Airway Impedance: A Novel Diagnostic Tool to Predict Extraesophageal Airway Inflammation.

OBJECTIVE: To validate a novel biomarker, airway impedance for extraesophageal disease. STUDY DESIGN: We prospectively recruited patients with respiratory symptoms undergoing combined endoscopy and direct laryngoscopy for the evaluation of symptoms. The direct laryngoscopy was performed and videotaped for blinded scoring by 3 otolaryngologists and an impedance catheter was placed onto the posterior larynx to obtain measurements. Following this, an endoscopy was performed and impedance measurements and biopsies were taken at 3 esophageal heights. Impedance values were compared within and between patients. RESULTS: Eighty-eight patients were recruited, of which 73 had complete airway and endoscopic exams. There was no significant correlation between airway impedance values and mean reflux finding scores (r2 = 0.45, P = .07). There was no significant positive correlation between airway impedance and esophageal impedance values (r2 = 0.097-0.138, P > .2). Patients taking proton pump inhibitors had significantly lower mean airway impedance values (706 ± 450 Ω) than patients not taking them (1069 ± 809 Ω, P = .06). Patients who had evidence of aspiration on video fluoroscopic swallow studies had lower airway impedance (871 ± 615 Ω) than patients without aspiration (1247 ± 360 Ω, P = .008). Inhaled steroids did not impact airway impedance levels (P = .7). CONCLUSIONS: Airway impedance may be an important diagnostic tool to diagnose gastroesophageal reflux or aspiration, eliminating the subjectivity of airway appearance alone.

Outpatient Respiratory Management of Infants, Children, and Adolescents with Post-Prematurity Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Premature birth affects millions of neonates each year, placing them at risk for respiratory disease due to prematurity. Bronchopulmonary dysplasia is the most common chronic lung disease of infancy, but recent data suggest that even premature infants who do not meet the strict definition of bronchopulmonary dysplasia can develop adverse pulmonary outcomes later in life. This post-prematurity respiratory disease (PPRD) manifests as chronic respiratory symptoms, including cough, recurrent wheezing, exercise limitation, and reduced pulmonary function. This document provides an evidence-based clinical practice guideline on the outpatient management of infants, children, and adolescents with PPRD. Methods: A multidisciplinary panel of experts posed questions regarding the outpatient management of PPRD. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. Results: The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Recommendations were developed for or against three common medical therapies and four diagnostic evaluations in the context of the outpatient management of PPRD. Conclusions: The panel developed recommendations for the outpatient management of patients with PPRD on the basis of limited evidence and expert opinion. Important areas for future research were identified.

Acid Suppression Does Not Improve Laryngomalacia Outcomes but Treatment for Oropharyngeal Dysphagia Might Be Protective.

OBJECTIVE: To determine whether the use of acid suppression and thickened feeds impact laryngomalacia outcomes in infants, including supraglottoplasty risk, time to supraglottoplasty, and hospitalization risk. STUDY DESIGN: We performed a retrospective cohort study to compare risk and time with supraglottoplasty and frequency and duration of hospitalizations for infants diagnosed with laryngomalacia at Boston Children's Hospital between January 1 and December 31, 2017. The primary outcomes were supraglottoplasty requirement, time to supraglottoplasty, and hospitalization risk. Multivariate analyses were performed to determine predictors of supraglottoplasty and hospitalization risk after adjusting for laryngomalacia severity and comorbidities in addition to propensity score adjustment. Kaplan-Meier curves were created to determine the impact of acid suppression use on time to supraglottoplasty. RESULTS: In total, 236 subjects with mean age 62.6 ± 4 days were included in the analysis; 55% were treated with acid suppression. Subjects treated with acid suppression had a greater risk of supraglottoplasty (hazard ratio 3.36, 95% CI 1.36-8.29, P = .009), shorter time to supraglottoplasty (5.64 ± 0.92 vs 7.98 ± 1.92 months, P = .006), and increased respiratory hospitalization risk (relative risk 1.97, 95% CI 1.01-3.85, 0.047), even after adjustment for covariates. Subjects receiving thickening had fewer respiratory hospitalization nights and longer time to supraglottoplasty (9.3 ± 1.7 vs 4.56 ± 0.73 months, P = .004), even after adjustment. CONCLUSIONS: Acid suppression use does not reduce the frequency of supraglottoplasty and related hospitalizations compared with untreated subjects. However, patients treated with thickening have decreased hospitalization and longer time to supraglottoplasty, suggesting that thickening of feeds may be a preferred intervention over acid suppression.

The Edematous and Erythematous Airway Does Not Denote Pathologic Gastroesophageal Reflux.

OBJECTIVE: To determine if the reflux finding score (RFS), a validated score for airway inflammation, correlates with gastroesophageal reflux measured by multichannel intraluminal impedance (MII) testing, endoscopy, and quality of life scores. STUDY DESIGN: We performed a prospective, cross-sectional cohort study of 77 children with chronic cough undergoing direct laryngoscopy and bronchoscopy, esophagogastroduodenoscopy, and MII testing with pH (pH-MII) between 2006 and 2011. Airway examinations were videotaped and reviewed by 3 blinded otolaryngologists each of whom assigned RFS to the airways. RFS were compared with the results of reflux testing (endoscopy, MII, symptom scores). An intraclass correlation coefficient was calculated for the degree of agreement between otolaryngologists' RFS. Receiver operating characteristic curves were created to determine the sensitivity of the RFS. Spearman correlation was calculated between the RFS and reflux measurements by pH-MII. RESULTS: The mean ± SD RFS was 12 ± 4. There was no correlation between pH-MII variables and mean RFS (|r| < 0.15). The concordance correlation coefficient for RFS between otolaryngologists was low (intraclass correlation coefficient = 0.32). Using pH-metry as a gold standard, the positive predictive value for the RFS was 29%. Using MII as the gold standard, the positive predictive value for the RFS was 40%. There was no difference in the mean RFS in patients with (12 ± 4) and without (12 ± 3) esophagitis (P = .9). There was no correlation between RFS and quality of life scores (|r| < 0.15, P > .3). CONCLUSIONS: The RFS cannot predict pathologic gastroesophageal reflux and an airway examination should not be used as a basis for prescribing gastroesophageal reflux therapies.

Discovery and visualization of miRNA-mRNA functional modules within integrated data using bicluster analysis.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at a post-transcriptional level. An miRNA may target many messenger RNA (mRNA) transcripts, and each transcript may be targeted by multiple miRNAs. Our understanding of miRNA regulation is evolving to consider modules of miRNAs that regulate groups of functionally related mRNAs. Here we expand the model of miRNA functional modules and use it to guide the integration of miRNA and mRNA expression and target prediction data. We present evidence of cooperativity between miRNA classes within this integrated miRNA-mRNA association matrix. We then apply bicluster analysis to uncover miRNA functional modules within this integrated data set and develop a novel application to visualize and query these results. We show that this wholly unsupervised approach can discover a network of miRNA-mRNA modules that are enriched for both biological processes and miRNA classes. We apply this method to investigate the interplay of miRNAs and mRNAs in integrated data sets derived from neuroblastoma and human immune cells. This study is the first to apply the technique of biclustering to model functional modules within an integrated miRNA-mRNA association matrix. Results provide evidence of an extensive modular miRNA functional network and enable characterization of miRNA function and dysregulation in disease.

Orchestrating osteogenic differentiation of mesenchymal stem cells--identification of placental growth factor as a mechanosensitive gene with a pro-osteogenic role.

Skeletogenesis is initiated during fetal development and persists through adult life as either a remodeling process in response to homeostatic regulation or as a regenerative process in response to physical injury. Mesenchymal stem cells (MSCs) play a crucial role providing progenitor cells from which osteoblasts, bone matrix forming cells are differentiated. The mechanical environment plays an important role in regulating stem cell differentiation into osteoblasts, however, the mechanisms by which MSCs respond to mechanical stimuli are yet to be fully elucidated. To increase understanding of MSC mechanotransuction and osteogenic differentiation, this study aimed to identify novel, mechanically augmented genes and pathways with pro-osteogenic functionality. Using collagen glycoaminoglycan scaffolds as mimics of native extracellular matrix, to create a 3D environment more representative of that found in bone, MSC-seeded constructs were mechanically stimulated in a flow-perfusion bioreactor. Global gene expression profiling techniques were used to identify potential candidates warranting further investigation. Of these, placental growth factor (PGF) was selected and expression levels were shown to strongly correlate to both the magnitude and duration of mechanical stimulation. We demonstrated that PGF gene expression was modulated through an actin polymerization-mediated mechanism. The functional role of PGF in modulating MSC osteogenic differentiation was interrogated, and we showed a concentration-dependent response whereby low concentrations exhibited the strongest pro-osteogenic effect. Furthermore, pre-osteoclast migration and differentiation, as well as endothelial cell tubule formation also maintained concentration-dependent responses to PGF, suggesting a potential role for PGF in bone resorption and angiogenesis, processes key to bone remodeling and fracture repair.

International pediatric otolaryngology group (IPOG) consensus on approach to aspiration.

OBJECTIVE: To provide recommendations for a comprehensive management approach for infants and children presenting with symptoms or signs of aspiration. METHODS: Three rounds of surveys were sent to authors from 23 institutions worldwide. The threshold for the critical level of agreement among respondents was set at 80 %. To develop the definition of "intractable aspiration," each author was first asked to define the condition. Second, each author was asked to complete a 5-point Likert scale to specify the level of agreement with the definition derived in the first step. RESULTS: Recommendations by the authors regarding the clinical presentation, diagnostic considerations, and medical and surgical management options for aspiration in children. CONCLUSION: Approach to pediatric aspiration is best achieved by implementing a multidisciplinary approach with a comprehensive investigation strategy and different treatment options.

Expressional alterations in functional ultra-conserved non-coding RNAs in response to all-trans retinoic acid--induced differentiation in neuroblastoma cells.

BACKGROUND: Ultra-conserved regions (UCRs) are segments of the genome (≥ 200 bp) that exhibit 100% DNA sequence conservation between human, mouse and rat. Transcribed UCRs (T-UCRs) have been shown to be differentially expressed in cancers versus normal tissue, indicating a possible role in carcinogenesis. All-trans-retinoic acid (ATRA) causes some neuroblastoma (NB) cell lines to undergo differentiation and leads to a significant decrease in the oncogenic transcription factor MYCN. Here, we examine the impact of ATRA treatment on T-UCR expression and investigate the biological significance of these changes. METHODS: We designed a custom tiling microarray to profile the expression of 481 T-UCRs in sense and anti-sense orientation (962 potential transcripts) in untreated and ATRA-treated neuroblastoma cell lines (SH-SY5Y, SK-N-BE, LAN-5). Following identification of significantly differentially expressed T-UCRs, we carried out siRNA knockdown and gene expression microarray analysis to investigate putative functional roles for selected T-UCRs. RESULTS: Following ATRA-induced differentiation, 32 T-UCRs were differentially expressed (16 up-regulated, 16 down-regulated) across all three cell lines. Further insight into the possible role of T-UC.300A, an independent transcript whose expression is down-regulated following ATRA was achieved by siRNA knockdown, resulting in the decreased viability and invasiveness of ATRA-responsive cell lines. Gene expression microarray analysis following knockdown of T-UC.300A revealed a number of genes whose expression was altered by changing T-UC.300A levels and that might play a role in the increased proliferation and invasion of NB cells prior to ATRA-treatment. CONCLUSIONS: Our results indicate that significant numbers of T-UCRs have altered expression levels in response to ATRA. While the precise roles that T-UCRs might play in cancer or in normal development are largely unknown and an important area for future study, our findings strongly indicate that the function of non-coding RNA T-UC.300A is connected with proliferation, invasion and the inhibition of differentiation of neuroblastoma cell lines prior to ATRA treatment.

The role of genetic and epigenetic alterations in neuroblastoma disease pathogenesis.

Neuroblastoma is a highly heterogeneous tumor accounting for 15 % of all pediatric cancer deaths. Clinical behavior ranges from the spontaneous regression of localized, asymptomatic tumors, as well as metastasized tumors in infants, to rapid progression and resistance to therapy. Genomic amplification of the MYCN oncogene has been used to predict outcome in neuroblastoma for over 30 years, however, recent methodological advances including miRNA and mRNA profiling, comparative genomic hybridization (array-CGH), and whole-genome sequencing have enabled the detailed analysis of the neuroblastoma genome, leading to the identification of new prognostic markers and better patient stratification. In this review, we will describe the main genetic factors responsible for these diverse clinical phenotypes in neuroblastoma, the chronology of their discovery, and the impact on patient prognosis.

Categorization of a Universal Coding System to Distinguish Use of Durable Medical Equipment and Supplies in Pediatric Patients.

Importance: Although durable medical equipment and supplies (DMES) are commonly used to optimize the health and function in pediatric patients, little is known about the prevalence of use and spending on DMES. Objective: To categorize the Healthcare Common Procedure Coding System (HCPCS) for distinguishing DMES types, and to measure the prevalence and related spending of DMES in pediatric patients using Medicaid. Design, Setting, and Participants: This study is a cross-sectional analysis of the 2018 Merative Medicaid Database and included 4 569 473 pediatric patients aged 0 to 21 years enrolled in Medicaid in 12 US states from January 1 to December 31, 2018. Data were analyzed from February 2019 to April 2023. Exposure: DMES exposure was identified with the Centers for Medicare & Medicaid Services HCPCS codes. Three pediatricians categorized HCPCS DMES codes submitted by vendors for reimbursement of dispensed DMES into DMES types and end-organ systems; 15 expert reviewers refined the categorization (2576 DMES codes, 164 DMES types, 14 organ systems). Main Outcomes and Measures: The main outcome was DMES prevalence & Medicaid spending. The χ2 test was used to compare DMES prevalence and Wilcoxon rank sum tests were used to compare per-member-per-year (PMPY) spending by complex chronic conditions (CCC). Results: Of the 4 569 473 patients in the study cohort, 49.3% were female and 56.1% were aged 5 to 15 years. Patients used 133 of 164 (81.1%) DMES types. The DMES prevalence was 17.1% (95% CI, 17.0%-17.2%) ranging from 10.1% (95% CI, 10.0%-10.2%) in patients with no chronic condition to 60.9% (95% CI, 60.8%-61.0%) for patients with 2 or more CCCs. The PMPY DMES spending was $593, ranging from $349 for no chronic condition to $4253 for 2 or more CCCs. Lens (7.9%), vision frames (6.2%), and orthotics for orthopedic injury (0.8%) were the most common DME in patients with no chronic condition. Enteral tube / feeding supplies (19.8%), diapers (19.2%), lower extremity orthotics (12.3%), wheelchair (9.6%), oxygen (9.0%), and urinary catheter equipment (4.2%) were among the most common DMES in children with 2 or more CCCs. Conclusions and Relevance: In this cross-sectional study, HCPCS distinguished a variety of DME types and use across pediatric populations. Further investigation should assess the utility of the HCPCS DMES categorization with efforts to optimize the quality and safety of DMES use.

International Pediatric Otolaryngology Group: Consensus guidelines on the diagnosis and management of non-tuberculous mycobacterial cervicofacial lymphadenitis.

INTRODUCTION: Non-tuberculous mycobacterial (NTM) infection commonly manifests as subacute or chronic cervicofacial lymphadenitis in immunocompetent children. The optimal management of this pathology remains controversial. OBJECTIVES: This international consensus guideline aims to understand the practice patterns for NTM cervicofacial lymphadenitis and to address the primary diagnostic and management challenges. METHODS: A modified three-iterative Delphi method was used to establish expert recommendations on the diagnostic considerations, expectant or medical management, and operative considerations. The recommendations herein are derived from current expert consensus and critical review of the literature. SETTING: Multinational, multi-institutional, tertiary pediatric hospitals. RESULTS: Consensus recommendations include diagnostic work-up, goals of treatment and management options including surgery, prolonged antibiotic therapy and observation. CONCLUSION: The recommendations formulated in this International Pediatric Otolaryngology Group (IPOG) consensus statement on the diagnosis and management of patients with NTM lymphadenitis are aimed at improving patient care and promoting future hypothesis generation.

MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-ß signalling pathway.

Transforming growth factor-ß (TGF-ß) signaling regulates many diverse cellular activities through both canonical (SMAD-dependent) and non-canonical branches, which includes the mitogen-activated protein kinase (MAPK), Rho-like guanosine triphosphatase and phosphatidylinositol-3-kinase/AKT pathways. Here, we demonstrate that miR-335 directly targets and downregulates genes in the TGF-ß non-canonical pathways, including the Rho-associated coiled-coil containing protein (ROCK1) and MAPK1, resulting in reduced phosphorylation of downstream pathway members. Specifically, inhibition of ROCK1 and MAPK1 reduces phosphorylation levels of the motor protein myosin light chain (MLC) leading to a significant inhibition of the invasive and migratory potential of neuroblastoma cells. Additionally, miR-335 targets the leucine-rich alpha-2-glycoprotein 1 (LRG1) messenger RNA, which similarly results in a significant reduction in the phosphorylation status of MLC and a decrease in neuroblastoma cell migration and invasion. Thus, we link LRG1 to the migratory machinery of the cell, altering its activity presumably by exerting its effect within the non-canonical TGF-ß pathway. Moreover, we demonstrate that the MYCN transcription factor, whose coding sequence is highly amplified in a particularly clinically aggressive neuroblastoma tumor subtype, directly binds to a region immediately upstream of the miR-335 transcriptional start site, resulting in transcriptional repression. We conclude that MYCN contributes to neuroblastoma cell migration and invasion, by directly downregulating miR-335, resulting in the upregulation of the TGF-ß signaling pathway members ROCK1, MAPK1 and putative member LRG1, which positively promote this process. Our results provide novel insight into the direct regulation of TGF-ß non-canonical signaling by miR-335, which in turn is downregulated by MYCN.

Genome-wide DNA methylation analysis of neuroblastic tumors reveals clinically relevant epigenetic events and large-scale epigenomic alterations localized to telomeric regions.

The downregulation of specific genes through DNA hypermethylation is a major hallmark of cancer, although the extent and genomic distribution of hypermethylation occurring within cancer genomes is poorly understood. We report on the first genome-wide analysis of DNA methylation alterations in different neuroblastic tumor subtypes and cell lines, revealing higher order organization and clinically relevant alterations of the epigenome. The methylation status of 33,485 discrete loci representing all annotated CpG islands and RefSeq gene promoters was assessed in primary neuroblastic tumors and cell lines. A comparison of genes that were hypermethylated exclusively in the clinically favorable ganglioneuroma/ganglioneuroblastoma tumors revealed that nine genes were associated with poor clinical outcome when overexpressed in the unfavorable neuroblastoma (NB) tumors. Moreover, an integrated DNA methylation and copy number analysis identified 80 genes that were recurrently concomitantly deleted and hypermethylated in NB, with 37 reactivated by 5-aza-deoxycytidine. Lower expression of four of these genes was correlated with poor clinical outcome, further implicating their inactivation in aggressive disease pathogenesis. Analysis of genome-wide hypermethylation patterns revealed 70 recurrent large-scale blocks of contiguously hypermethylated promoters/CpG islands, up to 590 kb in length, with a distribution bias toward telomeric regions. Genome-wide hypermethylation events in neuroblastic tumors are extensive and frequently occur in large-scale blocks with a significant bias toward telomeric regions, indicating that some methylation alterations have occurred in a coordinated manner. Our results indicate that methylation contributes toward the clinicopathological features of neuroblastic tumors, revealing numerous genes associated with poor patient survival in NB.

Dissection of the oncogenic MYCN transcriptional network reveals a large set of clinically relevant cell cycle genes as drivers of neuroblastoma tumorigenesis.

Amplification of the oncogenic transcription factor MYCN plays a major role in the pathogenesis of several pediatric cancers, including neuroblastoma, medulloblastoma, and rhabodomyosarcoma. For neuroblastoma, MYCN amplification is the most powerful genetic predictor of poor patient survival, yet the mechanism by which MYCN drives tumorigenesis is only partially understood. To gain an insight into the distribution of MYCN binding and to identify clinically relevant MYCN target genes, we performed an integrated analysis of MYCN ChIP-chip and mRNA expression using the MYCN repressible SHEP-21N neuroblastoma cell line. We hypothesized that genes exclusively MYCN bound in SHEP-21N cells over-expressing MYCN would be enriched for direct targets which contribute to the process of disease progression. Integrated analysis revealed that MYCN drives tumorigenesis predominantly as a positive regulator of target gene transcription. A high proportion of genes (24%) that are MYCN bound and up-regulated in the SHEP-21N model are significantly associated with poor overall patient survival (OS) in a set of 88 tumors. In contrast, the proportion of genes down-regulated when bound by MYCN in the SHEP-21N model and which are significantly associated with poor overall patient survival when under-expressed in primary tumors was significantly lower (5%). Gene ontology analysis determined a highly statistically significant enrichment for cell cycle related genes within the over-expressed MYCN target group which were also associated with poor OS. We conclude that the over-expression of MYCN leads to aberrant binding and over-expression of genes associated with cell cycle regulation which are significantly correlated with poor OS and MYCN amplification.

Tax 1-independent induction of vascular endothelial growth factor in adult T-cell leukemia caused by human T-cell leukemia virus type 1.

Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1). Elevated expression of vascular endothelial growth factor (VEGF) in ATL patients is associated with leukemic cell invasion and infiltration in different organs. The regulatory protein Tax 1 encoded by HTLV-1 plays a pivotal role in T-cell transformation by deregulating the function and expression of several cellular factors. In the present study, we examined the effect of Tax 1 on VEGF expression at transcriptional and posttranscriptional levels in order to elucidate the regulatory mechanisms involved. Using functional assays, we demonstrate that Tax 1 downregulates the VEGF promoter through a cluster of Sp1 sites located close to the transcriptional start site. Using gel mobility shift assays, we show that Tax 1 reduced Sp1:DNA complex formation. We demonstrate that the level of secreted VEGF was significantly lower in Tax 1-transfected 293T cells compared to nontransfected cells, which is consistent with the observed downregulatory effect of Tax 1 at the transcription level. We showed that VEGF was secreted by HTLV-1-transformed and nontransformed cells, irrespective of Tax 1 expression. Overall our data indicate that, contrary to a previous report, Tax 1 downregulates VEGF expression and suggest there are Tax 1-independent mechanisms of VEGF activation in ATL.

Variation in the Management of Children With Deep Neck Infections.

BACKGROUND AND OBJECTIVES: Children with deep neck infections (DNIs) are increasingly being managed nonsurgically with intravenous antibiotics. Our objective was to examine variation in the management of children with DNIs across US children's hospitals. METHODS: We conducted a retrospective cohort study using the Pediatric Health Information System database. Children ≤12 years of age hospitalized for retropharyngeal or parapharyngeal abscesses from 2010 to 2018 were included. Hospital variation in management modality and imaging use was described. Temporal trends in management modality were assessed by using logistic regression. Medical management alone versus a combination of medical and surgical management was assessed, and the characteristics of children in these 2 groups were compared. The relationship between hospital rates of initial medical management and failed medical management was assessed by using linear regression. RESULTS: Hospitals varied widely in their rates of surgical management from 17% to 70%. The overall rate of surgical management decreased from 42.0% to 33.5% over the study period. Children managed surgically had higher rates of ICU admission (11.5% vs 3.2%; P < .001) and higher hospital charges ($25 241 vs $15 088; P < .001) compared with those managed medically alone. Seventy-three percent of children underwent initial medical management, of whom 17.9% went on to undergo surgery. Hospitals with higher rates of initial medical management had lower rates of failed medical management (ß = -.43). CONCLUSIONS: Although rates of surgical management of pediatric DNI are decreasing over time, there remains considerable variation in management across US children's hospitals. Children managed surgically have higher rates of resource use and costs.

The Natural Product ß-Escin Targets Cancer and Stromal Cells of the Tumor Microenvironment to Inhibit Ovarian Cancer Metastasis.

The high mortality of OvCa is caused by the wide dissemination of cancer within the abdominal cavity. OvCa cells metastasize to the peritoneum, which is covered by mesothelial cells, and invade into the underlying stroma, composed of extracellular matrices (ECM) and stromal cells. In a study using a three-dimensional quantitative high-throughput screening platform (3D-qHTS), we found that ß-escin, a component of horse chestnut seed extract, inhibited OvCa adhesion/invasion. Here, we determine whether ß-escin and structurally similar compounds have a therapeutic potential against OvCa metastasis. Different sources of ß-escin and horse chestnut seed extract inhibited OvCa cell adhesion/invasion, both in vitro and in vivo. From a collection of 160 structurally similar compounds to ß-escin, we found that cardiac glycosides inhibited OvCa cell adhesion/invasion and proliferation in vitro, and inhibited adhesion/invasion and metastasis in vivo. Mechanistically, ß-escin and the cardiac glycosides inhibited ECM production in mesothelial cells and fibroblasts. The oral administration of ß-escin inhibited metastasis in both OvCa prevention and intervention mouse models. Specifically, ß-escin inhibited ECM production in the omental tumors. Additionally, the production of HIF1α-targeted proteins, lactate dehydrogenase A, and hexokinase 2 in omental tumors was blocked by ß-escin. This study reveals that the natural compound ß-escin has a therapeutic potential because of its ability to prevent OvCa dissemination by targeting both cancer and stromal cells in the OvCa tumor microenvironment.

International Pediatric Otolaryngology Group (IPOG) survey: Efforts to avoid complications in home tracheostomy care.

OBJECTIVE: To provide guidance for home care tracheostomy management in the pediatric population. The mission of the IPOG is to develop expertise-based recommendations for the management of pediatric otolaryngologic disorders with the goal of improving patient care. METHODS: Survey of expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). RESULTS: Survey results provide guidance for caregiver teaching, the reuse of tracheostomies and suction catheters while inpatient and following discharge, acceptable sterilization practices for tracheostomies, tracheitis workup and management, and outpatient follow-up practices. CONCLUSION: This presentation of common home tracheostomy care practices are aimed at improving patient-centered care in the pediatric population.

International Pediatric Otolaryngology Group (IPOG) management recommendations: Pediatric tracheostomy decannulation.

OBJECTIVES: To provide recommendations to otolaryngologists, pulmonologists, and allied clinicians for tracheostomy decannulation in pediatric patients. METHODS: An iterative questionnaire was used to establish expert recommendations by the members of the International Pediatric Otolaryngology Group. RESULTS: Twenty-six members completed the survey. Recommendations address patient criteria for decannulation readiness, airway evaluation prior to decannulation, decannulation protocol, and follow-up after both successful and failed decannulation. CONCLUSION: Tracheostomy decannulation recommendations are aimed at improving patient-centered care, quality and safety in children with tracheostomies.

Patient and caregiver experiences at a Multidisciplinary Tracheostomy Clinic.

INTRODUCTION: Children with tracheostomy are a heterogeneous population requiring care from multiple specialties. Multidisciplinary approaches to treating such patients helps to improve the quality of care they receive. Our institution established a Multidisciplinary Tracheostomy Clinics (MDTC) to address outpatient care coordination for tracheostomy patients by providing care from multiple disciplines at a single visit. We report patient/caregivers' experiences of our MDTC. METHODS: Patients with tracheostomy or their caregivers were prospectively recruited between Dec 2017-Oct 2019 to complete surveys assessing their experience at the MDTC. Demographic and satisfaction questionnaires were sent electronically by a REDCap survey distribution tool. Demographic data were collected, such as patient's residence and education level. Medical care variables assessed included history of MDTC attendance, commute time, medical specialties seen, tracheostomy "Go-Bag" use, home-care nursing, and MDTC satisfaction ratings. RESULTS: Twenty-nine patients/caregivers completed the satisfaction survey and 22 completed both the satisfaction survey and demographics questionnaire. Patient ages ranged from 11 months to 36 years. Twenty-three (79%) participants commuted for up to 2 h to the MDTC, and 6 (21%) commuted for more than 2 h. The median number of medical specialties seen at the MDTC was 3. All participants were satisfied that they saw all requested specialties. Tracheostomy supplies were checked for 25 of 28 patients. Twenty-three of 28 subjects rated staff teamwork as "excellent." Twenty-four of 28 patients were "highly likely" to recommend the MDTC. Twenty-three of 28 participants were "highly likely" to return, and 4 were "somewhat likely" to return. CONCLUSION: This study demonstrates that patients with tracheostomy and caregivers were satisfied with the improved coordination and facilitation of care through a Multidisciplinary Tracheostomy Clinic.