The role of adenoid immune phenotype in polysensitized children with allergic rhinitis and adenoid hypertrophy.

BACKGROUND: There is increasing interest in elucidating the relationship between adenoid hypertrophy (AH) and allergic rhinitis (AR). However, the impact of aeroallergen sensitization patterns on children with AH and AR remains unclear. METHODS: Patients aged 2-8 years (recruited from January 2019 to December 2022) with nasal symptoms were assessed for allergies, adenoid size, and respiratory viral infection history. The serum total immunoglobulin E (IgE) and specific IgE levels were measured, and flexible nasal endoscopy was performed. The relationship between AH, aeroallergen sensitization patterns, and lymphocyte subpopulations in adenoid samples was analyzed using flow cytometry. RESULTS: In total, 5281 children were enrolled (56.5% with AR; and 48.6% with AH). AH was more prevalent in children with AR. Compared to nonsensitized individuals, those polysensitized to molds had a higher prevalence of AH (adjusted OR 1.61, 95% CI 1.32-1.96) and a greater occurrence of two or more respiratory viral infections, particularly in adenoidectomy patients. The percentages and corrected absolute counts of regulatory T (Treg) cells, activated Tregs, class-switched memory B cells (CSMBs), natural killer (NK) T cells, and NK cell subpopulations were reduced in the adenoid tissues of children with both AH and AR (AH-AR) compared to AH-nAR children. Polysensitization in AH-AR children correlated with lower CSMB percentages. CONCLUSION: Polysensitivity to molds is associated with an increased risk of AH in children with AR. Fewer B cells, NK cells, and Treg cells with an effector/memory phenotype were detected in the adenoids of AR children, and these lower percentages of immune cells, particularly CSMBs, were closely linked to aeroallergen sensitization models and respiratory viral infection.

Auxiliary rehabilitation training after calf contouring with botulinum toxin type A injection reduces adverse reactions and improves satisfaction.

PURPOSE: To analyze the effect of adjuvant rehabilitation training after calf contouring with botulinum toxin type A (BTX-A) injection. METHODS: Clinical data of 48 female beauty seekers who underwent calf contouring at the Plastic Surgery Laser Center of Guangdong Second People's Hospital from January 2021 to June 2022 were retrospectively analyzed. Among them, 24 cases received routine care from January 2021 to December 2021 and were included in a control group, and 24 cases received rehabilitation care with auxiliary rehabilitation training from January 2022 to June 2022 that were in an observation group. The subjects were followed up for 24 weeks to observe the curative effect, and the injection efficacy was compared between the two groups. The maximum calf circumference (MCC) and gastrocnemius muscle thickness (GMT) were comparatively analyzed before and 2, 4, 12, and 24 weeks after treatment. The incidence of adverse reactions and satisfaction rate were also compared. RESULTS: Both groups showed reduced calf circumferences after injection, with soft and uniform calf curves. No inter-group statistical significance was identified in terms of curative effects. Reduced MCC and GMT were observed in both groups at 2, 4, 12, and 24 weeks after treatment, with lower values in the observation group than in the control group at week 2, 4, and 12. The observation group also showed markedly fewer adverse reactions and higher satisfaction rate than the control group. CONCLUSIONS: BTX-A injection is effective in calf contouring and can significantly reduce the MCC and GMT. In addition, post-injection rehabilitation training can significantly reduce the occurrence of adverse reactions and improve patient satisfaction.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

New approach to establish a surgical planning in infantile vallecular cyst synchronous with laryngomalacia based on aerodynamic analysis.

BACKGROUND AND OBJECTIVES: A large proportion of infants with vallecular cyst (VC) have coexisting laryngomalacia (LM). Feeding difficulties, regurgitation, occasional cough, and sleep-disordered breathing are the common symptoms in moderate to severe cases. The surgical management of these cases is more challenging and remains controversial. The purpose of this study is to help surgeons select the effective surgical strategies by computer-aided design (CAD) and computational fluid dynamics (CFD) simulations of the upper airway flow characteristics. METHODS: The three dimensional (3D) geometric model of the upper airway was reconstructed based on two dimensional (2D) medical images of the patient with VC accompanied with LM. Virtual surgeries were carried out preoperatively to simulate three possible post-operative states in silico. The different outcomes of virtual surgical strategies were predicted based on computational evaluations of airway fluid dynamics including pressure, resistance, velocity, and wall shear stress (WSS). RESULTS: The CFD results of this study suggested the importance of the angle between the rim of epiglottis and arytenoid epiglottic (AE) fold. There was a small impact on the upper airway flow field while the VC was removed and the angle of epiglottis was unchanged. The partial lifting of epiglottis can further improve the flow field. With performing supraglottoplasty (SGP) and the marsupialization of VC, epiglottis was completely recovered, and the flow field was significantly improved. The clinical symptoms of this patient improved greatly after surgeries and no recurrence or growth retardation were noted during 1-year follow-up. The clinical prognosis was consistent with the prediction of the CFD results. CONCLUSIONS: The state of epiglottis needs to be carefully checked to evaluate the necessity of performing further SGP in the patients with VC accompanied with LM. CFD and CAD could be developed as a new approach to help surgeons predict the post-operative outcomes through quantification of the airflow dynamics, and make the optimal and individualized surgical approaches for patients with airway obstruction.

Ectopic thymic tissue in subglottis of children: evaluation and management.

OBJECTIVES: Ectopic thymic tissue in the subglottis is an extremely rare disease that causes airway obstruction. Few cases reported were accurately diagnosed before surgery. METHODS: A case of a 2-year-old boy with airway obstruction caused by a left subglottic mass was reported. The presentation of radiological imaging, direct laryngoscopy and bronchoscopy, pathology, and surgical management were reviewed. An extensive search in PubMed, EMBASE, Web of Science, Google Scholar, and EBSCO of English literature was performed without a limit of time. RESULTS: Besides our case, only six cases were reported since 1987. The definitive diagnosis on these patients were made with the findings of pathology, of which, five were ectopic thymus and two were ectopic thymic cysts. Our case was the only one with a correct suspicion preoperatively. Four cases underwent open surgical resection, and two cases underwent microlaryngeal surgery, while one deceased after emergency tracheostomy. No recurrences were found by six patients during the follow-up after successful treatments. CONCLUSION: Ectopic thymus is a rare condition, infrequently considered in the differential diagnosis of subglottic masses. Modified laryngofissure may be an effective approach to removing the subglottic ectopic thymus and reconstructing the intact subglottic mucosa.

Ectopic thymic tissue in subglottis of children: evaluation and management

Abstract Objectives: Ectopic thymic tissue in the subglottis is an extremely rare disease that causes airway obstruction. Few cases reported were accurately diagnosed before surgery. Methods: A case of a 2-year-old boy with airway obstruction caused by a left subglottic mass was reported. The presentation of radiological imaging, direct laryngoscopy and bronchoscopy, pathology, and surgical management were reviewed. An extensive search in PubMed, EMBASE, Web of Science, Google Scholar, and EBSCO of English literature was performed without a limit of time. Results: Besides our case, only six cases were reported since 1987. The definitive diagnosis on these patients were made with the findings of pathology, of which, five were ectopic thymus and two were ectopic thymic cysts. Our case was the only one with a correct suspicion preoper-atively. Four cases underwent open surgical resection, and two cases underwent microlaryngeal surgery, while one deceased after emergency tracheostomy. No recurrences were found by six patients during the follow-up after successful treatments. Conclusion: Ectopic thymus is a rare condition, infrequently considered in the differential diagnosis of subglottic masses. Modified laryngofissure may be an effective approach to removing the subglottic ectopic thymus and reconstructing the intact subglottic mucosa.

Boundary-Preserved Deep Denoising of Stochastic Resonance Enhanced Multiphoton Images.

OBJECTIVE: With the rapid growth of high-speed deep-tissue imaging in biomedical research, there is an urgent need to develop a robust and effective denoising method to retain morphological features for further texture analysis and segmentation. Conventional denoising filters and models can easily suppress the perturbative noise in high-contrast images; however, for low photon budget multiphoton images, a high detector gain will not only boost the signals but also bring significant background noise. In such a stochastic resonance imaging regime, subthreshold signals may be detectable with the help of noise, meaning that a denoising filter capable of removing noise without sacrificing important cellular features, such as cell boundaries, is desirable. METHOD: We propose a convolutional neural network-based denoising autoencoder method - a fully convolutional deep denoising autoencoder (DDAE) - to improve the quality of three-photon fluorescence (3PF) and third-harmonic generation (THG) microscopy images. RESULTS: The average of 200 acquired images of a given location served as the low-noise answer for the DDAE training. Compared with other conventional denoising methods, our DDAE model shows a better signal-to-noise ratio (28.86 and 21.66 for 3PF and THG, respectively), structural similarity (0.89 and 0.70 for 3PF and THG, respectively), and preservation of the nuclear or cellular boundaries (F1-score of 0.662 and 0.736 for 3PF and THG, respectively). It shows that DDAE is a better trade-off approach between structural similarity and preserving signal regions. CONCLUSIONS: The results of this study validate the effectiveness of the DDAE system in boundary-preserved image denoising. CLINICAL IMPACT: The proposed deep denoising system can enhance the quality of microscopic images and effectively support clinical evaluation and assessment.

[Metagenome-wide association of gut microbiome features in children with moderate-severe house dust mite allergic rhinitis].

Objective:To draw a distinct gut microbiota pattern of children with moderate-severe dust mite-induced allergic rhinitis（DAR） and healthy children. Methods:3-10 years old moderate-severe DAR children（68 cases） and healthy children（38 cases） were involved in this study. General information was collected through questionnaires, and fecal samples were collected for metagenomic sequencing. MetaPhlAn3 was used to generate the microbiota composition abundance in detail, and Alpha and Beta diversity changes were calculated. The difference in species abundance at different taxonomic levels were compared. Differences in functional pathways were compared by LEfSe analysis. Results:The diversity of gut microbiota in children with moderate-severe DAR didn't change significantly compared with healthy children. A total of 37 microbial communities or species with significant abundance difference were found, mainly included Lachnoclostridium, Prevotella, Blautia wexlerae, Prevotella copri, Eubacterium eligens, Eubacterium sp CAG 180, etc. However, the metabolism functions of gut microbiota in children with moderate-severe DAR changed compared with healthy children. Various of fatty acids anabolism enhanced in DAR children. Conclusion:Compared with healthy children, there was no significant difference in gut microbial diversity in moderate-severe DAR children. The abundance of a series of specific microbe species had a marked alteration in DAR, accompanied with changes in certain microbial functional pathways.

The Correlation between the Inflammatory Effects of Activated Macrophages in Atherosclerosis and Aortic Dissection.

BACKGROUND: To study the correlation between lipid metabolism index, inflammatory factor index, and M1 macrophage content and aortic dissection. METHODS: Patients with only basic atherosclerotic diseases were selected as the control group, and patients with only basic atherosclerotic diseases and aortic dissection were set as the experiment group. Blood of patients was collected. Chemiluminescent immunoassay was applied to determine the concentration of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B1 (ApoB1). Enzyme-linked immunosorbent assay was applied to measure the concentration of tumor necrosis factor-α (TNF-α), Interleukin 1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10). The content of M1 macrophages in blood was measured with the flow cytometry (FCM) method. The correlation between the inflammatory effects of activated macrophages in atherosclerosis and aortic dissection was analyzed by a simple linear regression analysis. RESULTS: Concentration of TC, TG, LDL-C, and ApoB and the concentration of TNF-α, IL-1ß, and IL-6 in the experiment group were markedly higher compared to those in the control group, whereas the concentration of HDL-C and ApoA1 and IL-10 concentration in the experiment group was markedly lower. The content of M1 macrophage in the control group was significantly lower compared to the experiment group. The proportion of M1 macrophages, concentration of TC, TG, LDL, HDL, ApoA1, and ApoB1, and concentration of TNF-α, IL-1ß, IL-6, and IL-10 were all significantly correlated to the occurrence of aortic dissection. CONCLUSIONS: The proportion of M1 macrophages, concentration of TC, TG, LDL, HDL, ApoA1, and ApoB1, and concentration of TNF-α, IL-1ß, IL-6, and IL-10 are significantly correlated with the occurrence of aortic dissection.

Assessing the impact of air pollutants on clinical visits for childhood allergic respiratory disease induced by house dust mite in Shanghai, China.

BACKGROUND: The prevalence of allergic respiratory disease (ARD) is increasing worldwide during the last few decades, causing a great disease burden especially for children. Air pollution has been increasingly considered as a potential contributor to this trend, but its role in ARD induced by house dust mite (HDM-ARD) remains unclear, especially in time-series study. METHODS: A positive reporting of respiratory allergy to named allergens was included by serum specific IgE testing. A time series Quasi-Poisson regression with distributed lag non-linear model, combined with generalized linear model was used to examine the effects of air pollutants on ARD, HDM-ARD and ARD induced by non-house dust mite (NHDM-ARD). RESULTS: A total of 16,249 cases of ARD, including 8,719 HDM-ARD and 8,070 NHDM-ARD from 1 Jan 2013 to 31 Dec 2017 were involved in this study. Air pollutants were significantly associated with clinical visits for childhood ARD and HDM-ARD. Exposure to higher O3 and interquartile range (IQR) increment in O3 (40.6 µg/m3) increased the risks of clinical visits for childhood HDM-ARD (RRlag0-5 for the 95th percentile of O3: 1.26, 95% confidence interval (CI): 1.03, 1.55; RRlag0-5 for IQR increment (40.6 µg/m3): 1.09, 95% CI: 1.01, 1.17) and ARD (RRlag0-5 for the 95th percentile of O3: 1.19, 95% CI: 1.03, 1.38; RRlag0-5 for IQR increment (40.6 µg/m3): 1.06, 95% CI: 1.01, 1.12). In addition, higher O3 was associated with increased RR of boys with ARD (RRlag0-5 for the 95th percentile: 1.26, 95% CI: 1.05, 1.51; RRlag0-5 for IQR increment (40.6 µg/m3): 1.09, 95% CI: 1.02, 1.16) and HDM-ARD (RRlag0-5 for the 95th percentile: 1.36, 95% CI: 1.06, 1.75; RRlag0-5 for IQR increment (40.6 µg/m3): 1.11, 95% CI: 1.02, 1.22), but not in girls. CONCLUSIONS: Exposure to O3 appeared to be a trigger of clinical visits for childhood ARD, especially for HDM-ARD and boys. These findings provide novel evidence on the impact of air pollution on HDM-ARD, which may have significant implications for designing effective intervention programs to control and prevent childhood ARD, especially HDM-ARD, in China and other similar developing countries.

GWAS-identified variants to allergic disease and early environmental exposure in Chinese schoolchildren with allergic rhinitis induced by house dust mite.

BACKGROUND: There is growing evidence that environmental exposure in early life is associated with the development of childhood allergic rhinitis. OBJECTIVE: To investigate whether polymorphisms in previously published genome wide association studies (GWAS) allergic disease loci are associated with childhood house dust mite-induced allergic rhinitis (HDM-AR) and interaction effects of genetic and environmental factors on it. METHODS: 156 cases diagnosed by HDM-AR and 173 controls were enrolled. Potential confounders were analyzed by using Logistic regression. Twenty-one single nucleotide polymorphisms (SNPs) of GWAS-related allergic diseases including EMSY-LRRC32, IL18R1, IL18RAP, IL13, IL4, HLA region, KIF3A were genopyped and analyzed using the improved multiplex ligation detection reaction (imLDR) technique in all the subjects. RESULTS: Only IL18R1_rs2287037 was associated with HDM-AR in children. After adjusting for several likely confounders, the protective TT genotype of IL18R1_rs2287037 was found in the population analyzed with the fittest recessive model. (adjusted odds ratio [aOR]: 0.44; 95% confidence interval [CI]: 0.21-0.95). The rs2287037_ TT might interact with early-life exclusive breastfeeding in the first 4 months (aOR: 0.33; 95%CI: 014-0.97) or full-term birth (aOR: 0.45; 95%CI: 0.19-0.95) exposure to decrease the risk of HDM-AR. CONCLUSIONS: These data suggest that IL18R1 polymorphism may play a role in controlling risk to HDM-AR and underline the importance of early environmental exposure into studies of genetic risk factors.

Down-Regulated miR-130a/b Attenuates Rhabdomyosarcoma Proliferation via PPARG.

Background: Rhabdomyosarcoma (RMS) is one of the most common types of soft-tissue sarcomas in children, and it exhibits a low 5-years survival rate. The survival outcome has shown no significant improvements in the past 30 years miRNA profiling of RMS might therefore provide a novel insight into uncovering new molecular targets for therapy. Methods: We analyzed miRNA and RNA sequencing data from patients and the TARGET database to reveal the potential miRNA-mRNA axes and validated them in patients' samples. After the miRNA antagomirs were used to silence the target miRNAs in the cell model, qRT-PCR, western immunoblotting analysis, and proliferation assays were performed to explore the interaction between miR-130a/b and peroxisome proliferator-activated receptor gamma (PPARG) and their effects. Results: In RMS patients, the expression of miR-130a/b was augmented, and its related PPARG gene was suppressed. Bioinformatics analysis showed that miR-130a/b targeted the PPARG gene and inhibited the proliferation of human RMS cell lines. In addition, rosiglitazone maleate activated the expression of PPARG in human RMS cell lines to suppress proliferation. Conclusion: miR-130a/b regulates the malignant process in RMS by targeting PPARG. Furthermore, the PPARG agonist rosiglitazone maleate attenuated the proliferation of RD cells and might therefore be of benefit to RMS patients.

[Role of gut microbiota in children with allergic rhinitis with high serum total IgE level].

Objective:To study the role of gut microbiota in children with allergic rhinitis with high serum total IgE level. Method:A total of 17 cases of children in Shanghai Children's Medical Center of Shanghai Jiao Tong University School of Medicine, who suffered from perennial allergic rhinitis of grade 5-6, were enrolled in this study. Baseline information were collected from all participants. Peripheral blood was collected to test the level of serum total IgE and specific IgE. Fecal samples were collected for bacterial DNA extraction and sequenced by 16S rDNA high-throughput sequencing. R, Mother and LEfSe softwares were used for diversity analysis, relative abundance calculation and differential species detection. Result:Twenty-three fecal samples were collected in total, including thirteen in attack period（attack group） and ten in control period（control group）. In the attack group, six cases were serum total IgE positive（positive group） and seven were negative（negative group）. Compared with the control group, there was no significant difference in either Alpha diversity or Beta diversity of Weighted Unifrac in the attack group（P>0.05）. The relative abundance of odoribacteraceae and odoribacter were significantly increased in the attack group（LDA score>2）. The relative abundance of Porphyromonadaceae in positive group were significantly lower than that in negative group, while family Dethiosulfovibrionaceae genus Pyramidobacter was definitely higher on the contrast（LDA score>2）. Conclusion:Children with allergic rhinitis have different characteristics of intestinal flora during the attack and control period. Gut microbiota is associated with high serum total IgE level in children with allergic rhinitis. Specific microbial alterations play a potential role in disease pathophysiology.

Efficacy of Chinese Medicine Acupoint Application Combined with Montelukast on Children with Perennial Allergic Rhinitis: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of Chinese medicine acupoint application (CMAA) combined with Western medicine for perennial allergic rhinitis (PAR) in children. METHODS: In this prospective, parallel, randomized, placebo-controlled and single-blind trial from August to September, 2017, 180 children with PAR were randomly assigned to an integrative group (CMAA and Montelukast), CMAA group (CMAA and placebo tablet), or Montelukast group (placebo CMAA and Montelukast). Participants were applied with CMAA for 6 sessions over 2 weeks, and/or Montelukast Chewable Tablet orally once daily for 12 weeks. The changes in severity of symptoms were measured by Visual Analog Scale (VAS) and rhinitis control assessment test (RCAT) at 0, 2, 4 and 12 weeks of treatment. Blood samples were collected for serum interleukin-4, interferon gamma γ and T helper type 1 (Th1)/Th2 flow cytometric analysis at the time points of 0, 4 and 12 weeks. RESULTS: Eight cases dropped out from the trial, 3 in the integrative group, 2 in the CMAA group and 3 in the Montelukast group. The VAS scores decreased significantly while the RCAT scores increased significantly in all three groups at 4 and 12 weeks compared with baseline (P<0.01 or P<0.05). The VAS scores were significantly lower while the RCAT scores were significantly higher in the integrative and CMAA groups than the Montelukast group at 2 and 4 weeks (P<0.01 or P<0.05). At 2, 4 and 12 weeks, the scores of nasal congestion, sneezing, sleep problem, and rhinitis symptom control in the integrative and CMAA groups increased significantly compared with baseline (P<0.01 or P<0.05). The least percentages of Th2 and the most alleviated Th2 shift (highest Th1/Th2) were observed in the integrative group at 12 weeks compared with the other two groups (P<0.05). CONCLUSION: The combination of CMAA with Montelukast might be more effective and appropriate than either option alone for children with PAR. (Registered at Chinese Clinical Trial Register, registration No. ChiCTR-IOR-17012434).

Familial and genetic factors in laryngeal cleft: Have we learned anything?

INTRODUCTION: Laryngeal clefts are rare congenital anomalies characterized by failed fusion of the posterior cricoid lamina or incomplete development of the tracheoesophageal septum. While most cases are sporadic, laryngeal cleft may be associated with other congenital anomalies or syndromes. Though not frequently reported, familial occurrence of laryngeal cleft has been noted in our clinical experience. The goal of this research is to describe the existing literature and our own experience surrounding familial occurrence of laryngeal cleft that may help elucidate its underlying genetic basis. METHODS: Comprehensive literature search was conducted and retrospective chart review was performed on 8 sets of siblings diagnosed at our institution. Data assessed included demographics, type of cleft, and genetic findings. RESULTS: Laryngeal cleft appears to be mostly sporadic. We evaluated data at our institution over a 10-year period and identified 19 patients from 8 families demonstrating familial occurrence of laryngeal cleft. Six (75%) families had two affected siblings, one family (12.5%) had three affected siblings, and one family (12.5%) had four affected siblings. There was no evidence of sex predilection, with half the patients being male (10/19, 52.6%). Fourteen patients (73.7%) had Type 1 clefts and five (26.3%) had Type 2 clefts. Genetic findings were available for review in five patients from three families. CONCLUSION: Beyond a few known syndromes, laryngeal cleft has largely been thought to be sporadic. However, findings from the existing literature and our own experience with familial laryngeal cleft in eight families suggest additional genetic factors are yet to be elucidated.

Computational Evaluation of Surgical Design for Multisegmental Complex Congenital Tracheal Stenosis.

Multisegmental complex congenital tracheal stenosis (CTS) is an uncommon but potentially life-threatening malformation of the airway. Staged surgery is indicated for the complex pathophysiology of the abnormal trachea. Surgical intervention to fix the stenotic segments may result in different postoperative outcomes. However, only few studies reported the design of surgical correction for multisegmental CTS. We used computer-aided design (CAD) to simulate surgical correction under different schemes to develop a patient-specific tracheal model with two segmental stenoses. Computational fluid dynamics (CFD) was used to compare the outcomes of different designs. Aerodynamic parameters of the trachea were evaluated. An obvious interaction was found between the two segments of stenosis in different surgical designs. The surgical corrective order of stenotic segments greatly affected the aerodynamic parameters and turbulence flows downstream of tracheal stenosis and upstream of the bronchus. Patient-specific studies using CAD and CFD minimize the risk of staged surgical correction and facilitate quantitative evaluation of surgical design for multiple segments of complex CTS.

Current evaluation and management of plastic bronchitis in the pediatric population.

OBJECTIVE: To describe a multidisciplinary approach for the treatment of plastic bronchitis (PB) in children. METHODS: Retrospective chart review of children with PB between 1997 and 2017. Data regarding clinical presentation, diagnosis, management, and outcomes were analyzed. RESULTS: Of 34 patients presenting with PB, 24 had single ventricle (SV) heart disease, 9 had pulmonary disease, and one had no underlying disease. Median (IQR: interquartile range) age at the time of PB diagnosis was 5.5 years (IQR: 9.0). Presenting symptoms included cough productive of casts (n = 27, 79%), wheezing (n = 5, 15%), dyspnea (n = 18, 53%), hypoxia (n = 31, 91%), and respiratory failure (n = 9, 26%). Diagnosis was made based on clinical evaluation, bronchoscopy findings, and/or pathology of casts. Treatment methods included bronchoscopy for cast removal (25% of SV patients, 91% of non-SV patients), chest physiotherapy (SV: 92%, non-SV: 45%), albuterol (SV: 79%, non-SV: 73%), inhaled steroids (SV: 75%, non-SV: 18%), nebulized hypertonic saline (SV: 29%, non-SV: 9%), nebulized heparin (SV: 8%, non-SV: 55%), nebulized tissue plasminogen activator (tPA; SV: 33%, non-SV: 9%), inhaled Dornase Alfa (SV: 54%, non-SV: 9%), antibiotics (SV: 46%, non-SV: 45%), systemic steroids (SV: 13%, non-SV: 45%), and lymphatic embolization (SV: 8%, non-SV: 45%). Of SV patients, 11 had no recurrence, 5 underwent heart transplantation, one awaits transplant, and 3 died due to cardiac disease. Three patients with respiratory disease had recurrent PB and one died from MRSA pneumonia. CONCLUSION: PB is a highly morbid disease with limited treatment options. Bronchoscopy and chest physiotherapy for airway clearance are among the most-utilized therapies.

Genetic factors in isolated and syndromic laryngeal cleft.

A laryngotracheoesophageal cleft (LC) is a rare congenital anomaly of the upper aerodigestive tract resulting from the absence of fusion of the posterior cricoid lamina, which affects an abnormal communication between the larynx, trachea and esophagus. The genetic etiology of LC remains elusive. The involvement of genetic factors in the development of LC is suggested by reports of familial occurrence, and the increased prevalence of component features among first-degree relatives of affected individuals and murine knockout models. No consistent pattern of inheritance has been found in nonsyndromic patients, except for cases associated with described syndromes. Once the syndrome related to the laryngeal cleft is considered, an active search for the cleft must be initiated. The genetic evaluation of patients with LCs should be guided by the type and location of the malformation, specific medical history and a detailed physical examination. The application of genetic approaches, such as microarrays and exome sequencing might lead to elucidating the etiology of LCs.

Early-Life Environmental Factors, IFN-γ Methylation Patterns, and Childhood Allergic Rhinitis.

BACKGROUND: While early-life risk factors are known to influence the risk of allergies, the biological mechanisms underlying this observation are unclear. The aim of this study was to examine whether DNA methylation in childhood could underlie the association between early-life risk factors and allergic rhinitis (AR). METHODS: In total, 234 patients, aged 6 years, were recruited, i.e., 114 were patients with AR (AR group) and 120 healthy children without AR (NAR group). The DNA methylation patterns of the IFN-γ promoter regions in CD4+ cells were analyzed using bisulfite sequencing. The percentage of Th1 was investigated by flow cytometry. The relationship among DNA methylation, early-life environment, and AR was examined. RESULTS: After adjusting for several likely confounders, there was a higher likelihood of AR in children who had mothers with allergies than in children who had nonallergic mothers (OR = 5.19; 95% CI 1.18-29.41), in children who were born in autumn or winter than in children who were born in the summer or spring (OR = 2.69; 95% CI 1.34-5.40), and in children who lived with indoor carpet or wallpaper than in children who lived without indoor carpet or wallpaper (OR = 4.14; 95% CI 2.05-8.30). Compared to the NAR group, the AR group had higher mean methylation levels of the promoter region in IFN-γY, and lower numbers of IFN-γ+CD4+ cells were associated with autumn-winter birthdates. The season of birth had an indirect effect on AR at 6 years, which was mediated by the mean IFN-γ promoter methylation level. CONCLUSIONS: This study suggests that early-life environments affect AR, and this is supported by the finding of IFN-γY methylation as a mediator of the effect of an individual's season of birth on AR.