JAG1 is a ligand that activates the NOTCH signaling pathway which plays a crucial role in determining cell fate behavior through cell-to-cell signaling. JAG1-NOTCH signaling is required for mesenchymal stem cell (MSC) differentiation into cardiomyocytes and cranial neural crest (CNC) cells differentiation into osteoblasts, making it a regenerative candidate for clinical therapy to treat craniofacial bone loss and myocardial infarction. However, delivery of soluble JAG1 has been found to inhibit NOTCH signaling due to the requirement of JAG1 presentation in a bound form. For JAG1-NOTCH signaling to occur, JAG1 must be immobilized within a scaffold and the correct orientation between the NOTCH receptor and JAG1 must be achieved. The lack of clinically translatable JAG1 delivery methods has driven the exploration of alternative immobilization approaches. This review discusses the role of JAG1 in disease, the clinical role of JAG1 as a treatment, and summarizes current approaches for JAG1 delivery. An in-depth review was conducted on literature that used both in vivo and in vitro delivery models and observed the canonical versus non-canonical NOTCH pathway activated by JAG1. Studies were then compared and evaluated based on delivery success, functional outcomes, and translatability. Delivering JAG1 to harness its ability to control cell fate has the potential to serve as a therapeutic for many diseases.
Objective: To describe the implementation of telemedicine in a pediatric otolaryngology practice during the coronavirus disease 2019 (COVID-19) global pandemic. Methods: A descriptive paper documenting the development and application of telemedicine in a tertiary academic pediatric otolaryngology practice. Results: A total of 51 established patients were seen via telemedicine within the first 2 weeks of telemedicine implementation. Seven (7) patients were no shows to the appointment. The median patient age was 5 years old, with 55% male patients. Common diagnoses for the visits included sleep disordered breathing/obstructive sleep apnea (25%) and hearing loss (19.64%). Over half (50.98%) of visits were billed at level 4 visit code. Discussion: The majority (88%) of visits during the first 2 weeks of telemedicine implementation in our practice were completed successfully. Reasons that patients did not schedule telemedicine appointments included preference for in person appointments, and lack of adequate device at home to complete telemedicine visit. Limitations to our telemedicine practice included offering telemedicine only to patients who had home internet service, were established patients, and English-speaking. Trainees were not involved in this initial implementation of telemedicine. Conclusions: COVID-19 has driven the rapid adoption of telemedicine in outpatient medicine. Our group was able to institute an effective telemedicine practice during this time.
Introduction: Obstructive sleep apnea (OSA) is prevalent and may be more severe in children with Sickle Cell Disease (SCD) compared to the general pediatric population. Objectives: The objective of this study was to describe the therapeutic effects and complications of tonsillectomy and adenoidectomy (T&A) for treatment of OSA in children with SCD. Methods: A comprehensive database of pediatric SCD patients was reviewed to identify all patients who underwent T&A between 2010 and 2016. An IRB-approved, retrospective review of laboratory values, perioperative course, pre- and post-T&A hospital utilization, and polysomnography was conducted. Results: There were 132 SCD children (108 HbSS) who underwent T&A. Mean age was 7.6 ± 4.6 years. The mean baseline hemoglobin of these patients was 9.3 ± 1.4 g/dL; 72.7% of patients had pre-operative transfusion, such that the mean Hb at time of T&A was 11.4 ± 1.0 g/dL. The average admission length surrounding T&A was 3.5 ± 1.2 days. Complications were documented in 11.4% of operative cases. Polysomnography was available in 104 pre-T&A and 45 post-T&A. The Apnea-Hypopnea Index decreased on post-T&A polysomnogram (7.6 ± 8.7 vs. 1.3 ± 1.9, p = 0.0001). The O2 nadir improved on post-T&A polysomnogram (81.2 ± 10.8 vs. 89.3 ± 7, p = 0.0003). Emergency room visits (mean events per year) decreased post-operatively (2.6 ± 2.8 vs. 1.8 ± 2.2, p = 0.0002). Conclusions: T&A can be a safe and effective option to treat OSA in pediatric patients with SCD and was significantly associated with reduced AHI and fewer ER visits post-operatively.
Cleft lip and palate are common craniofacial deformities. The etiology underlying these deformities is complex and multifactorial and they can occur as part of one of many chromosomal syndromes, Mendelian single gene disorders, teratogenic effects, and as yet uncharacterized syndromes. Our paper will provide an overview of the multiple genes and molecular pathways that have been implicated in palatal fusion. We believe that understanding the molecular mechanisms of cleft formation can help clinicians anticipate which patients may have difficulties healing and in the future allow them to make surgical and medical treatment decisions based on genetic information.
Introduction:
Sensorineural hearing loss (SNHL) has been reported to occur at increased frequency in the pediatric sickle cell disease (SCD) population, likely secondary to ototoxic medication regimens and repeat sickling events that lead to end organ damage. Risk and protective factors of SNHL in this population are not fully characterized. The objective of this study was to describe audiology results in children with SCD and the prevalence and sequelae of SNHL.
Methods:
A comprehensive clinical database of 2600 pediatric SCD patients treated at 1 institution from 2010-16 was retrospectively reviewed to identify all patients who were referred for audiologic testing. Audiologic test results, patient characteristics, and SCD treatments were reviewed.
Results:
181 SCD children (97 male, 153 HbSS) underwent audiologic testing, with 276 total audiology encounters, ranging 1–9 per patient. Mean age at first audiogram was 8.9 ± 5.2 years. 29.8% had prior cerebrovascular infarct and an additional 25.4% had prior abnormal transcranial Doppler screens documented at time of first audiogram. Overall, 13.3% had documented hearing loss, with 6.6% SNHL. Mean pure tone average (PTA) among patients with SNHL ranged from mild to profound hearing loss (Right: 43.3 ± 28.9, Left: 40.8 ± 29.7), sloping to more severe hearing loss at higher frequencies.
Conclusions:
Hearing loss was identified in a significant subset of children with SCD and the hearing loss ranged from normal to profound. Though the overall prevalence of SNHL in SCD patients was low, baseline audiology screening should be considered.
Objective: The coronavirus disease 2019 (COVID-19) pandemic caused delays in medical and surgical interventions in most health care systems worldwide. Oral and maxillofacial surgeons (OMSs) delayed operations to protect themselves, patients, and staff. This article (1) presents one institution's experience in the management of pediatric craniomaxillofacial trauma during the COVID-19 pandemic and (2) suggests recommendations to decrease transmission. Methods: This was a retrospective review of children aged 18 years or younger who underwent surgery at Children's Healthcare of Atlanta in Atlanta, GA, between March and August 2020. Patients (1) were aged 18 years old or younger, (2) had one or more maxillofacial fractures, and (3) underwent surgery performed by an OMS, otolaryngologist, or plastic surgeon. Medical records were reviewed regarding (1) fracture location, (2) COVID-19 status, (3) timing, (4) personal protective equipment, and (5) infection status. Descriptive statistics were computed. Results: Fifty-eight children met the inclusion criteria. The most commonly injured maxillofacial location was the nose. Operations were performed 50.9 hours after admission. Specific prevention perioperative guidelines were used with all patients, with no transmission occurring from a patient to a health care worker. Conclusions: With application of our recommendations, there was no transmission to health care workers. We hope that these guidelines will assist OMSs during the COVID-19 pandemic.
In 2010, the FDA approved the administration of FTY720, S1P lipid mediator, as a therapy to treat relapsing forms of multiple sclerosis. FTY720 was found to sequester pro-inflammatory lymphocytes within the lymph node, preventing them from causing injury to the central nervous system due to inflammation. Studies harnessing the anti-inflammatory properties of FTY720 as a pro-regenerative strategy in wound healing of muscle, bone and mucosal injuries are currently being performed. This in-depth review discusses the current regenerative impact of FTY720 due to its anti-inflammatory effect stratified into an assessment of wound regeneration in the muscular, skeletal, and epithelial systems. The regenerative effect of FTY720 in vivo was characterized in three animal models, with differing delivery mechanisms emerging in the last 20 years. In these studies, local delivery of FTY720 was found to increase pro-regenerative immune cell phenotypes (neutrophils, macrophages, monocytes), vascularization, cell proliferation and collagen deposition. Delivery of FTY720 to a localized wound environment demonstrated increased bone, muscle, and mucosal regeneration through changes in gene and cytokine production primarily by controlling the local immune cell phenotypes. These changes in gene and cytokine production reduced the inflammatory component of wound healing and increased the migration of pro-regenerative cells (neutrophils and macrophages) to the wound site. The application of FTY720 delivery using a biomaterial has demonstrated the ability of local delivery of FTY720 to promote local wound healing leveraging an immunomodulatory mechanism.
Objectives. First branchial cleft anomalies (BCAs) constitute a rare entity with variable clinical presentations and anatomic findings. Given the high rate of recurrence with incomplete excision, identification of the entire tract during surgical treatment is of paramount importance. The objectives of this paper were to present five anatomic variations of first BCAs and describe the presentation, evaluation, and surgical approach to each one.
Methods. A retrospective case review and literature review were performed. We describe patient characteristics, presentation, evaluation, and surgical approach of five patients with first BCAs.
Results. Age at definitive surgical treatment ranged from 8 months to 7 years. Various clinical presentations were encountered, some of which were atypical for first BCAs. All had preoperative imaging demonstrating the tract. Four surgical approaches required a superficial parotidectomy with identification of the facial nerve, one of which revealed an aberrant facial nerve. In one case the tract was found to travel into the angle of the mandible, terminating as a mandibular cyst. This required en bloc excision that included the lateral cortex of the mandible.
Conclusions. First BCAs have variable presentations. Complete surgical excision can be challenging. Therefore, careful preoperative planning and the recognition of atypical variants during surgery are essential.
Following injury, the oral mucosa undergoes complex sequences of biological healing processes to restore homeostasis. While general similarities exist, there are marked differences in the genomics and kinetics of wound healing between the oral cavity and cutaneous epithelium. The lack of successful therapy for oral mucosal wounds has influenced clinicians to explore alternative treatments and potential autotherapies to enhance intraoral healing. The present in-depth review discusses current gold standards for oral mucosal wound healing and compares endogenous factors that dictate the quality of tissue remodeling. We conducted a review of the literature on in vivo oral wound healing models and emerging regenerative therapies published during the past twenty years. Studies were evaluated by injury models, therapy interventions, and outcome measures. The success of therapeutic approaches was assessed, and research outcomes were compared based on current hallmarks of oral wound healing. By leveraging therapeutic advancements, particularly within in cell-based biomaterials and immunoregulation, there is great potential for translational therapy in oral tissue regeneration.