Bilateral Vocal Cord Fibrosis: A Delayed Complication of Button Battery Ingestion.

A 14-month-old girl initially presented to the Accident and Emergency (A&E) department following a choking episode and subsequent vomiting. The child left the department before being seen but re-presented the following morning with stridor, drooling, and increased work of breathing. A chest and lateral neck soft tissue X-ray performed in the A&E department revealed an ingested button battery in the oesophagus. Emergency oesophagoscopy was performed and a 22 mm button battery was removed from the oesophagus at the level of the cricopharyngeus muscle, with no immediate complications. Following extubation, the patient was initially well but later required a prolonged hospital stay due to recurrent episodes of stridor, voice changes and aspiration pneumonia. Follow-up microlaryngoscopy and laryngeal electromyography (EMG) diagnosed bilateral vocal cord palsy and cricoarytenoid fibrosis. This case highlights the need for increased public awareness, urgent diagnosis and standardised management of battery ingestion, and discusses the potential for the development of serious latent complications.

Integrated single-cell transcriptomics and epigenomics reveals strong germinal center-associated etiology of autoimmune risk loci.

The germinal center (GC) response is critical for both effective adaptive immunity and establishing peripheral tolerance by limiting autoreactive B cells. Dysfunction in these processes can lead to defective immune responses to infection or contribute to autoimmune disease. To understand the gene regulatory principles underlying the GC response, we generated a single-cell transcriptomic and epigenomic atlas of the human tonsil, a widely studied and representative lymphoid tissue. We characterize diverse immune cell subsets and build a trajectory of dynamic gene expression and transcription factor activity during B cell activation, GC formation, and plasma cell differentiation. We subsequently leverage cell type­specific transcriptomic and epigenomic maps to interpret potential regulatory impact of genetic variants implicated in autoimmunity, revealing that many exhibit their greatest regulatory potential in GC-associated cellular populations. These included gene loci linked with known roles in GC biology (IL21, IL21R, IL4R, and BCL6) and transcription factors regulating B cell differentiation (POU2AF1 and HHEX). Together, these analyses provide a powerful new cell type­resolved resource for the interpretation of cellular and genetic causes underpinning autoimmune disease.

Sarcoidosis of the ear, nose and throat: A review of the literature.

OBJECTIVES: Sarcoidosis is a multisystemic inflammatory disease with extrathoracic manifestations, most commonly affecting the young and middle-aged, female and Black populations. Diagnosis usually requires evidence of non-caseating granulomata and, when treated, prognosis is usually favourable. We aim to establish the incidence, clinical features and optimal treatment of ENT manifestations of this disease. DESIGN: We performed a PubMed literature review to determine the evidence base supporting this. RESULTS: ENT manifestations are present in 5%-15% of patients with sarcoidosis, often as a presenting feature, and require vigilance for swift recognition and coordinated additional treatment specific to the organ. Laryngeal sarcoidosis presents with difficulty in breathing, dysphonia and cough, and may be treated by speech and language therapy (SLT) or intralesional injection, dilatation or tissue reduction. Nasal disease presents with crusting, rhinitis, nasal obstruction and anosmia, usually without sinus involvement. It is treated by topical nasal or intralesional treatments but may also require endoscopic sinus surgery, laser treatment or even nasal reconstruction. Otological disease is uncommon but includes audiovestibular symptoms, both sensorineural and conductive hearing loss, and skin lesions. CONCLUSIONS: The consequences of ENT manifestations of sarcoidosis can be uncomfortable, disabling and even life-threatening. Effective management strategies require good diagnostic skills and use of specific therapies combined with established treatments such as corticosteroids. Comparisons of treatment outcomes are needed to establish best practice in this area.

The role of antibiotics in the surgical management of paediatric obstructive sleep apnoea (OSA): a cohort study.

PURPOSE: Obstructive sleep apnoea (OSA) describes an irregular night-time breathing pattern that is present in approximately 1.8% of children and can have a negative impact on quality of life. The use of antibiotics postoperatively is controversial. They are commonly prescribed; however, they can also be associated with side effects and resistance. This study explores the role of antibiotics in the post-operative management of children with OSA in a cohort of children. METHODS: We conducted a retrospective cohort study of children undergoing surgery for OSA or sleep disordered breathing (SDB) at a tertiary paediatric ENT referral centre from November 2018 to November 2019. RESULTS: This study identified 382 children who had undergone surgical treatment for OSA or sleep disordered breathing (SDB); 319 underwent adenotonsillectomy, 53 adenoidectomy and 10 tonsillectomies. Antibiotics were given post-operatively to 158 (41%) patients and 18 (11%) of these patients presented to hospital with post-operative complications. A higher number of patients re-presented to hospital from the group who did not receive antibiotics (p = 0.982). Bleeding (p = 0.886) and infection (p = 0.823) were also more common in those children who did not receive antibiotics. CONCLUSION: Antibiotics led to fewer complications and re-presentations to hospital in children undergoing operative management of OSA; however, this trend was not found to be statistically significant.

Single-cell analysis of human B cell maturation predicts how antibody class switching shapes selection dynamics.

Protective humoral memory forms in secondary lymphoid organs where B cells undergo affinity maturation and differentiation into memory or plasma cells. Here, we provide a comprehensive roadmap of human B cell maturation with single-cell transcriptomics matched with bulk and single-cell antibody repertoires to define gene expression, antibody repertoires, and clonal sharing of B cell states at single-cell resolution, including memory B cell heterogeneity that reflects diverse functional and signaling states. We reconstruct gene expression dynamics during B cell activation to reveal a pre-germinal center state primed to undergo class switch recombination and dissect how antibody class-dependent gene expression in germinal center and memory B cells is linked with a distinct transcriptional wiring with potential to influence their fate and function. Our analyses reveal the dynamic cellular states that shape human B cell-mediated immunity and highlight how antibody isotype may play a role during their antibody-based selection.

Repetitive nasal allergen challenge in allergic rhinitis: Priming and Th2-type inflammation but no evidence of remodelling.

BACKGROUND: Local tissue eosinophilia and Th2 cytokines are characteristic features of seasonal allergic rhinitis. Airway remodelling is a feature of asthma whereas evidence for remodelling in allergic rhinitis (AR) is conflicting. OBJECTIVE: By use of a novel human repetitive nasal allergen challenge (RAC) model, we evaluated the relationship between allergic inflammation and features of remodelling in AR. METHODS: Twelve patients with moderate-severe AR underwent 5 alternate day challenges with diluent which after 4 weeks were followed by 5 alternate day challenges with grass pollen extract. Nasal symptoms, Th1/Th2 cytokines in nasal secretion and serum were evaluated. Nasal biopsies were taken 24 hours after the 1st and 5th challenges with diluent and with allergen. Sixteen healthy controls underwent a single challenge with diluent and with allergen. Using immunohistochemistry, epithelial and submucosal inflammatory cells and remodelling markers were evaluated by computed image analysis. RESULTS: There was an increase in early and late-phase symptoms after every allergen challenge compared to diluent (both P < .05) with evidence of both clinical and immunological priming. Nasal tissue eosinophils and IL-5 in nasal secretion increased significantly after RAC compared to corresponding diluent challenges (P < .01, P = .01, respectively). There was a correlation between submucosal mast cells and the early-phase clinical response (r = 0.79, P = .007) and an association between epithelial eosinophils and IL-5 concentrations in nasal secretion (r = 0.69, P = .06) in allergic rhinitis. No differences were observed after RAC with regard to epithelial integrity, reticular basement membrane thickness, glandular area, expression of markers of activation of airway remodelling including α-SMA, HSP-47, extracellular matrix (MMP7, 9 and TIMP-1), angiogenesis and lymphangiogenesis for AR compared with healthy controls. CONCLUSION: Novel repetitive nasal allergen challenge in participants with severe persistent seasonal allergic rhinitis resulted in tissue eosinophilia and increases in IL-5 but no structural changes. Our data support no link between robust Th2-inflammation and development of airway remodelling in AR.

National, Virtual Otolaryngology Training Day in the United Kingdom During the COVID-19 Pandemic: Results of a Pilot Survey.

The COVID-19 pandemic has forced an unprecedented worldwide change in our daily lives, particularly in healthcare. In response to the lockdown measure it has brought on, some deaneries cancelled planned teaching days, while others had delivered remote smaller scale teaching sessions electronically. Due to significant regional variation, the National Association of Program Directors in ENT (NAPDENT) set up a national educational program, matched to the Intercollegiate Surgical Curriculum Program. This is delivered virtually and for free. This pilot survey evaluates participants' learning experience of the first NAPDENT National Otology Training Day, which was held on 20 April 2020 via Zoom. This is a pilot survey evaluating the first online, national educational program delivered by the NAPDENT in the United Kingdom. In the times of the COVID-19 pandemic, our program has rapidly learnt from this initial experience and continues to build on lessons learnt for future editions. It is feasible to augment the national ENT curriculum with a collaborative, online teaching program. Regional buy-in is required to make this work. This modality allows for access to subject experts across the country. Synchronous delivery allows for participant interaction, while an online repository allows for asynchronous viewing when work or personal commitments do not allow live attendance. The key to participant engagement is adequate structure, appropriate breaks and opportunities for interaction. Even once the COVID-19 pandemic has passed, this teaching modality will remain as an opportunity to educate ENT surgeons of the future.

A Novel Quantitative Approach to Staging and Assessing Recovery from Type 1 Diabetes Mellitus: The Type 1 Diabetes Mellitus Metabolic Recovery Index.

Discovery of insulin in 1921 changed the lives of patients with type 1 diabetes (T1DM) forever. What had been a death sentence became a manageable, albeit chronic, disease. Insulin did not cure the disease, as it did not address the actual disease process, but instead treated its sequelae, namely elevated blood sugars. Importantly, insulin administration fails to ensure normoglycaemia. Even with the most sophisticated 'near closed-loop' methods, glucose homeostasis is not restored to normal. T1DM patients face complications, both short-term, such as hypo- and hyperglycaemia, and long-term, with increased glycosylation of proteins leading to eye, kidney, nervous system and other sequelae. These complications are associated with significant morbidity and mortality even after intensive insulin treatment. Nearly 100 years after the discovery of insulin, we continue to face the challenge of addressing the disease process itself, in order to fundamentally improve the life of these patients. There are major efforts to achieve just that: to completely arrest the autoimmune process destroying the insulin-producing cells in the pancreas, or at least significantly slow the process to blunt and delay short- and long-term complications. The aim of this Communication is to propose a novel assessment tool that would serve as a quantitative outcome measure by which therapies, short of clinical cure, may be compared and their true benefit to the treatment of diabetes assessed.

Sight preserving orbital decompression: a novel multidisciplinary approach to managing severe proptosis in neurofibromatosis type 2.

We describe the importance of collaboration between multiple surgical specialties in managing a complex case of sight-threatening severe proptosis in a young woman with type 2 neurofibromatosis (NF2) complicated by pre-existing contralateral blindness. Trans-nasal and lateral orbital surgical approaches were aided by stereotactic navigation to debulk a large frontal/sphenoid wing meningioma, which had been exerting pressure onto the right globe and optic nerve. The patient made an excellent postoperative recovery along with preserved residual visual acuity, normal neurology and a good aesthetic outcome.

IL-25/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) in Western countries is characterized by eosinophilia, IgE production, and TH2 cytokine expression. Type 2 innate lymphoid cells from polyps produce IL-5 and IL-13 in response to IL-25 and IL-33, although the relevance of this axis to local mucosal T-cell responses is unknown. OBJECTIVE: We sought to investigate the role of the IL-25/IL-33 axis in local mucosal T-cell responses in patients with CRSwNP. METHODS: Polyp tissue and blood were obtained from patients undergoing nasal polypectomy. Control nasal biopsy specimens and blood were obtained from healthy volunteers. Tissue was cultured in a short-term explant model. T-cell surface phenotype/intracellular cytokines were assessed by means of flow cytometry. T-cell receptor variable ß-chain analysis was performed with the immunoSEQ assay. Microarrays were performed for gene expression analysis. RESULTS: IL-25 receptor (IL-17RB)-expressing TH2 effector cells were identified in nasal polyp tissue but not the healthy nasal mucosa or periphery. IL-17RB(+)CD4(+) polyp-derived TH2 cells coexpressed ST2 (IL-33 receptor) and responded to IL-25 and IL-33 with enhanced IL-5 and IL-13 production. Within IL-17RB(+)CD4(+) T cells, several identical T-cell receptor variable ß-chain complementarity-determining region 3 sequences were identified in different subjects, suggesting clonal expansion driven by a common antigen. Abundant IL-17-producing T cells were observed in both healthy nasal mucosal and polyp populations, with TH17-related genes the most overexpressed compared with peripheral blood T cells. CONCLUSION: IL-25 and IL-33 can interact locally with IL-17RB(+)ST2(+) polyp T cells to augment TH2 responses in patients with CRSwNP. A local TH17 response might be important in healthy nasal mucosal immune homeostasis.

Severe Persistent Allergic Rhinitis. Inflammation but No Histologic Features of Structural Upper Airway Remodeling.

RATIONALE: Increases in airway smooth muscle, extracellular matrix, and vascularity are prominent features of airway remodeling in asthma, whereas the extent of such remodeling in patients with persistent allergic rhinitis (PAR) is unknown. OBJECTIVES: To test the hypothesis that upper airway remodeling is a feature of PAR. METHODS: Total nasal symptoms scores, nasal biopsies, and Th1 and Th2 cytokines from nasal lavage were assessed in subjects with severe PAR (n = 46) and healthy control subjects (n = 19). Angiolymphangiogenesis was examined using immunohistochemistry staining against CD31 (vascular endothelial cells), vascular endothelial growth factor-A, and D2-40 (lymphatic endothelial cells). Collagen and extracellular matrix proteins, such as heat shock protein-47 (markers of collagen synthesis), matrix metalloproteinase-9, and tissue inhibitor metalloproteinase-1, and α-smooth muscle actin (myofibroblasts) were evaluated as markers of activation of upper airway remodeling using image analysis, together with reticular basement membrane thickness, mucus gland area, collagen area, and submucosal effector inflammatory cells. MEASUREMENTS AND MAIN RESULTS: Total nasal symptoms scores, visual analog scale, and total quality of life were significantly higher in PAR compared with healthy control subjects (P < 0.0001). Nasal lavage cytokine levels of IL-4 (P < 0.01), IL-5, and IL-13 (P < 0.001, respectively) were significantly higher in PAR compared with healthy control subjects. In addition there was an increase in submucosal eosinophils (P = 0.06). No statistical difference in terms of angiogenesis, lymphangiogenesis, deposition of extracellular matrix, collagen markers, reticular basement membrane thickness, or glandular percentage area was observed between PAR and healthy control subjects. CONCLUSIONS: Our data suggest that tissue remodeling is not a feature of PAR and argues that in contrast to asthma, targeting remodeling in allergic rhinitis may not be appropriate as a therapeutic approach.