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Purpose of Review: COVID -19 associated olfactory dysfunction is widespread, yet effective treatment strategies remain unclear. This article aims to provide a comprehensive systematic review of therapeutic approaches and offers evidence-based recommendations for their clinical application., Recent Findings: A living Cochrane review, with rigorous inclusion criteria, has so far included 2 studies with a low certainty of evidence. In this systematic review we list clinical data of 36 randomised controlled trials (RCTs) and non-randomised studies published between Jan 1, 2020 and Nov 19, 2023 regarding treatment options for COVID-19 associated olfactory dysfunction. Nine treatment groups were analysed, including olfactory training, local and systemic corticosteroids, platelet-rich plasma (PRP), calcium chelators, vitamin supplements including palmitoylethanolamide with luteolin, insulin, gabapentin and cerebrolysin. Primary objective was the effect of the studied treatments on the delta olfactory function score (OFS) for objective/psychophysical testing. Treatments such as PRP and calcium chelators demonstrated significant improvements on OFS, whereas olfactory training and corticosteroids did not show notable efficacy for COVID-19 associated olfactory dysfunction., (© 2024. The Author(s).)

Background: Leukocyte- and platelet-rich fibrin (L-PRF) is an autologous platelet concentrate, prepared by centrifugation of blood and consisting of a dense fibrin network with incorporated leukocytes and platelets. This study aims to perform an in-depth analysis of the cells, growth factors, and transcriptome of L-PRF., Methods and Results: Fresh, 1 week and 2 weeks cultured human L-PRF membranes and liquid L-PRF glue were characterized on cellular and transcriptional level using flow cytometry (n = 4), single-cell RNA sequencing (n = 5) and RT-qPCR. Growth factor kinetics were investigated using ELISA (EGF, VEGF, PDGF-AB, TGF-β1, bFGF). L-PRF contained a large number of viable cells (fresh 97.14 ± 1.09%, 1 week cultured 93.57 ± 1.68%), mainly granulocytes in fresh samples (53.9 ± 19.86%) and T cells in cultured samples (84.7 ± 6.1%), confirmed with scRNA-seq. Monocytes differentiate to macrophages during 1 week incubation. Specifically arterial L-PRF membranes were found to release significant amounts of VEGF, EGF, PDGF-AB and TGF-β1., Conclusion: We characterized L-PRF using in vitro experiments, to obtain an insight in the composition of the material including a possible mechanistic role for tissue healing. This was the first study characterizing L-PRF at a combined cellular, proteomic, and transcriptional level., (© 2024. The Author(s).)

Given the increasing threat of antimicrobial resistance, scientists are urgently seeking adjunct antimicrobial strategies, such as phage therapy (PT). However, despite promising results for the treatment of musculoskeletal infections in our center, crucial knowledge gaps remain. Therefore, a prospective observational study (PHAGEFORCE) and a multidisciplinary approach was set up to achieve and optimize standardized treatment guidelines. At our center, PT is strictly controlled and monitored by a multidisciplinary taskforce. Each phage treatment follows the same pathway to ensure standardization and data quality. Within the PHAGEFORCE framework, we established a testing platform to gain insight in the safety and efficacy of PT, biodistribution, phage kinetics and the molecular interaction between phages and bacteria. The draining fluid is collected to determine the phage titer and bacterial load. In addition, all bacterial isolates are fully characterized by genome sequencing to monitor the emergence of phage resistance. We hereby present a standardized bench-to-bedside protocol to gain more insight in the kinetics and dynamics of PT for musculoskeletal infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bessems, Chen, Uyttebroek, Devolder, Lood, Verwimp, De Munter, Debaveye, Depypere, Spriet, Van Gerven, Dupont, Wagemans, van Noort, Lavigne, Metsemakers and Onsea.)

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Key Points: Treatment of cystic fibrosis-related chronic rhinosinusitis should target sinonasal biofilms. NaHCO 3 salts with/without xylitol have limited antibiofilm properties, whereas rhDNAse has not. Phage effectivity varies and depends on the phage and the combination with antibiotics., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wils, Backaert, Jacobs, Ruysseveldt, Cremer, Dilissen, Bullens, Talavera, Steelant, Van Gerven, Martens and Hellings.)

Background: The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of inhalant allergy. A novel device, SPAT or Skin Prick Automated Test, that enables more standardized allergy testing has been developed. Previous research has shown reduced intra-subject variability of histamine wheals by SPAT., Objective: This study aimed to evaluate within-test agreement (% of patients with consistent test results) to detect sensitization to common inhalant allergens when a SPT is executed automated by SPAT or by manual SPT (SPMT) procedure., Methods: The 110 volunteers prospectively enrolled underwent both SPAT and SPMT with 3 pricks of house dust mite, timothy grass and birch, 2 pricks of histamine and 1 prick of glycerol. The proportion of consistent (3x positive â€" 3 x negative) and inconsistent (2x positive/negative â€" 1x positive/negative) test results were analysed., Results: The proportion of inconsistent test results was significantly lower in the SPAT compared to the SPMT group. The delta histamine to control pricks was significantly higher in SPAT compared to SPMT group. Coefficient of variation was lower in SPAT compared to SPMT for house dust mite, timothy grass, birch pollen. Visual analogue scale for discomfort was significantly lower in SPAT compared to SPMT group., Conclusion: SPAT showed a 34% reduction in the number of inconsistent test results compared to manual SPT with common inhalant allergens. Patient experience is significantly improved when an allergy test is performed by SPAT compared to a manual SPT.

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 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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).