Modulated Fibrosis and Mechanosensing of Fibroblasts by SB525334 in Pediatric Subglottic Stenosis.

OBJECTIVE: Subglottic stenosis (SGS) may result from prolonged intubation where fibrotic scar tissue narrows the airway. The scar forms by differentiated myofibroblasts secreting excessive extracellular matrix (ECM). TGF-ß1 is widely accepted as a regulator of fibrosis; however, it is unclear how biomechanical pathways co-regulate fibrosis. Therefore, we phenotyped fibroblasts from pediatric patients with SGS to explore how key signaling pathways, TGF-ß and Hippo, impact scarring and assess the impact of inhibiting these pathways with potential therapeutic small molecules SB525334 and DRD1 agonist dihydrexidine hydrochloride (DHX). METHODS: Laryngeal fibroblasts isolated from subglottic as well as distal control biopsies of patients with evolving and maturing subglottic stenosis were assessed by α-smooth muscle actin immunostaining and gene expression for α-SMA, FN, HGF, and CTGF markers. TGF-ß and Hippo signaling pathways were modulated during TGF-ß1-induced fibrosis using the inhibitor SB525334 or DHX and analyzed by RT-qPCR for differential gene expression and atomic force microscopy for ECM stiffness. RESULTS: SGS fibroblasts exhibited higher α-SMA staining and greater inflammatory cytokine and fibrotic marker expression upon TGF-ß1 stimulation (p < 0.05). SB525334 restored levels to baseline by reducing SMAD2/3 nuclear translocation (p < 0.0001) and pro-fibrotic gene expression (p < 0.05). ECM stiffness of stenotic fibroblasts was greater than healthy fibroblasts and was restored to baseline by Hippo pathway modulation using SB525334 and DHX (p < 0.01). CONCLUSION: We demonstrate that distinct fibroblast phenotypes from diseased and healthy regions of pediatric SGS patients respond differently to TGF-ß1 stimulation, and SB525334 has the superior potential for subglottic stenosis treatment by simultaneously modulating TGF-ß and Hippo signaling pathways. LEVEL OF EVIDENCE: NA Laryngoscope, 134:287-296, 2024.

Guideline for Children With Cancer Receiving General Anesthesia for Procedures and Imaging.

Children with cancer and those undergoing hematopoietic stem cell transplantation frequently require anesthesia for imaging as well as diagnostic and therapeutic procedures from diagnosis through follow-up. Due to their underlying disease and side effects of chemotherapy and radiation, they are at risk for complications during this time, yet no published guideline exists for preanesthesia preparation. A comprehensive literature review served as the basis for discussions among our multidisciplinary panel of oncologists, anesthesiologists, nurse practitioners, clinical pharmacists, pediatric psychologists, surgeons and child life specialists at the Children's Hospital of Philadelphia. Due to limited literature available, this panel created an expert consensus guideline addressing anesthesia preparation for this population.

Development of a 3-Dimensional Middle Ear Model to Teach Anatomy and Endoscopic Ear Surgical Skills.

Mastery of ear anatomy and otologic surgical skills is challenging for trainees, and educational resources are limited. Advancements in 3-dimensional (3D) printing have enabled the construction of complex microscopic models. Otoendoscopy provides excellent visualization and has been shown to enhance anatomic learning. Our aim was to develop a 3D model of the middle ear and external auditory canal using computed tomography images of a pediatric temporal bone for use with otoendoscopes. Resulting models are life sized, anatomically accurate, and allow for identification of relevant middle ear structures. Forty-six trainees were recruited for a pilot study and randomized to study using the model or standard resources. There were no differences in pretest, posttest, or 1-week posttest performance between groups; however, trainees assigned to the model reported higher prospective interest, satisfaction, and subjective improvement. This model may be used with otoendoscopes for anatomic and surgical training and represents an advancement in otologic surgical simulation.

Preoperative ultrasound for the diagnosis of thyroglossal duct cysts: A validation study.

OBJECTIVES: To evaluate the use of ultrasound to distinguish between thyroglossal duct cysts (TGDC) and dermoid cysts (DC) for surgical planning. To validate the SIST (septae + irregular wall + solid components = TGDC) scoring system proposed by Oyewumi et al. [1]. METHODS: This was a retrospective chart review of pediatric patients with midline neck masses who presented between the years of 2005 and 2014 and underwent preoperative ultrasound and surgical resection. Two pediatric radiologists blinded to diagnosis reviewed each US for 14 separate characteristics. According to the SIST scoring system, one point was given for each of the following: internal septae, irregular walls, and solid components. RESULTS: 45 patients met inclusion criteria. Final pathologic diagnosis showed 29 patients had TGDC, 16 had DC. The majority of patients with both TGDC and DC earned SIST scores of 0. CONCLUSION: While ultrasound remains a useful part of the work-up of lesions of the head and neck in children, this small retrospective study was not able to validate the previously proposed SIST scoring system None of the parameters discussed in the original paper was found to be a statistically significant determinant of TGDC.

Short-stay hospital admission after free tissue transfer for head and neck reconstruction.

OBJECTIVES/HYPOTHESIS: To show that, for patients with few medical comorbidities and at low risk for airway compromise or fistula formation, early discharge after free tissue transfer for head and neck reconstruction is a safe and viable option. STUDY DESIGN: Retrospective chart review. METHODS: A cohort of patients who underwent free tissue transfer for head and neck reconstruction between February 2010 and December 2014 and who were discharged from the hospital by postoperative day 3 were reviewed. RESULTS: Fifty patients undergoing 51 free-tissue transfer surgeries were discharged by postoperative day 3. The surgeries performed included anterolateral thigh free flaps (ALT) (n = 46), radial forearm free flaps (n = 2), latissimus myogenous and myocutaneous free flaps (n = 1), supraclavicular free flap (n = 1), and serratus free flap (n = 1). All ALT flaps were harvested exclusively as perforator free flaps; and the vast majority used superficial temporal, angular, or facial vessels. All free flaps were viable without evidence of vascular compromise at discharge and the initial follow-up appointment. One patient required take-back for successful flap salvage. One patient experienced late flap failure (between 2-3 weeks postoperatively), requiring another surgery. This resulted in an overall success rate of 98% in this cohort. No other postoperative complications related to early discharge were identified. CONCLUSION: In a carefully selected subset of patients undergoing free tissue transfer, early discharge has been shown to be possible without compromising patient safety or surgery success rates. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2679-2683, 2016.