Airway necrosis and granulation tissue formation caused by Rhizopus oryzae leading to severe upper airway obstruction: a case report.

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host's immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.

miR-34c-5p inhibited fibroblast proliferation, differentiation and epithelial-mesenchymal transition in benign airway stenosis via MDMX/p53 pathway.

Benign airway stenosis (BAS) means airway stenosis or obstruction that results from a variety of non-malignant factors, including tuberculosis, trauma, benign tumors, etc. In consideration of the currently limited research on microRNAs in BAS, this study aimed to explore the role and mechanism of miR-34c-5p in BAS. The expression of miR-34c-5p in BAS granulation tissues showed a significant down-regulation compared with the normal control group. Moreover, miR-34c-5p mimics suppressed the proliferation and differentiation of human bronchial fibroblasts (HBFs) and the epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBE). Conversely, miR-34c-5p inhibitors aggravated those effects. A dual-luciferase reporter assay confirmed that miR-34c-5p can target MDMX rather than Notch1. The over-expression of MDMX can reverse the inhibiting effect of miR-34c-5p on HBFs proliferation, differentiation and EMT. Furthermore, the expressions of tumor protein (p53) and PTEN were down-regulated following the over-expression of MDMX. In addition, the expressions of PI3K and AKT showed an up-regulation. In conclusion, miR-34c-5p was down-regulated in BAS and may inhibit fibroblast proliferation differentiation and EMT in BAS via the MDMX/p53 signaling axis. These findings expand the understanding of the role of miR-34c-5p and will help develop new treatment strategies for BAS.

Structural brain morphology in young adult women who have been choked/strangled during sex: A whole-brain surface morphometry study.

INTRODUCTION: Being choked/strangled during partnered sex is an emerging sexual behavior, particularly prevalent among young adult women. Using a multiparameter morphometric imaging approach, we aimed to characterize neuroanatomical differences between young adult women (18-30 years old) who were exposed to frequent sexual choking and their choking naïve controls. METHODS: This cross-sectional study consisted of two groups (choking [≥4 times in the past 30 days] vs. choking-naïve group). Participants who reported being choked four or more times during sex in the past 30 days were enrolled in the choking group, whereas those without were assigned to the choking naïve group. High-resolution anatomical magnetic resonance imaging (MRI) data were analyzed using both volumetric features (cortical thickness) and geometric features (fractal dimensionality, gyrification, sulcal depth). RESULTS: Forty-one participants (choking n = 20; choking-naïve n = 21) contributed to the final analysis. The choking group showed significantly increased cortical thickness across multiple regions (e.g., fusiform, lateral occipital, lingual gyri) compared to the choking-naïve group. Widespread reductions of the gyrification were observed in the choking group as opposed to the choking-naïve group. However, there was no group difference in sulcal depth. The fractal dimensionality showed bi-directional results, where the choking group exhibited increased dimensionality in areas including the postcentral gyrus, insula, and fusiform, whereas decreased dimensionality was observed in the bilateral superior frontal gyrus and pericalcarine cortex. CONCLUSION: These data in cortical morphology suggest that sexual choking events may be associated with neuroanatomical alteration. A longitudinal study with multimodal assessment is needed to better understand the temporal ordering of sexual choking and neurological outcomes.

TREATMENT OF CONGENITAL LARYNGEAL CYSTS IN NEWBORNS.

Congenital laryngeal cysts are rare lesions that may occur in newborns, characterized by symptoms of respiratory obstruction and severe dyspnea. The aim of this study was to indicate optimal surgical treatment of congenital laryngeal cysts in newborns. We present a case series of five neonates treated for congenital laryngeal cysts during the 2011-2017 period at our pediatric tertiary care hospital. Patient age ranged from one day to 14 days. All patients had unilateral cysts. After surgical excision, burning of the walls of the cysts was performed by a CO2 laser. In one case, after four months, a recurrent cyst appeared, and re-operation was performed. Our relatively small case series indicates that symptoms such as stridor and labored breathing can occur already during the first days of life and potentially endanger the patient's life. Complete excision of the cyst and burning of its walls with CO2 laser leads to complete cure and prevent recurrence of the lesion.

Brachycephalic obstructive airway syndrome: much more than a surgical problem.

Brachycephalic obstructive airway syndrome (BOAS) is a chronic, lifelong, debilitating, primarily obstructive airway disease which adversely affects the quality of life of many popular dog breeds. Respiratory restriction in bulldog breeds, pugs and Boston terriers frequently co-exist with pathologies of the gastrointestinal tract. In addition, many brachycephalic dogs that appear clinically normal are, in fact suffering from chronic hypoxia and its systemic consequences. Concurrent gastroesophageal reflux-associated conditions, sleep disorders and systemic hypertension further impact the welfare of affected dogs. Acceptance of BOAS and associated clinical signs as being 'normal for the breed' is common amongst owners. While surgical correction of the upper airway is the mainstay of treatment, the provision of subsequent, frequently lifelong medical management is equally important for the maintenance of an acceptable quality of life, at least for some affected patients. Here we review the current knowledge concerning brachycephaly, combine it with shared clinical experience in the management of this debilitating condition, and discuss ethical considerations and the responsibility of veterinarians to contribute public education and to support appropriate breed standards for animals under our care.

[Assessment of clinical signs of brachycephalic obstructive airway syndrome and other breed-specific diseases in pug dogs - an online survey]. / Einschätzung von Symptomen des brachyzephalen obstruktiven Atemwegssyndroms und anderen rassetypischen Erkrankungen bei Mops-Hunden ­ eine Online-Umfrage.

OBJECTIVE: The aim of the study was to investigate the awareness for the breed-related brachycephalic obstructive airway syndrome (BOAS) and the occurrence of other breed-typical diseases within the framework of an online survey for pug owners. MATERIAL AND METHODS: A digital questionnaire for owners was created, distributed via social media and subsequently evaluated. RESULTS: The questionnaire was completed by 1220 pug owners. According to the owners, 32 % (344/1073) of the animals that did not undergo airway dilatation surgery show slight and 3 % (34/1073) show distinct breathing sounds when at rest. 86 % (326/378) of the owners perceive these breathing sounds as "normal, breed-specific" and 14 % (51/378) consider them as sign of "disease". 20 % (210/1073) of the animals are considered "somewhat" and 5 % (57/1073) "frequently tired and quickly short of breath" after a small amount of time. 24 % (245/1220) of all animals suffer from ocular diseases, 10 % (122/1220) from skin diseases and 11 % (134/1220) from spinal diseases, among others. CONCLUSION: The survey shows that with 67 % (814/1220) more than half of the pug owners perceive clinical signs of BOAS and/or other breed-specific diseases in their animals, however, a large proportion consider these as being non-problematic. CLINICAL RELEVANCE: The present study reveals that the animals' clinical limitations associated with brachycephaly are oftentimes not perceived as being pathologic and are hence underestimated by the owners.

Comparison of harmonic shears, diode laser, and scissor cutting and suturing for caudal palatoplasty in dogs with brachycephalic obstructive airway syndrome.

Traditionally, staphylectomy has been performed using scissors cutting and suturing. Alternative surgical techniques such as staphylectomy with monopolar electrocoagulation, CO2 or diode laser, bipolar vessel sealing device and harmonic shears have also been described. The purpose of this prospective study was to compare the difference in surgical time, intraoperative haemorrhage and histological damage between staphylectomy performed with harmonic shears (HSS), diode laser (DLS) and traditional scissor 'cutting and suturing' technique with Metzenbaum scissors (SIS). Group HSS included 17 dogs, whereas Group DLS and Group SIS included 10 dogs each. Double masked histological evaluation was performed on the excised specimens. The harmonic shears resulted in the shortest surgical times (HSS 46 s, DLS 300 s, SIS 360 s; P < 0.001). There was a difference in the intraoperative haemorrhage among the three techniques; intraoperative haemorrhage did not occur in HSS and DLS groups. HSS was associated with more frequent damage involving the connective tissue (P = 0.001), muscle (P = 0.038), salivary gland tissue (P < 0.001), but less oedema was observed (P < 0.001). HSS was the fastest of the techniques evaluated for caudal elongated soft palate resection, resulting in less tissue oedema, and no intra-operative haemorrhage. These characteristics might result in reduced postoperative swelling and airway obstruction compared to other techniques.

Role of IL-18-transformed CD274-expressing eosinophils in promoting airway obstruction in experimental asthma.

BACKGROUND: IL-5-dependent residential and IL-18-transformed pathogenic eosinophils have been reported; however, the role of IL-18-transformed CD274-expressing pathogenic eosinophils compared to IL-5-generated eosinophils in promoting airway obstruction in asthma has not yet been examined. METHODS: Eosinophils are detected by tissue anti-MBP and anti-EPX immunostaining, CD274 expression by flow cytometry, and airway resistance using the Buxco FinePointe RC system. RESULTS: We show that A. fumigatus-challenged wild-type mice, and different gene-deficient mice including naïve CC10-IL-18-transgenic mice, accumulate mostly peribronchial and perivascular CD274-expressing eosinophils except naïve CD2-IL-5-transgenic mice. Additionally, we show that CD2-IL-5 transgenic mice following rIL-18 treatment accumulate high number of CD274-expressing perivascular and peribronchial eosinophils with induced collagen, goblet cell hyperplasia and airway resistance compared to saline-challenged CD2-IL5 transgenic mice. Furthermore, we also show that even A. fumigatus-challenged IL-5 -/- mice and rIL-18 given ΔdblGATA mice accumulate CD274-expressing eosinophil-associated asthma pathogenesis including airway obstruction. Most importantly, we provide evidence that neutralization of CD274 and IL-18 in A. fumigatus-challenged mice ameliorate experimental asthma. Taken together, the data presented are clinically significant in establishing that anti-IL-18 neutralization is a novel immunotherapy to restrict asthma pathogenesis. CONCLUSIONS: We demonstrate that IL-18 is critical for inducing asthma pathogenesis, and neutralization of CD274 is a potential immunotherapeutic strategy for asthma.

Evaluating malformations of the lacrimal drainage system in brachycephalic dog breeds: A comparative computed tomography analysis.

OBJECTIVES: This study aimed to investigate and compare the anatomical features of the nasolacrimal drainage system (NDS) in three brachycephalic dog breeds with those of normocephalic dogs, taking into account how the NDS was related to the malformed brachycephalic head. ANIMALS: Fifty-one brachycephalic dogs were examined, comprising 23 Pugs, 18 French Bulldogs, and 10 English Bulldogs. Six normocephalic dogs of different breeds served as a comparison. METHODS: Computed tomographic dacryocystography was performed. Parameters such as length, angulation, and gradient were determined. Crossing of the nasolacrimal duct (NLD) beneath the maxillary canine root, as well as the incidence of an accessory opening, were also analyzed. RESULTS AND CONCLUSIONS: In all three brachycephalic breeds, the NDS was grossly malformed. We regard this as a further consequence of exaggerated breeding for a short head conformation. While the length of the NLD was substantially reduced by 41 to 57 percent in brachycephalic dogs, their lacrimal canaliculi were two to three times as long as those of normocephalic dogs. Varying parts of the nasolacrimal drainage system followed an inverse direction in short-headed dogs, giving the entire nasolacrimal apparatus an anomalous U- or V-shaped appearance. The NLD exhibited a three to five times steeper alignment in brachycephalic dogs than in normocephalic ones. Obviously, this strong slope did not cause clinical symptoms only because there was an aberrant outflow pathway. The brachycephalic dogs consistently exhibited an accessory opening, through which most of fluid escaped into the posterior nasal cavity instead of through the common route into the nasal vestibule via the nasolacrimal ostia.

Pediatric Obstructive Sleep Apnea Syndrome: Emerging Evidence and Treatment Approach.

OSA pediatric subjects suffer from episodes of upper airway obstruction that can be partial or complete, with atypical sleep patterns and blood-gas level alteration. If poor treated and/or diagnosed, it can cause cardiovascular disease, learning difficulties, behavioural issues, and retardation of growth. In the literature, there are conflicting evidence about OSA assessment and treatment in pediatric age, so the aim of this paper is to highlight the multidisciplinary approach in the management of sleep disorders, stressing the role of the pediatric dentist in both diagnosing and treating the OSAS in children, according to the current evidence of the treatment options effectiveness of the syndrome itself. Conclusions. Scientific evidence shows that OSAS management requires a multidisciplinary approach in order to make an early diagnosis and a correct treatment plan. The orthodontic treatment approach includes orthopedic maxillary expansion and mandibular advancement using intraoral appliances. Hence, the orthodontist and the pediatric dentist play an important role not only in early diagnosis but also in the treatment of pediatric OSAS.

VEGF receptor 2 (KDR) protects airways from mucus metaplasia through a Sox9-dependent pathway.

Mucus-secreting goblet cells are the dominant cell type in pulmonary diseases, e.g., asthma and cystic fibrosis (CF), leading to pathologic mucus metaplasia and airway obstruction. Cytokines including IL-13 are the major players in the transdifferentiation of club cells into goblet cells. Unexpectedly, we have uncovered a previously undescribed pathway promoting mucous metaplasia that involves VEGFa and its receptor KDR. Single-cell RNA sequencing analysis coupled with genetic mouse modeling demonstrates that loss of epithelial VEGFa, KDR, or MEK/ERK kinase promotes excessive club-to-goblet transdifferentiation during development and regeneration. Sox9 is required for goblet cell differentiation following Kdr inhibition in both mouse and human club cells. Significantly, airway mucous metaplasia in asthmatic and CF patients is also associated with reduced KDR signaling and increased SOX9 expression. Together, these findings reveal an unexpected role for VEGFa/KDR signaling in the defense against mucous metaplasia, offering a potential therapeutic target for this common airway pathology.

Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice.

The present study aimed to examine the effects of 2.5 µm particulate matter (PM2.5) on airway inflammation and to investigate the possible underlying mechanism. Specifically, the focus was on the imbalance of T helper (Th)1/Th2 cells and the dysregulated expression of transcription factors, including trans­acting T cell­specific transcription factor 3 (GATA3), runt­related transcription factor 3 (Runx3) and T­box transcription factor TBX21 (T­bet). In this study, ambient PM2.5 was collected and analyzed, male BALB/c mice were sensitized and treated with PBS, ovalbumin (OVA), PM2.5 or OVA + PM2.5. The effects of PM2.5 alone or PM2.5 + OVA on immunopathological changes, the expression of transcription factors GATA3, Runx3 and T­bet, and the imbalance of Th1/Th2 were investigated. It was found that PM2.5 + OVA co­exposure significantly enhanced inflammatory cell infiltration, increased higher tracheal secretions in lung tissue and upregulated respiratory resistance response to acetylcholine compared with PM2.5 or OVA single exposure and control groups. In addition, higher protein and mRNA expression levels of Th2 inflammatory mediators interleukin (IL)­4, IL­5 and IL­13 in bronchoalveolar lavage fluid were observed in PM2.5 + OVA treated mice, whereas the expression levels of GATA3 and STAT6 were exhibited in mice exposed to OVA + PM2.5 compared with the OVA and PM2.5 groups. By contrast, PM2.5 exposure decreased the protein and mRNA expression levels of Th1 cytokine interferon­Î³ and transcription factors Runx3 and T­bet, especially among asthmatic mice, different from OVA group, PM2.5 exposure only failed to influence the expression of T­bet. To conclude, PM2.5 exposure evoked the allergic airway inflammation response, especially in the asthmatic mouse model and led to Th1/Th2 imbalance. These effects worked mainly by upregulating GATA3 and downregulating Runx3. These data suggested that Runx3 may play an important role in PM2.5­aggravated asthma in BALB/c mice.

Assisting PNA transport through cystic fibrosis human airway epithelia with biodegradable hybrid lipid-polymer nanoparticles.

Cystic fibrosis (CF) is characterized by an airway obstruction caused by a thick mucus due to a malfunctioning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky mucus restricts drugs in reaching target cells limiting the efficiency of treatments. The development of new approaches to enhance drug delivery to the lungs represents CF treatment's main challenge. In this work, we report the production and characterization of hybrid core-shell nanoparticles (hNPs) comprising a PLGA core and a dipalmitoylphosphatidylcholine (DPPC) shell engineered for inhalation. We loaded hNPs with a 7-mer peptide nucleic acid (PNA) previously considered for its ability to modulate the post-transcriptional regulation of the CFTR gene. We also investigated the in vitro release kinetics of hNPs and their efficacy in PNA delivery across the human epithelial airway barrier using an ex vivo model based on human primary nasal epithelial cells (HNEC) from CF patients. Confocal analyses and hNPs transport assay demonstrated the ability of hNPs to overcome the mucus barrier and release their PNA cargo within the cytoplasm, where it can exert its biological function.

Endotracheal Tube Obstruction Among Patients Mechanically Ventilated for ARDS Due to COVID-19: A Case Series.

BACKGROUND: Patients with COVID-19 and ARDS on prolonged mechanical ventilation are at risk for developing endotracheal tube (ETT) obstruction that has not been previously described in patients with ARDS due to other causes. The purpose of this report is to describe a case series of patients with COVID-19 and ARDS in which ETT occlusion resulted in significant clinical consequences and to define the pathology of the obstructing material. METHODS: Incidents of ETT occlusion during mechanical ventilation of COVID-19 patients were reported by clinicians and retrospective chart review was conducted. Statistical analysis was performed comparing event rates between COVID-19 and non-COVID 19 patients on mechanical ventilation over the predefined period. Specimens were collected and submitted for pathological examination. FINDINGS: Eleven COVID-19 patients experienced endotracheal tube occlusion over a period of 2 months. Average age was 69 (14.3, range 33-85) years. Mean APACHE III score was 73.6 (17.3). All patients had AKI and cytokine storm. Nine exhibited biomarkers for hypercoagulability. Average days on mechanical ventilation before intervention for ETT occlusion was 14 (5.18) days (range of 9 to 23 days). Five patients were discharged from the ICU, and 4 expired. Average documented airway resistance on admission was 14.2 (3.0) cm H2O/L/sec. Airway resistance before tube exchange was 28.1 (8.0) cm H2O /L/sec. No similar events of endotracheal tube occlusion were identified in non-COVID patients on mechanical ventilation during the same time period. Microscopically, the material consisted of mucin admixed with necrotic cell debris, variable numbers of degenerated inflammatory cells, oral contaminants and red blood cells. INTERPRETATION: Patients with COVID-19 and ARDS on prolonged mechanical ventilation are at risk for developing ETT obstruction due to deposition of a thick, tenacious material within the tube that consists primarily of mucin and cellular debris. Clinicians should be aware of this dangerous but treatable complication.

Variable Mechanisms of Sudden and Unexpected Death in Cases of Occult Carcinoma of the Larynx.

ABSTRACT: Two cases of clinically undiagnosed laryngeal squamous cell carcinomas in men aged 57 and 66 years, respectively, are reported that resulted in sudden death from upper airway occlusion. The cause of the terminal event differed between the 2 cases with acute airway narrowing being precipitated by tenacious mucopurulent secretions in case 1 and hemorrhage from surface ulceration with glottic occlusion by blood clot in case 2. At autopsy, the immediate cause of acute airway compromise in cases of space-occupying laryngeal lesions may, therefore, be due to the synergistic effects of different factors.

Huge Tornwaldt Cyst With Otitis Media With Effusion.

Tornwaldt cyst is a relatively rare lesion that is found in the posterior wall of the nasopharynx. It occurs in the midline bursa of the nasopharynx and represents a persistent communication between the roof of the nasopharynx and the notochordal remnants. Smaller cysts are usually asymptomatic; cysts exceeding a diameter of 1 to 2 cm may be symptomatic. Magnetic resonance imaging is the best imaging modality for diagnosing Tornwaldt cyst. We present a rare case of a huge Tornwaldt cyst completely obstructing the nasopharyngeal airway.

Analysis of snoring to determine the site of obstruction in obstructive sleep apnea syndrome.

BACKGROUND: The aim of this study was to integrate the physical findings of drug-induced sleep endoscopy with snoring sound analysis in patients with obstructive sleep apnea/hypopnea syndrome (OSAS) and to compare the findings with previously published data. METHODS: This was a prospective, non-randomized study. Participants were all candidates for surgical treatment of OSAS and formed three groups, retropalatal (RP) obstructions, retrolingual (RL) obstructions, and multilevel (ML) obstructions. At the time of DISE, recordings of concurrent snoring sounds were made. Mean pitch frequency, peak sound frequency, and fundamental frequency (Fo) components were determined. RESULTS: A total of 55 participants had mean age 46.2 ± 7.3 years, mean BMI 30.0 ± 3.7 kg/m2, and included 11 women (20%). Differences in mean pitch frequency, Fo, and peak sound frequency were all statistically significant between the RP and RL (p = 0.001), between ML and RL (p = 0.025) but were not significantly different between RP and ML. Mean pitch frequency of RP was lower than RL, and ML frequency was between RL and RP. The sound analysis graphics revealed RP waves with sharp peaks and lower frequencies and RL with smooth curves and higher frequencies. ML showed irregular patterns. Mean pitch frequency of RL was always above 400 Hz, whereas RP was below this value. CONCLUSIONS: It is feasible to apply sound analysis to determine the site of obstruction during DISE. Combining the data may help surgeons make more accurate assessments of the pattern of the disease.

The evolution of pulmonary function in childhood onset Mucopolysaccharidosis type I.

Respiratory outcomes in Mucopolysaccharidosis Type I (MPS I), have mainly focused on upper airway obstruction, with the evolution of the restrictive lung disease being poorly documented. We report the long-term pulmonary function outcomes and examine the potential factors affecting these in 2 cohorts of MPS I patients, those who have undergone Haematopoietic Stem Cell Transplantation (HSCT) and those treated with Enzyme Replacement Therapy (ERT). The results were stratified using the American Thoracic Society (ATS) guidelines. 66 patients, capable of adequately performing testing, were identified by a retrospective case note review, 46 transplanted (45 Hurler, 1 Non-Hurler) and 20 having ERT (17 Non-Hurler and 3 Hurler diagnosed too late for HSCT). 5 patients died; 4 in the ERT group including the 3 Hurler patients. Overall 14% of patients required respiratory support (non-invasive ventilation (NIV) or supplemental oxygen)) at the end of follow up. Median length of follow-up was 12.2 (range = 4.9-32) years post HSCT and 14.34 (range = 3.89-20.4) years on ERT. All patients had restrictive lung disease. Cobb angle and male sex were significantly associated with more severe outcomes in the HSCT cohort, with 49% having severe to very severe disease. In the 17 Non-Hurler ERT treated patients there was no variable predictive of severity of disease with 59% having severe to very severe disease. During the course of follow up 67% of the HSCT cohort had no change or improved pulmonary function as did 52% of the ERT patients. However, direct comparison between therapeutic modalities was not possible. This initial evidence would suggest that a degree of restrictive lung disease is present in all treated paediatrically diagnosed MPS I and is still a significant cause of morbidity, though further stratification incorporating diffusing capacity for carbon monoxide (DLCO) is needed.