Rare presence and function of neuroendocrine cells in the nasal mucosa.

There is growing evidence that neurogenic inflammation contributes to the pathophysiology of upper airway diseases, with nasal hyperreactivity (NHR) being a key symptom. The rare neuroendocrine cells (NECs) in the epithelium have been linked to the pathophysiology of bronchial and intestinal hyperreactivity, however their presence in the nasal mucosa and their potential role in NHR remains unclear. Therefore, we studied the presence of NECs in the nasal epithelium of controls, allergic rhinitis patients and chronic rhinosinusitis with nasal polyps patients, and their link to NHR. The expression of typical NECs markers, CHGA, ASCL1 and CGRP, were evaluated on gene and protein level in human samples using real-time quantitative PCR (RT-qPCR), western blot, immunohistochemistry fluorescence staining, RNA scope assay, flow cytometry and single cell RNA-sequencing. Furthermore, the change in peak nasal inspiratory flow after cold dry air provocation and visual analogue scale scores were used to evaluate NHR or disease severity, respectively. Limited gene expression of the NECs markers CHGA and ASCL1 was measured in patients with upper airway diseases and controls. Gene expression of these markers did not correlate with NHR severity nor disease severity. In vitro, CHGA and ASCL1 expression was also evaluated in primary nasal epithelial cell cultures from patients with upper airway disease and controls using RT-qPCR and western blot. Both on gene and protein level only limited CHGA and ASCL1 expression was found. Additionally, NECs were studied in nasal biopsies of patients with upper airway diseases and controls using immunohistochemistry fluorescence staining, RNA scope and flow cytometry. Unlike in ileum samples, CHGA could not be detected in nasal biopsies of patients with upper airway diseases and control subjects. Lastly, single cell RNA-sequencing of upper airway tissue could not identify a NEC cluster. In summary, in contrast to the bronchi and gut, there is only limited evidence for the presence of NECs in the nasal mucosa, and without correlation with NHR, thereby questioning the relevance of NECs in upper airway pathology.

Leukocyte- and Platelet-Rich Fibrin versus Commercially Available Fibrin Sealants in Elective Cranial Surgery: A Cost-Minimization Analysis.

BACKGROUND: Previous findings from a clinical trial demonstrated noninferiority of Leukocyte- and platelet-rich fibrin (L-PRF) compared to commercially available fibrin sealants in preventing postoperative cerebrospinal fluid leakage, necessitating intervention. This cost-effectiveness evaluation aims to assess the value-for-money of both techniques for dural closure in supratentorial and infratentorial surgeries. METHODS: Cost-effectiveness was estimated from a health care payer's perspective alongside a randomized clinical trial comprising 328 patients. The analysis focused on clinical and health-related quality of life outcomes, as well as direct medical costs including inpatient costs, imaging and laboratory costs, and outpatient follow up costs up to twelve weeks after surgery. RESULTS: Clinical and health-related quality of life data showed no significant differences between L-PRF (EuroQol five dimensions questionnaire 0.75 ± 0.25, 36-item Short Form Survey 63.93% ± 20.42) and control (EuroQol five dimensions questionnaire 0.72 ± 0.22, 36-item Short Form Survey 60.93% ± 20.78) groups. Pharmaceutical expenses during initial hospitalization were significantly lower in the L-PRF group (€190.4, interquartile range 149.9) than in the control group (€394.4, interquartile range 364.3), while other cost categories did not show any significant differences, resulting in an average cost advantage of €204 per patient favoring L-PRF. CONCLUSIONS: This study demonstrates L-PRF as a cost-effective alternative for commercially available fibrin sealants in dural closure. Implementing L-PRF can lead to substantial cost savings, particularly considering the frequency of these procedures.

Leukocyte- and platelet-rich fibrin in cranial surgery: a single-blinded, prospective, randomized controlled noninferiority trial.

OBJECTIVE: CSF leakage is a major complication after cranial surgery, and although fibrin sealants are widely used for reinforcing dural closure, concerns exist regarding their safety, efficacy, and cost. Leukocyte- and platelet-rich fibrin (L-PRF), an autologous platelet concentrate, is readily available and inexpensive, making it a cost-effective alternative for commercially available fibrin sealants. This study aimed to demonstrate the noninferiority of L-PRF compared with commercially available fibrin sealants in preventing postoperative CSF leakage in supra- and infratentorial cranial surgery, with secondary outcomes focused on CSF leakage risk factors and adverse events. METHODS: In a single-blinded, prospective, randomized controlled interventional trial conducted at a neurosurgery department of a tertiary care center (UZ Leuven, Belgium), patients undergoing elective cranial neurosurgery were randomly assigned to receive either L-PRF (active treatment) or commercially available fibrin sealants (control) for dural closure in a 1:1 ratio. RESULTS: Among 350 included patients, 328 were analyzed for the primary endpoint (44.5% male, mean age 52.3 ± 15.1 years). Six patients (5 in the control group, 1 in the L-PRF group) presented with CSF leakage requiring any intervention (relative risk [RR] 0.20, one-sided 95% CI -∞ to 1.02, p = 0.11), confirming noninferiority. Of these 6 patients, 1 (in the control group) presented with CSF leakage requiring revision surgery. No risk factors for reconstruction failure in combination with L-PRF were identified. RRs for adverse events such as infection (0.72, 95% CI -∞ to 1.96) and meningitis (0.36, 95% CI -∞ to 1.25) favored L-PRF treatment, although L-PRF treatment showed slightly more bleeding events (1.44, 95% CI -∞ to 4.66). CONCLUSIONS: Dural reinforcement with L-PRF proved noninferior to commercially available fibrin sealants, with no safety issues. Introducing L-PRF to standard clinical practice could result in important cost savings due to accessibility and lower cost. Clinical trial registration no.: NCT03812120 (ClinicalTrials.gov).

Protocol for postmortem bedside endoscopic procedure to sample human respiratory and olfactory cleft mucosa, olfactory bulbs, and frontal lobe.

We present a protocol for the rapid postmortem bedside procurement of selected tissue samples using an endoscopic endonasal surgical technique that we adapted from skull base surgery. We describe steps for the postmortem collection of blood, cerebrospinal fluid, a nasopharyngeal swab, and tissue samples; the clean-up procedure; and the initial processing and storage of the samples. This protocol was validated with tissue samples procured postmortem from COVID-19 patients and can be applied in another emerging infectious disease. For complete details on the use and execution of this protocol, please refer to Khan et al. (2021)1 and Khan et al. (2022).2.