Suprazygomatic Maxillary Nerve Blocks and Opioid Requirements in Pediatric Adenotonsillectomy: A Randomized Clinical Trial.

Importance: Pain management following pediatric adenotonsillectomies is opioid-inclusive, leading to potential complications. Objective: To investigate the use of suprazygomatic maxillary nerve (SZMN) blocks to reduce pain and opioid use after pediatric intracapsular adenotonsillectomy and to measure recovery duration and incidence of complications. Design, Setting, and Participants: This was a randomized, blinded, prospective single-center tertiary pediatric hospital that included 60 pediatric patients (2-14 years old) scheduled for intracapsular adenotonsillectomy from November 2021 to March 2023. Patients were excluded for having combined surgical procedures, developmental delay, coagulopathy, chronic pain history, known or predicted difficult airway, or unrepaired congenital heart disease. Participants were randomized to receive bilateral SZMN blocks (block group) or not (control group). Intervention: SZMN block administered bilaterally under general anesthesia for intracapsular adenotonsillectomy. Primary Outcomes and Measures: Opioid consumption, FLACC (Face, Legs, Activity, Cry, Consolability) scores, and rates of opioid-free postanesthesia care unit (PACU) stay. Secondary outcomes were recovery duration and incidence of adverse effects, ie, nausea, vomiting, block site bleeding, and emergency delirium. Results: The study population included 53 pediatric patients (mean [SD] age, 6.5 [3.6] years; 29 [55%] females; 24 [45%] males); 26 were randomly assigned to the SZMN block group and 27 to the control group. The mean (SD) opioid morphine equivalent consumption during PACU stay was 0.15 (0.14) mg/kg for the 27 patients in the control group compared with 0.07 (0.11) mg/kg for the 26 patients in the block group (mean difference, 0.08; 95% CI, 0.01-0.15; Cohen d, 0.64). The block group had a higher incidence of opioid-free PACU stays (n = 7 patients; 58%) compared with the control group (n = 15 patients; 26%) (mean difference, 32%; 95% CI, 5%-53%). Patients in the block group experienced lower FLACC scores (0.7 vs 1.6; mean difference, 0.9; 95% CI, 0.2-1.6; Cohen d, 0.7). The overall occurrence of adverse events was similar in the 2 groups, with no reported nerve block-related complications. Conclusions and Relevance: The results of the randomized clinical trial indicate that SZMN blocks are a useful adjunct tool for managing postoperative pain in pediatric intracapsular adenotonsillectomy. Use of these blocks during adenotonsillectomy provided clinically meaningful reductions of postoperative opioid consumption with a low risk of complications. Trial Registration: ClinicalTrials.gov Identifier: NCT04797559.

Use of temporary tracheostomy occlusion to reduce the risk of sternal wound infection after sternotomy in congenital cardiac surgery.

OBJECTIVE: To describe a method of reducing the risk of sternal wound infection after sternotomy in children with a pre-existing tracheostomy. To report our outcomes using this method from 1 January, 2013 to 31 August, 2023. METHODS: We describe a method for temporarily occluding the tracheal stoma with a removable implant with the primary goal of reducing the risk of sternotomy wound infection by preventing soilage due to tracheostomal secretions. We then performed a retrospective review of all children who underwent temporary tracheostomal occlusion between 1 January, 2013 and 31 August, 2023 at our quaternary care children's hospital. Clinical variables were extracted from the hospital medical records. The rates of antibiotic use and minor and major complications during the period when the stoma plug was in place were recorded. RESULTS: Totally, 19 patients underwent tracheal stoma plugging prior to sternotomy and were included in our analysis. There were two cases of sternal wound infection; one case occurred while the stoma plug was in place, and one developed four days following plug removal. There was one minor complication, with one patient requiring stoma revision via serial dilation at bedside at the time of recannulation. There were no deaths. CONCLUSION: Temporary occlusion of the tracheal stoma with an impermeable plug is a viable option for reducing the risk of sternal wound infection in children with a pre-existing tracheostomy who are undergoing sternotomy.

The safety and efficacy of radiofrequency ablation in benign pediatric thyroid disease in the US: An initial case series.

Objective: To evaluate the efficacy and safety of radiofrequency ablation (RFA) for benign nonfunctional thyroid nodules or functional lingual thyroid gland in a pediatric population. Methods: Four pediatric patients (four female; mean age 13.50 ± 4.04, range 8-17 years) with either benign thyroid nodules or mildly obstructive lingual thyroid glands were treated with RFA from 2020 to 2021 were evaluated. The inclusion criteria for RFA therapy were (i) age < 18 years; (ii) benign cytopathological results on ultrasound guided fine needle aspiration; (iii) pressure or pain symptoms caused by the thyroid nodules; (iv) dysphagia or obstruction caused by the lingual thyroid tissue; (v) follow up for >6 months with otolaryngology or endocrinology. Results: Two patients had benign non-functioning thyroid nodules and two had mildly obstructive functioning lingual thyroid glands. Mean follow up was 10.75 ± 4.79 months. Each patient underwent one RFA session with no complications. For the patients with thyroid nodules, there was >74% reduction in nodule size at last follow up with improvement in neck swelling and pain. For the patients with lingual thyroid glands, both did not have any other functional thyroid gland identified. Both had visible decrease in size of the gland as visualized transorally with improvement in dysphagia and obstructive symptoms when lying flat. Conclusion: RFA is a safe and effective option for managing benign thyroid nodules and lingual thyroid glands in a pediatric patient population. Level of evidence: 4.

Use of Neoadjuvant Vandetanib in Aggressive Pediatric Medullary Thyroid Carcinoma.

Novel use of vandetanib in a child with aggressive MTC with prolonged response to treatment.

Cough Sounds in Screening and Diagnostics: A Scoping Review.

OBJECTIVE: The aim of the study was to examine applications of cough sounds towards screening tools and diagnostics in the biomedical and engineering literature, with particular focus on disease types, acoustic data collection protocols, data processing and analytics, accuracy, and limitations. DATA SOURCES: PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, IEEE Xplore, Engineering Village, and ACM Digital Library were searched from inception to August 2021. REVIEW METHODS: A scoping review was conducted on screening and diagnostic uses of cough sounds in adults, children, and animals, in English peer-reviewed and gray literature of any design. RESULTS: From a total of 438 abstracts screened, 108 articles met inclusion criteria. Human studies were most common (77.8%); the majority focused on adults (57.3%). Single-modality acoustic data collection was most common (71.2%), with few multimodal studies, including plethysmography (15.7%) and clinico-demographic data (7.4%). Data analytics methods were highly variable, with 61.1% using machine learning, the majority of which (78.8%) were published after 2010. Studies commonly focused on cough detection (41.7%) and screening of COVID-19 (11.1%); among pediatric studies, the most common focus was diagnosis of asthma (52.6%). CONCLUSION: Though the use of cough sounds in diagnostics is not new, academic interest has accelerated in the past decade. Cough sound offers the possibility of an accessible, noninvasive, and low-cost disease biomarker, particularly in the era of rapid development of machine learning capabilities in combination with the ubiquity of cellular technology with high-quality recording capability. However, most cough sound literature hinges on nonstandardized data collection protocols and small, nondiverse, single-modality datasets, with limited external validity. Laryngoscope, 134:1023-1031, 2024.

Safety and effectiveness of vocal fold injection laryngoplasty in infants less than one year of age.

INTRODUCTION: Injection laryngoplasty (IL) is commonly performed for unilateral vocal fold immobility (UVFI). However, the safety and efficacy in patients <1 year of age are not widely recognized. This study analyzes the safety and swallow outcomes in a cohort of patients <1 year who underwent IL. METHODS: This retrospective analysis evaluated patients at a tertiary children's institution between 2015 and 2022. Patients were eligible if they underwent IL for UVFI and were <1 year at time of injection. Baseline characteristics, perioperative data, oral diet tolerance, and preoperative and postoperative swallow data were collected. RESULTS: 49 patients were included, 12 (24%) of whom were premature. The average age at injection was 3.9 months (SD 3.8), time from UVFI onset to injection 1.3 months (2.0), and weight at injection 4.8 kg (2.1). The baseline American Association of Anesthesiologists physical status classification scores were 2 (14%), 3 (61%), and 4 (24%). 89% of patients had improvements in objective swallow function postoperatively. Of the 35 patients who were preoperatively enterally-dependent and did not have medical circumstances precluding advancement to oral feeds, 32 (n = 91%) tolerated an oral diet postoperatively. There were no long-term sequelae. Two patients had intraoperative laryngospasm, one intraoperative bronchospasm, and one with subglottic and posterior glottic stenosis was intubated for <12 h for increased work of breathing. CONCLUSIONS: IL is a safe and effective intervention that can reduce aspiration and improve diet in patients <1 year old. This procedure can be considered at institutions with the appropriate personnel, resources, and infrastructure.

Parathyroid Autofluorescence in Pediatric Thyroid Surgery: Experience With False Positive and False Negative Results.

Devices for near-infrared light stimulation of autofluorescence (NIRAF) allow for intraoperative identification of parathyroid glands with high sensitivity in adults. However, their performance in the pediatric population is unknown. In this case series with chart review at a tertiary academic children's hospital, we investigated pediatric patients undergoing thyroid surgery and concurrent use of a probe-based NIRAF device. Thirteen patients (ages 6-18 years) underwent thyroid and/or neck dissection procedures, and 2 patients had revision procedures for a total of 15 cases with the NIRAF device. Eight cases had NIRAF values that matched surgeon opinion of parathyroid tissue or histology when available. Six cases had false positive NIRAF readings (40.0%) and 1 case had false negative readings (6.7%). Compared with surgeon opinion or histology, the NIRAF device confirmed 26 of 34 parathyroid gland candidates (76.5%). These devices need further investigation in pediatric patients, whose tissues may have different autofluorescence characteristics.

Ankyloglossia: Clinical and Sociodemographic Predictors of Diagnosis and Management in the United States, 2004 to 2019.

OBJECTIVE: The past 2 decades have seen a rapid increase in the diagnosis of ankyloglossia. Patients are often managed by lingual frenotomy. The objective is to define the clinical and socioeconomic factors that determine which patients receive frenotomy. STUDY DESIGN: A retrospective analysis of commercially insured children. SETTING: Optum Data Mart database. METHODS: Trends in frenotomy including provider and setting were described. Multiple logistic regression was used to determine predictors of frenotomy. RESULTS: Diagnosis of ankyloglossia increased from 2004 to 2019 (from 3377 in 2004 to 13,200 in 2019), while lingual frenotomy similarly increased from 1483 in 2004 to 6213 in 2019. The proportion of inpatient frenotomy procedures increased from 6.2% to 16.6% from 2004 to 2019, with pediatricians having the highest odds of performing inpatient frenotomies (odds ratio: 4.32, 95% confidence interval: 4.08, 4.57). Additionally, during the study period, the proportion of frenotomies performed by pediatricians increased from 13.01% in 2004 to 28.38% in 2019. In multivariate regression analyses, frenotomy was significantly associated with the male sex, white non-Hispanic ethnicity, higher parental income and education, and a greater number of siblings. CONCLUSION: Ankyloglossia has been increasingly diagnosed in the past 2 decades, and among patients with ankyloglossia, frenotomy is increasingly performed. This trend was driven at least in part due to increasing rates of pediatricians as proceduralists. After accounting for maternal and patient-level clinical factors, socioeconomic differences in the management of ankyloglossia were observed.

Sociodemographic Disparities in the Diagnostic Management of Pediatric Thyroid Nodules.

Importance: Thyroid cancer is the most common pediatric endocrine malignant neoplasm. Disparities in the workup of thyroid nodules may be significantly associated with thyroid cancer outcomes. Objective: To determine the association of sociodemographic factors with the odds of receiving a biopsy, timeliness of the procedure, and risk of nodule malignancy. Design, Setting, and Participants: This was a retrospective cross-sectional study using insurance claims data from the Optum Clinformatics Data Mart database. The study cohort comprised pediatric patients diagnosed with single thyroid nodules between 2003 and 2020. Data analysis was performed from January 1, 2003, to June 30, 2020. Main Outcomes and Measures: Multivariable logistic regression models were used to identify demographic variables associated with biopsy and nodule malignant neoplasm. A multivariable linear regression model was used to assess the time between thyroid nodule diagnosis and biopsy. Results: Of 11 643 children (median [IQR] age at diagnosis or procedure, 15 [12-17] years; 8549 [73.2%] were female and 3126 [26.8%] were male) diagnosed with single thyroid nodules, 2117 (18.2%) received a biopsy. Among the patients who received a biopsy, 304 (14.4%) were found to have a malignant nodule. Greater parental education was associated with a shorter diagnosis-to-biopsy interval (mean difference, -7.24 days; 95% CI, -13.75 to -0.73). Older age at nodule diagnosis (odds ratio [OR], 1.11; 95% CI, 1.09-1.13) and female gender (OR, 1.25; 95% CI, 1.11-1.40) were associated with increased odds of receiving a biopsy, while Black/African American (OR, 0.80; 95% CI, 0.65-0.99) and Hispanic (OR, 0.84; 95% CI, 0.72-0.99) patients had lower odds of receiving a biopsy compared with White patients. Finally, female gender (OR, 1.08; 95% CI, 0.80-1.47) was not associated with lower odds of nodule malignant neoplasm. Conclusions and Relevance: Findings of this cross-sectional study highlight disparities in the diagnostic management of pediatric thyroid nodules. These results call for future work to ensure equitable access to thyroid care for all children.

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Evaluation and management of congenital tracheal stenosis.

OBJECTIVES: To outline an expert-based consensus of recommendations for the diagnosis and management of pediatric patients with congenital tracheal stenosis. METHODS: Expert opinions were sought from members of the International Pediatric Otolaryngology Group (IPOG) via completion of an 18-item survey utilizing an iterative Delphi method and review of the literature. RESULTS: Forty-three members completed the survey providing recommendations regarding the initial history, clinical evaluation, diagnostic evaluation, temporizing measures, definitive repair, and post-repair care of children with congenital tracheal stenosis. CONCLUSION: These recommendations are intended to be used to support clinical decision-making regarding the evaluation and management of children with congenital tracheal stenosis. Responses highlight the diverse management strategies and the importance of a multidisciplinary approach to care of these patients.

Airway Characteristics of Patients With 22q11 Deletion Undergoing Pulmonary Artery Reconstruction Surgery: Retrospective Cohort Study.

OBJECTIVES: We have previously shown that patients with a chromosome 22q11 microdeletion are at risk for prolonged respiratory failure after pulmonary artery reconstruction surgery compared with those with normal genotype. We sought to describe preexisting airway abnormalities in this patient population and examine relationships between airway abnormalities and outcomes. DESIGN: Single-center retrospective chart review from Society of Thoracic Surgery and Pediatric Cardiac Critical Care Consortium databases and the electronic medical record. SETTING: Lucile Packard Children's Hospital at Stanford from September 2017 to February 2019. PATIENTS: All patients undergoing pulmonary artery reconstruction surgery were considered for inclusion. INTERVENTIONS: We identified 127 patients meeting study inclusion criteria. Thirty-nine patients met specific criteria and underwent screening preoperative bronchoscopy including microdirect laryngoscopy and lower airway examination. Postoperative bronchoscopy was performed at the discretion of the intensive care team. MEASUREMENTS AND MAIN RESULTS: Airway abnormalities were detected in 25/26 of children (96%) with a chromosome 22q11 deletion who underwent preoperative bronchoscopy. Upper and lower airway pathologies were found in 19/25 (73%) and 21/25 (81%) patients, respectively, and it was common for patients to have more than one abnormality. Presence of 22q11 deletion was associated with longer duration of mechanical ventilation (9.1 vs 4.3 d; p = 0.001), use of noninvasive positive pressure support (13 vs 6 d; p = 0.001), and longer hospital stays (30 vs 14 d; p = 0.002). These outcomes were worse when compared with patients with known airway abnormalities who did not have 22q11 deletion. CONCLUSIONS: Preexisting upper and lower airway pathologies are common in patients with a chromosome 22q11 deletion who undergo pulmonary artery reconstruction surgery. Despite similar postoperative hemodynamics and outcomes as their counterparts without 22q11 deletion, 22q11 deletion is associated with more postoperative respiratory complications not entirely explained by preexisting airway abnormalities.

Nonsurgical Orthodontic Airway Plate Treatment for Newborns With Robin Sequence.

Despite promising outcomes for >50 years, nonsurgical orthodontic airway plates (OAP) are only infrequently offered for babies with Robin sequence in a few parts of the world. This article demonstrates possibility of providing functional improvement using an OAP to help these babies overcome their functional and structural difficulties on their own. Two consecutively treated cases are presented exemplifying that OAP treatment that had originated from Europe is reproducible and effective in an institution in the United States.

Effects of Social Determinants of Health Care on Pediatric Thyroid Cancer Outcomes in the United States.

OBJECTIVE: To identify social determinants of health care that are associated with poorer pediatric well-differentiated thyroid cancer (WDTC) outcomes and increased stage at presentation. STUDY DESIGN: Using the SEER database (Surveillance, Epidemiology, and End Results), we retrospectively gathered data on pediatric WDTC across the United States between 1973 and 2015. SETTING: All patients between 0 and 19 years old with a diagnosis of WDTC were included. METHODS: Patient variables were analyzed for relationships to AJCC stage at presentation (American Joint Committee on Cancer), overall survival, and disease-specific survival. RESULTS: Among 3913 patients with pediatric thyroid cancer, 3185 were female (81.4%), 3366 had papillary thyroid cancer (85.3%), and 367 had follicular thyroid cancer (9.4%). Two- and 5-year overall and disease-specific survival approached 100%. However, when outcomes were analyzed by specific populations, male sex, non-Caucasian race, poverty, and language isolation were linked to worse overall survival. Male sex and poverty were associated with poorer disease-specific survival. Regarding overall AJCC stage at presentation, male sex and Black race were related to higher overall presenting AJCC stage. Later AJCC T stage at presentation was seen in male, Hispanic, Asian, and Black patients. There were no variables significantly related to following through with recommended surgery. CONCLUSION: Pediatric WDTC continues to carry an excellent prognosis in the United States. However, when we consider specific populations, the social determinants of health care affect survival and disease burden at presentation: male sex, poverty, language isolation, and race affected survival and/or AJCC stage at presentation in pediatric WDTC.

Next-Generation Sequencing as an Auxiliary Tool in Pediatric Laryngeal Lymphoma Diagnosis.

Lymphomatous involvement of the larynx is a rare entity. We present a case of atypical laryngotracheitis as the initial manifestation of non-Hodgkin's lymphoma in a pediatric patient. The diagnosis was aided through the use of microbial cell-free DNA (mcfDNA) testing, which detected the presence of Epstein-Barr virus in the patient's plasma. This enabled the consideration of an Epstein-Barr virus-related lymphoproliferative process, leading to additional workup and the final diagnosis of lymphoma. To our knowledge, this is the first case of mcfDNA testing leading not simply to an infectious organism, but further to a new oncologic diagnosis. Plasma mcfDNA testing has the potential to inform clinical practice beyond classic infectious disease manifestations. In this article, we review both the possible future applications and the areas of further investigation that remain.

Opioid-Free Postoperative Pain Management After Adenotonsillectomy With Nasal Turbinate Reduction Using Bilateral Suprazygomatic Infratemporal-Pterygopalatine Fossa Injections: A Case Report.

Adenotonsillectomies are one of the most common otolaryngologic surgeries performed to alleviate obstructive sleep-disordered breathing and apnea in children. The pain management following adenotonsillectomy continues to be a challenge for both pediatric anesthesiologists and otolaryngologists due to the mortality that stems from the use of opioid pain medications in children who have an increased baseline risk airway obstruction and apnea that is exacerbated by any exposure to opioids. We present a case utilizing bilateral suprazygomatic maxillary nerve (SZMN) blocks or, more accurately, suprazygomatic infratemporal-pterygopalatine fossa injections to achieve opioid-free perioperative analgesia for pediatric adenotonsillectomy with nasal turbinate reduction.

Pediatric Subspecialty Adoption of Telemedicine Amidst the COVID-19 Pandemic: An Early Descriptive Analysis.

Telemedicine has rapidly expanded in many aspects of pediatric care as a result of the COVID-19 pandemic. However, little is known about what factors may make pediatric subspeciality care more apt to long-term adoption of telemedicine. To better delineate the potential patient, provider, and subspecialty factors which may influence subspecialty adoption of telemedicine, we reviewed our institutional experience. The top 36 pediatric subspecialties at Stanford Children's Health were classified into high telemedicine adopters, low telemedicine adopters, and telemedicine reverters. Distance from the patient's home, primary language, insurance type, institutional factors such as wait times, and subspecialty-specific clinical differences correlated with differing patterns of telemedicine adoption. With greater awareness of these factors, institutions and providers can better guide patients in determining which care may be best suited for telemedicine and develop sustainable long-term telemedicine programming.

Modeling human adaptive immune responses with tonsil organoids.

Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. STUDY DESIGN: Delphi method-based survey series. METHODS: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. RESULTS: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). CONCLUSION: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E1941-E1949, 2021.

Risk Assessment and Early Mobilization Pathway Following Pediatric Tracheostomy: A Pilot Study.

OBJECTIVES/HYPOTHESIS: To confirm the standard of care pertaining to postoperative mobilization practices following initial tracheostomy, to establish face validity of novel early mobilization tools, and to conduct a safety and feasibility pilot study. STUDY DESIGN: Multi-institutional survey and prospective cohort study. METHODS: Experts at our tertiary-care children's hospital developed an Early Pediatric Mobility Pathway for tracheostomy patients utilizing a novel risk-assessment tool. Surveys were distributed to professional colleagues in similar children's hospitals to establish face validity and incorporate respondent feedback. Additional surveys were disseminated to tertiary-care children's hospitals across the country to establish the current standard of care, and a pilot study was conducted. RESULTS: Seventy-seven percent of respondents from tertiary hospitals across the country confirmed the standard of care to defer mobilization until the first trach change. Greater than 83% of the respondents used to establish face validity of the tools agreed with the clinical components and scoring structure. The safety and feasibility of early mobilization prior to initial trach change was confirmed with a pilot of 10 pediatric patients without any adverse events. CONCLUSIONS: Mobilization of pediatric patients prior to initial trach change is feasible and can be safe when risk factors are assessed by a multidisciplinary team. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E653-E658, 2021.