middle ear cavity 6 h and in the inner ear 24 h after drug administration. We performed cytotoxicity in vitro and ototoxicity in vivo studies. Cell viability shows no significant difference between the applied TLipo concentration and control. Furthermore, auditory brainstem response (ABR) reveals no hearing loss in 1 week and 1 month post-administration. Immunohistochemistry results demonstrate no evidence of hair cell loss in the cochlea at 1 month following TLipo administration. Together, the data suggested that TLipo can be used as a vehicle for topical drug delivery to the middle ear and inner ear.

Comparison and evaluation of three techniques for treating auricular pseudocyst.

BACKGROUND: Auricular pseudocyst is a benign cystic lesion in cartilages of the auricle. Different methods are currently used to manage this disease. In these methods, simple aspiration combined with pressure dressing, local steroid injection and surgery are the most prevalent therapies. OBJECTIVE: To find the best clinical path for the treatment of auricular pseudocyst. METHODS: Eighty-four subjects were randomly allocated into three equal groups (Group A: simple suction combined with pressure dressing; Group B: suction and local steroid injection; and, Group C: surgery). Two otolaryngologists assessed effective rate, sequelae and degree of satisfaction at three-month follow-up. A visual analog scale was used to determine degree of satisfaction. RESULTS: Group A had the lowest effective rate (54%). Group C was highest in terms of effectiveness (100%) but also in incidence of sequelae (71%). Group B had a slightly lower effective rate (86%) than Group C, but the incidence of sequelae was lowest (42%). Degree of satisfaction was highest (7.0 ± 2.7) for Group B. CONCLUSION: Local steroid injection should be the first choice for the treatment of auricular pseudocyst because of high satisfaction, favorable effectiveness and few sequelae. Where this method is ineffective, surgery should be used.

Production and Characterization of Chitooligosaccharides: Evaluation of Acute Toxicity, Healing, and Anti-Inflammatory Actions.

The search for promising biomolecules such as chitooligosaccharides (COS) has increased due to the need for healing products that act efficiently, avoiding complications resulting from exacerbated inflammation. Therefore, this study aimed to produce COS in two stages of hydrolysis using chitosanases derived from Bacillus toyonensis. Additionally, this study aimed to structurally characterize the COS via mass spectrometry, to analyze their biocompatibility in acute toxicity models in vivo, to evaluate their healing action in a cell migration model in vitro, to analyze the anti-inflammatory activity in in vivo models of xylol-induced ear edema and zymosan-induced air pouch, and to assess the wound repair action in vivo. The structural characterization process pointed out the presence of hexamers. The in vitro and in vivo biocompatibility of COS was reaffirmed. The COS stimulated the fibroblast migration. In the in vivo inflammatory assays, COS showed an antiedematogenic response and significant reductions in leukocyte migration, cytokine release, and protein exudate. The COS healing effect in vivo was confirmed by the significant wound reduction after seven days of the experiment. These results indicated that the presence of hexamers influences the COS biological properties, which have potential uses in the pharmaceutical field due to their healing and anti-inflammatory action.

Relapsing polychondritis: state-of-the-art review with three case presentations.

BACKGROUND: Relapsing polychondritis (RPC) is a complex immune-mediated systemic disease affecting cartilaginous tissue and proteoglycan-rich organs. The most common and earliest clinical features are intermittent inflammation involving the auricular and nasal regions, although all cartilage types can be potentially affected. The life-threatening effects of rpc involve the tracheobronchial tree and cardiac connective components. Rpc is difficult to identify among other autoimmune comorbidities; diagnosis is usually delayed and based on nonspecific clinical symptoms with limited laboratory aid and investigations. Medications can vary, from steroids, immunosuppressants, and biologics, including anti-tnf alpha antagonist drugs. METHOD: Information on updated etiology, clinical symptoms, diagnosis, and treatment of rpc has been obtained via extensive research of electronic literature published between 1976 and 2019 using PubMed and medline databases. English was the language of use. Search inputs included 'relapsing polychondritis,' 'polychondritis,' 'relapsing polychondritis symptoms,' and 'treatment of relapsing polychondritis.' Published articles in English that outlined and reported rpc's clinical manifestations and treatment ultimately met the inclusion criteria. Articles that failed to report the above and reported on other cartilaginous diseases met the exclusion criteria. RESULT: Utilizing an extensive overview of work undertaken in critical areas of RPC research, this review intends to further explore and educate the approach to this disease in all dimensions from pathophysiology, diagnosis, and management. CONCLUSION: RPC is a rare multi-systemic autoimmune disease and possibly fatal. The management remains empiric and is identified based on the severity of the disease per case. The optimal way to advance is to continue sharing data on RPC from reference centers; furthermore, clinical trials in randomized control groups must provide evidence-based treatment and management. Acquiring such information will refine the current knowledge of RPC, which will improve not only treatment but also diagnostic methods, including imaging and biological markers.

Screening Anti-Inflammatory Effects of Flavanones Solutions.

There are a large number of remedies in traditional medicine focused on relieving pain and inflammation. Flavanones have been a potential source in the search for leading compounds and biologically active components, and they have been the focus of much research and development in recent years. Eysenhardtia platycarpa is used in traditional medicine for the treatment of kidney diseases, bladder infections, and diabetes mellitus. Many compounds have been isolated from this plant, such as flavones, flavanones, phenolic compounds, triterpenoid acids, chalcones, sugars, and fatty acids, among others. In this paper, natural flavanone 1 (extracted from Eysenhardtia platycarpa) as lead compound and flavanones 1a-1d as its structural analogues were screened for anti-inflammatory activity using Molinspiration® and PASS Online in a computational study. The hydro alcoholic solutions (FS) of flavanones 1, 1a-1d (FS1, FS1a-FS1d) were also assayed to investigate their in vivo anti-inflammatory cutaneous effect using two experimental models, a rat ear edema induced by arachidonic acid (AA) and a mouse ear edema induced by 12-O-tetradecanoylphorbol acetate (TPA). Histological studies and analysis of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were also assessed in AA-inflamed rat ear tissue. The results showed that the flavanone hydro alcoholic solutions (FS) caused edema inhibition in both evaluated models. This study suggests that the evaluated flavanones will be effective when used in the future in skin pathologies with inflammation, with the results showing 1b and 1d to be the best.

Erythematous ear with drainage.

This case reminded us that not every moist, erythematous, crusting eruption is purely infectious.

Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative.

Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.7 cells. The inflammatory process began with incubation with lipopolysaccharide (LPS). Nitric oxide production levels were also determined, exceeding 75% inhibition of NO for a concentration of 1 µg/mL of OADP. Cell-cycle analysis showed a reversal of the arrest in the G0/G1 phase in LPS-stimulated RAW 264.7 cells. Furthermore, through Western blot analysis, we have determined the probable molecular mechanism activated by OADP; the inhibition of the expression of cytokines such as TNF-α, IL-1ß, iNOS, and COX-2; and the blocking of p-IκBα production in LPS-stimulated RAW 264.7 cells. Finally, we have analyzed the anti-inflammatory action of OADP in a mouse acute ear edema, in male BL/6J mice treated with OADP and tetradecanoyl phorbol acetate (TPA). Treatment with OADP induced greater suppression of edema and decreased the ear thickness 14% more than diclofenac. The development of new derivatives such as OADP with powerful anti-inflammatory effects could represent an effective therapeutic strategy against inflammation and tumorigenic processes.

[Modern aspects of inflammatory external ear diseases treatment]. / Sovremennye aspekty lecheniya vospalitel'nykh zabolevanii naruzhnogo ukha.

The article deals with the problem of inflammatory diseases of the external ear. A review of pruritic dermatoses of the external auditory canal was carried out. It has been shown that in chronic dermatoses, the contamination of the skin with bacterial and fungal pathogens significantly increases, which leads to a high risk of developing secondary infectious pathological processes. Treatment of dermatological inflammatory ear diseases includes careful daily hygiene of the external auditory canal and pharmacotherapy, a key aspect of which is the use of topical etiotropic, anti-inflammatory, and symptomatic drugs. The advantage of the combined drug candiderm is described, which, thanks to the unique combination of beclomethasone, gentamicin and clotrimazole in the composition, effectively relieves the symptoms of external ear dermatoses.

Intralesional Hyaluronic Acid Injection for Chondrodermatitis Nodularis Helicis: A Novel Treatment for Rapid Relief of Pain and Healing of Ulcerations.

BACKGROUND: Chondrodermatitis nodularis helicis (CNH) is a common chronic condition characterized by a tender nodule on the helix or antihelix of the ear which may or may not have accompanying crusting, scaling, or ulceration and that is often difficult to treat. OBJECTIVE: Develop an easy, effective, and durable treatment to reduce the pain and clinical signs including ulcerations associated with CNH using injectable hyaluronic acid (HA). MATERIALS AND METHODS: Twenty-four patients were injected and followed up in 2 to 4 weeks intervals using 0.2 to 0.3 mL of various HA with a high G-Prime. RESULTS: Injectable HA significantly improved the symptoms and also the clinical appearance of all patients treated after 1 or 2 injections except 1 patient. Extrusion of the material through a preexisting ulcer usually required a second follow-up injection 2 weeks later. No adverse events were noted with the injections other than the intentional visible bulging of the injected region with HA. CONCLUSION: Injectable HA provides almost immediate relief from the discomfort of CNH in most cases in less than 1 or 2 weeks, significantly improves the clinical appearance over time and resolves accompanying ulcerations.

Chloroquine attenuates thymic stromal lymphopoietin production via suppressing caspase-1 signaling in mast cells.

Thymic stromal lymphopoietin (TSLP) produced by mast cells is involved in allergic inflammation pathogenesis. Chloroquine (CQ) is known to be an anti-malarial drug; however, additional protective functions of CQ have been discovered. This study aims to clarify an anti-inflammatory effect of CQ through modulating TSLP levels using an in vitro model of phorbol myristate acetate (PMA) + A23187-activated human mast cell line (HMC-1) and an in vivo model of PMA-irritated ear edema. CQ treatment reduced the production and mRNA expression levels of TSLP in activated HMC-1 cells. CQ down-regulated caspase-1 (CASP1), MAPKs, and NF-κB levels enhanced by stimulation with PMA + A23187. Moreover, ear thickness in ear edema was suppressed following CQ treatment. CQ decreased CASP1 and NF-κB levels in the ear tissue. TSLP levels in the ear tissue and serum were reduced following CQ treatment. Collectively, the above findings elucidate that CQ inhibits the pro-inflammatory mechanisms of TSLP via the down-regulation of distinct intracellular signaling cascade in mast cells. Therefore, CQ may have protective roles against TSLP-mediated inflammatory disorders.

Sarcoidosis of the ear, nose and throat: A review of the literature.

OBJECTIVES: Sarcoidosis is a multisystemic inflammatory disease with extrathoracic manifestations, most commonly affecting the young and middle-aged, female and Black populations. Diagnosis usually requires evidence of non-caseating granulomata and, when treated, prognosis is usually favourable. We aim to establish the incidence, clinical features and optimal treatment of ENT manifestations of this disease. DESIGN: We performed a PubMed literature review to determine the evidence base supporting this. RESULTS: ENT manifestations are present in 5%-15% of patients with sarcoidosis, often as a presenting feature, and require vigilance for swift recognition and coordinated additional treatment specific to the organ. Laryngeal sarcoidosis presents with difficulty in breathing, dysphonia and cough, and may be treated by speech and language therapy (SLT) or intralesional injection, dilatation or tissue reduction. Nasal disease presents with crusting, rhinitis, nasal obstruction and anosmia, usually without sinus involvement. It is treated by topical nasal or intralesional treatments but may also require endoscopic sinus surgery, laser treatment or even nasal reconstruction. Otological disease is uncommon but includes audiovestibular symptoms, both sensorineural and conductive hearing loss, and skin lesions. CONCLUSIONS: The consequences of ENT manifestations of sarcoidosis can be uncomfortable, disabling and even life-threatening. Effective management strategies require good diagnostic skills and use of specific therapies combined with established treatments such as corticosteroids. Comparisons of treatment outcomes are needed to establish best practice in this area.

Anti-inflammatory effects of Morus alba Linne bark on the activation of toll-like receptors and imiquimod-induced ear edema in mice.

BACKGROUND: Morus alba L. bark has been widely used in traditional medicine for treating several inflammatory diseases, such as hypertension, diabetes mellitus and coughing; however, the molecular mechanisms underlying its anti-inflammatory effects are not well understood. METHODS: We examined the effects of an extract of Morus alba L. bark (MabE) on Toll-like receptor (TLR) ligand-induced activation of RAW264.7 macrophages using a luciferase reporter assay and immunoassays. For the in vivo experiment, we used an imiquimod-induced ear edema model to examine the anti-inflammatory effects of MabE. RESULTS: MabE inhibited the TLR ligand-induced activation of NF-κB in RAW264.7 cells without affecting their viability. Consistent with the inhibition of NF-κB activation, MabE also inhibited the production of IL-6 and IL-1ß from TLR ligand-treated RAW264.7 cells. In vivo MabE treatment inhibited the ear swelling of IMQ-treated mice, in addition to the mRNA expression of IL-17A, IL-1ß and COX-2. The increases in splenic γδT cells in IMQ-treated mice and the production of IL-17A from splenocytes were significantly inhibited by MabE treatment. CONCLUSION: Our study suggests that the anti-inflammatory effects of MabE on the activation of the macrophage cell line RAW246.7 by TLRs and IMQ-induced ear edema are through the inhibition of NF-κB activation and IL-17A-producing γδT cells, respectively.

Two cases of refractory eosinophilic granulomatosis with polyangiitis wherein mepolizumab was effective against pulmonary and ear lesions.

Recently, mepolizumab, an interleukin (IL)-5 inhibitor, has been indicated for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) refractory to standard therapies. However, no reports have compared the efficacy of mepolizumab according to symptoms and organ lesions. Herein, we report two cases in which mepolizumab was highly effective in the management of EGPA with lung lesions and otitis media refractory to treatment with multiple immunosuppressive agents. These two cases suggest that mepolizumab is effective in treating pulmonary and ear lesions in EGPA.

Volatile Oil of Platycladus Orientalis (L.) Franco Leaves Exerts Strong Anti-inflammatory Effects via Inhibiting the IκB/NF-κB Pathway.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1ß and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

Successful treatment of erythematous-squamous disorders of the external auditory canal with tacrolimus and clotrimazole in otic oil: Our experience in 25 patients.

The external auditory canal (EAC) comprises a special area where erythematous-scaly diseases are located. Among the main dermatoses that can affect EAC seborrheic dermatitis, psoriasis, irritant or allergic contact dermatitis, chronic external otitis (atrial eczematoid dermatitis) and cutaneous lupus should be considered. In this study, 25 consecutive patients were recruited on our dermatological outpatient clinic, 9 men and 16 women, with a clinical diagnosis of localized erythematous-squamous dermatoses in EAC. The mean age was 48.8 years (16-83). The mean time of evolution of the dermatoses was 11.44 months (2-36). Regarding the diagnosis, 14 patients were diagnosed with seborrheic dermatitis (56%), 9 patients with psoriasis (36%), 1 patient with subacute cutaneous lupus (4%), and 1 patient with allergic contact dermatitis to corticosteroids (4%). The indicated treatment was tacrolimus 0.1% and clotrimazole 1% in otic oil, twice a day, for 1 month. The EAC had to be cleaned initially with saline solution impregnated on a swab from the ears. The IGA score and pruritus showed a high results, with important improvement of almost all patients. The satisfaction of the patients obtained with the TSQM-9 questionnaire was 95.2. Retreatment showed an equal efficacy observed during the first treatment period. The efficacy and the absence of side effects with the treatment make this magistral formula an adequate therapeutic option for these dermatoses.

A rare case of tympanostomy tube otorrhea: Pigmentiphaga.

Tympanostomy tube otorrhea (TTO) is a common complication of tympanostomy tubes. The most common bacteria associated with TTO include Haemophalis influenza, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. We present the first case of a 9 year-old female with a history of 22q11 syndrome, hemifacial microsomia, Tetralogy of Fallot, and hearing aid dependence with left-sided profound sensorineural and right-sided moderate conductive hearing loss who presented with TTO caused by the bacteria Pigmentiphaga daeguenesis/kulla, a gram-negative bacteria often found in soil. This patient's otorrhea did not respond to typical otic antibiotic formulations, but was ultimately treated successfully with intramuscular ceftriaxone. We describe the natural history, presentation and management for a case of TTO caused by a rare bacteria from the genus Pigmentiphaga.

Prevalence of prescription medication use in preschool-age children seen in pediatric otolaryngology.

OBJECTIVE: To examine the prevalence of daily medication use and prescribing patterns in preschool aged children presenting to otolaryngology clinics. STUDY DESIGN: Retrospective summary of prescription-related data from PEDSnet database of two tertiary care children's hospitals within single health system. METHODS: All new patients between birth and 5 years of age seen in otolaryngology clinics from October 1, 2016 through September 30, 2017 were included. Existing diagnoses, active prescriptions at time of visit, prescription dates, and demographics were abstracted. Summary analysis was performed on medication prevalence, quantity and duration of use, comparing all variables between age, gender, and geographical regions. RESULTS: Of 7532 patient encounters, 20% presented with active daily medication use. Eustachian tube dysfunction and otitis media were the most common diagnoses regardless of daily medication usage. Corticosteroids, specifically hydrocortisone (Delaware) and Flovent (Florida), were the most common medication prescribed. The number of medications strongly correlated with the number of encounter diagnoses. Overall, patients in Delaware were 4.5 times more likely to have at least one prescription prior to encounter (p < 0.05, 95% CI 3.2-4.8). This pattern was preserved across age and gender. Patients with medication in Delaware and Florida had a median of 2 (IQR 3.0-1.0) and 1 prescriptions (IQR 2.0-1.0), respectively (p < 0.001). There were no differences based on insurance type and no correlations between medication count and age or gender. CONCLUSION: Children in Delaware presented to otolaryngology clinics with significantly more prescribed medications than in Florida. Regional differences were consistent across age and gender. Most children were on these medications for a significant duration.