Altered protein conformation and lower stability of the dystrophic transforming growth factor beta-induced protein mutants.

PURPOSE: Transforming growth factor beta-induced protein (TGFBIp) is a widely expressed extracellular matrix protein that plays roles in cell adhesion and migration, differentiation, apoptosis, bone morphogenesis, and carcinogenesis. Mutations of TGFBIp have been linked to stromal corneal dystrophies, a group of protein conformational diseases characterized by abnormal protein aggregations in the cornea. However, the underlying pathogenic mechanism remains elusive due to a lack of insight into the molecular properties of the disease-causing mutants. In the current study, we applied spectroscopic tools to compare the conformation and protein stability of recombinant wild-type (WT) TGFBIp to two dystrophic mutants, R124C and R555W. METHODS: A serum-free expression system was used to produce the recombinant TGFBIp proteins. Fluorescence and far-ultraviolet circular dichroism spectroscopies were used to compare WT and dystrophic mutants under various conditions. RESULTS: Our results showed that dystrophic mutants were processed differentially by the expressing cells and produced different proteolytic fragment patterns by proteolysis. Intrinsic tryptophan fluorescence studies revealed moderate shifts in the emission maxima and increased quenching by iodide ion of mutant TGFBIp, suggesting a different conformation than WT protein. Denaturation experiments indicated a difference in protein stability between WT and mutant proteins. Under oxidizing conditions, the mutants produced higher 1-anilinonaphthalene-8-sulfonic acid and thioflavin T fluorescence signals than the WT, indicating increased protein unfolding and fibril formation, respectively. Finally, far-ultraviolet circular dichroism spectroscopy revealed that WT TGFBIp undergoes concentration-dependent conformational changes; similar experiments were not possible on mutant TGFBIp, which remained soluble only at low concentrations. CONCLUSIONS: Our study provides new evidence for the pathogenic mechanism of dystrophic mutants. Although mutant TGFBIp has moderate but consistent structural perturbations, other factors such as oxidation or degradation may be required to cause the phenotypic abnormal aggregations.

Impact of Deductible Health Plans on Parental Decision Making for Common Pediatric Otolaryngology Procedures.

Objective To describe how deductible health plans affect parental decision making for common pediatric otolaryngology operations. Study Design A cross-sectional survey study. Setting Tertiary care pediatric hospital. Subjects and Methods Caregivers of patients aged <18 years were surveyed to assess factors in decision making related to common otolaryngologic surgical procedures, including outpatient tympanostomy tubes and adenotonsillectomy, between July 2015 and June 2016. Children in foster care and those who underwent nonelective surgery were excluded. Decision-making factors were statistically analyzed with univariate and multivariate ordinal logistic regression. Results A total of 155 caregivers completed the survey. The median age of the patient at the time of the surgery was 3 years. Surgical procedures included tympanostomy tube placement (51%), adenotonsillectomy (37%), tympanostomy tube placement with adenotonsillectomy (10%), and other (2%). The mean ± SD annual deductible per child was $1870 ± $140, and the mean maximum out-of-pocket expense was $3833 ± $235. The odds of having the deductible or out-of-pocket expense affect surgical decision making was greater for those covered under a high-deductible health plan (odds ratio = 2.27; 95% CI, 1.25-4.12; P = .007). Conclusion High-deductible health plans and out-of-pocket expenses can influence parental decision making for common otolaryngology operations, such as tympanostomy tube placement and adenotonsillectomy. Future studies are needed to determine if such policies affect access to care in the pediatric population.

Predictors of complicated airway foreign body extraction.

OBJECTIVES: To evaluate outcomes of foreign body aspiration (FBA) and to investigate surgeon and hospital volume as risk factors for a complicated course. STUDY DESIGN: Retrospective case series. METHODS: Children with FBA in a multihospital network were identified from January 2005 to September 2015. Demographic information, surgeon, and hospital location were reviewed. Mean operative time and hospital length of stay were recorded. Cases requiring intensive care unit admission, hospital stay greater than 24 hours, need for more than one bronchoscopy, operative time greater than 1 hour, or death were considered "complicated." RESULTS: A total of 450 cases of airway foreign body extraction were performed. Patient ages ranged from 0.6 to 18.8 years, with a median age of 1.9 years. Bronchoscopy with foreign body extraction was performed by 55 different surgeons at 11 different facilities. There were one to 24 surgeons for each facility, with an average number of 5.4 surgeons per facility. A total of 88 (19.6%) cases were considered complicated, including five (1.1%) deaths. Increased rates of complications were seen with unwitnessed aspiration (P = 0.008) and hyperlucency (P < 0.001) or infiltrates (P = 0.001) on chest radiographs. No significant association was found between surgeon type or facility as related to a complicated case. CONCLUSIONS: Unwitnessed aspiration events and abnormalities on chest radiograph may be associated with a more complicated course in children with FBA. This multihospital study identified a low number of procedures by many surgeons; however, surgeon and hospital volume did not significantly correlate with higher complication rates. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:490-495, 2018.

Comparison of pediatric adenoidectomy techniques.

OBJECTIVES: Evaluate the effects of electrocautery, microdebrider, and coblation techniques on outpatient pediatric adenoidectomy costs and complications. STUDY DESIGN: Observational retrospective cohort study. METHODS: An observational cohort study was performed in a multihospital network using a standardized accounting system. Children < 18 years of age who underwent outpatient adenoidectomy were included from January 2008 to September 2015. Cases with additional procedures were excluded. The cohorts were divided into children who underwent electrocautery, microdebrider, or coblator adenoidectomy. Data regarding costs, postoperative complications, and revision surgeries were analyzed. RESULTS: A total of 1,065 cases of adenoidectomy were performed with electrocautery (34.9%), microdebrider (26.1%), and coblation (39.0%). There was an increased after direct cost associated with the microdebrider, $833 (standard deviation [SD] $363) and the coblator, $797 (SD $262) compared to the electrocautery, $597 (SD $361) (P < 0.0001). There was a greater overall operating room (OR) time associated with use of the microdebrider (mean 28.7, SD 11.0 minutes) compared with both the electrocautery (mean 24.7, SD 8.1 minutes) and coblator (mean 26.2, SD 9.8 minutes) (P < 0.0001). No significant difference was found with regard to complication rates. The incidence of repeat adenoidectomies was significantly greater for microdebrider (9.7%) compared to electrocautery (2.7%; P = 0.0002) and coblator (5.3%; P = 0.0336) techniques. CONCLUSION: These results suggest that adenoidectomy with electrocautery is significantly less expensive than microdebrider and coblator, with no differences in complication rates or surgical times among the techniques. Microdebrider adenoidectomy was associated with a longer overall OR time and a higher rate of adenoid regrowth, requiring revision surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:745-749, 2018.

Upper aerodigestive injuries from detergent ingestion in children.

OBJECTIVES: To describe the clinical presentations and management of detergent pod ingestion at a tertiary children's hospital. STUDY DESIGN: Case series. METHODS: A retrospective chart review of children diagnosed with detergent pod ingestion from June 2010 and March 2015. RESULTS: Nine cases of detergent pod ingestion were included over a 5-year period. The average age was 26.3 months (range, 11-43 months). Eight (89%) of the cases were female. The patients had ingested laundry detergent pods (n = 7) and dishwasher detergent pods (n = 2). The majority of patients (67%) had more than one clinical manifestation from ingestion. Presenting symptoms included emesis (78%), respiratory symptoms (56%), throat pain (22%), drooling (33%), and foaming at the mouth (33%). The management of patients depended on the severity of their symptoms and included admission to an overnight observation unit (n = 5), discharge to home directly from the emergency department (n = 2), and admission to the hospital (n = 2). Two (22%) children underwent esophagogastroduodenoscopy. One child (11%) required intubation from bilateral vocal fold immobility. CONCLUSION: Injuries to the upper aerodigestive tract after detergent ingestion range from mild gastrointestinal symptoms to respiratory compromise. The majority of children improve with observation alone; however, clinicians should maintain a low threshold for endoscopic evaluation in cases of severe symptoms and airway involvement. LEVEL OF EVIDENCE: 4. Laryngoscope, 2016 127:509-512, 2017.

Anatomic distribution of cervicofacial lymphatic malformations based on lymph node groups.

OBJECTIVES: To evaluate radiographic characteristics and to identify locations of cervicofacial lymphatic malformations in children based on known lymph node groupings. METHODS: Retrospective chart review of pediatric patients with cervicofacial lymphatic malformations who underwent imaging with magnetic resonance imaging (MRI), computed tomography (CT) or ultrasonography (US). Ninety charts were reviewed from November 2005 to June 2015. Demographic information and imaging characteristics were evaluated. RESULTS: Ninety children were included. The average age at presentation was 52 months (range, 1 day to 170 months). Imaging modalities were MRI in 73 (81%), CT in 7 (8%), US in 6 (7%), and multimodality imaging in 4 (4%) cases. Nearly half (49%) of lesions were found in the parotid and submandibular nodal group, 32% in the cervical group, and 19% in the midline face and oral cavity group. The lymphatic malformations were found on the left in 39 (43%) of cases, on the right in 30 (33%) of cases, and were bilateral in 21 (23%) cases. Nineteen (21%) lesions were macrocystic, twenty-two (24%) were microcystic, and forty-nine (49%) had mixed features. Mixed lesions were more likely to be extensive and involve multiple lymph node groups (P = 0.0005). Adjacent lymphadenopathy was present in 20 (22%) among all subjects, with an average size of 1.22 (± 1.92) cm in the short-axis. CONCLUSION: The results of this study demonstrate three lymph node groupings in which LM are commonly identified. The midline face and oral cavity lesions are predominantly microcystic, the parotid and submandibular lesions are predominately of mixed morphology, and the cervical lesions are predominately macrocystic and mixed. Further studies are needed to determine if such a classification system demonstrates clinically significant difference in disease progression and response to therapy.

International Frontal Sinus Anatomy Classification and anatomic predictors of low-lying anterior ethmoidal arteries.

BACKGROUND: The International Frontal Sinus Anatomy Classification (IFAC) was introduced to more accurately characterize ethmoid and frontal sinus pneumatization patterns. The prevalence of IFAC cells and their anatomic associations have not been described. OBJECTIVE: The goal was to examine the prevalence of IFAC cells and determine radiologic features associated with a low-lying anterior ethmoidal artery (LAEA). METHODS: Imaging of adult patients who underwent computed tomographies from January 2015 to March 2016 were retrospectively reviewed by using the IFAC classification. We also measured the distance from the skull base to the anterior ethmoidal artery (AEA), the height of the lateral lamella of the cribriform plate, and anterior-posterior diameter from the anterior wall of the frontal sinus to the skull base (APF). Patients with a history of sinus surgery, trauma, malignancy, or congenital anomaly were excluded. Statistical analysis was performed by using Pearson correlation coefficients and χ2 tests. RESULTS: A total of 95 patients met the inclusion criteria. There was a significant association between supraorbital ethmoid cells and an LAEA (p < 0.001), with a significant effect size (φ = 0.276, p = 0.007). An inverse relationship was observed between Keros type I classification I and an LAEA (p < 0.001), with a significant effect size (φ = -0.414, p = 0.000). Significant associations were found between the AEA distance from the skull base and the cribriform lateral lamella height (R = 0.576, p < 0.001). In addition, there was a significant association between the AEA distance from the skull base and the APF (R = 0.497, p < 0.001). CONCLUSION: The presence of a supraorbital ethmoid cell and a wide APF were associated with an LAEA. There was a significant relationship between Keros type I classification and the AEA adjacent to the skull base. Delineation of these anatomic relationships may be helpful during endoscopic sinus surgery to avoid complications.

Does canal wall down mastoidectomy benefit syndromic children with congenital aural stenosis?

OBJECTIVES: To determine whether a canal wall down mastoidectomy can provide long-term benefit for children with aural stenosis. METHODS: Retrospective case series of children with congenital aural stenosis having undergone a canal wall down mastoidectomy over a twelve-year period at a tertiary children's hospital. RESULTS: Data from thirteen children who underwent a total of twenty canal wall down mastoidectomies for aural stenosis were reviewed. The mean age at surgery was 7.1 years (range, 3.3-12.3 years). All patients had genetic syndromes including Trisomy 21 (n = 7), Trisomy 21 and Pierre Robin sequence (n = 1), Angelmann (n = 1), Cri-du-chat (n = 1), Branchio-oto-renal syndrome (n = 1), Spina bifida (n = 1) and Nager syndrome (n = 1). Seven (54%) children underwent bilateral canal wall down mastoidectomies. All thirteen ears that could not be visualized preoperatively had improved ease of office examination following surgery. Only one patient required revision surgery and all canals were patent at the last clinic visit. The mean follow-up was 4.9 years. There were no cases of facial nerve injury or cerebrospinal fluid leak. CONCLUSION: Syndromic children with congenital aural stenosis with poorly pneumatized mastoids may benefit from canal wall down mastoidectomy to improve ease of office examinations.

Variation in costs among surgeons and hospitals in Pediatric tympanostomy tube placement.

OBJECTIVES/HYPOTHESIS: 1) Identify the major expenses for outpatient pediatric tympanostomy tube placement in a multihospital network. 2) Compare differences for variations in costs among hospitals and surgeons. METHODS: An observational cohort study in a multihospital network using a standardized activity-based accounting system to determine hospital costs for tympanostomy tube placement from February 2011 to January 2015. Children aged 6 months to less than 3 years old who underwent same-day surgery (SDS) for tympanostomy tubes at 15 hospital facilities were included. Subjects with additional procedures were excluded. Hospital costs were subdivided into categories including operating room (OR), SDS preoperative, SDS postoperative, postanesthesia care unit, anesthesia, pharmacy, and OR supplies. RESULTS: The study cohort included 5,623 patients undergoing tympanostomy tube placement by 67 surgeons. Mean cost per surgery was $769 ± $3. Significant variations (P < 0.001) in mean cost per procedure were identified by hospital (range $1212 ± $38 to $509 ± $11) and by surgeon (range $1330 ± $75 to $660 ± $11). Operating room and SDS preoperative were the greatest expenditures; each category accounted for over 30% of overall costs. Pharmacy costs and OR costs were some of the major drivers of cost variation among surgeons. CONCLUSION: This study demonstrates that OR and SDS preoperative costs accounted for the greatest expenditure in tympanostomy tube placement, and significant variation exists among surgeons and hospitals within a multihospital network. Further research is needed to elucidate factors accounting for such variation in cost and the overall impact on patient outcomes. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1935-1939, 2016.

Soft tissue trauma and scar revision.

Numerous techniques and treatments have been described for scar revision, with most studies focusing on the adult population. A comprehensive review of the literature reveals a paucity of references related specifically to scar revision in children. This review describes the available modalities in pediatric facial scar revision. The authors have integrated current practices in soft tissue trauma and scar revision, including closure techniques and materials, topical therapy, steroid injection, cutaneous laser therapy, and tissue expanders.

Use of the carbon dioxide laser for tracheobronchial lesions in children.

IMPORTANCE: Obstructing tracheobronchial diseases in children can be treated by a variety of techniques. The nonfiberoptic delivery of the carbon dioxide laser coupled to a rigid bronchoscope has rarely been described for this purpose and has unique advantages over other treatment methods. OBJECTIVES: To report the indications, safety, efficacy, and limitations of the carbon dioxide laser delivered through a rigid bronchoscope for tracheobronchial lesions in the pediatric population. DESIGN: Case series of patients undergoing treatment for tracheobronchial lesions at a single institution from December 2, 2001, through December 14, 2011. SETTING: Tertiary care children's hospital. PARTICIPANTS: Seventeen patients aged 3 months to 17 years with endotracheal and endobronchial disease. INTERVENTION: Carbon dioxide laser treatment through a rigid bronchoscope. MAIN OUTCOME MEASURES: Reduction in tumor burden or improvement of ventilation. RESULTS: A total of 234 laser bronchoscopies were performed on 17 patients. Mean operative time was 29 (range, 2-89) minutes. Blood loss and complications were minimal. Sixteen patients received carbon dioxide laser delivered through a rigid bronchoscope with a proximal coupler or flexible fiber. The most common indication was tracheobronchial granulation tissue (n = 10), followed by prolapsed cartilage causing tracheal obstruction (n = 3), recurrent respiratory papillomatosis (n = 2), and granular cell tumor (n = 1). Of these patients, 15 (94%) underwent successful treatment. One patient was treated electively with the Nd:YAG laser owing to a vascular malformation. CONCLUSIONS AND RELEVANCE: The carbon dioxide laser delivered through a rigid bronchoscope is a suitable tool for managing nonvascular endotracheal and endobronchial lesions in the pediatric population. Its unique wavelength properties offer a safe, effective alternative to other lasers and open resection.

Retained drug-eluting stents and recalcitrant chronic rhinosinusitis: A case report.

Corticosteroids are the mainstay of treatment for refractory chronic rhinosinusitis. The off-label use of steroid-eluting stents has increasingly gained popularity in functional endoscopic sinus surgery for decreasing postoperative inflammation and synechiae formation. However, there is a paucity of data outlining the safety profile of this device despite its widespread use. This study was designed to report a newly described complication of retained drug-eluting stents from endoscopic sinus surgery for refractory rhinosinusitis. This report highlights a potential risk of the drug-eluting stent in the treatment of recalcitrant rhinosinusitis and the need for further clinical investigations whenever a novel medical device becomes available on the market.

Rare presentation of a gastrointestinal stromal tumor with spontaneous esophageal perforation: A case report.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) of the alimentary canal are malignant tumors with <1% of cases diagnosed in esophagus. These cases require special consideration given their close proximity to vital structures and propensity to be highly aggressive. Management of patients with GISTs has been transformed since the introduction of tyrosine kinase inhibitors. In this report, we present an unusual case of GIST with spontaneous esophageal perforation. PRESENTATION OF CASE: A 39-year-old Caucasian male presented to our hospital with complaints of severe chest and abdominal pain. A diagnostic chest radiograph revealed a moderate right-sided pleural effusion. Subsequently, an esophagram demonstrated a perforation proximal to an elongated stricture in the distal esophagus. A left thoracotomy was performed whereby a large mediastinal mass firmly attached to the esophagus and gastroesophageal junction was encountered. The neoplasm involved proximal one-third of the stomach and perforated into the right hemithorax. Histopathological evaluation of the tumor led to a diagnosis of GIST. DISCUSSION: GISTs of the gastroesophageal junction are uncommon and may rarely present with esophageal perforation. The standard of care for treating GIST at present includes tyrosine kinase inhibitors. This pharmacologic agent, along with improved surgical techniques and understanding of molecular markers for accurate diagnosis, will assuredly continue to improve overall survival of patients with GISTs. CONCLUSION: When stricture or achalasia is detected on imaging, GIST should be considered in the differential diagnosis for individual patients. Additionally, chest and abdomen CT scans of may be performed to confirm presence of a tumor mass, thereby ruling out achalasia.