External airway splint placement for severe pediatric tracheobronchomalacia.

OBJECTIVE: To present external airway splinting with bioabsorbable airway supportive devices (ASD) for severe, life-threatening cases of pediatric tracheomalacia (TM) or tracheobronchomalacia (TBM). METHODS: A retrospective cohort was performed for 5 pediatric patients with severe TM or TBM who underwent ASD placement. Devices were designed and 3D-printed from a bioabsorbable material, polycaprolactone (PCL). Pre-operative planning included 3-dimensional airway modeling of tracheal collapse and tracheal suture placement using nonlinear finite element (FE) methods. Pre-operative modeling revealed that triads along the ASD open edges and center were the most effective suture locations for optimizing airway patency. Pediatric cardiothoracic surgery and otolaryngology applied the ASDs by suspending the trachea to the ASD with synchronous bronchoscopy. Respiratory needs were trended for all cases. Data from pediatric patients with tracheostomy and diagnosis of TM or TBM, but without ASD, were included for discussion. RESULTS: Five patients (2 Females, 3 Males, ages 2-9 months at time of ASD) were included. Three patients were unable to wean from respiratory support after vascular ring division; all three weaned to room air post-ASD. Two patients received tracheostomies prior to ASD placement, but continued to experience apparent life-threatening events (ALTE) and required ventilation with supraphysiologic ventilator settings. One patient weaned respiratory support successfully after ASD placement. The last patient died post-ASD due to significant respiratory co-morbidity. CONCLUSION: ASD can significantly benefit patients with severe, unrelenting tracheomalacia or tracheobronchomalacia. Proper multidisciplinary case deliberation and selection are key to success with ASD. Pre-operative airway modeling allows proper suture placement to optimally address the underlying airway collapse.

Clinical grade manufacture of 3D printed patient specific biodegradable devices for pediatric airway support.

Implantable patient-specific devices are the next frontier of personalized medicine, positioned to improve the quality of care across multiple clinical disciplines. Translation of patient-specific devices requires time- and cost-effective processes to design, verify and validate in adherence to FDA guidance for medical device manufacture. In this study, we present a generalized strategy for selective laser sintering (SLS) of patient-specific medical devices following the prescribed guidance for additive manufacturing of medical devices issued by the FDA in 2018. We contextualize this process for manufacturing an Airway Support Device, a life-saving tracheal and bronchial implant restoring airway patency for pediatric patients diagnosed with tracheobronchomalacia and exhibiting partial or complete airway collapse. The process covers image-based modeling, design inputs, design verification, material inputs and verification, device verification, and device validation, including clinical results. We demonstrate how design and material assessment lead to verified Airway Support Devices that achieve desired airway patency and reduction in required Positive End-Expiratory Pressure (PEEP) after patient implantation. We propose this process as a template for general quality control of patient-specific, 3D printed implants.

Sustaining standardized opioid prescribing practices after pediatric tonsillectomy.

INTRODUCTION: Opioid prescribing patterns after pediatric tonsillectomy are highly variable, and opioids may not improve pain control compared to over-the-counter pain relievers. We evaluated whether a standardized, opioid-sparing analgesic protocol effectively reduced opioid prescriptions without compromising patient outcomes. METHODS: A quality improvement project was initiated in July 2019 to standardize analgesic prescribing after hospital-based tonsillectomy with/without adenoidectomy. An electronic order set provided weight-based dosing and defaulted to non-opioid prescriptions (acetaminophen and ibuprofen). Patients ages 0-6 received non-opioid analgesics alone. Patients ages 7-18 received non-opioid analgesics as first-line pain control, and providers could manually add hydrocodone-acetaminophen for breakthrough pain. Opioid prescriptions and quantities were compared for 18 months of cases pre- versus post-standardization. Postoperative returns to the system were reviewed as a balancing measure. RESULTS: From 2018 through 2020, 1817 cases were reviewed. The frequency of opioid prescriptions decreased significantly post-standardization, from 64.9% to 33.5% of cases (P < .001). Opioid prescribing for young children steadily decreased from over 50% to 2.4%. Protocol adherence improved over time; outlier prescriptions were eliminated. Opioid quantities per prescription decreased by 16.3 doses on average (P < .001), and variance decreased significantly post-standardization (P < .001). The incidence of returns to the system did not change (P = .33), including returns for pain or decreased intake (P = .28). CONCLUSION: An age-based and weight-based analgesic protocol reduced post-tonsillectomy opioid prescriptions without a commensurate increase in returns for postoperative complaints. Standardized protocols can facilitate sustained changes in prescribing patterns and limit potentially unnecessary pediatric opioid exposure.

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach.

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder affecting respiratory control and autonomic nervous system function caused by variants in the paired-like homeobox 2B (PHOX2B) gene. Although most patients are diagnosed in the newborn period, an increasing number of patients are presenting later in childhood, adolescence, and adulthood. Despite hypoxemia and hypercapnia, patients do not manifest clinical features of respiratory distress during sleep and wakefulness. CCHS is a lifelong disorder. Patients require assisted ventilation throughout their life delivered by positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and/or diaphragm pacing. At different ages, patients may prefer to change their modality of assisted ventilation. This requires an individualized and coordinated multidisciplinary approach. Additional clinical features of CCHS that may present at different ages and require periodic evaluations or interventions include Hirschsprung's disease, gastrointestinal dysmotility, neural crest tumors, cardiac arrhythmias, and neurodevelopmental delays. Despite an established PHOX2B genotype and phenotype correlation, patients have variable and heterogeneous clinical manifestations requiring the formulation of an individualized plan of care based on collaboration between the pulmonologist, otolaryngologist, cardiologist, anesthesiologist, gastroenterologist, sleep medicine physician, geneticist, surgeon, oncologist, and respiratory therapist. A comprehensive multidisciplinary approach may optimize care and improve patient outcomes. With advances in CCHS management strategies, there is prolongation of survival necessitating high-quality multidisciplinary care for adults with CCHS.

Tracheostomy decannulation to noninvasive positive pressure ventilation in congenital central hypoventilation syndrome.

PURPOSE: Noninvasive positive pressure ventilation (NPPV) may permit tracheostomy decannulation (TD) in patients with congenital central hypoventilation syndrome (CCHS) requiring nocturnal positive pressure ventilation via tracheostomy (PPV-T). There is limited evidence on optimal strategies for transitioning patients from PPV-T to NPPV. This study aimed to describe the clinical course and outcome of children with CCHS who underwent TD and transitioned from PPV-T to NPPV. METHODS: Retrospective review was conducted on patients with CCHS using nocturnal PPV-T who underwent TD to NPPV. The results of clinical evaluations, airway endoscopy, polysomnography, and clinical course leading to TD were analyzed. RESULTS: We identified 3 patients with CCHS aged 8-17 years who required PPV-T only during sleep. Patients underwent systematic multidisciplinary evaluations with a pediatric psychologist, pulmonologist, sleep physician, and otolaryngologist utilizing a TD algorithm. These included evaluation in the sleep clinic, NPPV mask fitting and desensitization, endoscopic airway evaluation, daytime tracheostomy capping, acclimatization to low-pressure NPPV, polysomnography with capped tracheostomy and NPPV titration, and if successful, TD. All patients underwent successful TD following optimal titration of NPPV during polysomnography. The duration to TD from decision to pursue NPPV was between 2.4 and 10.6 months, and the duration of hospitalization for TD was between 4 and 5 days. There were no NPPV-related complications; however, all patients required surgical closure of tracheocutaneous fistula. CONCLUSION: NPPV may be an effective and feasible option for patients with CCHS requiring PPV-T during sleep and permits TD. In patients with CCHS, a systematic multidisciplinary algorithm may optimize successful transition to NPPV and TD.

Sensorineural hearing loss in children with sickle cell disease.

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 ±â€¯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 ±â€¯28.9, Left: 40.8 ±â€¯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.

Airway Anomalies.

This article reviews congenital anomalies involving the larynx and trachea, including congenital subglottic stenosis, laryngeal webs, laryngeal cleft, and tracheal stenosis. Presenting signs and symptoms, prevailing surgical repair techniques, and postoperative care are discussed.

Adenotonsillectomy in children with sickle cell disease and obstructive sleep apnea.

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 ±â€¯4.6 years. The mean baseline hemoglobin of these patients was 9.3 ±â€¯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 ±â€¯1.0 g/dL. The average admission length surrounding T&A was 3.5 ±â€¯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 ±â€¯8.7 vs. 1.3 ±â€¯1.9, p = 0.0001). The O2 nadir improved on post-T&A polysomnogram (81.2 ±â€¯10.8 vs. 89.3 ±â€¯7, p = 0.0003). Emergency room visits (mean events per year) decreased post-operatively (2.6 ±â€¯2.8 vs. 1.8 ±â€¯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.

Structural airway abnormalities contribute to dysphagia in children with esophageal atresia and tracheoesophageal fistula.

BACKGROUND: Long-term dysphagia occurs in up to 50% of repaired esophageal atresia and tracheoesophageal fistula (EA/TEF) patients. The underlying factors are unclear and may include stricture, esophageal dysmotility, or associated anomalies. Our purpose was to determine whether structural airway abnormalities (SAA) are associated with dysphagia in EA/TEF. METHODS: We conducted a retrospective chart review of children who underwent EA/TEF repair in our hospital system from 2007 to 2016. Children with identified SAA (oropharyngeal abnormalities, laryngeal clefts, laryngomalacia, vocal cord paralysis, and tracheomalacia) were compared to those without airway abnormalities. Dysphagia outcomes were determined by the need for tube feeding and the modified pediatric Functional Oral Intake Scale (FOIS) at 1 year. RESULTS: SAA was diagnosed in 55/145 (37.9%) patients with EA/TEF. Oropharyngeal aspiration was more common in children with SAA (58.3% vs. 36.4%, p=0.028). Children with SAA were more likely to require tube feeding both at discharge (79.6% vs. 48.3%, p<0.001) and at 1 year (52.7% vs. 13.6%, p<0.001) and had lower mean FOIS (4.18 vs. 6.21, p<0.001). In the logistic regression model adjusting for gestational age, long gap EA, and esophageal stricture, the presence of SAA remained a significant risk factor for dysphagia (OR 4.17 (95% CI 1.58-11.03)). CONCLUSION: SAA are common in children with EA/TEF and are associated with dysphagia, even after accounting for gestational age, esophageal gap and stricture. This study highlights the need for a multidisciplinary approach, including early laryngoscopy and bronchoscopy, in the evaluation of the EA/TEF child with dysphagia. LEVEL OF EVIDENCE: Level II retrospective prognostic study.

Open staple diverticulectomy for a large recurrent Zenker's diverticulum: still a valid procedure.

OBJECTIVES: We demonstrate indications for external mechanical stapler diverticulectomy in the modern era of endoscopic treatment. We review treatment of a large diverticulum and discuss considerations that should be made in deciding on the type of surgical treatment. METHODS: The index case was in a 75-year-old man who had undergone open cricopharyngeal myotomy with diverticulopexy 35 years earlier. He presented with 25 years of recurrent symptoms. A swallow study showed a 6.5 x 5.0-cm diverticulum. The diverticulum was deemed too large for standard endoscopic myotomy, so diverticulectomy was performed with a stapler. RESULTS: The patient was discharged on postoperative day 3 without complications. A swallow study on postoperative day 5 demonstrated no diverticulum or extravasation of barium. The patient resumed a normal diet with resolution of dysphagia. Two additional patients with large Zenker's diverticula that were managed similarly are also discussed. CONCLUSIONS: Although endoscopic laser cricopharyngeal myotomy and stapler diverticulostomy have become standard treatments for Zenker's diverticulum, this case of a large recurrent diverticulum illustrates a situation in which older techniques may be preferred. Use of the mechanical stapler allowed for a shorter surgery time than traditional suture techniques, and the potential for an earlier return to a normal diet.

Intraoral metal contact allergy as a possible risk factor for oral squamous cell carcinoma.

OBJECTIVES: Intraoral exposure to dental restorations can cause contact allergy that may induce carcinogenesis. We investigated the relationship of intraoral metal contact allergy to epithelial carcinogenesis. METHODS: The prevalence of positive patch test reactions to dental restoration metals in 65 prospectively enrolled patients with newly or previously diagnosed oral squamous cell carcinoma (SCC) was compared to that in 48 control patients. The relative risk of oral SCC was estimated by calculating odds ratios for exposure to dental metals resulting in allergy. RESULTS: Of the 65 patients with oral SCC, 34% were allergic to at least 1 adjacent metal. They were 1.57 times as likely as control patients to have metal contact allergy (odds ratio, 1.57; 95% confidence interval, 0.65 to 3.80) and more than 3 times as likely to react to mercury (odds ratio, 3.20; 95% confidence interval, 0.42 to 33.20). CONCLUSIONS: Patients with oral SCC who have metal dental restorations should undergo patch testing and possible removal of the restorations if their reactions are positive.

Laryngomalacia: disease presentation, spectrum, and management.

Laryngomalacia is the most common cause of stridor in newborns, affecting 45-75% of all infants with congenital stridor. The spectrum of disease presentation, progression, and outcomes is varied. Identifying symptoms and patient factors that influence disease severity helps predict outcomes. Findings. Infants with stridor who do not have significant feeding-related symptoms can be managed expectantly without intervention. Infants with stridor and feeding-related symptoms benefit from acid suppression treatment. Those with additional symptoms of aspiration, failure to thrive, and consequences of airway obstruction and hypoxia require surgical intervention. The presence of an additional level of airway obstruction worsens symptoms and has a 4.5x risk of requiring surgical intervention, usually supraglottoplasty. The presence of medical comorbidities predicts worse symptoms. Summary. Most with laryngomalacia will have mild-to-moderate symptoms and not require surgical intervention. Those with gastroesophageal reflux and/or laryngopharyngeal reflux have symptom improvement from acid suppression therapy. Those with severe enough disease to require supraglottoplasty will have minimal complications and good outcomes if multiple medical comorbidities are not present. Identifying patient factors that influence disease severity is an important aspect of care provided to infants with laryngomalacia.

Closely opposed apurinic/apyrimidinic sites are converted to double strand breaks in Escherichia coli even in the absence of exonuclease III, endonuclease IV, nucleotide excision repair and AP lyase cleavage.

Multiply damaged sites (MDSs) consist of two or more damages within 20 base pairs (bps) and are introduced into DNA by ionizing radiation. Using a plasmid assay, we previously demonstrated that repair in Escherichia coli generated a double strand break (DSB) from two closely opposed uracils when uracil DNA glycosylase initiated repair. To identify the enzymes that converted the resulting apurinic/apyrimidinic (AP) sites to DSBs, repair was examined in bacteria deficient in AP site cleavage. Since exonuclease III (xth) and endonuclease IV (nfo) mutant bacteria were able to introduce DSBs at the MDSs, we generated unique bacterial mutants deficient in UvrA, Xth and Nfo. However, the additional disruption of nucleotide excision repair (NER) did not prevent DSB formation. xth- nfo- nfi- bacteria also converted the MDSs to DSBs, ruling out endonuclease V as the candidate AP endonuclease. By using MDSs containing tetrahydrofuran (an AP site analog), it was determined that even in the absence of Xth, Nfo, NER and AP lyase cleavage, DSBs were formed from closely opposed AP sites. This finding implies that there is an unknown enzyme/repair pathway for MDSs, and multiple underlying repair systems in cells that can process closely opposed DNA damage into lethal lesions following exposure to ionizing radiation.

The mutation frequency of 8-oxo-7,8-dihydroguanine (8-oxodG) situated in a multiply damaged site: comparison of a single and two closely opposed 8-oxodG in Escherichia coli.

A multiply damaged site (MDS) is defined as > or =2 lesions within a distance of 10-15 base pairs (bp). MDS generated by ionizing radiation contain oxidative base damage, and in vitro studies have indicated that if the base damage is <3bp apart, repair of one lesion is inhibited until repair of the lesion in the opposite strand is completed. Inhibition of repair could result in an increase in the mutation frequency of the base damage. We have designed an assay to determine whether a closely opposed lesion causes an increase in adenine insertion opposite an 8-oxodG in bacteria. We have positioned the MDS (an 8-oxodG in the transcribed strand and a second 8-oxodG immediately 5' to this lesion in the non-transcribed strand) within the firefly luciferase coding region. During two rounds of replication, insertion of adenine opposite the 8-oxodG in the transcribed (T) or non-transcribed (NT) strand results in a translation termination codon at position 444 or 445, respectively. The truncated luciferase protein is inactive. We have generated double-stranded oligonucleotides that contain no damage, each single 8-oxodG or the MDS. Each double-stranded molecule was ligated into the reporter vector and the ligation products transformed into wild-type or Mut Y-deficient bacteria. The plasmid DNA was isolated and sequenced from colonies that did not express luciferase activity. In wild-type bacteria, we detected a translation stop at a frequency of 0.15% (codon 444) and 0.09% (codon 445) with a single 8-oxodG in the T or NT strand, respectively. This was enhanced approximately 3-fold when single lesions were replicated in Mut Y-deficient bacteria. Positioning an 8-oxodG in the T strand within the MDS enhanced the mutation frequency by approximately 2-fold in wild-type bacteria and 8-fold in Mut Y-deficient bacteria, while the mutation frequency of the 8-oxodG in the NT strand increased by 6-fold in Mut Y-deficient bacteria. This enhancement of mutation frequency supports the in vitro MDS studies, which demonstrated the inability of base excision repair to completely repair closely opposed lesions.