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Experimental and Therapeutic Medicine Oct 2020Ocular cicatricial pemphigoid is a particular form of mucous membrane pemphigoid and it is characterized by a chronic bilateral conjunctivitis with relapsing-remitting... (Review)
Review
Ocular cicatricial pemphigoid is a particular form of mucous membrane pemphigoid and it is characterized by a chronic bilateral conjunctivitis with relapsing-remitting periods. Without therapy 75% of the cases develop visual loss due to major ocular complications (e.g. severe dry-eye syndrome, corneal erosions, corneal keratinization, entropion, symblepharon). Pathogenesis remains uncertain and probably linked to an autoimmune type II hypersensitivity response in patients with a genetic predisposition and exposure to different environmental triggers. With a worldwide distribution, no racial predilection and an estimated incidence that largely varies from 1/10,000-1/60,000, ocular cicatricial pemphigoid predominantly affects women aged ~60 years. Conjunctival biopsy with direct immunofluorescence is the gold standard in diagnosis confirmation, but up to 40% of the patients have a negative biopsy result that does not rule out the diagnosis. The skin and many other mucous membranes (e.g. oral, trachea, esophagus, pharynx, larynx, urethra, vagina and anus) may be involved. The disease grading relies on Foster staging system (based on clinical signs) and Mondino and Brown system (based on the inferior fornix depth loss). The differential diagnosis includes atopy, allergies, trauma, chemical burns, radiation, neoplasia, infectious, inflammatory and autoimmune etiologies. The main goals of the treatment are to stop disease progression, to relieve symptoms and to prevent complications. With long-term systemic therapy 90% of the cases can be efficiently controlled. While Dapsone is the first-line treatment in mild to moderate disease in patients without G6PD deficiency, more severe cases require immunosuppressant therapy with azathioprine, mycophenolate mofetil, methotrexate or cyclosporine. Cyclophosphamide, biologics (etanercept or rituximab) and intravenous immunoglobulin therapy are usually reserved for recalcitrant disease and unsatisfactory results to conventional therapy. Dry eye syndrome requires constant lubricating medication and topical steroids, cyclosporine-A and tacrolimus. Surgery should be planed only in quiescent phase as minor conjunctival trauma can significantly worsen the disease.
PubMed: 32905166
DOI: 10.3892/etm.2020.8972 -
Development (Cambridge, England) Oct 2019The upper airway epithelium, which is mainly composed of multiciliated, goblet, club and basal cells, ensures proper mucociliary function and can regenerate in response...
The upper airway epithelium, which is mainly composed of multiciliated, goblet, club and basal cells, ensures proper mucociliary function and can regenerate in response to assaults. In chronic airway diseases, defective repair leads to tissue remodeling. Delineating key drivers of differentiation dynamics can help understand how normal or pathological regeneration occurs. Using single-cell transcriptomics and lineage inference, we have unraveled trajectories from basal to luminal cells, providing novel markers for specific populations. We report that: (1) a precursor subgroup of multiciliated cells, which we have entitled deuterosomal cells, is defined by specific markers, such as DEUP1, FOXN4, YPEL1, HES6 and CDC20B; (2) goblet cells can be precursors of multiciliated cells, thus explaining the presence of hybrid cells that co-express markers of goblet and multiciliated cells; and (3) a repertoire of molecules involved in the regeneration process, such as keratins or components of the Notch, Wnt or BMP/TGFβ pathways, can be identified. Confirmation of our results on fresh human and pig airway samples, and on mouse tracheal cells, extend and confirm our conclusions regarding the molecular and cellular choreography at work during mucociliary epithelial differentiation.
Topics: Animals; Cell Differentiation; Cells, Cultured; Epithelial Cells; Goblet Cells; Humans; Mice; RNA-Seq; Respiratory Mucosa; Swine; Trachea
PubMed: 31558434
DOI: 10.1242/dev.177428 -
Case Reports in Otolaryngology 2021Upper airway granulomas are commonly encountered benign masses and are a result of pronounced tissue reactivity to localized respiratory mucosal trauma. The mechanism of...
BACKGROUND
Upper airway granulomas are commonly encountered benign masses and are a result of pronounced tissue reactivity to localized respiratory mucosal trauma. The mechanism of injury to respiratory epithelium is most commonly iatrogenic and associated with intubation or indwelling tracheostomy. . A 40-year-old obese female with a history of multiple intubations, poorly controlled diabetes mellitus type II, and history of tracheal stenosis presented with sudden onset respiratory distress requiring intubation at an outside hospital. Direct laryngoscopy revealed a rapidly forming transglottic tissue mass, measuring 5.0 × 2.2 × 0.8 cm. The following case represents an unusual exception to our experience with granulomas given its rapidity of onset and migration of tissue around the endotracheal tube. Discussion. Laryngeal erythema and granulation formation are expected postintubation findings in most patients; however, the large size of granuloma tissue and rapid onset of symptoms in this case make it remarkable. Our patient had multiple risk factors for postintubation stenosis: female sex, poorly controlled diabetes, hypertension, obesity, and multiple prior intubations for periods lasting longer than forty-eight hours.
CONCLUSION
Our case highlights a rare laryngeal finding of a large granulation tissue mass causing sudden onset airway obstruction.
PubMed: 33688444
DOI: 10.1155/2021/6697478 -
Nature Feb 2022It is not fully understood why COVID-19 is typically milder in children. Here, to examine the differences between children and adults in their response to SARS-CoV-2... (Comparative Study)
Comparative Study
It is not fully understood why COVID-19 is typically milder in children. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.
Topics: Adult; Bronchi; COVID-19; Chicago; Cohort Studies; Dendritic Cells; Disease Progression; Epithelial Cells; Female; Humans; Immunity, Innate; Interferons; Killer Cells, Natural; London; Male; Nasal Mucosa; SARS-CoV-2; Single-Cell Analysis; T-Lymphocytes, Cytotoxic; Trachea; Young Adult
PubMed: 34937051
DOI: 10.1038/s41586-021-04345-x -
Nature Cell Biology May 2021Coordination of stem cell function by local and niche-derived signals is essential to preserve adult tissue homeostasis and organismal health. The vasculature is a...
Coordination of stem cell function by local and niche-derived signals is essential to preserve adult tissue homeostasis and organismal health. The vasculature is a prominent component of multiple stem cell niches. However, its role in adult intestinal homeostasis remains largely understudied. Here we uncover a previously unrecognised crosstalk between adult intestinal stem cells in Drosophila and the vasculature-like tracheal system, which is essential for intestinal regeneration. Following damage to the intestinal epithelium, gut-derived reactive oxygen species activate tracheal HIF-1α and bidirectional FGF/FGFR signalling, leading to reversible remodelling of gut-associated terminal tracheal cells and intestinal stem cell proliferation following damage. Unexpectedly, reactive oxygen species-induced adult tracheal plasticity involves downregulation of the tracheal specification factor trachealess (trh) and upregulation of IGF2 messenger RNA-binding protein (IGF2BP2/Imp). Our results reveal an intestine-vasculature inter-organ communication programme that is essential to adapt the stem cell response to the proliferative demands of the intestinal epithelium.
Topics: Adaptation, Physiological; Adult Stem Cells; Animals; Drosophila; Homeostasis; Intestinal Mucosa; RNA-Binding Proteins; Regeneration; Signal Transduction; Stem Cell Niche; Stem Cells
PubMed: 33972729
DOI: 10.1038/s41556-021-00676-z -
Indian Journal of Surgical Oncology Mar 2022Thyroid cancer invading the trachea can be asymptomatic, but when tumour invasion reaches the mucosal surface, it causes bloody sputum and dyspnoea. The treatment plan... (Review)
Review
Thyroid cancer invading the trachea can be asymptomatic, but when tumour invasion reaches the mucosal surface, it causes bloody sputum and dyspnoea. The treatment plan for thyroid cancer is determined based on the site, depth, and extent of the invasion. Different from tumours arising from the tracheal mucosa, in thyroid cancer, invasion begins outside the airway and progresses toward the lumen, making it difficult to accurately diagnose the extent of the invasion even with bronchoscopy. Therefore, surgeons must determine the range of resection during surgery. Invasion reaching the tracheal mucosa requires full-thickness resection and is performed using tracheal window resection combined with tracheocutaneous fistula or tracheal sleeve resection followed by end-to-end anastomosis. The airway is safely secured with window resection, but closing the tracheal stoma often requires multi-stage reconstruction. Sleeve resection is an oncologically appropriate surgical method that can be completed in one stage, although there is a risk of serious complications associated with anastomotic dehiscence. Since well-differentiated thyroid cancer progresses slowly, some degree of survival can be expected even with incomplete resection. However, when shaving is performed for tumours with deep invasion that reaches the tracheal mucosa, the residual tumour tissue continues to grow steadily and eventually leads to airway stenosis. Since reoperation for tracheal resection is difficult, radical full-thickness resection should be performed in the initial surgery. Although this surgical intervention is far more demanding for both patients and surgeons than shaving, the procedure eventually improves patient's prognosis and quality of life.
PubMed: 35462665
DOI: 10.1007/s13193-021-01466-7 -
International Journal of Molecular... Feb 2022Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing... (Review)
Review
Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.
Topics: Biomarkers; Biomechanical Phenomena; Cytokines; Genetic Predisposition to Disease; Humans; Intercellular Signaling Peptides and Proteins; Laryngostenosis; Mechanotransduction, Cellular; Tracheal Stenosis
PubMed: 35269565
DOI: 10.3390/ijms23052421 -
Frontiers in Pharmacology 2023Postoperative sore throat (POST) is one of the most reported complications after general anesthesia with an incidence of as high as 60% which may impact patient... (Review)
Review
Postoperative sore throat (POST) is one of the most reported complications after general anesthesia with an incidence of as high as 60% which may impact patient satisfaction and increase the cost of treatment. The aim of this review is to summarize the currently accepted approaches and new trends intended to reduce the risk and increase the treatment efficacy of POST. Difficult intubation, traumatic intubation, and several other factors contribute to the development of POST. Endotracheal intubation using a stylet-loaded tube exerts excessive pressure on the anterior tracheal wall predisposing to mucosal trauma and contributing to development of POST. Pharmacological interventions are aimed at prevention, amelioration of symptoms, and treatment of POST. Medications suggested for this purpose include corticosteroids, topical sprays and creams, non-steroidal anti-inflammatory drugs (NSAID), and N-methyl-D-aspartate (NMDA) receptor antagonists. The use of video-laryngoscopes (VL) for endotracheal intubation improves the glottic view and increases the success rates with less force required to ensure adequate laryngoscopic view. Nevertheless, despite advances in laryngoscopic devices, the incidence of POST remains high. A novel intubation technique with endotracheal tube (ETT) rotation 180 degrees (ETT 180°) has been suggested to overcome stylet related injury and, possibly, decrease the POST. To date, no clinical trials have been conducted to test the efficacy of ETT 180° in reducing the incidence of POST. Undoubtedly, the suggested method deserves further investigation to determine its role in patient care.
PubMed: 38074131
DOI: 10.3389/fphar.2023.1284071