Office-based blue laser therapy for vocal fold polyps and Reinke's edema: a case study and review of the literature.

PURPOSE: To report the efficacy of blue laser in the treatment of vocal fold polyps and Reinke's edema in an office setting. METHODS: The medical records and video-recordings of patients who underwent office-based blue laser therapy in a tertiary referral center for vocal fold polyps and/or Reinke's edema were reviewed. The primary outcome measures were the Voice Handicap Index-10 (VHI-10) score and disease regression. Acoustic and aerodynamic parameters were also analyzed. RESULTS: Thirty-five patients (21 with vocal fold polyps and 14 with Reinke's edema) were included and a total of 47 lesions were treated. Out of the 35 patients, 7 patients were lost for follow-up. The mean VHI-10 score dropped significantly after surgery by 17.41 ± 8.67 points (p < 0.001). The endoscopic examinations of 38 lesions were reviewed (17 vocal fold polyps and 21 Reinke's edema) before and up to 6 months after laser therapy. In the subgroup with vocal fold polyps (N = 17), there was complete disease regression in 13 and partial in 4. In the subgroup with Reinke's edema (N = 21), there was complete disease regression in 7 and partial disease regression in 14. For patients with vocal fold polyp, there was a significant decrease in shimmer and a significant increase in maximum phonation time postoperatively. For patients with Reinke's edema, there was a significant decrease in shimmer and noise-to-harmonic ratio following treatment. CONCLUSION: Office-based blue laser therapy is an effective treatment for vocal fold polyps and Reinke's edema leading to complete or partial disease regression. All patients had improvement in voice quality.

Update on the pediatric adverse vocal behavior voice disorders: a clinical practice review.

The main causes of voice disorders in children with adverse vocal behavior include benign lesions of the vocal folds caused by voice abuse or misuses, such as vocal fold nodules, vocal fold polyps, and laryngitis. Long-term voice disorders can affect the physical and mental health of children. Reviewing the literature of the last two decades on "Vocal Fold Nodules," "Vocal Fold Polyp," "Voice disorder," "Voice Abuse," "Voice Misuse," "Pediatrics," and "Children" with the appropriate Boolean operators.  Conclusion: A total of 315 results were returned on an initial PubMed search. All articles from 2000 to 2022 written in English or Chinese were screened. Duplicate articles, those relating to adults only or concerned with the malignant lesion of the vocal cord, were excluded, resulting in 196 articles of interest. Relevant references and books have also been consulted, and we provide a review of the pathogenesis, diagnosis, and treatment of these maladaptive vocal behavioral voice disorders. What is Known: • Hoarseness is the most common voice symptom in children, and there are various causes of hoarseness in children. However, there is a lack of reviews on voice disorders caused by adverse vocal habits in children. • Voice training is a conservative treatment method for children with voice disorders , and it is important to clarify the factors that influence the effectiveness of voice training for children. What is New: • This review of the personality and family characteristics of children with adverse vocal behavioural voice disorders provides a valuable guide to the clinical planning of subsequent treatment. • This article discusses and summarises some of the factors that may influence the effectiveness of voice training in children and collates some of the scales and questionnaires currently used in children that are important in predicting the effectiveness of voice training.

Immunohistochemical Localization of D-ß-Aspartic Acid and Periostin in Vocal Fold Polyps.

Long-term voice abuse or sudden vocal fold microvascular disruption may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and also in various otolaryngological diseases. D-ß-aspartic acid is the major isomer of D-aspartic acid found in elderly tissue. In this study we investigated the expression and the role of D-ß-aspartic acid and periostin in the formation of vocal fold polyps. The expression patterns of D-ß-aspartic acid and periostin in 36 surgical specimens of vocal fold polyps from 36 patients were investigated immunohistochemically. In the epithelium of vocal polyps, D-ß-aspartic acid was expressed in all cases. Expression of D-ß-aspartic acid was detected in 25 samples obtained from patients with vocal fold polyps stroma. Expression of periostin was detected in 28 samples obtained from patients with vocal fold polyps. Two patterns of D-ß-aspartic acid expression were observed in vocal fold polyps stroma: positive type and negative type. The following four patterns of periostin expression were observed in vocal fold polyps: negative type, superficial type, infiltrative type, and diffuse type. An association was observed between D-ß-aspartic acid expression patterns and periostin expression patterns. From these findings we speculate that periostin and D-ß-aspartic acid participate in certain pathological changes in vocal fold polyps, such as extracellular matrix accumulation, local fibrosis, and the formation and development of vocal fold polyps.

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.

Expression of Periostin in Vocal Fold Polyps.

Long-term voice abuse or sudden vocal fold microvascular disruption may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and also in various otolaryngological diseases. The aim of this article was to investigate the expression and the role of periostin in the formation of vocal fold polyps. The expression patterns of periostin in 59 surgical specimens of vocal fold polyps from 54 patients were investigated immunohistochemically. Normal vocal fold mucosa specimens from 5 patients who had undergone total laryngectomy were used as the control group. Retrospective study with planned data collection was conducted at Tohoku Medical and Pharmaceutical University. Expression of periostin was detected in 43 (72.9%) samples and four patterns of periostin expression were observed in vocal fold polyps: negative type, superficial type, infiltrative type, and diffuse type. An association was observed between periostin expression patterns and the histological subtypes of vocal fold polyps. The infiltrative pattern of periostin expression was significantly dominant in vascular-hyaline types. Expression of transforming growth factor-ß (TGF-ß) was also detected in the vocal fold polyps. Our results confirmed that periostin might be involved in certain pathological changes in vocal fold polyps, such as extracellular matrix accumulation, local fibrosis, and formation and development of vocal fold polyps.

Localized laryngeal amyloidosis: A systematic review.

OBJECTIVE: The larynx is the most common site of localized head and neck amyloidosis. Our study aimed to review the clinical features, treatments, and outcomes associated with localized laryngeal amyloidosis (LA). We also compared these features between two different time periods to evaluate the evolution of LA management. METHODS: A literature search using PubMed, CINAHL, Embase, and Cochrane Library identified cases of LA published between 1891 and 2021. Biopsy-proven cases of localized LA were included. Non-English studies, animal studies, and reviews were excluded. RESULTS: 282 patients (1891-1999: 142 patients, 2000-2021: 140 patients) from 129 studies were included. Results are reported as 1891-2000 vs. 2000-2021: Mean age was 48.5 years (range, 8-90 years) vs. 46.0 years (range, 9-84 years). The most common presenting symptoms were dysphonia (n = 30, 95 % vs. n = 127, 96 %) and difficulty breathing (n = 37, 27 % vs. n = 35, 27 %). A total of 62 (44 %) vs. 46 (33 %) lesions were found in the true vocal folds and 35 (25 %) vs. 59 (42 %) were found in the false vocal folds. 133 (94 %) vs. 137 (98 %) patients underwent surgical interventions to investigate and/or treat LA. Recurrent LA was reported in 27 (19 %) vs. 33 (24 %) patients with a mean time to recurrence of 25.4 months (range, 0.3-132 months) vs. 34.5 months (range, 0.8-144 months). Of cases reporting survival rate, 104 (97 %) vs. 107 (99 %) were alive at source study endpoints. CONCLUSION: LA typically exhibits an indolent course; therefore, early intervention may address longstanding symptoms. Recurrent disease poses a clinical challenge in patients with LA.

Paediatric vocal fold nodules: management strategies to restore normal phonation-Speech-Language Pathologists perspective: A cross-sectional survey.

Vocal fold nodules are benign vocal cord lesions which develop in voice abusers, including children, though chronic cough, sinusitis, and reflux may also be the causative agents. Since low or no-evidence treatment strategies, like the boone technique, are in use in paediatrics, this study was conducted to determine the treatment strategies used by speech-language pathologists in paediatric vocal fold nodules using a cross-sectional survey at Riphah International University, Lahore, from October 2016 to May 2017. Sixty-five speech-language pathologists working with children in private clinics and multidisciplinary settings were recruited using purposive sampling. A self-structured questionnaire was used for data collection. Analysis using SPSS -18 revealed that a combination of voice therapy and vocal hygiene was the most favoured treatment used by 65 (100%) speech-language pathologists, followed by 58 (89.2%) who also favoured respiratory and relaxation exercises, and 56 (86.2%) who also included parental counselling. Hence, a combination of voice therapy and vocal hygiene is a good therapeutic technique being practiced by speech pathologists for the treatment of vocal nodules among paediatric population.

Laryngeal oncocytic cystadenoma and sudden death.

An 86-year-old woman with Alzheimer disease collapsed in her nursing home and was not able to be resuscitated. At autopsy, the major findings were in the larynx where a pedunculated oncocytic cystadenoma had occluded the glottis. Oncocytic cysts or cystadenomas of the larynx are rare histologically benign lesions that account for only 0.1-1% of laryngeal lesions. While the usual presentation is of a sensation of a mass in the throat, hoarseness, or stridor, very occasionally, there may be acute airway compromise and sudden death. Oncocytic cystadenoma should, therefore, be included in the differential diagnosis of potentially lethal obstructive laryngeal lesions.

Association of neutrophil-to-lymphocyte ratio with severe radiation-induced mucositis in pharyngeal or laryngeal cancer patients: a retrospective study.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that informs clinical decisions regarding recurrence and overall survival in most epithelial cancers. Radiotherapy for head and neck cancer leads to mucositis in almost all patients and severe radiation-mucositis affects their quality of life (QOL). However, little is known about the NLR for severe mucositis. Therefore, this study aimed to show the association between the NLR and severe radiation-induced mucositis in hypopharyngeal or laryngeal cancer patients. METHODS: In this retrospective study, we determined the incidence of grade 3 mucositis in 99 patients who were receiving definitive radiotherapy or chemoradiotherapy (CRT) for hypopharyngeal or laryngeal cancer. We performed univariate and multivariate logistic regression analyses to investigate the characteristics of grade 3 mucositis. Kaplan-Meier curves and log-rank tests were used to evaluate the occurrence of grade 3 mucositis between two groups with high (NLR > 5) or low (NLR < 5) systemic inflammation. RESULTS: The incidence of grade 3 mucositis was 39%. Univariate logistic regression analysis showed that the NLR (Odd ratio [OR] = 1.09; 95% confidence interval [CI] = 1.02-1.16; p = 0.016) and smoking (OR = 1.02; 95% CI = 1.00-1.03; p = 0.048) were significantly associated with grade 3 mucositis. Multivariate logistic regression analysis showed that the NLR was independently associated with grade 3 mucositis (OR = 1.09; 95% CI = 1.01-1.17; p = 0.021). Kaplan-Meier curves also showed that patients with higher NLR (NLR > 5) prior to radiotherapy developed grade 3 mucositis more frequently than those with lower NLR during radiotherapy (p = 0.045). CONCLUSION: This study suggests that a higher NLR is a risk factor and predictor of severe radiation-induced mucositis in hypopharyngeal or laryngeal cancer patients.

Mechanisms of larynx and vocal fold development and pathogenesis.

The larynx and vocal folds sit at the crossroad between digestive and respiratory tracts and fulfill multiple functions related to breathing, protection and phonation. They develop at the head and trunk interface through a sequence of morphogenetic events that require precise temporo-spatial coordination. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as specification of the laryngeal field, epithelial lamina formation and recanalization as well as the development and differentiation of mesenchymal cell populations. Nevertheless, many gaps remain in our knowledge, the filling of which is essential for understanding congenital laryngeal disorders and the evaluation and treatment approaches in human patients. This review highlights recent advances in our understanding of the laryngeal embryogenesis. Proposed genes and signaling pathways that are critical for the laryngeal development have a potential to be harnessed in the field of regenerative medicine.

Laryngeal mucous membrane pemphigoid serves as a prognostic factor for poor response to treatment with rituximab.

Mucous membrane pemphigoid (MMP) is an autoimmune blistering, scarring and occasionally mutilating disease that may progress to blindness or airway obstruction. Over the past few years, rituximab (RTX) has emerged as a potential therapeutic solution for MMP; however, the literature regarding its efficacy in the treatment of severe MMP is sparse. We studied four patients with recalcitrant MMP who were treated with RTX. Three of these had recalcitrant laryngeal disease; two were unresponsive to RTX, while the third patient achieved complete remission (CR) but relapsed twice. The fourth patient, who had oral and ocular disease, also achieved CR. In addition, we reviewed 143 cases of MMP treated with RTX reported in the literature to date. Of these, 120 had late observation endpoints, of whom 81 (67.5%) achieved CR, 24 (20%) received partial remission and 15 (12.5%) had no remission. Based on this study, the presence of laryngeal MMP seems to predict refractoriness to RTX treatment. In conclusion, we found that RTX can ameliorate the MMP course and that laryngeal involvement, which is known to be a prognostic factor for severe MMP, may also predict poor response to RTX.

Atypical presentation of immunoglobulin G4-related disease as subglottic stenosis: a case-based review.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory pathology that has been reported to affect principally the retroperitoneum, hepatobiliary system, salivary glands, orbital structures or lymph nodes. However, IgG4-RD with laryngeal involvement is a very rare entity. Our aims were to describe a case of subglottic stenosis as first and only manifestation of IgG4-RD and review the literature. A patient with IgG4-RD affecting the larynx that presented as subglottic stenosis is described. A MEDLINE database search of IgG4-RD cases with laryngopharyngeal manifestations was also conducted. A 30-year-old Caucasian woman was referred to a tertiary care hospital for dyspnea on exertion, which had been increasing for the last 4 months. Medical and surgical procedures revealed a subglottic stenosis, with a histological finding of IgG4 positive plasma cell infiltration. There was no evidence of other organ involvement. She was successfully treated with oral glucocorticoids and rituximab infusions. Glucocorticoids were rapidly tapered and the rituximab regimen was optimized, with no evidence of relapses. In the literature review, we found a total of 12 reported cases with laryngopharyngeal involvement, two of them with subglottic stenosis. IgG4-RD of the larynx is rare but should be considered after excluding more common disorders.

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.

[Molecular laryngology : A new chapter in the understanding of laryngeal diseases]. / Molekulare Laryngologie : Ein neues Kapitel im Verständnis laryngealer Erkrankungen.

BACKGROUND: Despite considerable advances in laryngological research, there is still a plethora of (benign) vocal fold pathologies that cannot be treated causally. This is due to the limited accessibility and sensitive microarchitecture of the vocal folds, which cannot be investigated at a cellular level. Consequently, current pathophysiological knowledge is frequently based on macroscopic findings. The impact of interventions is mainly evaluated endoscopically or via indirect diagnostic methods. OBJECTIVE: The aim of this article is to discuss state-of-the-art biotechnological methods used in laryngological research, illustrated by practical examples. RESULTS: In recent years, animal and in vitro experiments have significantly contributed to a continuous expansion of knowledge in this field, particularly regarding vocal fold inflammation and scar formation. Vocal fold fibroblasts, the most important cellular component of the lamina propria, can be accredited a central role in these processes. CONCLUSION: Our knowledge regarding macroanatomy and macropathophysiology of several pathologies has increased considerably in recent years. In vitro trials have shown, e.g., that vocal fold fibroblasts in an inflammatory setting secrete less profibrotic and proinflammatory cytokines when exposed to vibration. Early vocal exercises after surgical interventions on the vocal folds may therefore promote better wound healing and consequently improved phonation. Research in molecular laryngology should create a solid basis of knowledge for subsequent clinical studies.

A mutant MATR3 mouse model to explain multisystem proteinopathy.

Mutations in the Matrin 3 (MATR3) gene have been identified as a cause of amyotrophic lateral sclerosis (ALS) or vocal cord and pharyngeal weakness with distal myopathy (VCPDM). This study investigated the mechanism by which mutant MATR3 causes multisystem proteinopathy (MSP) including ALS and VCPDM. We first analyzed the muscle pathology of C57BL/6 mice injected with adeno-associated viruses expressing human WT or mutant (S85C) MATR3. We next generated transgenic mice that overexpress mutant (S85C) MATR3, driven by the CMV early enhancer/chicken ß-actin promoter, and evaluated their clinicopathological features. Intramuscular injection of viruses expressing WT and mutant MATR3 induced similar myogenic changes, including smaller myofibers with internal nuclei, and upregulated p62 and LC3-II. Mutant MATR3 transgenic mice showed decreased body weight and lower motor activity. Muscle histology demonstrated myopathic changes including fiber-size variation, internal nuclei and rimmed vacuoles. Spinal cord histology showed a reduced number of motor neurons, and activation of microglia and astrocytes. Comprehensive proteomic analyses of muscle demonstrated upregulation of proteins related to chaperones, stress response, protein degradation, and nuclear function. Overexpression of WT and mutant MATR3 similarly caused myotoxicity, recapitulating the clinicopathological features of MSP. These models will be helpful for analyzing MSP pathogenesis and for understanding the function of MATR3. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Which one is favorable in the elderly? Transoral rigid laryngoscopy or transnasal flexible fiberoptic laryngoscopy.

PURPOSE: To determine whether transoral rigid laryngeal endoscopy (TORLE) or transnasal flexible fiberoptic laryngoscopy (TNFFL) is more favorable for laryngeal endoscopic examination in the elderly population. METHODS: This randomized prospective study carried out in a tertiary reference center. TORLE or TNFFL were performed to patients who were over 65 years at their first visit according to randomization list. At their second visit, other method was performed. Patients' physiological parameters (Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and oxygen (O2) saturation before and immediately after laryngeal examination were recorded. Patients' pain-irritation, gag reflex, and dyspnea status were evaluated using visual analog scale after first and second endoscopic examinations. Further patient preferences for TORLE and TNFFL were recorded. RESULTS: Of 96 patients included in the study, 69.8% (n = 67) preferred TORLE while 30.2% (n = 29) preferred TNFFL. Major factor influencing patient preferences was pain-irritation in TNFFL. Pain-irritation scores were significantly higher in TNFFL than those in TORLE (p < 0.001). However, no significant difference was found between two methods with respect to gag reflex and dyspnea scores (p = 0.194, p = 0.327, respectively). In TORLE, there was no statistically significant difference between the values measured before and after examination in terms of SBP, DBP, HR, and O2 saturation (p = 0.641, p = 0.134, p = 0.119, p = 0.414, respectively). However, in TNFFL, statistically significant decrease was observed after examination in HR and O2 saturation (p < 0.001, p < 0.001, respectively). CONCLUSION: TORLE is more suitable for laryngeal examination in elderly patients since it is more comfortable for patient and does not change physiological parameters.

Anxiety and depression in patients with vocal fold nodules, edema and polyps.

PURPOSE: To compare the prevalence and severity of depression and anxiety among patients with vocal fold (VF) nodules, polyps and edema. At the same time the aim was to analyse association between severity of distress and the level of vocal handicap as well as to identify other factors related to severity of depression and anxiety in these patients. METHODS: To all participants were given five questionnaires: (1) questionnaire on socio-demographic and some other characteristics of patient; (2) Beck's Depression Inventory (BDI); (3) State-Trait Anxiety Inventory (STAI) 1 (State Anxiety); (4) STAI 2 (Trait Anxiety); and (5) Voice Handicap Index (VHI)-10. RESULTS: A total of 205 patients were included in this study. Mild-to-severe depression, according to BDI was present in 79 (38.6%) patients. Mild-to-severe state anxiety and trait anxiety were present in 199 (97.1%) and 200 (97.6%) patients, respectively. Only 10 patients had VHI-10 score ≤ 11. Multivariate analyses showed that there were no significant differences in the level of depression and anxiety between patients with VF nodules, polyps and edema. The VHI-10 score was significantly higher in patients with VF edema in comparison with VF nodule patients (p = 0.001), as well as in comparison with VF polyp patients (p = 0.001). CONCLUSION: The present study identified a high prevalence of psychological and vocal distress among patients with vocal disorders. Severity of depression and anxiety did not differ between patients with VF nodules, polyps and edema, and it was not related to the level of vocal handicap.

Value of pre- and intraoperative diagnostic methods in suspected glottic neoplasia.

PURPOSE: To evaluate the individual and combined ability of videostroboscopy (VS), high-speed digital imaging (HSDI), enhanced endoscopy (EE) and saline infusion (SI) to predict neoplasia, defined as glottic precursor lesion (GPL) or T1a glottic cancer, in patients suspected for glottic neoplasia. METHODS: A nationwide prospective cohort study of patients treated by cordectomy for suspected GPL or T1a glottic cancer from August 1st 2016 to October 31st 2018 was conducted in the five Danish University Departments of Head and Neck surgery. Sensitivity, specificity, negative and positive predictive values, and area under Receiver Operating Curves (AUC-ROC) were calculated with 95% confidence intervals with respect to the histological diagnosis. Logistic regression with an imputation model for missing data was applied. RESULTS: 261 patients aged 34-91 years participated; 79 (30.3%) with non-neoplasia (i.e., inflammation, papilloma, hyperkeratosis) and 182 (69.7%) neoplasia, hereof 95 (36.4%) with GPL and 87 (33.3%) with T1a glottic cancer. Data from 188 VS, 60 HSDI, 100 preoperative EE, 209 intraoperative EE, and 234 SI were analyzed. In the complete case analysis the AUC-ROC of each diagnostic test was low, but increased when the tests were combined and especially if the combination included EE. However, multinomial logistic regression with imputation showed significant association (p < 0.05) only between age, male gender, and perpendicular vasculature in intraoperative EE, and the endpoint neoplasia. CONCLUSIONS: Intraoperative EE was the most accurate diagnostic method in detecting neoplasia. The prediction ability of methods applied preoperatively was more limited, but improved when test modalities were combined.

Effect of Urban Particulate Matter on Vocal Fold Fibrosis through the MAPK/NF-κB Signaling Pathway.

Particulate matter (PM) is an environmental exposure factor that adversely affects human health. PM is a risk factor for various diseases. However, the mechanism by which PM affects the vocal folds (VF) has not yet been evaluated. Thus, we investigated the cytotoxic effects of PM on human vocal fold fibroblasts (hVFF) and the underlying signaling pathways. hVFF were isolated from human VF. The effect of PM on hVFF, and the underlying mechanism, were analyzed using Western blot, quantitative real-time polymerase chain reaction, and flow cytometry. In addition, a histological evaluation was performed in animal experiments. Cell proliferation decreased after the PM treatment. PM increased the expression of interleukin (IL)-6 and IL-1ß. The generation of reactive oxygen species (ROS) in PM-treated hVFF and subsequent activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were confirmed. Furthermore, PM increased the expression of fibrosis-related markers and induced the accumulation of collagen in the extracellular matrix. As a result, PM exposure significantly enhances the inflammatory response on VF through the ROS-mediated activation of the MAPK and NF-κB signaling pathways. In addition, PM promotes differentiation into myofibroblasts and induces fibrosis. These results suggest that PM triggers an inflammatory reaction through ROS production and causes VF fibrosis.

Death Shortly after Delivery Caused by Congenital High Airway Obstruction Syndrome.

Background: Congenital High Airway Obstruction Syndrome (CHAOS) is an uncommon anomaly. Prenatal ultrasonography allows a prenatal diagnosis to prepare for immediate surgical correction at birth. If the obstruction is severe and a correct therapeutic approach is not planned, CHAOS can cause neonatal death shortly after delivery from a potentially surgically correctable lesion.Case report: This neonate died unexpectedly shortly after delivery due to CHAOS. Ultrasonographic findings of enlarged echogenic lungs, dilated airways distal to the obstruction, flattened or inverted diaphragms, or ascites were absent. This was due to a type-II laryngeal-atresia and a type-C esophageal-atresia, with a resultant distal fistula that allowed intrauterine decompression of the fluid in the lungs.Conclusions: The absence of prenatal ultrasonographic findings of CHAOS may be due to a lower fistula between respiratory and gastrointestinal tracts. This set of associations may not be a surgically correctable cause of CHAOS.