Real-life effectiveness of dupilumab in chronic rhinosinusitis with nasal polyps. Results from eight Hungarian centres with 12-month follow-up.

BACKGROUND: Research on the immune mechanism behind chronic rhinosinusitis (CRS) has revealed various new endotypes, leading to targeted therapies, especially for severe uncontrolled CRS. Biologics are novel therapeutic strategies providing targeted treatment for the difficult-to-treat recalcitrant CRSwNP patients. Dupilumab is a fully human-derived monoclonal antibody that binds to IL4Rα, inhibiting the signalling of both IL-4 and IL-13. In Hungary, it is approved for the treatment of uncontrolled CRSwNP according to criteria based on the EPOS2020 and the Hungarian guidelines. METHODOLOGY: This study aimed to collect and evaluate real-world therapeutic data of CRSwNP patients treated with dupilumab. One hundred thirty-five patients from eight different referral centres have been enrolled in this study, who received dupilumab since 2020. All subjects were adult patients (over 18 years) with uncontrolled CRSwNP. Baseline data collection included demographics, medical history, previous surgeries, related comorbidities, total endoscopic nasal polyp score (NPS), SNOT22, nasal congestion parameters measured with visual analogue scale (VAS) and nasal obstruction evaluation scale (NOSE), loss of smell score (LSS) and eosinophil count. 300 mg dupilumab was administered subcutaneously every second week. Follow up visits were performed after 6 and 12 months. RESULTS: After 6 and 12 months of treatment significant improvement was detected in all clinical parameters. Safety was proved, no severe side effects occurred, and no rescue treatment was necessary. CONCLUSIONS: Our real-life findings show that continuous dupilumab treatment is effective and safe in daily clinical practice in CRSwNP and other type 2 comorbidities such as bronchial asthma and NERD.

Upregulation of extraneuronal TRPV1 expression in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is a multifactorial upper airway disease with unclear etiology. Neuronal Transient Receptor Potential Vanilloid 1 (TRPV1) and Ankyrin 1 (TRPA1) channels have been implicated in the pathogenesis of CRS. We aimed to detect the expression of extraneuronal TRPV1 and TRPA1 receptors in nasal polyp (NP) tissue samples. METHODOLOGY: Samples were obtained from fourty-two CRS pateints with nasal polyp and sixteen healthy controls to measure receptor gene expression by quantitative PCR, protein localization by immunohistochemistry and cytokine profile by multiplex bead immunoassay. RESULTS: Non-neuronal TRPV1, TRPA1 receptors were expressed in biopsy samples of NP. A population of mast cells and macrophages were immunopositive for TRPV1 and TRPA1. A fraction of plasma cells expressed TRPV1 but not TRPA1 and neither receptor was present on eosinophils. The local gene expression of extraneuronal TRPV1, TRPA1 receptors was also proven. TRPV1 mRNA levels were significantly increased in CRSwNP patients with asthma and allergic rhinitis compared to their NP counterparts. CONCLUSIONS: Elevated TRPV1 levels in comorbid asthma and allergy may have a function in CRSwNP. Subpopulation-specific TRPV1 presence on plasma and mast cells can indicate delicate roles in regulating activation and release of inflammatory mediators.

Comparing intermediate-term hearing results of NiTiBOND and Nitinol prostheses in stapes surgery.

OBJECTIVE: To statistically analyse the hearing thresholds of two cohorts undergoing stapedotomy for otosclerosis with two different prostheses. METHOD: A retrospective study was conducted comparing NiTiBOND (n = 53) and Nitinol (n = 38) prostheses. RESULTS: Average follow-up duration was 4.1 years for NiTiBOND and 4.4 years for Nitinol prostheses. The post-operative air-bone gap was 10 dB or less, indicating clinical success. The p-values for differences between (1) pre- and post-operative values in the NiTiBOND group, (2) pre- and post-operative values in the Nitinol group, (3) pre-operative values and (4) post-operative values in the two groups were: air-bone gap - p < 0.001, p < 0.001, p = 0.631 and p = 0.647; four-frequency bone conduction threshold - p = 0.076, p = 0.129, p < 0.001 and p = 0.005; four-frequency air conduction threshold - p < 0.001, p < 0.001, p = 0.043 and p = 0.041; three-frequency (1, 2 and 4 kHz) bone conduction threshold pre-operatively - p = 0.639, p = 0.495, p = 0.001 and p = 0.01; and air conduction threshold at 4 kHz: - p < 0.001, p < 0.001, p = 0.03 and p = 0.058. CONCLUSION: Post-operative audiological outcomes for NiTiBOND and Nitinol were comparable.

Delayed Facial Paralysis following Uneventful KTP Laser Stapedotomy: Two Case Reports and a Review of the Literature.

Facial palsy that occurs immediately after middle ear surgery (stapedectomy, stapedotomy, and tympanoplasty) can be a consequence of the local anesthetics and it regresses completely within a few hours. In the case of delayed facial palsy, the alarming symptom occurs several days or even weeks after uneventful surgery. The mechanism of the neural dysfunction is not readily defined. Surgical stress, intraoperative trauma, or laceration of the chorda tympani nerve with a resultant retrograde facial nerve edema can all be provoking etiological factors. A dehiscent bony facial canal or a multiple microporotic fallopian canal (microtrauma or laser effect) can also contribute to the development of this rare phenomenon. The most popular theory related to the explanation of delayed facial palsy at present is the reactivation of dormant viruses. Both the thermal effect of the laser and the elevation of the tympanomeatal flap can reactivate viruses resting inside the ganglion geniculi, facial nerve, or facial nuclei. The authors report the case histories of a 55-year-old female, and a 45-year-old male who presented with a delayed facial palsy following laser stapedotomy. The clinical characteristics, the therapeutic options, and the possibility of prevention are discussed.