Airway findings in trisomy 13 and trisomy 18: A 10-year retrospective review.

BACKGROUND AND OBJECTIVES: Trisomy 18 and trisomy 13 are the most common autosomal trisomies following trisomy 21, with overall incidence rising. Both diagnoses are characterized by multisystem involvement and were previously thought to be incompatible with life. New data suggest that prolonged survival is possible, and thus many families are opting for more aggressive medical interventions. This study aims to describe airway findings in trisomy 18 and trisomy 13, as these have not been comprehensively studied and can impact medical decision-making. We hypothesize that most children with trisomy 18 and trisomy 13 will have abnormal findings on airway endoscopy. METHODS: This a 10-year retrospective analysis of children with trisomy 13 or trisomy 18 who underwent endoscopic airway evaluation at a single center between 2011 and 2021. A total of 31 patients were evaluated. RESULTS: Thirty-one patients were included and underwent flexible bronchoscopy by a pediatric pulmonologist, often in conjunction with rigid bronchoscopy performed by pediatric otolaryngology. Findings were typically complimentary. All patients had at least one clinically significant finding on evaluation, and most patients had both upper and lower airway, as well as static and dynamic airway findings. The most common airway findings in children with trisomy 13 and 18 include tracheomalacia, bronchomalacia, laryngomalacia, hypopharyngeal collapse, glossoptosis, and bronchial compression. CONCLUSION: These findings can have significant implications for clinical care, and thus knowledge of trends has the potential to improve counseling on expected clinical course, presurgical planning, and informed consent before interventions.

Factors associated with success following transcervical innominate artery suspension.

OBJECTIVE: Aortopexy including innominate artery suspension is a well-established treatment of anterior vascular compression and associated tracheomalacia. We report the results of our case series of cervical approach to innominate artery suspension and hypothesize that increased distance from the innominate to the sternum is predictive of superior symptomatic outcome. STUDY DESIGN: Retrospective Case Series. METHODS: All cases of cervical innominate artery suspension at our institution over the last 10 years were reviewed. CT scans of the neck and chest were reviewed to obtain anatomical measurements including anterior-posterior thoracic outlet distance, thymic thickness, and sternum-innominate artery distance. Measurements were compared with surgical outcomes as verified by follow up bronchoscopy and clinical course to determine factors predictive of success. RESULTS: Ten cases of cervical innominate artery suspension were performed by the otolaryngology service at our institution over the last 10 years. Six patients had improvement in their symptoms. The average sternum-innominate artery distance (SID) was larger (14.4 mm (95% CI 9.1-19.7)) in patients who had improvement in clinical symptoms following innominate suspension compared to those that did not improve (6.3 mm (95% CI 2.5-10.1)) (p value = 0.02). Similarly, the anterior-posterior distance of the thoracic outlet was larger (34.9 mm (95% CI 27.4-42.4)) in patients who had improvement post-op compared to those that did not improve (22.6 mm (95% CI 18.2-27.2) (p value = 0.01). Two patients required spine surgery to achieve improvement in their symptoms. CONCLUSION: Cervical innominate artery suspension is successful in carefully selected patients. More space in the thoracic outlet and larger distance from the innominate artery to the sternum is associated with symptomatic improvement.

Modified Head and Neck Swallow Scale: Using EORTC-QLQ-H&N35 to Predict Overall Survival.

OBJECTIVES/HYPOTHESIS: Dysphagia is a treatment-related complication of head and neck cancer (HNCA). We demonstrate the predictive value of a modified head and neck swallow scale (m-HNSW) adapted from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 (EORTC-QLQ-H&N35). STUDY DESIGN: Retrospective Cohort Study. METHODS: Retrospective, single-center cohort study utilizing a prospectively collected database of HNCA patients in a high-volume tertiary referral center. 736 HNCA patients more than 2 years from completion of treatment were identified. EORTC-QLQ-H&N35 data collected from at least one of three defined episodes of care were used. The m-HNSW uses three questions to form a 9-point dysphagia scale. A Cox proportional hazards model was used to determine the effect of the m-HNSW while controlling for demographics, tumor staging, site, and treatment. RESULTS: Using data from 3, 6, 12 months from treatment, we analyzed a subset that included 328 patients. Three months after the completion of therapy, the m-HNSW score had a significant association with 1 (HR = 1.24, P = .0005) and 5 year survival (HR = 1.19, P = .0002) after accounting for body mass index. Six (HR = 1.14, P = .014) and 12 month (hazard ratio (HR) = 1.33, P < .0001) scores post completion of therapy predict 5-year survival. An increase of the m-HNSW score by 1 point was associated with an increase in death by 24%, and 19% at 1 and 5 years following therapy. CONCLUSIONS: The m-HNSW is a simple assessment of dysphagia using previously validated EORTC-QLC-H&N35 data that when taken at 3, 6, and 12 months after completion of therapy is predictive of overall survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2478-2482, 2021.

Polysomnographic Outcomes After Observation for Mild Obstructive Sleep Apnea in Children Younger Than 3 Years.

OBJECTIVE: Mild obstructive sleep apnea (OSA), particularly in young children, is often treated with observation. However, there is little evidence regarding the outcomes with this approach. Our aim was to assess the impact of observation on sleep for children aged <3 years with mild OSA. STUDY DESIGN: Case-control study. SETTING: Pediatric tertiary care center. METHODS: We reviewed cases of children (<3 years old) diagnosed with mild OSA (obstructive apnea-hypopnea index, 1-5 events/h) who were treated with observation between 2012 and 2017 and had at least 2 polysomnograms performed 3 to 12 months apart. Demographic data and comorbid diagnoses were collected. RESULTS: Twenty-six children met inclusion criteria; their median age was 7.2 months (95% CI, 1.2-22.8). Nine (35%) were female and 24 (92%) were White. Their median body mass index percentile was 39 (95% CI, 1-76). Comorbidities included cardiac disease (42.3%), laryngomalacia (42.3%), allergies (34.6%), reactive airway disease (23.1%), and prematurity (7.7%). The obstructive apnea-hypopnea index significantly decreased from 2.7 events/h (95% CI, 1-4.5) to 1.3 (95% CI, 0-4.5; P = .013). There was no significant improvement in median saturation nadir (baseline, 86%; P = .76) or median time with end-tidal carbon dioxide >50 mm Hg (baseline, 0 minutes; P = .34). OSA resolved in 8 patients (31%) and worsened in 1 (3.8%). Only race was a significant predictor of resolution per regression analysis; however, only 2 non-White children were included. CONCLUSION: In our cohort, resolution of mild OSA occurred in 31% of patients treated with 3 to 12 months of observation. The presence of laryngomalacia, asthma, and allergies did not affect resolution. Larger studies are needed to better identify factors (including race) associated with persistent OSA and optimal timing of intervention for these children. LEVEL OF EVIDENCE: 4.

Circadian Dysregulation: The Next Frontier in Obstructive Sleep Apnea Research.

OBJECTIVE: To review the effects of the circadian clock on homeostasis, the functional interaction between the circadian clock and hypoxia-inducible factors, and the role of circadian dysregulation in the progression of cardiopulmonary disease in obstructive sleep apnea (OSA). DATA SOURCES: The MEDLINE database was accessed through PubMed. REVIEW METHODS: A general review is presented on molecular pathways disrupted in OSA, circadian rhythms and the role of the circadian clock, hypoxia signaling, crosstalk between the circadian and hypoxia systems, the role of the circadian clock in cardiovascular disease, and implications for practice. Studies included in this State of the Art Review demonstrate the potential contribution of the circadian clock and hypoxia in animal models or human disease. CONCLUSIONS: Molecular crosstalk between the circadian clock and hypoxia-inducible factors has not been evaluated in disease models of OSA. IMPLICATIONS FOR PRACTICE: Pediatric OSA is highly prevalent and, if left untreated, may lead to cardiopulmonary sequelae. Changes in inflammatory markers that normally demonstrate circadian rhythmicity are also seen among patients with OSA. Hypoxia-inducible transcription factors interact with core circadian clock transcription factors; however, the interplay between these pathways has not been elucidated in the cardiopulmonary system. This gap in knowledge hinders our ability to identify potential biomarkers of OSA and develop alternative therapeutic strategies. A deeper understanding of the mechanisms by which OSA impinges on clock function and the impact of clock dysregulation on the cardiopulmonary system may lead to future advancements for the care of patients with OSA. The aim of this review is to shed light on this important clinical topic.

Early but not late administration of glucagon-like peptide-2 following ileo-cecal resection augments putative intestinal stem cell expansion.

Expansion of intestinal progenitors and putative stem cells (pISC) occurs early and transiently following ileo-cecal resection (ICR). The mechanism controlling this process is not defined. We hypothesized that glucagon-like peptide-2 (GLP-2) would augment jejunal pISC expansion only when administered to mice immediately after ICR. Since recent reports demonstrated increases in intestinal insulin-like growth factor (IGF)-I following GLP-2 administration, we further hypothesized that increased intestinal IGF-I expression would correlate with pISC expansion following ICR. To assess this, GLP-2 or vehicle was administered to mice either immediately after resection (early) or before tissue harvest 6 wk following ICR (late). Histological analysis quantified proliferation and intestinal morphometrics. Serum levels of GLP-2 were measured by ELISA and jejunal IGF-I mRNA by qRT-PCR. Expansion of jejunal pISC was assessed by fluorescent-activated cell sorting of side population cells, immunohistochemistry for phosphorylated beta-catenin at serine 552 (a pISC marker), percent of crypt fission, and total numbers of crypts per jejunal circumference. We found that early but not late GLP-2 treatment after ICR significantly augmented pISC expansion. Increases in jejunal IGF-I mRNA correlated temporally with early pISC expansion and effects of GLP-2. Early GLP-2 increased crypt fission and accelerated adaptive increases in crypt number and intestinal caliber. GLP-2 increased proliferation and intestinal morphometrics in all groups. This study shows that, in mice, GLP-2 promotes jejunal pISC expansion only in the period immediately following ICR. This is associated with increased IGF-I and accelerated adaptive increases in mucosal mass. These data provide clinical rationale relevant to the optimal timing of GLP-2 in patients with intestinal failure.

Bacterial-dependent up-regulation of intestinal bile acid binding protein and transport is FXR-mediated following ileo-cecal resection.

BACKGROUND: Bile acid (BA) reclamation following ileo-cecal resection (ICR) may prevent colonic mucosa from chronic injury. In this study, we hypothesized that in a murine model of ICR the remnant colon would upregulate the cellular machinery necessary for BA reclamation and would do so in an FXR- and bacteria-dependent manner. METHODS: Conventional (WT), conventional FXR knockout (FXR null) and germ-free (GF) mice were randomized to undergo either ICR or sham operation. The ascending colon was harvested for histology and immunohistochemistry and changes in bile acid homeostatic gene expression determined by real-time polymerase chain reaction (RT-PCR) 7 days following surgery. RESULTS: Following ICR WT mice showed significant increases in the expression of genes regulating bile acid transport including IBABP, Asbt, Ost beta and FGF 15. Increased expression of IBABP and Asbt was confirmed by immunohistochemistry. Induction of bile acid transport genes was absent or attenuated in FXR null and GF mice. CONCLUSION: Bacterial dependent up regulation of IBABP is FXR mediated in the colon following ICR. Mice lacking microbiota (GF) or FXR are unable to increase the expression of IBABP or FGF 15.