Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth.

PURPOSE: PIK3CA-related overgrowth spectrum (PROS) conditions of the head and neck are treatment challenges. Traditionally, these conditions require multiple invasive interventions, with incomplete malformation removal, disfigurement, and possible dysfunction. Use of the PI3K inhibitor alpelisib, previously shown to be effective in PROS, has not been reported in PIK3CA-associated head and neck lymphatic malformations (HNLMs) or facial infiltrating lipomatosis (FIL). We describe prospective treatment of 5 children with PIK3CA-associated HNLMs or head and neck FIL with alpelisib monotherapy. METHODS: A total of 5 children with PIK3CA-associated HNLMs (n = 4) or FIL (n = 1) received alpelisib monotherapy (aged 2-12 years). Treatment response was determined by parental report, clinical evaluation, diary/questionnaire, and standardized clinical photography, measuring facial volume through 3-dimensional photos and magnetic resonance imaging. RESULTS: All participants had reduction in the size of lesion, and all had improvement or resolution of malformation inflammation/pain/bleeding. Common invasive therapy was avoided (ie, tracheotomy). After 6 or more months of alpelisib therapy, facial volume was reduced (range 1%-20%) and magnetic resonance imaging anomaly volume (range 0%-23%) were reduced, and there was improvement in swallowing, upper airway patency, and speech clarity. CONCLUSION: Individuals with head and neck PROS treated with alpelisib had decreased malformation size and locoregional overgrowth, improved function and symptoms, and fewer invasive procedures.

Novel role of Giα2 in cell migration: Downstream of PI3-kinase-AKT and Rac1 in prostate cancer cells.

Tumor cell motility is the essential step in cancer metastasis. Previously, we showed that oxytocin and epidermal growth factor (EGF) effects on cell migration in prostate cancer cells require Giα2 protein. In the current study, we investigated the interactions among G-protein coupled receptor (GPCR), Giα2, PI3-kinase, and Rac1 activation in the induction of migratory and invasive behavior by diverse stimuli. Knockdown and knockout of endogenous Giα2 in PC3 cells resulted in attenuation of transforming growth factor ß1 (TGFß1), oxytocin, SDF-1α, and EGF effects on cell migration and invasion. In addition, knockdown of Giα2 in E006AA cells attenuated cell migration and overexpression of Giα2 in LNCaP cells caused significant increase in basal and EGF-stimulated cell migration. Pretreatment of PC3 cells with Pertussis toxin resulted in attenuation of TGFß1- and oxytocin-induced migratory behavior and PI3-kinase activation without affecting EGF-induced PI3-kinase activation and cell migration. Basal- and EGF-induced activation of Rac1 in PC3 and DU145 cells were not affected in cells after Giα2 knockdown. On the other hand, Giα2 knockdown abolished the migratory capability of PC3 cells overexpressing constitutively active Rac1. The knockdown or knockout of Giα2 resulted in impaired formation of lamellipodia at the leading edge of the migrating cells. We conclude that Giα2 protein acts at two different levels which are both dependent and independent of GPCR signaling to induce cell migration and invasion in prostate cancer cells and its action is downstream of PI3-kinase-AKT-Rac1 axis.

Parent, dentist, and orthodontist satisfaction following alveolar cleft repair using recombinant human bone morphogenic protein.

OBJECTIVE: Our aim was to evaluate dental/orthodontic outcomes for patients who underwent recombinant human bone morphogenic protein (rhBMP-2) alveolar cleft repair and to examine parental satisfaction following the procedure. Design Retrospective review. Setting Tertiary children's hospital. Participants Parents, dentists, and orthodontists completed satisfaction questionnaires. Main Outcome Measures Parent, dentist, and orthodontist satisfaction with the use of rhBMP-2 in alveolar cleft repair. Results Parent response rate was 71.4% (30/42). The dentist response rate was 60% (18/30). The orthodontist response rate was 53.3% (16/30). Parent and patient satisfaction was 93.3% and 83.3%, respectively. Of dentist respondents, 55.6% reported that the bone quality and alveolar ridge mucosal repair allowed for dental treatment. Of orthodontist respondents, 87.5% reported the graft enabled treatment, and 73.3% felt the graft prevented tooth root exposure and resorption. Conclusions Parents, dentists, and orthodontists are satisfied with outcomes when rhBMP-2 is used for alveolar cleft repair. The bone formed was reported as adequate to support dental and orthodontic treatment in most cases with few complications. Because of safety concerns over the use of this product in an off-label manner, further controlled studies are warranted.

Clinical presentation of cervical ribs in the pediatric population.

Cervical ribs may cause thoracic outlet syndrome in adults, but symptoms are poorly described in children. In our series, 88.8% of the 322 children were asymptomatic. The most common symptoms were neck mass and pain. Useful diagnostic tools were cervical spine and chest radiographs. Differential diagnosis of a supraclavicular mass includes cervical ribs.

Primary targeted medical therapy for management of bilateral head and neck lymphatic malformations in infants.

OBJECTIVES: Patients born with bilateral head and neck lymphatic malformations (BHNLMs) often require multiple invasive treatments, including tracheostomy. We hypothesized that primary targeted medical therapy (pTMT) with diagnostic needle aspiration reduces the need for invasive therapy such as surgical resection and/or sclerotherapy. METHODS: Retrospective case review was performed of infants with BHNLMs (Grade 2 or De Serres stage IV and V) treated only at our institution from 2000 to 2021. Patients were divided into two cohorts: those managed with pTMT and those managed with observation, sclerotherapy, or surgical intervention (non-pTMT). Data regarding interventions, clinical outcomes, morbidity, and mortality were analyzed with descriptive statistics. RESULTS: Nine children with BHNLMs met inclusion criteria. Three (33%) were in the pTMT cohort and six (66%) were non-pTMT. Eight (89%) malformations were genotyped, and all demonstrated hotspot PIK3CA variants. All pTMT patients had sirolimus initiated in the first month of life and underwent needle aspiration of malformation cyst fluid for cell-free DNA samples. All pTMT patients tolerated medical therapy. For the non-pTMT cohort, primary treatment included none (deceased, n = 1, 17%), observation with needle aspiration (n = 1, 17%), surgical resection (n = 2, 33%), or combination surgery and sclerotherapy (n = 2, 33%). Intubation duration, intensive care and initial hospital length of stay were not different between cohorts. Four non-pTMT patients (67%) required tracheostomy, and two (33%) died prior to discharge. All pTMT patients survived and none required tracheostomy. Non-pTMT patients required a median of two invasive therapies prior to discharge (IQR 1-4) and a mean total of 13 over the course of their lifetime (IQR 1-16), compared to the pTMT group who did not require any lifetime invasive therapy, even after initial pTMT and discharge home. CONCLUSION: This study compares patients with BHNLMs (Grade 2) treated with pTMT versus those treated with observation or invasive therapy. Patients treated with pTMT required no surgical or invasive procedural treatment of their malformations, no tracheostomy placement, no unplanned readmissions after discharge, and had no mortalities. Needle aspiration was useful as a therapeutic adjunct for cell-free DNA diagnosis of PIK3CA variants, which guided TMT.

COVID-19 Airway Management Isolation Chamber.

OBJECTIVE: During the coronavirus pandemic (COVID-19), health care workers are innovating patient care and safety measures. Unfortunately, many of these are not properly tested for efficacy. The objective of this study was to determine the efficacy of the novel COVID-19 Airway Management Isolation Chamber (CAMIC) to contain and evacuate particulate. STUDY DESIGN: Multi-institutional proof-of-concept study. SETTING: Two academic institutions: Walter Reed National Military Medical Center (WRNMMC) and Madigan Army Medical Center (MAMC). SUBJECTS AND METHODS: Smoke, saline nebulizer, and simulated working port models were developed to assess the efficacy of the CAMIC to contain and remove ultrafine particles. Particulate counts were collected at set time intervals inside and outside the system. RESULTS: With the CAMIC on, smoke particulate counts inside the chamber significantly decreased over time: r(18) = -0.88, P < .001, WRNMMC; r(18) = -0.91, P < .001, MAMC. Similarly, saline nebulizer particulate counts inside the chamber significantly decreased over time: r(23) = -0.82, P < .001, WRNMMC; r(23) = -0.70, P < .001, MAMC. In the working port model, particulate counts inside the chamber significantly decreased over time: r(23) = -0.95, P < .001, WRNMMC; r(23) = -0.85, P < .001, MAMC. No significant leak was detected in the smoke, saline nebulizer, or working port model when the CAMIC was turned on. CONCLUSIONS: The CAMIC system appears to provide a barrier that actively removes particles from within the chamber and limits egress. Further studies are necessary to determine clinical applicability. The CAMIC may serve as an adjunct to improve health care worker safety and patient outcomes.

Reconstructing the Face of War.

INTRODUCTION: Ongoing combat operations in Iraq, Afghanistan, and other theaters have led to an increase in high energy craniomaxillofacial (CMF) wounds. These challenging injuries are typically associated with complex tissue deficiencies, evolving areas of necrosis, and bony comminution with bone and ballistic fragment sequestrum. Restoring form and function in these combat-sustained CMF injuries is challenging, and frequently requires local and distant tissue transfers. War injuries are different than the isolated trauma seen in the civilian sector. Donor sites are limited on patients with blast injuries and they may have preferences or functional reasons for the decisions to choose flaps from the available donor sites. METHODS: A case series of patients who sustained severe combat-related CMF injury and were treated at Walter Reed National Military Medical Center (WRNMMC) is presented. Our study was exempt from Institutional Review Board review, and appropriate written consent was obtained from all patients included in the study for the use of representative clinical images. RESULTS: Four patients treated by the CMF team at Walter Reed National Military Medical Center are presented. In this study, we highlight their surgical management by the CMF team at WRNMMC, detail their postoperative course, and illustrate the outcomes achieved using representative patient clinical images. We also supplement this case series demonstrating military approaches to complex CMF injuries with CMF reconstructive algorithms utilized by the senior author (EDR) in the management of civilian complex avulsive injuries of the upper, mid, and lower face are thoroughly reviewed. CONCLUSION: While the epidemiology and characteristics of military CMF injuries have been well described, their management remains poorly defined and creates an opportunity for reconstructive principles proven in the civilian sector to be applied in the care of severely wounded service members. The War on Terror marks the first time that microsurgery has been used extensively to reconstruct combat sustained wounds of the CMF region. Our manuscript reviews various options to reconstruct these devastating CMF injuries and emphasizes the need for steady communication between the civilian and military surgical communities to establish the best care for these complex patients.

Pediatric facial fractures: Demographic determinants influencing clinical outcomes.

OBJECTIVES/HYPOTHESIS: There is limited data linking demographic determinants to clinical outcomes in facial trauma, particularly when comparing regional to national datasets; these are the aims of the present study. STUDY DESIGN: Retrospective chart review. METHODS: A 10-year, retrospective single-institutional chart review was undertaken at Children's Hospital Colorado (CHC) to characterize a pediatric population with facial fractures. A comparative analysis between the CHC and National Trauma Data Bank (NTDB) datasets was also conducted. RESULTS: In the CHC dataset, increased hospital stay was positively predicted by bilateral mandible fracture, skull, intracranial, spine, thoracic, abdominal, and limb injuries. Predictors of increased intensive-care unit (ICU) stay included skull, spine, and limb injuries. The CHC cohort had younger subjects, more females, fewer African Americans, and more Hispanics than the NTDB dataset. They were more likely to be injured by nonviolent activities than by altercations. Divergent facial and associated injuries between the datasets were found. Multivariate models showed longer length of hospital stay for the CHC group (P = .0085), but the NTDB group had higher ICU admission (P = .04) and longer lengths of ICU stay (P = .007). CONCLUSION: The demographic disparities (age, ethnicity, mechanism of injury, and injury type) resulted in divergent injury patterns and likely influenced clinical outcomes. LEVEL OF EVIDENCE: 4.

Auditing of operating room times: a quality improvement project.

OBJECTIVE: A quality improvement project to evaluate operating room efficiency and utilization and to identify areas for improvement. METHODS: A retrospective assessment of a single surgeon's surgical cases over a 6-month period at a tertiary children's hospital. Primary outcomes included case timing defined as T1, T2, T3 and T4. (T1)-Patient enters OR-to-procedure start. (T2)-Procedure start-to-procedure end. (T3)-Procedure end-to-patient exits OR. (T4)-Patient exits OR-to-next patient enters OR (turnover). Comparison to existing literature was performed and results were presented to stakeholders. RESULTS: A total of 180 surgical cases were reviewed, 92 adenotonsillectomies (T&A), 33 Bilateral Pressure Equalization Tube Placement (PET) and 55 microlaryngoscopies and bronchoscopies (MLB). All outcomes were calculated by case type, except T4, and compared to available published data. T2 was compared to published benchmarks for otolaryngology demonstrating favorable operative times for T&A and PET. However, T4 was considerably longer at our institution (average 31.09). Overall OR efficiency was 20.58%. CONCLUSIONS: The operating room represents one of a hospital's most costly resources. Ensuring that this resource is designed, staffed and utilized efficiently is of major importance to both the quality of patient care and financial productivity. Surgeons are key components of operating room efficiency, utilization and other measurements of institutional performance. How surgeons schedule and perform cases directly impacts, and is impacted by, these measurements of performance. For fields dominated by high volume, short duration procedures such as pediatric otolaryngology, T4 may be the most important variable in determining OR efficiency. By utilizing modern electronic medical records, surgeons can easily track OR time points thereby determining the potential causes of and solutions for OR inefficiency.

Incidence of acute mastoiditis in Colorado children in the pneumococcal conjugate vaccine era.

BACKGROUND: Acute otitis media is among the most common reasons young children seek medical care, with Streptococcus pneumoniae the most common pathogen. Despite introduction of heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, recent experience suggests an increase in complications of acute otitis media, particularly acute mastoiditis. METHODS: We performed a retrospective review of acute mastoiditis in children from 1999 to 2008 using inpatient data from the Colorado Hospital Association and the Children's Hospital Colorado. The study included patients with documentation of acute mastoiditis or mastoidectomy and excluded those with chronic mastoiditis, chronic otitis media or cholesteatoma. RESULTS: The annual incidence of acute mastoiditis in children <2 years/100,000 population was 11.0 in 2001 before decreasing to 4.6 in 2002 and 4.5 in 2003. The incidence then increased to 12.0 in 2008 (total N = 242). The proportion of S. pneumoniae isolates nonsusceptible to penicillin increased from 0% (0/16) between 1999 and 2004 to 38% (5/13) between 2005 and 2008 (P = 0.03). CONCLUSIONS: The incidence of acute mastoiditis in Colorado children <2 years of age exhibited a dynamic pattern from 1999 to 2008: a significant decline early after introduction of PCV7 that paralleled initial vaccine uptake, followed by an increase in subsequent years to pre-PCV7 levels. Replacement with non-PCV7 pneumococcal serotypes and increased pneumococcal antibiotic resistance may be responsible for the increase in incidence to pre-PCV7 rates. Surveillance of mastoiditis incidence, pathogen distribution and resistance patterns following introduction of 13-valent PCV is warranted.

Current practice patterns for sleep-disordered breathing in children.

OBJECTIVES/HYPOTHESIS: Since the primary therapy for children with sleep-disordered breathing(SDB) is adenotonsillectomy, a survey was developed to determine the current practice patterns for children with SDB by pediatric otolaryngologists. STUDY DESIGN: Cross-sectional survey METHODS: An Internet-based survey was sent to all American Society of Pediatric Otolaryngology members. In addition to descriptive statistics, a logistic regression was performed to assess if years in practice, polysomnogram (PSG) wait time, or frequency of evaluating snoring children changes management. RESULTS: The response rate was 39% (135/345). Children with SDB were "most of the time" referred for PSGs by 4% of respondents. Sixty-five percent referred for PSG "sometimes," and 31% referred "rarely" or "never." An increased wait time was a significant predictor of PSG frequency (OR = 1.10, 95% CI: 0.92-1.0, P = 0.039). Children with Down syndrome or obesity had preoperative PSG requested "always" 20% and 8% of the time. The primary reason for requesting a PSG in a normal child was inconsistent clinical evaluation (58%). To diagnose obesity, most (72%) record height and weight, but only 34% record BMI% for age. Overnight observation was performed "most of the time" for the following groups: Obese (70%), Down syndrome (83%), and <3 years (83%). CONCLUSIONS: Pediatric otolaryngologists are noncompliant with the 2002 American Academy of Pediatrics and the 2011 American Academy of Otolaryngology-Head and Neck Surgery guidelines. Despite noncompliance, they fortunately have a lower threshold to monitor high-risk children overnight following surgery. The recommended Center for Disease Control measures to diagnose childhood obesity occasionally are being utilized. An educational campaign is necessary to update clinicians who take care of children on the new evidence-based guidelines.

Standardized letter of recommendation for otolaryngology residency selection.

OBJECTIVES/HYPOTHESIS: Develop a standardized letter of recommendation (SLOR) for otolaryngology residency application that investigates the qualities desired in residents and the letter writer's experience. Compare this SLOR to narrative letters of recommendation (NLORs). STUDY DESIGN: Prospective SLOR/NLOR comparison. METHODS: The SLOR was sent to an NLOR writer for each applicant. The applicant's NLOR/SLOR pair was blinded and ranked in seven categories by three reviewers. Inter-rater reliability and NLOR/SLOR rankings were compared. Means of cumulative NLOR and SLOR scores were compared to our departmental rank list. RESULTS: Thirty-one SLORs (66%) were collected. The SLORs had higher inter-rater reliability for applicant's qualifications for otolaryngology, global assessment, summary statement, and overall letter ranking. Writer's background, comparison to contemporaries/predecessors, and letter review ease had higher inter-rater reliability on the NLORs. Mean SLOR rankings were higher for writer's background (P = .0007), comparison of applicant to contemporaries/predecessors (P = .0031), and letter review ease (P < .0001). Mean SLOR writing time was 4.17 ± 2.18 minutes. Mean ranking time was significantly lower (P < .0001) for the SLORs (39.24 ± 23.45 seconds) compared to the NLORs (70.95 ± 40.14 seconds). Means of cumulative SLOR scores correlated with our rank list (P = .004), whereas means of cumulative NLOR scores did not (P = .18). Means of cumulative NLOR and SLOR scores did not correlate (P = .26). CONCLUSIONS: SLORs require little writing time, save reviewing time, and are easier to review compared to NLORs. Our SLOR had higher inter-rater reliability in four of seven categories and was correlated with our rank list. This tool conveys standardized information in an efficient manner.

Risk of post-tonsillectomy hemorrhage by clinical diagnosis.

OBJECTIVES/HYPOTHESIS: Obstructive sleep apnea (OSA) has been associated with upregulation of prothrombotic factors. We hypothesize that diagnosis of OSA may be protective against postoperative hemorrhage. This study investigates the relationships between preoperative clinical diagnosis and postoperative hemorrhage. STUDY DESIGN: Seven-year retrospective case-control study. METHODS: Medical records of tonsillectomy subjects with and without hemorrhage were reviewed for demographics, clinical diagnosis, and treatment. Clinical diagnoses included OSA confirmed by polysomnogram, sleep-disordered breathing (SDB), chronic tonsillitis, and a mixed group. RESULTS: A total of 9,023 tonsillectomy patients were identified (52.0% male, 48.0% female; mean age, 6.9 years). Of these, 2.4% (n = 212) presented with hemorrhage. There were 48 (22.6%) primary and 164 (77.4%) secondary hemorrhages. The control group consisted of 1,488 nonhemorrhage patients. A multivariate logistic regression analysis compared the two groups controlling for age, sex, and clinical diagnosis. OSA patients were half as likely to hemorrhage compared to chronic tonsillitis patients (P = .04). SDB patients also had a lower chance of hemorrhage compared to chronic tonsillitis patients; this result was not significant (P = .09). Patients older than 6 years had a higher hemorrhage rate (P < .001). CONCLUSIONS: This study demonstrates that patients with OSA may be less likely to have postoperative hemorrhage than patients with chronic tonsillitis. Younger age was associated with fewer hemorrhages.

Standardized letter of recommendation for pediatric fellowship selection.

OBJECTIVES/HYPOTHESIS: To develop a pediatric otolaryngology fellowship selection standardized letter of recommendation (SLOR). STUDY DESIGN: SLOR and narrative letter of recommendation (NLOR) comparison study. METHODS: An SLOR was created to investigate qualities desired in fellows using five content-based categories: writer background, comparison of the applicant to contemporaries and predecessors, applicant's qualifications for pediatric otolaryngology, a global assessment of the applicant, and a summary statement about the applicant. In phase I, the SLORs were completed, including writing time, by the applicant's pediatric otolaryngology chief. In phase II, letters were ranked on Likert-type scales for the content-based categories, reviewer's overall ranking, and ease of review by six otolaryngologists. Reviewers recorded time needed to review each letter. RESULTS: Nineteen SLORs (73%) were collected. Mean writing time was 8.84 ± 3.87 minutes. Interrater reliability was higher on the SLORs in the content-based sections and the overall ranking. Ranking times were lower on the SLORs. Mean and median rankings were higher on the SLORs for writer background, comparison of the applicant to contemporaries and predecessors, applicant's qualifications for pediatric otolaryngology, and ease of review; mean global assessment of the applicant, summary statement about the applicant, and overall rankings were lower on the SLORs. CONCLUSIONS: To our knowledge, this is the first inquiry using an SLOR developed for otolaryngology. SLORs are an alternative to NLORs for fellowship selection that offers improved reliability and efficiency. Further investigation using SLORs in otolaryngology residency selection is merited.

Early intervention: distraction osteogenesis of the mandible for severe airway obstruction.

OBJECTIVE: To determine benefits of early intervention in neonates with symptomatic micrognathia who underwent bilateral mandibular distraction osteogenesis within the first 90 days of life as relates to growth, need for supportive care, and further invasive procedures. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care, academic children's hospital. SUBJECTS AND METHODS: Review of neonates with symptomatic micrognathia who underwent bilateral mandibular distraction osteogenesis in the past 5 years. Inclusion criteria included mandibular distraction osteogenesis performed within the first 90 days of life. Outcome measures included hospital course, growth curves, supportive home care needs, and airway at cleft repair. RESULTS: Twenty-four patients met inclusion criteria. The mean age at distraction was 30 days, and the average discharge was postoperative day 14. One patient required home oxygen, 50% were able to feed exclusively by oral diet, and no patients required tracheotomy. In addition, airway results were substantial, with 90% of patients showing objective improvement in airway grade from time of mandibular distraction to time of cleft repair. CONCLUSION: We present our initial outcomes on mandibular distraction osteogenesis in neonates with symptomatic micrognathia. Early intervention allows discharge to home with minimal supportive care needs by avoiding tracheostomy and facilitating transition to oral feeds. The airway improvement is significant and is sustained and allows for easier intubation at time of cleft repair.

Minimal access and standard cochlear implantation: a comparative study.

OBJECTIVE: To compare the operative times and complications between patients who underwent minimal access cochlear implantation and standard technique cochlear implantation. METHODS: Patients who underwent unilateral cochlear implantation by a single surgeon from 2001 to 2010. The minimal access technique of an approximately 2.5-3 cm post-auricular incision with creation of subperiosteal pocket for the device was compared to the longer standard "S" incision into the scalp (~8-10 cm) with bone well creation and suture fixation. Outcomes include operative times and complications. RESULTS: There were 122 unilateral implants, 73 (59.8%) in the minimal access group and 49 (40.2%) in the standard group. Mean total time in the operating room was lower in the minimal access group compared to the standard group (200±31 vs. 255±49 min, p<.0001) as well as mean operative time (149.5±28 vs. 200±45 min, p<.0001 respectively). There were 17 complications in the entire cohort with 8 and 9 complications in the minimal and standard groups respectively. Of the 17 complications, 12 were surgical technique-specific. Although it appeared that there were higher rates of major, technique-specific, and overall complications in the standard access group, these differences did not reach statistical significance. CONCLUSIONS: Patients undergoing minimal access cochlear implantation require shorter operative times when compared to the standard access cochlear implantation. In addition, low complication rates are observed for major, technique-specific, and overall complications. Minimal access cochlear implantation may be considered an equivalent and potentially superior technique.