calcitonin (Fortical)

Post-Traumatic Nasal Pyramid Reconstruction with a Custom-Made Titanium Implant: A Case Report with Ultrastructural Evaluation.

Chatzistefanou Ioannis I, Tsokkou Sophia S, Karachrysafi Sofia S, Papadopoulou Kyriaki K et al.

Background/Objectives: Post-traumatic nasal pyramid reconstruction is challenging in patients with severe deformity and exhausted autologous graft options, particularly after multiple failed surgeries. Custom-made titanium implants may offer precise structural support, but data on their mucosal integration and ultrastructural tissue response in nasal reconstruction are lacking. The aim of this study is to describe what is, to the best of our knowledge, the first reported case of nasal pyramid reconstruction using an IPS (Individual Patient Solutions) custom-made titanium implant and to evaluate peri-implant tissue response with transmission electron microscopy (TEM). Methods: A 50-year-old male military personnel with long-standing saddle-nose deformity, nasal obstruction, and prior failed graft-based reconstructions underwent open rhinoplasty with placement of a patient-specific titanium implant designed with three-dimensional virtual surgical planning on the basis of established nasal anthropometric parameters and manufactured as a custom-made device under Regulation (EU) 2017/745. The implant reconstructed the nasal dorsum from nasion to tip and was stabilized with cortical screws; an additional thin titanium plate was used for tip support. Biopsies of nasal mucosa and adjacent connective tissue obtained 24 months postoperatively were processed for TEM to assess epithelial, stromal, vascular, and implant-tissue interface characteristics. Results: Clinically, nasal airway patency improved immediately after packing removal, with restoration of nasal contour and stable functional and aesthetic outcomes at 24-month follow-up without complications. Ultra-structurally, the respiratory epithelium showed preserved stratification, intact basal and ciliated cells, normal nuclei and mitochondria, and organized extracellular matrix closely opposed to discrete titanium particles, without granulomatous foreign-body reaction, dense inflammatory infiltrate, or fibrotic encapsulation. Focal ciliary damage, cytoplasmic vacuolization, lamina propria thickening, and vascular elastic lamina remodeling were interpreted as adaptive or transient stress-related changes rather than chronic implant toxicity. Conclusions: Custom-made IPS titanium implants can provide stable structural support, satisfactory functional and aesthetic outcomes, and a well-tolerated mucosal interface in complex post-traumatic nasal pyramid reconstruction after failed graft-based surgeries. The ultrastructural findings are being consistent with good local tolerance of the implant at 24 months, showing predominantly preserved epithelial and stromal architecture with only focal, adaptive stress-related changes rather than chronic implant-related toxicity. However, as this is a single case assessed without conventional histology, immunohistochemistry or objective measurement of nasal airflow, these observations cannot establish biocompatibility, efficacy or long-term safety, and require confirmation in larger series with longer follow-up.

Corrigendum to "Collagen Hydrogel with Rg1-Loaded Chitosan Nanoparticles and Adipose Stem Cells Improves Nasal Bone Healing in Rats".

Quantitative Assessment of Schlemm's Canal Morphology and Observer Variability Using Swept-Source as-OCT in Healthy Eyes with Open and Narrow Angles.

Hatami Mohammad Mehdi MM, Doozandeh Azadeh A, Zare Mohsen M, Marandi Samaneh S et al.

This cross-sectional study assessed Schlemm's Canal (SC) morphology in healthy eyes with open and narrow angles using anterior segment optical coherence tomography (AS-OCT) and evaluated inter- and intraobserver variability in SC measurements. AS-OCT images were obtained from 97 eyes from 97 patients. Two horizontal images were captured from the nasal region and one image from the temporal region. Two observers measured the following SC parameters: cross-sectional area (CSA), width, and height. Differences between open- and narrow-angle groups were compared, and interobserver and intraobserver reproducibility were measured using Intraclass Correlation Coefficients (ICC). Pearson's correlation coefficients were used to assess linear associations between measurements. Schlemm's canal CSA values in nasal images were significantly higher in open-angle eyes (4704 ± 1859 vs 3222 ± 1084 µm2, p = 0.003). However, differences in width or height between the two groups were nonsignificant. Interobserver agreement was good for CSA (ICC = 0.85), moderate to good for width (ICC = 0.74), and moderate for height (ICC = 0.66). Intraobserver repeatability was good for CSA (ICC = 0.86) and moderate to good for width (ICC = 0.73) but poor for height (ICC = 0.41). Visibility of SC was higher in nasal images than in temporal images (65-76% vs 39%). Nasal CSA and ACA were larger in the open-angle group and demonstrated good interobserver and intraobserver reproducibility. However, the significance of CSA, its utility in glaucoma patients and its relationship with functional measures of aqueous outflow remain unclear. This calls for longitudinal studies to determine the clinical applicability of this parameter.

Conditionally Reprogrammed Patient-Derived Nasal Epithelial Cell Cultures for In Vitro Diagnostics and Pharmacological Profiling in Primary Ciliary Dyskinesia.

Urbantat Ruth M RM, Balázs Anita A, Seidel Kathrin K, Drescher Marika M et al.

Air-liquid interface (ALI) cultures of patient-derived primary nasal epithelial cells (pNEC) can support diagnostics and in vitro phenotyping of primary ciliary dyskinesia (PCD); however, low cell yield remains a limitation. We aimed to establish and optimize conditionally reprogrammed cell (CRC) technology for pNEC from individuals with PCD and use it as a diagnostic tool for inconclusive cases and for pharmacological testing. pNEC from 36 individuals (8 healthy controls (HC), 26 PCD, 2 PCD candidates) were expanded using CRC and differentiated at ALI. Ciliary beat frequency (CBF), mucociliary transport velocity (MCTV), and culture morphology were assessed. Further, we assessed the effect of the β-receptor agonist clenbuterol on cilia function in pNEC of HC, PCD (DNAH11, CCDC40) and PCD candidates harboring biallelic DNAH1 variants. CRC expansion demonstrated a >90% success rate, yielding high cell counts (mean 9.65 × 106). Differentiation at ALI resulted in pseudostratified ciliated pNEC cultures. CBF was comparable between native and cultured pNEC. MCTV was significantly reduced in PCD vs. HC cultures (p < 0.0001). Clenbuterol significantly increased CBF in HC and DNAH1, but not in CCDC40 or DNAH11 cultures. MCTV was significantly increased in HC by clenbuterol treatment. CRC technology provides a scalable platform for the expansion of pNEC that recapitulate in vivo ciliary function. By enabling genotype-specific pharmacological screening, CRC may serve as a tool for functional diagnostics and precision medicine in PCD.