Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffolds improves subchondral bone repair.

Osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair remained suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed to improve the bone repair potential of this scaffold by incorporating newly developed strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100-150 µm). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 ± 0.04 wt%. Then 30 wt% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well embedded and distributed in the collagen matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed with in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone was observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold-only, in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone repair.

The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics.

The rupture of an atherosclerotic plaque cap overlying a lipid pool and/or necrotic core can lead to thrombotic cardiovascular events. In essence, the rupture of the plaque cap is a mechanical event, which occurs when the local stress exceeds the local tissue strength. However, due to inter- and intra-cap heterogeneity, the resulting ultimate cap strength varies, causing proper assessment of the plaque at risk of rupture to be lacking. Important players involved in tissue strength include the load-bearing collagenous matrix, macrophages, as major promoters of extracellular matrix degradation, and microcalcifications, deposits that can exacerbate local stress, increasing tissue propensity for rupture. This review summarizes the role of these components individually in tissue mechanics, along with the interplay between them. We argue that to be able to improve risk assessment, a better understanding of the effect of these individual components, as well as their reciprocal relationships on cap mechanics, is required. Finally, we discuss potential future steps, including a holistic multidisciplinary approach, multifactorial 3D in vitro model systems, and advancements in imaging techniques. The obtained knowledge will ultimately serve as input to help diagnose, prevent, and treat atherosclerotic cap rupture.

Bone formation by human paediatric marrow stromal cells in a functional allogeneic immune system.

Allogeneic stem-cell based regenerative medicine is a promising approach for bone defect repair. The use of chondrogenically differentiated human marrow stromal cells (MSCs) has been shown to lead to bone formation by endochondral ossification in immunodeficient pre-clinical models. However, an insight into the interactions between the allogeneic immune system and the human MSC-derived bone grafts has not been fully achieved yet. The choice of a potent source of MSCs isolated from pediatric donors with consistent differentiation and high proliferation abilities, as well as low immunogenicity, could increase the chance of success for bone allografts. In this study, we employed an immunodeficient animal model humanised with allogeneic immune cells to study the immune responses towards chondrogenically differentiated human pediatric MSCs (ch-pMSCs). We show that ch-differentiated pMSCs remained non-immunogenic to allogeneic CD4 and CD8 T cells in an in vitro co-culture model. After subcutaneous implantation in mice, ch-pMSC-derived grafts were able to initiate bone mineralisation in the presence of an allogeneic immune system for 3 weeks without the onset of immune responses. Re-exposing the splenocytes of the humanised animals to pMSCs did not trigger further T cell proliferation, suggesting an absence of secondary immune responses. Moreover, ch-pMSCs generated mature bone after 8 weeks of implantation that persisted for up to 6 more weeks in the presence of an allogeneic immune system. These data collectively show that human allogeneic chondrogenically differentiated pediatric MSCs might be a safe and potent option for bone defect repair in the tissue engineering and regenerative medicine setting.

A tissue-engineered model of the atherosclerotic plaque cap: Toward understanding the role of microcalcifications in plaque rupture.

Rupture of the cap of an atherosclerotic plaque can lead to thrombotic cardiovascular events. It has been suggested, through computational models, that the presence of microcalcifications in the atherosclerotic cap can increase the risk of cap rupture. However, the experimental confirmation of this hypothesis is still lacking. In this study, we have developed a novel tissue-engineered model to mimic the atherosclerotic fibrous cap with microcalcifications and assess the impact of microcalcifications on cap mechanics. First, human carotid plaque caps were analyzed to determine the distribution, size, and density of microcalcifications in real cap tissue. Hydroxyapatite particles with features similar to real cap microcalcifications were used as microcalcification mimics. Injected clusters of hydroxyapatite particles were embedded in a fibrin gel seeded with human myofibroblasts which deposited a native-like collagenous matrix around the particles, during the 21-day culture period. Second harmonic multiphoton microscopy imaging revealed higher local collagen fiber dispersion in regions of hydroxyapatite clusters. Tissue-engineered caps with hydroxyapatite particles demonstrated lower stiffness and ultimate tensile stress than the control group samples under uniaxial tensile loading, suggesting increased rupture risk in atherosclerotic plaques with microcalcifications. This model supports previous computational findings regarding a detrimental role for microcalcifications in cap rupture risk and can further be deployed to elucidate tissue mechanics in pathologies with calcifying soft tissues.

A Case Report of Wire-localised Excision of Impalpable Recurrent Papillary Thyroid Carcinoma and Discussion of Wire-guided Excision in the Head and Neck Pathology.

INTRODUCTION/BACKGROUND: Wire localisation techniques are used widely for precision surgery in many specialities. This convenient technique has not yet become mainstream in the field of head and neck surgery. With limited space and many vital structures coursing through the head and neck region, pathological nodes that are difficult to palpate can be a challenge for clinicians. CASE PRESENTATION: A patient with a history of papillary thyroid cancer treated with surgery and radioactive iodine had a single pathological node detected on ultrasound surveillance. An isolated recurrence of papillary thyroid carcinoma was confirmed. An excisional biopsy was performed using ultrasound wire guidance to successfully remove the diseased node with minimal morbidity. CONCLUSION: Wire-guided lymph node excision biopsy is a safe and effective method that can be applied to multiple pathologies. As of yet, it is not routine practice to employ this technique. Larger studies would increase the generalisability and safety profile of this technique in the head and neck region.

Addition of heparin binding sites strongly increases the bone forming capabilities of BMP9 in vivo.

Bone Morphogenetic proteins (BMPs) like BMP2 and BMP7 have shown great potential in the treatment of severe bone defects. In recent in vitro studies, BMP9 revealed the highest osteogenic potential compared to other BMPs, possibly due to its unique signaling pathways that differs from other osteogenic BMPs. However, in vivo the bone forming capacity of BMP9-adsorbed scaffolds is not superior to BMP2 or BMP7. In silico analysis of the BMP9 protein sequence revealed that BMP9, in contrast to other osteogenic BMPs such as BMP2, completely lacks so-called heparin binding motifs that enable extracellular matrix (ECM) interactions which in general might be essential for the BMPs' osteogenic function. Therefore, we genetically engineered a new BMP9 variant by adding BMP2-derived heparin binding motifs to the N-terminal segment of BMP9's mature part. The resulting protein (BMP9 HB) showed higher heparin binding affinity than BMP2, similar osteogenic activity in vitro and comparable binding affinities to BMPR-II and ALK1 compared to BMP9. However, remarkable differences were observed when BMP9 HB was adsorbed to collagen scaffolds and implanted subcutaneously in the dorsum of rats, showing a consistent and significant increase in bone volume and density compared to BMP2 and BMP9. Even at 10-fold lower BMP9 HB doses bone tissue formation was observed. This innovative approach of significantly enhancing the osteogenic properties of BMP9 simply by addition of ECM binding motifs, could constitute a valuable replacement to the commonly used BMPs. The possibility to use lower protein doses demonstrates BMP9 HB's high translational potential.

The response of human macrophages to 3D printed titanium antibacterial implants does not affect the osteogenic differentiation of hMSCs.

Macrophage responses following the implantation of orthopaedic implants are essential for successful implant integration in the body, partly through intimate crosstalk with human marrow stromal cells (hMSCs) in the process of new bone formation. Additive manufacturing (AM) and plasma electrolytic oxidation (PEO) in the presence of silver nanoparticles (AgNPs) are promising techniques to achieve multifunctional titanium implants. Their osteoimmunomodulatory properties are, however, not yet fully investigated. Here, we studied the effects of implants with AgNPs on human macrophages and the crosstalk between hMSCs and human macrophages when co-cultured in vitro with biofunctionalised AM Ti6Al4V implants. A concentration of 0.3 g/L AgNPs in the PEO electrolyte was found to be optimal for both macrophage viability and inhibition of bacteria growth. These specimens also caused a decrease of the macrophage tissue repair related factor C-C Motif Chemokine Ligand 18 (CCL18). Nevertheless, co-cultured hMSCs could osteogenically differentiate without any adverse effects caused by the presence of macrophages that were previously exposed to the PEO (±AgNPs) surfaces. Further evaluation of these promising implants in a bony in vivo environment with and without infection is highly recommended to prove their potential for clinical use.

Why Animal Experiments Are Still Indispensable in Bone Research: A Statement by the European Calcified Tissue Society.

Major achievements in bone research have always relied on animal models and in vitro systems derived from patient and animal material. However, the use of animals in research has drawn intense ethical debate and the complete abolition of animal experimentation is demanded by fractions of the population. This phenomenon is enhanced by the reproducibility crisis in science and the advance of in vitro and in silico techniques. 3D culture, organ-on-a-chip, and computer models have improved enormously over the last few years. Nevertheless, the overall complexity of bone tissue cross-talk and the systemic and local regulation of bone physiology can often only be addressed in entire vertebrates. Powerful genetic methods such as conditional mutagenesis, lineage tracing, and modeling of the diseases enhanced the understanding of the entire skeletal system. In this review endorsed by the European Calcified Tissue Society (ECTS), a working group of investigators from Europe and the US provides an overview of the strengths and limitations of experimental animal models, including rodents, fish, and large animals, as well the potential and shortcomings of in vitro and in silico technologies in skeletal research. We propose that the proper combination of the right animal model for a specific hypothesis and state-of-the-art in vitro and/or in silico technology is essential to solving remaining important questions in bone research. This is crucial for executing most efficiently the 3R principles to reduce, refine, and replace animal experimentation, for enhancing our knowledge of skeletal biology, and for the treatment of bone diseases that affect a large part of society. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

In Vitro Mineralisation of Tissue-Engineered Cartilage Reduces Endothelial Cell Migration, Proliferation and Tube Formation.

Tissue engineering bone via endochondral ossification requires the generation of a cartilage template which undergoes vascularisation and remodelling. While this is a promising route for bone repair, achieving effective cartilage vascularisation remains a challenge. Here, we investigated how mineralisation of tissue-engineered cartilage affects its pro-angiogenic potential. To generate in vitro mineralised cartilage, human mesenchymal stromal cell (hMSC)-derived chondrogenic pellets were treated with ß-glycerophosphate (BGP). After optimising this approach, we characterised the changes in matrix components and pro-angiogenic factors by gene expression analysis, histology and ELISA. Human umbilical vein endothelial cells (HUVECs) were exposed to pellet-derived conditioned media, and migration, proliferation and tube formation were assessed. We established a reliable strategy to induce in vitro cartilage mineralisation, whereby hMSC pellets are chondrogenically primed with TGF-ß for 2 weeks and BGP is added from week 2 of culture. Cartilage mineralisation determines loss of glycosaminoglycans, reduced expression but not protein abundance of collagen II and X, and decreased VEGFA production. Finally, the conditioned medium from mineralised pellets showed a reduced ability to stimulate endothelial cell migration, proliferation and tube formation. The pro-angiogenic potential of transient cartilage is thus stage-dependent, and this aspect must be carefully considered in the design of bone tissue engineering strategies.

Effectiveness of BMP-2 and PDGF-BB Adsorption onto a Collagen/Collagen-Magnesium-Hydroxyapatite Scaffold in Weight-Bearing and Non-Weight-Bearing Osteochondral Defect Bone Repair: In Vitro, Ex Vivo and In Vivo Evaluation.

Despite promising clinical results in osteochondral defect repair, a recently developed bi-layered collagen/collagen-magnesium-hydroxyapatite scaffold has demonstrated less optimal subchondral bone repair. This study aimed to improve the bone repair potential of this scaffold by adsorbing bone morphogenetic protein 2 (BMP-2) and/or platelet-derived growth factor-BB (PDGF-BB) onto said scaffold. The in vitro release kinetics of BMP-2/PDGF-BB demonstrated that PDGF-BB was burst released from the collagen-only layer, whereas BMP-2 was largely retained in both layers. Cell ingrowth was enhanced by BMP-2/PDFG-BB in a bovine osteochondral defect ex vivo model. In an in vivo semi-orthotopic athymic mouse model, adding BMP-2 or PDGF-BB increased tissue repair after four weeks. After eight weeks, most defects were filled with bone tissue. To further investigate the promising effect of BMP-2, a caprine bilateral stifle osteochondral defect model was used where defects were created in weight-bearing femoral condyle and non-weight-bearing trochlear groove locations. After six months, the adsorption of BMP-2 resulted in significantly less bone repair compared with scaffold-only in the femoral condyle defects and a trend to more bone repair in the trochlear groove. Overall, the adsorption of BMP-2 onto a Col/Col-Mg-HAp scaffold reduced bone formation in weight-bearing osteochondral defects, but not in non-weight-bearing osteochondral defects.

Outcomes from 7 years of a direct to audiology referral pathway.

BACKGROUND: The direct to audiology via ENT referral pathway was designed to enhance patient access to audiology services. The pathway is recommended in the Otolaryngology Head & Neck Surgery: a model of care for Ireland report, published in 2019. AIMS: This study aimed to review the outcomes of all patients that attended our institution over the last seven years. METHODS: A retrospective review of the direct to audiology referral service from March 2014 to December 2021 was conducted. Outcomes were defined by the pathway each patient took following attendance at the audiology clinic. Patients were either (i) discharged, (ii) referred for hearing aid(s) or (iii) identified as candidates for further diagnostic assessments, including a follow-up at the ENT outpatient clinic. RESULTS: During the time frame, 419 patients were triaged to the pathway. The average wait time was 13 days. The average age was 53 years (range 16-96 years, SD = 6.1). Approximately 34% (n = 143) of all patients referred were discharged back to the GP by the audiologist, but 66% (n = 276) presented with 'red flags' and needed further investigation in the ENT clinic, with 30% (n = 73) ultimately requiring imaging studies. Over half (n = 254, 61%) were referred for hearing aids. CONCLUSION: The direct to audiology initiative has proven effective at reducing waiting times for ENT patients solely in need of audiological intervention. Approximately one-third of these referrals to the ENT service can be assessed comprehensively in the audiology clinic, thereby reducing the demand for ENT clinics, enhancing service provision and expediting onwards referral for amplification.

How Feasible Are Digital Intraoperative Plain Radiographs in Orthopaedic Trauma Surgery?

The purpose of this study is to evaluate the feasibility and outcomes of obtaining routine intraoperative plain radiographs during orthopaedic trauma surgery. Seventy consecutive orthopaedic trauma patients in which intraoperative plain films were obtained in addition to fluoroscopy were reviewed. For each patient the time it took to obtain intraoperative plain radiographs was prospectively measured, in addition to the number of images taken, and quality of image. Then relative imaging times based on fracture locations were compared and the need for revision surgery based on mal-reduction or implant mal-positioning assessed. The average time required for intraoperative plain films to be obtained and reviewed by the surgeon was 3 minutes and 45 seconds. On average, 2.8 images were taken during each surgery. Proximal images took on average 44 seconds longer than distal images to obtain (p = 0.047). There was no significant difference in imaging times for upper versus lower extremities (p = 0.448). High quality images were obtained on all patients. There were no re-operations required in this series for mal-reduction of fracture, mal-positioning of implants or infection. In this study, there were no re-operations or perioperative complications when intraoperative plain films were obtained. Intraoperative plain films are a valuable tool for complex periarticular surgery or other cases where fracture reduction or implant location may be in question. (Journal of Surgical Orthopaedic Advances 32(3):160-163, 2023).

The Effect of the 2021 Irish Cyber-Attack on Otolaryngology Outpatient Non-attendance at a Model 4 Hospital in the Post-COVID Era.

Aim This study investigates the rate of non-attendance at ENT outpatient appointments in the post-COVID era and the effect of the 2021 Irish cyber-attack on non-attendance. Methods A retrospective review of the rates of non-attendance in a post-COVID pre-cyber-attack era wherein patients received an automated text message reminder about their appointment was compared to a post-cyber-attack era wherein the text message reminder system was disabled. In addition, these were compared with rates of non-attendance prior to when the reminder system was introduced. Three periods were compared, two weeks prior to the introduction of the text reminder system, two weeks pre-cyber-attack, and two weeks post-cyber-attack. Results Period 1 measured rates of non-attendance prior to the introduction of the text reminder system. Period 2 measured rates of non-attendance at outpatient appointments and consisted of nine clinic days, with two clinics per day. Period 3 similarly measured rates of non-attendance at outpatient appointments and consisted of 10 clinic days, with two clinics per day. The text reminder service was disabled during this collection period because of the cyber-attack. The average non-attendance rate was 16.99% for period 1, 13.00% for period 2, and 16.13% for period 3. A Fisher Exact Test was carried out on data with a p-value set at <0.05. Results reached statistical significance. Conclusion Our data shows non-attendance at ENT outpatient appointments increased without the text reminder system. Over two weeks after the attack, non-attendance increased by approximately 3%, which was statistically significant.

Site-Directed Immobilization of an Engineered Bone Morphogenetic Protein 2 (BMP2) Variant to Collagen-Based Microspheres Induces Bone Formation In Vivo.

For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2's bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.

Chondrogenically Primed Human Mesenchymal Stem Cells Persist and Undergo Early Stages of Endochondral Ossification in an Immunocompetent Xenogeneic Model.

Tissue engineering approaches using progenitor cells such as mesenchymal stromal cells (MSCs) represent a promising strategy to regenerate bone. Previous work has demonstrated the potential of chondrogenically primed human MSCs to recapitulate the process of endochondral ossification and form mature bone in vivo, using immunodeficient xenogeneic models. To further the translation of such MSC-based approaches, additional investigation is required to understand the impact of interactions between human MSC constructs and host immune cells upon the success of MSC-mediated bone formation. Although human MSCs are considered hypoimmunogenic, the potential of chondrogenically primed human MSCs to induce immunogenic responses in vivo, as well as the efficacy of MSC-mediated ectopic bone formation in the presence of fully competent immune system, requires further elucidation. Therefore, the aim of this study was to investigate the capacity of chondrogenically primed human MSC constructs to persist and undergo the process of endochondral ossification in an immune competent xenogeneic model. Chondrogenically differentiated human MSC pellets were subcutaneously implanted to wild-type BALB/c mice and retrieved at 2 and 12 weeks post-implantation. The percentages of CD4+ and CD8+ T cells, B cells, and classical/non-classical monocyte subsets were not altered in the peripheral blood of mice that received chondrogenic MSC constructs compared to sham-operated controls at 2 weeks post-surgery. However, MSC-implanted mice had significantly higher levels of serum total IgG compared to sham-operated mice at this timepoint. Flow cytometric analysis of retrieved MSC constructs identified the presence of T cells and macrophages at 2 and 12 weeks post-implantation, with low levels of immune cell infiltration to implanted MSC constructs detected by CD45 and CD3 immunohistochemical staining. Despite the presence of immune cells in the tissue, MSC constructs persisted in vivo and were not degraded/resorbed. Furthermore, constructs became mineralised, with longitudinal micro-computed tomography imaging revealing an increase in mineralised tissue volume from 4 weeks post-implantation until the experimental endpoint at 12 weeks. These findings indicate that chondrogenically differentiated human MSC pellets can persist and undergo early stages of endochondral ossification following subcutaneous implantation in an immunocompetent xenogeneic model. This scaffold-free model may be further extrapolated to provide mechanistic insight to osteoimmunological processes regulating bone regeneration and homeostasis.

The Releasate of Avascular Cartilage Demonstrates Inherent Pro-Angiogenic Properties In Vitro and In Vivo.

OBJECTIVE: Cartilage is avascular and numerous studies have identified the presence of single anti- and pro-angiogenic factors in cartilage. To better understand the maintenance hyaline cartilage, we assessed the angiogenic potential of complete cartilage releasate with functional assays in vitro and in vivo. DESIGN: We evaluated the gene expression profile of angiogenesis-related factors in healthy adult human articular cartilage with a transcriptome-wide analysis generated by next-generation RNAseq. The effect on angiogenesis of the releasate of cartilage tissue was assessed with a chick chorioallantoic membrane (CAM) assay as well as human umbilical vein endothelial cell (HUVEC) migration and proliferation assays using conditioned media generated from tissue-engineered cartilage derived from human articular and nasal septum chondrocytes as well as explants from bovine articular cartilage and human nasal septum. Experiments were done with triplicate samples of cartilage from 3 different donors. RESULTS: RNAseq data of 3 healthy human articular cartilage donors revealed that the majority of known angiogenesis-related factors expressed in healthy adult articular cartilage are pro-angiogenic. The releasate from generated cartilage as well as from tissue explants, demonstrated at least a 3.1-fold increase in HUVEC proliferation and migration indicating a pro-angiogenic effect of cartilage. Finally, the CAM assay demonstrated that cartilage explants can indeed attract vessels; however, their ingrowth was not observed. CONCLUSION: Using multiple approaches, we show that cartilage releasate has an inherent pro-angiogenic capacity. It remains vessel free due to anti-invasive properties associated with the tissue itself.

The environmental impact of personal protective equipment in a pre and post COVID era in the ENT clinic.

PURPOSE: The use of single use plastic items and plastic wrapping has increased over the last number of decades. Outside of the medical field there has been a conscious drive to reduce single use plastic and reuse items to reduce the amount of waste we produce. We undertook this investigation to quantify our plastic waste production and generate ideas to reduce this volume. METHODOLOGY: Data was collected from a University Hospital ENT outpatient department via real-time recording methods using standard data collection forms. We measured plastic unit usage pre and post COVID restrictions and compared this to our number of patient encounters. Projections of plastic usage were determined via a hypothetical resumption of patient services model. RESULTS: In total there were 440 patients included. In period one the mean units of plastic used per day was 65.1 (median 67; range 27-84). In the second period, the mean number of plastic units was 23.4 (median 22; range 1-7). Blue nitrile gloves and masks were the most commonly used single use items. The hypothetical projection model predicted a 147.6% increase in single use items following the introduction of COVID precautions. CONCLUSION: We have a duty of care not only to our patients but future generations of patients and the environment which we share. Single use items and excessive plastic wrapping have benefits in terms of convenience and sterility, but these conveniences can be easily extended to reusable types to limit our volume of waste, reduce our waste management costs and protect our environment.

Predictors of airway intervention in acute supraglottitis (AS), a recent 7- year experience.

AIMS: Acute supraglottitis (AS) can be a life threatening infection that may lead to sudden airway obstruction. Thankfully, paediatric instances have decreased with public health vaccination programmes. Owing to the nature of the location of pathology, this time sensitive emergency requires astute clinical acumen and awareness of early warning signs. This study aimed to i) determine if the incidence of AS has changed over time; ii) investigate geographical and seasonal variation of infection; iii) identify features of presentation which may predict airway intervention; iv) assess efficacy of treatment and make recommendations for management. MATERIALS AND METHOD: All adult patients admitted to a tertiary hospital with the diagnosis of acute supraglottitis between 2013 and 2021 were included. Diagnosis was confirmed with flexible nasendoscopy and consultant review. Demographics, management and outcomes were recorded. Statistical analysis was performed by calculating means and standard deviation for descriptive purposes. Fischer's exact test and two tailed t-test for categorical and continuous variables respectively. Results were deemed significant if P values of less than or equal to 0.05 were calculated. RESULTS: Forty-three adults were identified. Five patients (11.6%) required airway intervention. Stridor, respiratory distress and CRP of >100 mg/L were noted to be significant predictive factors for airway intervention. Intubated patients had a significantly longer hospital stay. Regions with a higher population density were noted to have a higher incidence but this did not prove to be significant. CONCLUSION: This is the largest study of AS in Ireland to date. There is a trend towards increasing incidence of acute supraglottitis in adults. Factors such as stridor, respiratory distress and elevated CRP should alert the clinician to the possible need for airway intervention. Acute supraglottitis is more common in higher density populated regions.

NK/T-cell lymphoma of the nasal cavity: an unexpected diagnosis.

Nasal-type Natural Killer/T-cell Lymphoma (NKTL) is a rare form of extranodal non-Hodgkin's lymphoma, typically arising in the nasopharynx and displaying an aggressive and ultimately fatal clinical course. The disease is linked to Epstein-Barr virus infection and is endemic to Asia and South America, but extremely few cases have been reported in Europe. We present two cases of nasal NKTL unexpectedly diagnosed in elderly patients, following very different presentations to our otolaryngology service. The first case is that of a 73-year-old Irish man with recurrent nasal vestibulitis despite antibiotic treatment. The second case involves a 79-year-old Irish woman presenting with a large mass on the hard palate, found to invade into the floor of the nose. NKTL can pose diagnostic challenges, as the initial clinical presentation can be non-specific and overlap with other nasal conditions, leading to a delay in diagnosis. Biopsy with histopathological and immunohistochemistry analysis is required to establish the definitive diagnosis. Treatment involves multidisciplinary input from radiotherapy and medical oncologists. Clinicians must be aware of this disease and have an index of suspicion when dealing with persistent or aggressive nasal conditions.

COMP and TSP-4: Functional Roles in Articular Cartilage and Relevance in Osteoarthritis.

Osteoarthritis (OA) is a slow-progressing joint disease, leading to the degradation and remodeling of the cartilage extracellular matrix (ECM). The usually quiescent chondrocytes become reactivated and accumulate in cell clusters, become hypertrophic, and intensively produce not only degrading enzymes, but also ECM proteins, like the cartilage oligomeric matrix protein (COMP) and thrombospondin-4 (TSP-4). To date, the functional roles of these newly synthesized proteins in articular cartilage are still elusive. Therefore, we analyzed the involvement of both proteins in OA specific processes in in vitro studies, using porcine chondrocytes, isolated from femoral condyles. The effect of COMP and TSP-4 on chondrocyte migration was investigated in transwell assays and their potential to modulate the chondrocyte phenotype, protein synthesis and matrix formation by immunofluorescence staining and immunoblot. Our results demonstrate that COMP could attract chondrocytes and may contribute to a repopulation of damaged cartilage areas, while TSP-4 did not affect this process. In contrast, both proteins similarly promoted the synthesis and matrix formation of collagen II, IX, XII and proteoglycans, but inhibited that of collagen I and X, resulting in a stabilized chondrocyte phenotype. These data suggest that COMP and TSP-4 activate mechanisms to protect and repair the ECM in articular cartilage.