Risk-adjusted analysis of perioperative outcomes after the Sistrunk procedure.

Objectives: Thyroglossal duct cyst (TGDC) is the most common pediatric congenital neck mass. The Sistrunk procedure is the standard method of excision and is associated with low rates of recurrence. This study aimed to review our institution's outcomes following the Sistrunk procedure, specifically the rates of wound complications and cyst recurrence. Methods: This was a retrospective case series of pediatric patients undergoing the Sistrunk procedure from June 2009 to April 2021. Results: A total of 273 patients were included. Of these, 139 (53%) patients were male and 181 (66%) were white. The average age at the time of surgery was 7.1 years. The overall cyst recurrence rate was 11%. The most common wound complications were seroma (14%) and surgical site infections (SSIs) (12%). Wound complications were associated with prior history of cyst infection (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.07-3.60, z-test 2.2, p = .03). Pediatric surgery was associated with fewer wound complications (OR 0.18; 95% CI 0.05-0.6, z-test -2.78, p = .005). However, pediatric surgery operated on fewer patients with a history of cyst infection (36% vs. 55%, p = .012). Drain placement and postoperative antibiotics did not affect rates of wound complications. Conclusions: Prior cyst infection is associated with increased rates of postoperative wound complications. Postoperative antibiotics and drain placement did not significantly affect complication rates. Level of Evidence: 4.

Characteristics and Outcomes of Surgical Treatment for Bronchial Anomalies.

OBJECTIVES: Bronchial anomalies are rare but challenging conditions to treat in children, encompassing a variety of structural abnormalities that could compromise airway patency. This includes complete rings, absent cartilage, traumatic avulsions, bronchoesophageal fistulas, and cartilaginous sleeves. The objective of this study is to describe the characteristics and outcomes of a series of pediatric cases of bronchial anomalies that were treated by slide tracheobronchoplasty. METHODS: This is a single-institution retrospective case series of pediatric patients with bronchial anomalies who underwent surgical treatment between February 2004 and April 2020. Data extracted from electronic medical records included patient demographics, comorbidities, and surgical outcomes. RESULTS: There were a total of 29 patients included in the study, of which 14 had complete bronchial rings, 8 had absent bronchial rings, 4 had traumatic bronchial avulsions, 2 had bronchoesophageal fistulas, and one had a cartilaginous sleeve. Median follow-up time was 13 months (with a range of 0.5-213 months). The overall mortality rate was 17.2% (5 patients), all of whom had complete bronchial rings. Patients with complete bronchial rings also had a higher rate of not only cardiac (85.7%) and pulmonary comorbidities (85.7%) but also secondary airway lesions (78.6%). CONCLUSION: This is the largest series to date describing surgical treatment for bronchial anomalies. Complete bronchial rings were the most common anomaly treated, followed by absent rings and trauma. Surgical treatment can be successful but mortality rates are higher in patients with complete bronchial rings, possibly due to higher rates of pulmonary and cardiac comorbidities. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3334-3340, 2023.

Anti-NMDA Receptor Autoimmune Encephalitis: Diagnosis and Management Strategies.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most recognized form of autoimmune encephalitis. It is characterized by a constellation of neurologic and psychiatric features along with positive NMDAR antibody, which is more sensitive and specific in CSF than serum. All patients should be screened at least once for neoplasm, with ovarian teratoma being found in most tumor-related cases. In the acute phase, first-line immunotherapy, often a combination of high-dose steroids, immunoglobulins, and/or plasma exchange, is strongly recommended. When first-line therapy fails, escalation to second-line immunotherapy, particularly rituximab, can further improve outcomes and prevent relapses. In refractory cases, additional complementary immunotherapies, such as cyclophosphamide, bortezomib and/or tocilizumab may be considered. Relapses occur in 10-30% of cases, mostly within the first two years from onset. Individuals should be followed up to determine if chronic maintenance therapy is required.

Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13.

Selective degradation of the cyclin-dependent kinases 12 and 13 (CDK12/13) presents a novel therapeutic opportunity for triple-negative breast cancer (TNBC), but there is still a lack of dual CDK12/13 degraders. Here, we report the discovery of the first series of highly potent and selective dual CDK12/13 degraders by employing the proteolysis-targeting chimera (PROTAC) technology. The optimal compound 7f effectively degraded CDK12 and CDK13 with DC50 values of 2.2 and 2.1 nM, respectively, in MDA-MB-231 breast cancer cells. Global proteomic profiling demonstrated the target selectivity of 7f. In vitro, 7f suppressed expression of core DNA damage response (DDR) genes in a time- and dose-dependent manner. Further, 7f markedly inhibited proliferation of multiple TNBC cell lines including MFM223, with an IC50 value of 47 nM. Importantly, 7f displayed a significantly improved antiproliferative activity compared to the structurally similar inhibitor 4, suggesting the potential advantage of a CDK12/13 degrader for TNBC targeted therapy.

Refractory Anti-NMDA Receptor Encephalitis in Early Pregnancy: A Case Report of Treatment Course and Pregnancy Outcomes.

BACKGROUND AND OBJECTIVES: Anti-N-methyl d-aspartate receptor (NMDAR) encephalitis classically affects women of childbearing age, producing a disproportionate number of pregnant women with anti-NMDAR encephalitis. The typical presentation includes progressive neuropsychiatric symptoms, seizures, and alterations in consciousness, all of which present potential risks to the fetus. First-line and second-line treatments similarly pose teratogenic potential; therefore, randomized studies with supportive data on pregnancy and fetal outcomes are lacking. METHODS: We present a case of refractory anti-NMDAR encephalitis during the first and second trimesters of pregnancy with the successful use of rituximab and cyclophosphamide and resultant healthy pregnancy. RESULTS: The patient was treated with an escalating immunotherapy regimen from 11 to 15 weeks of gestation, including steroids, plasma exchange, IV immunoglobulins, and rituximab, with no clinical response. At 16 weeks of gestation, she received cyclophosphamide with clinical improvement after 4 weeks. She subsequently gave birth to a healthy, term baby boy, who continued to do well at the follow-up. DISCUSSION: This case illustrates the effective use of cyclophosphamide in the second trimester of pregnancy for anti-NMDAR encephalitis. The use of second-line therapies remains an individualized decision because the relative risk-to-benefit ratio in pregnant women is incompletely understood.

Nationwide tracheostomy among neonatal admissions - A cross-sectional analysis.

OBJECTIVE: To describe characteristics and outcomes of infants admitted as neonates requiring tracheostomy placement. METHODS: A cross-sectional analysis of the Kids' Inpatient Database (KID) between 2003 and 2016 included all children admitted within the first 28 days of life that had a tracheostomy placed prior to discharge. Patient characteristics and surgical outcomes were compared between term (≥37 weeks gestation) and preterm (<37 weeks gestation) infants. A subset analysis for Black or African American neonates was performed given disproportional preterm births. RESULTS: An estimated 4268 (95% CI: 4123-4414) tracheostomies were performed in infants admitted as a neonate with preterm infants accounting for 47% (1998/4268). Among preterm children, 20% were Black or African American compared to 12% in the term group (P < .001). More preterm infants had bronchopulmonary dysplasia (46% vs. 14%, P < .001), cardiac defects (66% vs. 58%, P < .001) and developed pneumonia, newborn sepsis, or sepsis during admissions (P < .001). Laryngotracheal anomalies (25% vs. 18%, P < .001) and vocal cord paralysis (11% vs. 4.9%, P < .001) were more common in term infants. Median length of stay (LOS) (154 vs. 100 days, P < .001) and total charges ($1,395,106 vs. $917,478, P < .001) were greater among preterm infants. Mortality was no different between groups (13% vs. 15%, P = .07). Characteristics strongly associated with preterm status were newborn sepsis (OR: 2.31, 95% CI: 1.97-2.72, P < .001), bronchopulmonary dysplasia (OR: 2.17, 95% CI: 1.77-2.65, P < .001) and Black or African American race (OR: 1.78, 95% CI: 1.46-2.17, P < .001). The following factors increased among all neonates between the baseline year 2003 to the final study year 2016: complications of care (OR: 1.9, 95% CI: 1.5-2.5, P < .001); sepsis (OR: 4.1, 95% CI: 3.0-5.5, P < .001); congenital cardiac anomalies (OR: 5.8, 95% CI: 4.5-7.4, P < .001); and respiratory failure (OR: 1.9, 95% CI: 1.5-2.4, P < .001). Compared to other races, median LOS and total charges were greater among Black or African American infants. CONCLUSION: Tracheostomies among preterm infants admitted as neonates reflect a growing and complex group with increased costs and hospitalization lengths. Black or African American children are disproportionately born preterm with higher costs and LOS compared to other racial cohorts. Future work will be necessary to design quality-improvement initiatives to improve outcomes for this vulnerable population.

Gist Inference Scores Predict Cloze Comprehension "In Your Own Words" for Native, Not ESL Readers.

Three patient education texts from the National Cancer Institute (NCI) were subjected to a Coh-Metrix analysis, then further analyzed to obtain Gist Inference Scores (GIS), a new measure of the likelihood that readers will make appropriate inferences about a text's bottom-line meaning. In the GIS formula, the Coh-Metrix psycholinguistic variables referential cohesion, deep cohesion, and latent semantic analysis (LSA) verb overlap increase GIS because cohesive texts that describe related actions are likely to induce gist representations. The Coh-Metrix variables word concreteness, imagability for content words, and hypernymy for nouns and verbs are negatively weighted because they tend to promote verbatim mental representations. NCI texts were modified for a cloze procedure with every tenth word replaced by a blank starting with the second sentence. Participants in two studies received all three cloze-modified texts. Fuzzy-Trace Theory suggests that people are more likely to comprehend high GIS texts "in their own words," and thus fill-the-blanks with multiple words that differ from those omitted by the cloze procedure expressing comparable meaning. In Study One, non-native English speakers appropriately filled blanks with different words at the same rate for all three texts of low-, medium-, and high-GIS. In Study Two, replicating previous findings, for high GIS texts, native English speakers filled blanks appropriately with words other than those removed significantly more often than for medium- or low-GIS texts. High GIS texts apparently afford readers more semantic and lexical flexibility, but non-native English speakers may be ill-equipped to capitalize on this characteristic of high GIS texts.

Pediatric paraneoplastic neuromyelitis optica spectrum disorder associated with ovarian teratoma.

Neuromyelitis optica spectrum disorder is an inflammatory condition of the central nervous system typically manifesting as myelitis, optic neuritis, and/or area postrema syndrome. Here, we present a pediatric patient who developed symptoms consistent with area postrema syndrome with positive anti-aquaporin-4 (AQP4) antibodies who was also found to have an ovarian teratoma. Pathological specimens revealed the presence of aquaporin-4. This was felt to be the antigenic trigger that led to the patient's condition. She suffered no further clinical attacks and seroconverted to negative AQP4 status upon teratoma removal. This case varies from others, in that the paraneoplastic presentation occurred in a pediatric patient and in that the patient has not required maintenance immunotherapy after teratoma removal.

Racial Influences on Pediatric Tracheostomy Outcomes.

OBJECTIVES/HYPOTHESIS: To determine the impact of race on outcomes after pediatric tracheostomy. STUDY DESIGN: Retrospective case series. METHODS: A case series of tracheostomies at an urban, tertiary care children's hospital between 2014 and 2019 was conducted. Children were grouped by race to compare neurocognition, mortality, and decannulation rate. RESULTS: A total of 445 children with a median age at tracheostomy of 0.46 (interquartile range [IQR]: 0.97) years were studied. The cohort was 32% Hispanic, 31% White, 30% Black, 2.9% Asian, and 4.3% other race. Black compared to White children had a lower median birth weight (2,022 vs. 2,449 g, P = .005), were more often extremely premature (≤28 weeks gestation: 62% vs. 57%, P = .007), and more frequently had bronchopulmonary dysplasia (BPD) (35% vs. 17%, P = .002). Hispanic compared to Black children had higher median birth weight (2,529 g, P < .001), less extreme prematurity (44%, P < .001), and less BPD (21%, P = .04). The proportion of Black children was higher (30% vs. 19%, P < .001), while the proportion of Hispanic children with a tracheostomy was lower (32% vs. 42%, P = .003) compared to the racial distribution of all pediatric admissions. Racial differences were not seen for rates of severe neurocognitive disability (P = .51), decannulation (P = .17), or death (P = .92) after controlling for age, sex, prematurity, and ventilator dependence. CONCLUSION: Black children disproportionately underwent tracheostomy and had a higher comorbidity burden than White or Hispanic children. Hispanic children had proportionally fewer tracheostomies. Neurocognitive ability, decannulation, and mortality were similar for all races implying that health disparities by race may not change long-term outcomes after pediatric tracheostomy. Laryngoscope, 132:1118-1124, 2022.

Assessment and Management of Acute Disseminated Encephalomyelitis (ADEM) in the Pediatric Patient.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that typically presents in childhood and is associated with encephalopathy and multifocal brain lesions. Although ADEM is thought to be a post-infectious disorder, the etiology is still poorly understood. ADEM is often a monophasic disorder, in contrast to other demyelinating disorders such as multiple sclerosis and neuromyelitis optica spectrum disorder. With increasing awareness, understanding, and testing for myelin oligodendrocyte glycoprotein antibodies, this disease is now known to be a cause of pediatric ADEM and also has the potential to be relapsing. Diagnostic evaluation for ADEM involves neuroimaging and laboratory studies to exclude potential infectious, inflammatory, neoplastic, and genetic mimics of ADEM. Acute treatment modalities include high-dose intravenous corticosteroids, therapeutic plasma exchange, and intravenous immunoglobulin. Long-term outcomes for ADEM are generally favorable, but some children have significant morbidity related to the severity of acute illness and/or manifest ongoing neurocognitive sequelae. Further research related to the optimal management of pediatric ADEM and its impact on prognosis is needed. This review summarizes the current knowledge of the pathogenesis, epidemiology, clinical features, diagnostic evaluation, treatment approaches, and outcomes in pediatric ADEM.

Autologous hematopoietic stem cell transplantation in a pediatric patient with aquaporin-4 neuromyelitis optica spectrum disorder.

We report on a child with an early and severe manifestation of an Aquaporin-4 (AQP-4) positive Neuromyelitis Optica Spectrum Disorder (NMOSD) who had a refractory disease course despite aggressive immunotherapy and underwent autologous hematopoietic stem cell transplant (AHSCT).

Intraoperative Cardiac Arrest During Adult Liver Transplantation: Incidence and Risk Factor Analysis From 7 Academic Centers in the United States.

BACKGROUND: Intraoperative cardiac arrest (ICA) has a reported frequency of 1 in 10,000 anesthetics but has a much higher estimated incidence in orthotopic liver transplantation (OLT). Single-center studies of ICA in OLT are limited by small sample size that prohibits multivariable regression analysis of risks. METHODS: Utilizing data from 7 academic medical centers, we performed a retrospective, observational study of 5296 adult liver transplant recipients (18-80 years old) between 2000 and 2017 to identify the rate of ICA, associated risk factors, and outcomes. RESULTS: ICA occurred in 196 cases (3.7% 95% confidence interval [CI], 3.2-4.2) and mortality occurred in 62 patients (1.2%). The intraoperative mortality rate was 31.6% in patients who experienced ICA. In a multivariable generalized linear mixed model, ICA was associated with body mass index (BMI) <20 (odds ratio [OR]: 2.04, 95% CI, 1.05-3.98; P = .0386), BMI ≥40 (2.16 [1.12-4.19]; P = .022), Model for End-Stage Liver Disease (MELD) score: (MELD 30-39: 1.75 [1.09-2.79], P = .02; MELD ≥40: 2.73 [1.53-4.85], P = .001), postreperfusion syndrome (PRS) (3.83 [2.75-5.34], P < .001), living donors (2.13 [1.16-3.89], P = .014), and reoperation (1.87 [1.13-3.11], P = .015). Overall 30-day and 1-year mortality were 4.18% and 11.0%, respectively. After ICA, 30-day and 1-year mortality were 43.9% and 52%, respectively, compared to 2.6% and 9.3% without ICA. CONCLUSIONS: We established a 3.7% incidence of ICA and a 1.2% incidence of intraoperative mortality in liver transplantation and confirmed previously identified risk factors for ICA including BMI, MELD score, PRS, and reoperation and identified new risk factors including living donor and length of surgery in this multicenter retrospective cohort. ICA, while rare, is associated with high intraoperative mortality, and future research must focus on therapy to reduce the incidence of ICA.

A Longitudinal Analysis of Outcomes in Tracheostomy Placement Among Preterm Infants.

OBJECTIVES: To study a case series of preterm and extremely preterm infants, comparing their decannulation and survival rates after tracheostomy. METHODS: We performed a single-institution longitudinal study of preterm infants with a tracheostomy. Infants were categorized as premature (born > 28 weeks and < 37 weeks) and extremely premature (born ≤ 28 weeks). Decannulation and survival rates were determined using the Kaplan-Meier method. Neurocognitive quality of life (QOL) was reported as normal, mild/moderately, and severely impaired. Statistical significance was set at P < .05. RESULTS: This study included 240 patients. Of those, 111 were premature and 129 were extremely preterm. The median age (interquartile range) at tracheostomy was 4.8 months (0.4). Premature infants were more likely than extremely preterm to have airway obstruction (54% vs. 32%, P < .001); whereas extremely preterm infants were more likely to have bronchopulmonary dysplasia (68% vs. 15%, P < .001) and to be ventilation-dependent (68% vs. 54%, P < .001). The 5-year decannulation rate for premature infants was 46% and for extremely preterm was 64%. The 5-year survival rate post-tracheostomy for preterm was 79% and for extremely preterm was 73%. The log-rank test of equality showed that decannulation and survival were similar (P > .05) for both groups, even after controlling for potentially confounding factors like race, age, gender, birth weight, and age at tracheostomy. For neurocognitive QOL, 47% of patients survived with severely impaired QOL after tracheostomy. Preterm had 56% with severely impaired QOL and extremely preterm had 40% with severely impaired QOL (P = .03). CONCLUSION: This study demonstrated that the time to decannulation and the likelihood of survival did not vary among premature and extremely premature infants even when controlling for other confounding variables. LEVEL OF EVIDENCE: 3b Laryngoscope, 131:417-422, 2021.

Chronic rhinosinusitis and endoscopic sinus surgery in children admitted for pulmonary exacerbations of cystic fibrosis.

OBJECTIVE: Non-surgical management of chronic rhinosinusitis (CRS) in children with cystic fibrosis (CF) has been increasing over the last decade. This study examines inpatient children with pulmonary exacerbation of CF who were also diagnosed with CRS and underwent endoscopic sinus surgery (ESS). STUDY DESIGN: We used the 2003 to 2016 Kids Inpatient Database to perform a cross-sectional analysis of inpatients (ages 0-21 years) diagnosed with CF and CRS in the United States from 2003 to 2016. Demographics and CF-associated comorbidities were recorded and rates of CRS and ESS in children with CF were examined. RESULTS: 49,110 children were included in the study. A total of 9334 (19%) were diagnosed with CRS. The average age was 13 (SD 5.9) years; the majority were female (56%), and White (67%). The prevalence of CRS increased from 2003 to 2016 (14%-23%, p < 0.001) while the rate of ESS decreased (20%-11%, p < .001). Patients with CRS that underwent ESS more commonly had CF-associated comorbidities including GI manifestations (15%-25%, p < .001) and liver disease (15%-30%, p < .001). CONCLUSION: The diagnosis of CRS in children with CF hospitalized for pulmonary exacerbation has increased while ESS has decreased in the last decade. Patients with CRS that underwent ESS more commonly had CF-associated comorbidities. Studies to determine whether children with CF-associated comorbidities are more likely to benefit from ESS are needed.

Palatine Tonsilloliths and Actinomyces: A Multi-institutional Study of Adult Patients Undergoing Tonsillectomy.

OBJECTIVE: To better characterize associations between Actinomyces and tonsillolith versus nontonsillolith tonsillectomy specimens. STUDY DESIGN: Bi-institutional retrospective case-case study. SETTING: University and county hospital. SUBJECTS AND METHODS: Adult patients with a clinical history of tonsilloliths who underwent tonsillectomy from January 2006 to December 2018 were included. Patients undergoing tonsillectomy for tonsillar hypertrophy and chronic tonsillitis were identified as comparative cases. Similarly, patients with ipsilateral oropharyngeal cancer (OPC) who underwent contralateral tonsillectomy of a normal-appearing tonsil for prophylaxis against a second primary cancer were also included as comparative cases. RESULTS: The study population comprised 134 patients who underwent tonsillectomy: 62 tonsillolith and 72 nontonsillolith (tonsillar hypertrophy, n = 30; chronic tonsillitis, n = 30; normal-appearing contralateral tonsil in patients with ipsilateral OPC, n = 12). Actinomyces was reported in 11% of the patients with tonsilloliths on initial pathology reports but in 95% after re-evaluation (n = 54 of 57). Actinomyces prevalence was significantly higher in patients with tonsilloliths as compared with patients with recurrent tonsillitis (73%, n = 22 of 30, P < .001) and normal-appearing contralateral tonsils in patients with ipsilateral OPC (58%, n = 7 of 12, P < .001). Actinomyces prevalence was not significantly different between patients with tonsilloliths and tonsillar hypertrophy (83%, n = 25 of 30, P = .11). CONCLUSION: The prevalence of Actinomyces in tonsillolith tonsil specimens is high; however, Actinomyces routinely colonizes nontonsillolith tonsil specimens. Therefore, Actinomyces is unlikely to be the primary driver of tonsillolith pathogenesis, and Actinomyces-targeted treatment of tonsilloliths may not be effective. Treatment strategies addressing tonsilloliths should be further investigated.

Tonsillectomy Outcomes among Children with Mental Health Disorders in the United States.

OBJECTIVES: Recent evidence suggests that children with mental health disorders are more likely to have postoperative complications. Our aim was to determine if mental health disorders affect postoperative complications after tonsillectomy with or without adenoidectomy (T&A). SETTING: Cross-sectional analysis of national databases. SUBJECTS AND METHODS: The 2006 to 2016 Kids Inpatient Database and the 2014 Nationwide Readmission Database were used to identify children (age <21 years) who underwent T&A. We compared children with mental health disorders (eg, autism, developmental delays, or mood disorders) to those without a mental health disorder. We contrasted gender, race, length of stay, complications, and 30-day readmissions. RESULTS: We estimated that 37,386 children underwent T&A, and there were 2138 (5.7%) diagnosed with a mental health disorder. Children with mental health disorders were older (6.0 vs 5.3 years, P < .001), more commonly males (64% vs 58%, P < .001), had a longer length of stay (3.4 days vs 2.3 days, P < .001), and had higher total charges even after controlling for length of stay ($19,000 vs $14,000, P < .001). Children with a mental health disorder were more likely to have a complication (odds ratio [OR] = 2.1; 95% confidence interval [CI], 1.7 to 3.4; P < .001) including intubation, mechanical ventilation, or both (OR = 3.3; 95% CI, 2.6 to 3.8; P < .001). The 30-day all-cause readmission rate was higher (12% vs 4.0%, P < .001). CONCLUSION: Children with mental health disorders, especially development delays, have more frequent complications, longer lengths of stay, and readmissions than children without mental health disorders. This information should be included in preoperative counseling.