A Novel Surgical Landmark to Identify the Recurrent Laryngeal Nerve

Background: Although several surgical landmarks have been proposed to localize the recurrent laryngeal nerve (RLN), there is still no reliable landmark. Aims: To validate the reliability of a novel reference point at the intersection of the inferior border of the cricopharyngeal muscle and the inferior cornu of thyroid cartilage for locating the RLN. Study Design: Cadaver dissection study in the academic department of otolaryngology-head and neck surgery. Methods: Sixty-four RLNs in cadavers were assessed, and measurements of different surgical landmarks in conjunction with the proposed surgical landmark were obtained. Descriptive statistics, Pearson's chi-squared test, and Student's t-test were performed to analyze the data using GraphPad Prism (version 9.4.1; Dotmatics, Boston, Massachusetts, USA). Results: The average distance from the proposed landmark to the RLN was 2.3 ± 0.85 mm. The RLN was located just posterior to the reference point in 95.31% of the cadavers. The RLN passed under the inferior constrictor muscle in 90.63% of the cadavers. There was no statistically significant difference between right- and left-sided RLNs in terms of their relation with the reference point. Conclusion: The proposed reference point can be used as a reliable landmark to locate the RLN. This reference point may help surgeons during difficult thyroidectomy surgeries by providing an additional anatomical landmark.

Removal of airway foreign bodies complicated by an unstable cervical spine fracture.

Aspiration of foreign bodies is common and among the leading causes of accidental death in children. When detected promptly, an experienced physician can successfully manage foreign bodies of the airway. However, uncommon objects and physical trauma can complicate their removal. Inhalation of organic and inorganic foreign bodies of all types is well documented, but glass in the airway is an unusual and difficult problem. Further, airway foreign bodies in conjunction with an unstable cervical spine are rare. Polytrauma tends to complicate any case. We present a case illustrating both circumstances: tempered automotive glass in the airway of a child with an unstable cervical spine fracture.

Effect of gold laser energy delivery on postoperative adenotonsillectomy complications.

BACKGROUND: This study aimed to determine if the energy delivered by the Gold laser impacted postoperative complication rates after adenoidectomy, tonsillectomy, or adenotonsillectomy. METHODS: A retrospective chart review identified 420 patients who met the criteria within the last five years. Indications for the surgeries included recurrent tonsillitis, obstructive sleep apnea, sleep-disordered breathing, adenoiditis, peritonsillar abscess, and other indications. The relationship between the energy delivered (kJ) and various complications such as bleeding, pain, dehydration, readmission, emergency center visits, and clinic calls was evaluated. RESULTS: There was a significant correlation between higher kJ delivered and the incidence of major bleeding requiring cauterization in the operating room (p = 0.0311). In addition, emergency center visits (p = 0.0131) and readmission (p = 0.0210) showed a significant correlation with the amount of energy (kJ) delivered. Furthermore, higher energy correlated to higher maximum post-operative pain scores (p = 0.0302). Attendings displayed a different pattern of energy delivery compared to residents (p < 0.0001), which also differed by PGY (p < 0.0001). CONCLUSION: There are significant correlations between higher energy delivered in kJ using the Gold laser and less desirable post-operative results. In addition, residents tend to utilize higher energy levels than attendings, but this trend tapers off in the 4th and 5th years. Clinicians utilizing the Gold laser during these procedures should be mindful of the amount of kJ they use.

Intrathyroidal Parathyroid Carcinoma: Case Report and Literature Review.

Intrathyroidal parathyroid carcinoma (PC) is a rare malignancy that is usually difficult to diagnose. We present a case of a 31-year-old male with a history of hyperparathyroidism who was found to have intrathyroidal PC upon review of immunostains along with a review of the current literature. A systematic review of the literature utilizing the PubMed database identified 24 relevant, full-text articles. 25 cases were analyzed, including our own report. The case of a 31-year-old man with a history of hyperparathyroidism managed with subtotal thyroidectomy and subtotal parathyroidectomy who had persistent hypercalcemia and elevated parathyroid hormone. Abnormal radiotracer uptake was noted in the left thyroid gland. Neck exploration with left parathyroidectomy and revision thyroidectomy was performed. A candidate left inferior parathyroid was found within the left thyroid lobe remnant and identified as parathyroid carcinoma. Immunostains determined an intrathyroidal parathyroid carcinoma. The literature review shows the average presenting age was 50.9 years. 54.17% (CI, 43-82%) of affected patients are female. Right-sided thyroid involvement is seen in 54.17% (CI, 34-74%) of cases. The inferior aspect of the thyroid is involved in 66.67% of cases (CI, 53-89%). Intrathyroidal parathyroid carcinoma is a rare and challenging diagnosis due to similarities with other more common endocrine abnormalities. This review found that the inferior parathyroid is more likely to be located within the thyroid gland. Surgeons may consider aberrant anatomical locations, including intrathyroidal locations, for the inferior parathyroid glands.

Screening Awareness of HPV-Related Oropharyngeal Cancers and Attitudes and Concerns towards HPV Vaccination Among Parents : HPV and Oropharyngeal Cancer.

Baseline population opinions on human papillomavirus (HPV) and HPV vaccination must be understood before physicians can address knowledge gaps in that population and encourage timely vaccination. To determine the opinions of parents of children age 9 to 18 on HPV-related oropharyngeal cancers (OPC); the associations with education level, socioeconomic status, and having a family member/friend with OPC; and the main concerns against having a vaccination., An anonymous survey was created and administered. Parents were asked to complete the survey if they met the inclusion criteria. After the survey, results were tabulated, and the answers for each question were analyzed. The target population was surveyed in the clinic. The target population was parents with children between 9 and 18 years old: the background knowledge and awareness of HPV-related OPC and associations with education level, socioeconomic status, having a family member/friend with OPC, and concerns about vaccination. Our study results showed that the age of parents, education level, marital status, personal vaccination status, and gender of the child are significant factors for background knowledge about HPV-related diseases. Similarly, the education level, the gender of the child, and personal vaccination status are significant factors towards attitudes against having children vaccinated. There is a strong correlation between background knowledge and attitudes. The main issues about vaccination are concerns about effectiveness and side effects, concerns about safe sex experiences, and the cost of vaccination. This is the first study designed to provide information on parents' knowledge of HPV-related cancers, prevalence of HPV vaccination, and attitudes and concerns about HPV vaccination in the USA. The lack of awareness of HPV-related cancers is a significant factor in attitudes against HPV vaccination.

Utilization of Advanced Practice Providers in Advanced Practice Provider-Led Stroke Clinic to Expand Outpatient Stroke Follow-up Care.

Stroke follow-up care with neurology specialty advanced practice providers is critical to focus on stroke prevention. The need for which is underscored by results of a recent study noting that many stroke survivors of first-ever strokes were not receiving stroke standard-of-care prevention measures including consistent antiplatelet therapies and regular exercise. Study findings further note the rates of usage for stroke prevention interventions (daily anti-platelet therapy, smoking cessation, regular exercise, hypertension control) were between 50% and 70%. Clinical nurse specialists along with nurse practitioner and physician assistant advanced practice providers are uniquely suited to manage outpatient ischemic stroke care to reduce the recurrence of stroke and improve patient outcomes.

Unilateral Tessier 7 cleft: Case report of Z-plasty with geometric broken line repair and literature review.

Tessier 7 clefts are a rare congenital anomaly, usually surgically repaired with Z-plasty or other reconstructive methods, although undesirable scars may result. We present a review of the literature and a case of unilateral Tessier 7 cleft repaired with a novel reconstruction technique using a combined Z-plasty and geometric broken line closure (GBLC) to camouflage and irregularize the otherwise linear scar. We present this case to expand the armamentarium of surgical options to address Tessier 7 clefts and to review techniques for repair.

Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage.

Lumisterol (L3) is a stereoisomer of 7-dehydrocholesterol and is produced through the photochemical transformation of 7-dehydrocholesteol induced by high doses of UVB. L3 is enzymatically hydroxylated by CYP11A1, producing 20(OH)L3, 22(OH)L3, 20,22(OH)2L3, and 24(OH)L3. Hydroxylumisterols function as reverse agonists of the retinoic acid-related orphan receptors α and γ (RORα/γ) and can interact with the non-genomic binding site of the vitamin D receptor (VDR). These intracellular receptors are mediators of photoprotection and anti-inflammatory activity. In this study, we show that L3-hydroxyderivatives significantly increase the expression of VDR at the mRNA and protein levels in keratinocytes, both non-irradiated and after UVB irradiation. L3-hydroxyderivatives also altered mRNA and protein levels for RORα/γ in non-irradiated cells, while the expression was significantly decreased in UVB-irradiated cells. In UVB-irradiated keratinocytes, L3-hydroxyderivatives inhibited nuclear translocation of NFκB p65 by enhancing levels of IκBα in the cytosol. This anti-inflammatory activity mediated by L3-hydroxyderivatives through suppression of NFκB signaling resulted in the inhibition of the expression of UVB-induced inflammatory cytokines, including IL-17, IFN-γ, and TNF-α. The L3-hydroxyderivatives promoted differentiation of UVB-irradiated keratinocytes as determined from upregulation of the expression at the mRNA of involucrin (IVL), filaggrine (FLG), and keratin 14 (KRT14), downregulation of transglutaminase 1 (TGM1), keratins including KRT1, and KRT10, and stimulation of ILV expression at the protein level. We conclude that CYP11A1-derived hydroxylumisterols are promising photoprotective agents capable of suppressing UVB-induced inflammatory responses and restoring epidermal function through targeting the VDR and RORs.

Designing a Low-Cost Thyroid Ultrasound Phantom for Medical Student Education.

Using ultrasound for the diagnostic workup of thyroid lesions is a widely accepted technique. An inexpensive phantom model of thyroid lesions would be an invaluable tool for engaging medical students in learning the diagnostic algorithm for thyroid lesions and how to perform fine needle aspiration (FNA). The aim of this study was to devise an inexpensive and reproducible training phantom model for thyroid lesion detection, image interpretation and in vitro FNA using ultrasound guidance. A simple phantom model imitating benign cystic lesions, intermediately suspicious lesions and highly suspicious lesions was developed using a chicken breast, red seedless grapes, pimento olives and blackberries. The phantom was constructed for a total cost of $4.09 per unit and constructed in approximately 3 min. Nine models were constructed in total, demonstrating that the model design is replicable. This thyroid FNA phantom is an inexpensive, easy-to-produce model that allows medical students to practice measuring lesions and performing FNAs using ultrasonography. Future studies could be explored to assess this model's role in medical student education.

Electrospun scaffolds limit the regenerative potential of the airway epithelium.

OBJECTIVE: Significant morbidity and mortality are associated with clinical use of synthetic tissue-engineered tracheal grafts (TETG). Our previous work focused on an electrospun polyethylene terephthalate and polyurethane (PET/PU) TETG that was tested in sheep using a long-segment tracheal defect model. We reported that graft stenosis and limited epithelialization contributed to graft failure. The present study determined if the epithelialization defect could be attributed to: 1) postsurgical depletion of native airway basal stem/progenitor cells; 2) an inability of the PET/PU-TETG to support epithelial migration; or 3) compromised basal stem/progenitor cell proliferation within the PET/PU environment. STUDY DESIGN: Experimental. METHODS: Basal stem/progenitor cell frequency in sheep that underwent TETG implantation was determined using the clone-forming cell frequency (CFCF) method. A novel migration model that mimics epithelial migration toward an acellular scaffold was developed and used to compare epithelial migration toward a control polyester scaffold and the PET/PU scaffold. Basal stem/progenitor cell proliferation within the PET/PU scaffold was evaluated using the CFCF assay, doubling-time analysis, and mitotic cell quantification. RESULTS: We report that TETG implantation did not decrease basal stem/progenitor cell frequency. In contrast, we find that epithelial migration toward the PET/PU scaffold was significantly less extensive than migration toward a polyester scaffold and that the PET/PU scaffold did not support basal stem/progenitor cell proliferation. CONCLUSIONS: We conclude that epithelialization of a PET/PU scaffold is compromised by poor migration of native tissue-derived epithelial cells and by a lack of basal stem/progenitor cell proliferation within the scaffold. LEVEL OF EVIDENCE: NA.

Factors Influencing Poor Outcomes in Synthetic Tissue-Engineered Tracheal Replacement.

OBJECTIVES: Humans receiving tissue-engineered tracheal grafts have experienced poor outcomes ultimately resulting in death or the need for graft explantation. We assessed the performance of the synthetic scaffolds used in humans with an ovine model of orthotopic tracheal replacement, applying standard postsurgical surveillance and interventions to define the factors that contributed to the complications seen at the bedside. STUDY DESIGN: Large animal model. SETTING: Pediatric academic research institute. SUBJECTS AND METHODS: Human scaffolds were manufactured with an electrospun blend of polyethylene terephthalate and polyurethane reinforced with polycarbonate rings. They were seeded with autologous bone marrow-derived mononuclear cells and implanted in sheep. Animals were evaluated with routine bronchoscopy and fluoroscopy. Endoscopic dilation and stenting were performed to manage graft stenosis for up to a 4-month time point. Grafts and adjacent native airway were sectioned and evaluated with histology and immunohistochemistry. RESULTS: All animals had signs of graft stenosis. Three of 5 animals (60%) designated for long-term surveillance survived until the 4-month time point. Graft dilation and stent placement resolved respiratory symptoms and prolonged survival. Necropsy demonstrated evidence of infection and graft encapsulation. Granulation tissue with signs of neovascularization was seen at the anastomoses, but epithelialization was never observed. Acute and chronic inflammation of the native airway epithelium was observed at all time points. Architectural changes of the scaffold included posterior wall infolding and scaffold delamination. CONCLUSIONS: In our ovine model, clinically applied synthetic tissue-engineered tracheas demonstrated infectious, inflammatory, and mechanical failures with a lack of epithelialization and neovascularization.

Cell Therapy for Cystic Fibrosis Lung Disease: Regenerative Basal Cell Amplification.

The human airway epithelium is regenerated by basal cells. Thus, basal cell therapy has the potential to cure cystic fibrosis (CF) lung disease. We previously reported that the human basal cells repopulated the mouse airway epithelium after transplantation, and we estimated that 60 million cells would be needed to treat a human patient. To further develop cell therapy, we compared the proliferation potential of non-CF and CF tissue-derived bronchial basal cells. Three methods were used: regenerative cell frequency, burst size, and cell division frequency. Second, we used a serial passage strategy to determine if CF basal cells could be amplified to the estimated therapeutic dose. These studies evaluated that tissue-derived bronchial basal cells and the basal cells that were recovered by brushing bronchial airways or the nasal respiratory epithelium. Finally, we used the limiting dilution method to isolate non-CF and CF basal cell clones. The proliferation assays and the air-liquid-interface differentiation method were used to determine if cell amplification altered the proliferation and/or differentiation potential of clonal isolates. We demonstrate that: (a) non-CF and CF basal cell proliferation is similar, (b) CF basal cells can be amplified to a therapeutic cell dose, and (c) amplified non-CF and CF basal cell clones differentiate normally. Despite these encouraging findings, we also find that the cell amplification process depletes the regenerative basal cell pool. Analysis of basal cell clones indicates that serial passage selects for long-lived basal cells and raise the possibility that prospective isolation of these stem-like cells will improve the efficacy of cell replacement therapy. Stem Cells Translational Medicine 2019;8:225&235.

Evaluation of the effect of pre-operative oral midazolam on post-operative oral fluid intake after tonsillectomy.

INTRODUCTION: The objective of this study was to determine if pre-operative oral midazolam administration decreased postoperative oral fluid intake after tonsillectomy with or without adenoidectomy. METHODS: A retrospective chart review identified 104 patients who were undergoing tonsillectomy with and without adenoidectomy who were not given midazolam preoperatively and 182 who were given midazolam preoperatively. Indications for tonsillectomy with or without adenoidectomy included obstructive sleep apnea, recurrent acute streptococcal pharyngotonsillitis, and, in selected cases, periodic fever with aphthous stomatitis, pharyngitis and adenopathy. All patients were evaluated in the pre-operative area by the attending anesthesiologist, who then determined whether or not he/she felt the patient would benefit from premedication with oral midazolam prior to surgery. Patients whom the attending anesthesiologist judged would benefit from midazolam were then given a 0.12-1.06 mg/kg dose (mean 0.35 mg/kg, STD 0.12), at the discretion of the anesthesiologist. Various methods were used to perform tonsillectomy, such as coblation and electrocautery, at the discretion of the otolaryngologist. Results were not stratified by surgical technique. Oral fluid intake was calculated by establishing the time of return to the floor from surgery and determining the documented oral fluid intake for the next 12 h. Oral fluid intake per kg per hour was then calculated. The amount of midazolam given was documented. RESULTS: There was no significant difference in oral fluid intake by group when adjusting for age and weight, F(1, 282) = 0.383, p = 0.537. Also, there was no significant difference in ml/kg/hr by group when adjusting for age and weight, F(1, 282) = 2.813, p = 0.095. CONCLUSIONS: There was no significant difference in oral fluid intake between the no midazolam and midazolam groups, indicating that clinicians can continue to use their judgement in administering midazolam to select anxious patients prior to tonsillectomy with or without adenoidectomy. Future work could include multi-center retrospective reviews or a randomized placebo-controlled trial to examine more carefully the effects of midazolam on postoperative oral fluid intake. LEVEL OF EVIDENCE: Level IV.

The wound healing capacity of undifferentiated and differentiated airway epithelial cells in vitro.

INTRODUCTION: Congenital or acquired tracheal lesions alter airway epithelial structure and can lead to long-segment tracheal defects. Tissue engineered tracheal grafts (TETG) have the potential to cure such defects; however, clinical applications have been plagued with numerous complications including delayed graft epithelialization. The knowledge that epithelial cells migrate from native tissue to the TETG raises the possibility that TETG performance can be improved by increasing the rate of epithelialization. OBJECTIVES: We developed a model that can be used quantify epithelial migration in clinically-relevant conditions. METHODS: Existing histological analyses determined the differentiation status of the normal and injured human tracheal epithelium and were used to identify in vitro culture conditions that mimic these parameters. The classical scratch assay was adapted to permit analysis of migratory velocity as a function of differentiation status. Migration of undifferentiated (UD), partially-differentiated (PD), and well-differentiated (WD) epithelia was quantified. RESULTS: The normal and injured epithelium can be modeled using human cells that are cultured using a modified air-liquid-interface culture system. PD cell cultures are similar to the remodeled epithelium; whereas; WD cultures are similar to the normal epithelium. Preliminary results indicate that PD cells migrate more rapidly than WD cells and that PD and WD cells migrate more rapidly than UD cells. CONCLUSION: Pending verification of these results, we suggest that epithelial migration is significantly altered by differentiation status. Thus, efforts to improve TETG epithelialization should use model systems that faithfully-represent the differentiation state of the native tissue.

Finding water scarcity amid abundance using human-natural system models.

Water scarcity afflicts societies worldwide. Anticipating water shortages is vital because of water's indispensable role in social-ecological systems. But the challenge is daunting due to heterogeneity, feedbacks, and water's spatial-temporal sequencing throughout such systems. Regional system models with sufficient detail can help address this challenge. In our study, a detailed coupled human-natural system model of one such region identifies how climate change and socioeconomic growth will alter the availability and use of water in coming decades. Results demonstrate how water scarcity varies greatly across small distances and brief time periods, even in basins where water may be relatively abundant overall. Some of these results were unexpected and may appear counterintuitive to some observers. Key determinants of water scarcity are found to be the cost of transporting and storing water, society's institutions that circumscribe human choices, and the opportunity cost of water when alternative uses compete.

Naïve Simplicity: The Overlooked Piece of the Complexity-Simplicity Paradigm.

Concepts of simplicity and complexity in modeling have been explored in papers, editorials, and talks. The concept is not well understood because there are at least two flavors of simplicity. Modelers envision simplicity (i.e., elegant simplicity) as the sought-after goal in modeling, but naïve simplicity, which is the focus of this paper, is commonly unrecognized and dangerous. The problem is that naïve or simple ideas are often mistaken for settled science and come with the prospect of being more wrong than right. The concept of the so-called simplicity cycle, in relation to classical problems of carbon-14 age and salinity in closed-basin lakes, is used to illustrate these points. The emerging problems of water-mosquitoes-diseases show the value of mapping new problems to the simplicity cycle. Researchers can "know what they do not know" and avoid the dangers of naïve simplicity.

Monitoring diagnostic accuracy and complications. A report from the Children's Oncology Group Hodgkin lymphoma study.

BACKGROUND/PURPOSE: Cancer studies mandate quality assurance programs for clinical trials. Surgeons consistently play 2 roles early in the management of Hodgkin lymphoma in children and adolescents: obtaining a specimen for pathologic diagnosis and placing a central venous catheter to assist with therapy delivery. A surgical quality assurance program was embedded as part of the of the Hodgkin lymphoma study (AHODOOO31) to assess diagnostic accuracy and complications. METHODS: Surgical checklists and operative and pathology reports were reviewed concurrently. Diagnostic technique, success rate, location of biopsy, combined procedures under one anesthetic, and complications are reported. RESULTS: One hundred eighty-five cases were reviewed, with 169 having complete data. Diagnostic techniques included open biopsy (n = 148), computed tomography-guided core biopsy (n = 5), thoracoscopic/laparoscopic biopsy (n = 10) and fine-needle aspirations (n = 4). No staging laparotomies were performed. Biopsy sites included cervical (133), mediastinal (18), axillary (7), and others (11). Diagnostic accuracy was 145 of 148 (98.5%) for the open biopsy; 4 of 5, core biopsy (80%); 6 of 10 (60%), thoracoscopic/laparoscopic biopsy; and 1 of 4, fine-needle aspiration (25%). Eighteen had mediastinal disease only, 9 of whom had a thoracoscopic biopsy with a 55% diagnostic accuracy. Inadequate sample was the only reason for a lack of diagnosis. A second open operation was required in these cases for diagnosis. At biopsy, frozen section confirmed a malignancy in 68. In 38 of these 68 children, a central line was placed during the same anesthetic. The most common complication was inadequate sampling. Three wound infections were reported. CONCLUSIONS: With an appropriate surgical approach to obtain an adequate tissue specimen, diagnostic accuracy is high and surgical complications are low in children with Hodgkin lymphoma. Diagnostic technique should ensure adequate tissue sampling especially when not using an open procedure. When possible, central line insertion should be performed under the same anesthetic. Fine-needle aspiration was not used enough to assess its role in the diagnosis of children with Hodgkin lymphoma.