Jaw Thrust: A Simple Predictor of Success in Mandibular Distraction Osteogenesis.

BACKGROUND: The hypoplastic mandible in the congenital condition Pierre Robin sequence (PRS) displaces the base of the tongue posteriorly, which results in upper airway obstruction (UAO) that can potentially be corrected with mandibular distraction osteogenesis (MDO). Jaw thrust (JT) is routinely performed during evaluation of the airway; similar to MDO, it projects the mandible and tongue anteriorly to open the airway. The authors demonstrate that JT can be used as a criterion to predict successful MDO outcomes in infants with PRS. METHODS: The study was a single-center, retrospective chart review of infants diagnosed with PRS between 2016 and 2023. Data regarding their demographics, comorbid diagnoses, JT success, airway anomalies, laryngeal grade of view, apnea-hypopnea index, and perioperative course were statistically analyzed. RESULTS: Of the 16 patients included in the study, 11 had successful relief of their airway obstruction with JT and proceeded with MDO. The unsuccessful JT group had significantly greater proportions of females, birth prematurity, gastrostomies, tracheostomies, and longer hospital stays. In the successful JT group, both the mean laryngeal grade of view (P=0.029) and mean apnea-hypopnea index (P=0.025) improved significantly post-MDO. Post-MDO tracheostomy was also avoided in all but 1 patient who was not previously tracheostomized. CONCLUSIONS: There is no widely accepted algorithm to guide craniofacial surgeons on the optimal intervention for relieving UAO in infants with PRS. In our institutional experience, patients whose preoperative JT relieved UAO also successfully relieved UAO with MDO. In patients with PRS, JT may be a useful criterion for selecting appropriate candidates for MDO.

Methods of measurement for pneumothorax in pediatric patients: a systematic review.

Accurate measurement of pneumothorax (PTX) size is necessary to guide clinical decision making; however, there is no consensus as to which method should be used in pediatric patients. This systematic review seeks to identify and evaluate the methods used to measure PTX size with CXR in pediatric patients. A systematic review of the literature through 2021 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was conducted using the following databases: Ovid/MEDLINE, Scopus, Cochrane Database of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar. Original research articles that included pediatric patients (< 18 years old) and outlined the PTX measurement method were included. 45 studies were identified and grouped by method (Kircher and Swartzel, Rhea, Light, Collins, Other) and societal guideline used. The most used method was Collins (n = 16; 35.6%). Only four (8.9%) studies compared validated methods. All found the Collins method to be accurate. Seven (15.6%) studies used a standard classification guideline and 3 (6.7%) compared guidelines and found significant disagreement between them. Pediatric-specific measurement guidelines for PTX are needed to establish consistency and uniformity in both research and clinical practice. Until there is a better method, the Collins method is preferred.

United States insurance coverage of immediate lymphatic reconstruction.

INTRODUCTION: Immediate Lymphatic Reconstruction (ILR) is a prophylactic microsurgical lymphovenous bypass technique developed to prevent breast cancer related lymphedema (BCRL). We investigated current coverage policies for ILR among the top insurance providers in the United States and compared it to our institutional experience with obtaining coverage for ILR. METHODS: The study analyzed the publicly available ILR coverage statements for American insurers with the largest market share and enrollment per state to assess coverage status. Institutional ILR coverage was retrospectively analyzed using deidentified claims data and categorizing denials based on payer reason codes. RESULTS: Of the 63 insurance companies queried, 42.9% did not have any publicly available policies regarding ILR coverage. Of the companies with a public policy, 75.0% deny coverage for ILR. In our institutional experience, $170,071.80 was charged for ILR and $166 118.99 (97.7%) was denied by insurance. CONCLUSIONS: Over half of America's major insurance providers currently deny coverage for ILR, which is consistent with our institutional experience. Randomized trials to evaluate the efficacy of ILR are underway and focus should be shifted towards sharing high level evidence to increase insurance coverage for BCRL prevention.

The Role of Digital Surgical Planning and Surgical Guides in the Treatment of Unilateral Condylar Hyperplasia.

Unilateral condylar hyperplasia (UCH) results in facial asymmetry, malocclusion, and temporomandibular joint dysfunction. Treatment consists of both surgical and orthodontic intervention. A review was performed for 4 patients with UCH who underwent digital surgical planning (DSP)-assisted condylectomy. All patients were female, aged 14 to 35 years at the time of operation with facial asymmetry and class III malocclusion. None of the patients had prior treatment and all had perioperative orthodontic appliances to provide fixation and postoperative elastic therapy. All patients underwent DSP-guided condylectomy, and intraoperative surgical cutting guides were used for 3 of the patients. All had significant improvement in facial symmetry and occlusion. None had recurrence, and additional intervention has not been required. If UCH is recognized before marked secondary changes in the maxilla, mandible, and occlusion, future orthognathic surgery may be potentially obviated. Craniomaxillofacial surgeons should consider using DSP and surgical guides in the treatment of UCH.

Crouzon Syndrome Spanning Three Generations: Advances in the Treatment of Syndromic Midface Deficiency.

Background: Crouzon syndrome is an autosomal dominant genetic disorder characterized by craniosynostosis, midface retrusion, and exophthalmos. Over the past century, the treatment of craniofacial disorders like Crouzon syndrome has evolved significantly. Methods: An institutional review board-approved retrospective study was conducted to ascertain the treatment of three individuals with Crouzon syndrome from one family, complemented with a series of literature searches to examine the evolution of craniofacial surgical history. Results: Dr. David Williams Cheever developed the Le Fort I level to correct malocclusion, maxillomandibular malformations, and midface hypoplasia. Later, Dr. Paul Tessier introduced the Le Fort II and III osteotomies to treat syndromic midface hypoplasia. In 1978, Dr. Fernando Ortiz-Monasterio and Dr. Antonio Fuente del Campo published the first series of monobloc osteotomies, allowing for simultaneous correction of supraorbital and midface malformations, although complicated by blood loss and high infection rates. In 1992, McCarthy et al introduced the concept of gradual distraction to the craniofacial skeleton. In 1995, Polley et al performed the first monobloc advancement using external distraction. Subsequently, in 1997, Polley and Figueroa introduced a rigid external distraction device with multiple vector control to manage severe cleft maxillary hypoplasia. The technique was further refined and applied to treat syndromic midface hypoplasia, reducing complication rates. Currently, either external or internal distraction approaches are used to safely treat this challenging group of patients. Conclusion: The treatment of syndromic midface deficiency has significantly evolved over the past 50 years, as evidenced by this report of three generations of Crouzon syndrome.

Tracheostomy, the Not So Definitive Airway?: Tracheostomy Morbidity in Pediatric Craniofacial Patients.

BACKGROUND: Tracheostomy is the definitive treatment for airway management in severe cases of craniofacial-associated upper airway obstruction, like the Pierre-Robin sequence, but is associated with significant morbidity. The purpose of this study was to examine tracheostomy-associated morbidities and mortalities in craniofacial patients to identify opportunities to improve clinical care and patient prognosis. METHODS: The study was a retrospective review of pediatric craniofacial patients who were tracheostomized between 2016 and 2022. Data regarding their demographics, craniofacial diagnoses, endoscopic airway anomalies, intubation grade of view classification, tracheostomy-related complications, and causes of mortality were analyzed. RESULTS: Sixteen of the 17 tracheostomized pediatric patients had the Pierre-Robin sequence, with 5 of those patients having an additional syndromic craniofacial diagnosis. Additional airway anomalies were found in 82.4% of the patients. The mean length of hospital stay after tracheostomy was 4.08 months. Infection was the most common complication, observed in 94.1% of patients, followed by stomal granulation in 76.5% of patients. Two mortalities were observed: one following the compassionate removal of ventilator support and the other following the accidental dislodgment of the tracheostomy tube. CONCLUSIONS: Tracheostomy-related complications were observed in all craniofacial patients in this group. Compared with the general pediatric population, tracheostomized craniofacial patients may endure longer hospital stays and greater stomal granulation rates. Mandibular distraction osteogenesis may allow for tracheostomy avoidance in these patients, and future research should focus on comparing the long-term complication rates and outcomes between tracheostomy mandibular distraction osteogenesis in this challenging patient population.

TMJ Ankylosis Following Mandibular Distraction Osteogenesis: Management With Simultaneous Midface External Distraction and Bilateral Temporomandibular Joint Replacement.

Early mandibular distraction osteogenesis (MDO) can decrease upper airway and feeding complications in pediatric patients with micrognathia; however, temporomandibular joint (TMJ) complications like TMJ ankylosis (TMJA) may occur. TMJA can disturb pediatric patients' function and craniofacial growth, resulting in significant physical and psychosocial consequences. Additional surgical procedures may also be required, increasing the burden of care on patients and their families. CMF surgeons must discuss the potential complications of early MDO surgery with families as well as potential solutions should these problems occur. This report presents the case of a 17-year-old male with a severe craniofacial anomaly with features of Treacher-Collins syndrome (TCS) and a surgical history of tracheostomy, cleft palate repair, mandibular reconstruction with harvested costochondral grafts, and MDO with resultant bilateral TMJA and limited mouth opening. The patient Was treated with bilateral custom alloplastic TMJ replacements and simultaneous maxillary DO using a Rigid External Distraction (RED) device.

Uvular Dermoid Cyst: More Than Just a Lump in the Throat-Management of Resultant Velopharyngeal Insufficiency.

To seal the passage between the nasal and oral cavities during speech and swallowing, velopharyngeal closure is required. However, in velopharyngeal dysfunction, uncoupling of the nasal and oral cavities can be impaired, resulting in hypernasality, nasal air emission, and decreased vocal intensity. Velopharyngeal dysfunction can develop following velopharyngeal mislearning, oral surgery, or a congenital palatal malformation. Rare dermoid cysts of the palate may interrupt normal palatal development, resulting in velopharyngeal insufficiency (VPI). While speech therapy is the standard treatment, some cases may necessitate surgical correction of structural insufficiencies. In this report, we present the case of a 7-year-old female with a past surgical history of a uvular dermoid cyst removal at 14 months of age with VPI that was treated with Furlow Z-palatoplasty. To the author's knowledge, this is one of but a few cases of a uvular dermoid cyst with VPI.

An Updated Review of Hypertrophic Scarring.

Hypertrophic scarring (HTS) is an aberrant form of wound healing that is associated with excessive deposition of extracellular matrix and connective tissue at the site of injury. In this review article, we provide an overview of normal (acute) wound healing phases (hemostasis, inflammation, proliferation, and remodeling). We next discuss the dysregulated and/or impaired mechanisms in wound healing phases that are associated with HTS development. We next discuss the animal models of HTS and their limitations, and review the current and emerging treatments of HTS.

Spontaneous Closure of Congenital Cranial Defect: Is Early Surgical Intervention Warranted?

Infantile cranial development typically occurs in a predictable sequence of events; however, less is known about how the development occurs in isolated, nonsyndromic congenital craniofacial anomalies. Furthermore, the timing of pediatric cranioplasty has been extrapolated from adult studies. Thus, the management of nonsyndromic congenital craniofacial anomalies presents with unique challenges to the craniofacial surgeon. The authors describe the case of a baby girl who was born with right Tessier 3 cleft, cleft palate, anophthalmos, and severe left craniofacial microsomia with Pruzansky grade III left mandibular anomaly. By analyzing 3-dimensional chronological models of the patient, the authors found that her abnormal fontanelle initially increased in size until 22 weeks of age, with subsequent spontaneous closure at a rate of 60.53 mm2/y. Although similar cranial anomalies are typically surgically corrected early in life, delaying treatment until after 2 years of age may be appropriate in some patients, obviating surgical morbidity in the newborn period.

Quality of Life in Children With Sturge-Weber Syndrome.

AIM: We assessed the utilization of the National Institutes of Health Quality of Life in Neurological Disorders (Neuro-QoL) in pediatric patients with Sturge-Weber syndrome, a rare neurovascular disorder which frequently results in seizures, brain atrophy, calcification, and a range of neurological impairments. METHODS: Subjects were seen clinically and consented for research. All 22 patients filled out the Pediatric Neuro-QoL. The Neuro-QoL subscores were converted to T-scores to compare with the referenced control population. Twenty-one participants also filled out the Brain Vascular Malformation Consortium Database Questionnaire containing data pertaining to Sturge-Weber syndrome-related medical history, medications, comorbidities, and family history. All data were analyzed with a significance threshold of P < 0.05. RESULTS: Cognitive function quality of life was significantly lower (P < 0.001) in pediatric patients with Sturge-Weber syndrome compared with referenced control subjects. Male gender (P = 0.02) was associated with lower cognitive function Neuro-QoL. The extent of skin (R = -0.46, P = 0.04), total eyelid port-wine birthmark (R = -0.56, P = 0.007), eye (R = -0.58, P = 0.005), and total Sturge-Weber syndrome involvement (R = -0.63, P = 0.002) were negatively correlated with cognitive function Neuro-QoL. A younger age at seizure onset was associated with lower cognitive function Neuro-QoL (hazard ratio = 0.90, P = 0.004) even after controlling for extent of brain, skin, or eye involvement. Antidepressant use was associated with lower cognitive function Neuro-QoL (P = 0.005), and cognitive function Neuro-QoL was negatively correlated with depression Neuro-QoL; however, after adjusting for depression this relationship was no longer significant. CONCLUSIONS: The results suggest targeting cognitive function Neuro-QoL in treatment trials and reiterate the prognostic value of early seizure onset. In addition, sex-related differences were noted, which should be further studied.

In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor.

Dolutegravir (DTG; S/GSK1349572) is a potent HIV-1 integrase inhibitor with a distinct resistance profile and a once-daily dose regimen that does not require pharmacokinetic boosting. This work investigated the in vitro drug transport and metabolism of DTG and assessed the potential for clinical drug-drug interactions. DTG is a substrate for the efflux transporters P-glycoprotein (Pgp) and human breast cancer resistance protein (BCRP). Its high intrinsic membrane permeability limits the impact these transporters have on DTG's intestinal absorption. UDP-glucuronosyltransferase (UGT) 1A1 is the main enzyme responsible for the metabolism of DTG in vivo, with cytochrome P450 (P450) 3A4 being a notable pathway and UGT1A3 and UGT1A9 being only minor pathways. DTG demonstrated little or no inhibition (IC(50) values > 30 µM) in vitro of the transporters Pgp, BCRP, multidrug resistance protein 2, organic anion transporting polypeptide 1B1/3, organic cation transporter (OCT) 1, or the drug metabolizing enzymes CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, UGT1A1, or 2B7. Further, DTG did not induce CYP1A2, 2B6, or 3A4 mRNA in vitro using human hepatocytes. DTG does inhibit the renal OCT2 (IC(50) = 1.9 µM) transporter, which provides a mechanistic basis for the mild increases in serum creatinine observed in clinical studies. These in vitro studies demonstrate a low propensity for DTG to be a perpetrator of clinical drug interactions and provide a basis for predicting when other drugs could result in a drug interaction with DTG.

The role of efflux and uptake transporters in [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, lapatinib) disposition and drug interactions.

Lapatinib [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine, GW572016, Tykerb] is a tyrosine kinase inhibitor approved for use in combination with capecitabine to treat advanced or metastatic breast cancers overexpressing HER2 (ErbB2). In this work we investigated the role of efflux and uptake transporters in lapatinib disposition and drug interactions. In vitro studies evaluated whether lapatinib is a substrate for efflux transporters or an inhibitor of efflux/uptake transporters. In vivo studies included whole-body autoradiography and an evaluation of the role of efflux transporters on the intestinal absorption and brain penetration of lapatinib using chemical or genetic knockout animals. Lapatinib is a substrate for the efflux transporters P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP). Furthermore, lapatinib is an inhibitor (IC(50) values 0.025-5 muM) of Pgp, BCRP, and organic anion transporting polypeptide 1B1 (a hepatic uptake transporter). In contrast, lapatinib yielded little inhibition on renal transporters (organic anion transporters, organic cation transporters, and uric acid transporter). In vivo studies demonstrated that brain concentrations of lapatinib were low and influenced by efflux transporters at the blood-brain barrier. In contrast, systemic exposure of lapatinib after oral dosing was unchanged when efflux by Pgp and BCRP was absent from the gastrointestinal tract. These in vitro and in vivo preclinical investigations provide a mechanistic basis for elucidating clinical drug interactions.