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A Heterotopic Mouse Model for Studying Laryngeal Transplantation
Published on: January 13, 2023
A multicenter study analyzing the impact of pre-existing comorbidities on laryngotracheal reconstruction (LTR)
Ian N Jacobs1, Teresa Giordano1, Ashley Soaper2
1Division of Otolaryngology, Children's Hospital of Philadelphia, 3500 Civic Center Boulevard, 5th Floor, Philadelphia, PA, 19104, USA.
Insights
This study found that patient factors, including stage and severity of stenosis, along with pulmonary and gastrointestinal conditions, significantly impact the success of Laryngotracheal Reconstruction (LTR). These findings refine predictive models for LTR outcomes.
Area of Science:
- Otolaryngology
- Pediatric Surgery
- Respiratory Medicine
Background:
- Comorbidities like chronic lung disease, GERD, and prematurity can affect Laryngotracheal Reconstruction (LTR) success.
- Previous single-center studies on LTR outcomes were limited by small patient numbers and statistical power.
Purpose of the Study:
- To assess the impact of specific comorbidities on LTR surgical success in a large multicenter cohort.
- To validate and refine a predictive model for LTR surgical success using a multicenter dataset.
Main Methods:
- A retrospective 10-year multicenter review of 542 patients undergoing LTR.
- Data collection included patient demographics, comorbidities, surgical details, and diagnostic test results (EGD, pH/impedance, bronchoscopy).
- Multivariate Bayesian analysis, logistic regression, and Kaplan-Meier analysis were employed to evaluate outcomes.
Main Results:
- The study identified 542 patients, with an overall LTR success rate of 86.4% and operation-specific success of 69.2%.
- Key factors impacting success included stenosis stage/level, bronchiectasis, pulmonary hypertension, GERD, Trisomy 21, and specific aerodigestive findings.
- A validated predictive model demonstrated strong performance (AUC 0.827 for single surgery, 0.797 for overall success).
Conclusions:
- This large multicenter study confirms that patient-specific factors, particularly stenosis severity and pulmonary/GI comorbidities, are critical for LTR success.
- The refined predictive model improves upon previous single-center data for forecasting LTR outcomes.
- Future prospective studies aim to further optimize outcome prediction and patient management strategies for LTR.
Introduction:
Comorbidities such as chronic lung disease and gastroesophageal reflux (GERD), prematurity, and numerous other conditions may impact the success of LTR. Single-center studies are limited in terms of patient numbers and may be underpowered.
Objectives:
To analyze the impact of specific comorbidities on the operation-specific and overall surgical success of LTR in a large multicenter cohort and validate a predictive model for surgical success.
Methods:
A large retrospective multicenter 10-year review was undertaken to validate the data of a previous single-center study (Wertz et al. Laryngoscope 2020) which identified specific predictive comorbidities which impacted LTR outcomes. A Monte Carlo simulation based on the previous data set suggested that 300-400 cases would be needed to optimize the statistical power of a Bayesian model developed from the single-center data to predict surgical success. An IRB-approved data-sharing agreement was executed for 4 large U.S.
Centers:
A virtual REDCap® data entry form inquired about patient characteristics that best predicted surgical success in the single-center model. These included demographics, surgical approaches, cardiac, airway, genetic, endocrine, musculoskeletal, gastrointestinal, and pulmonary comorbidities; details of the surgical procedures, and results of esophagogastroduodenoscopy (EGD), esophageal pH/impedance and flexible bronchoscopy with bronchioalveolar lavage (BAL) were included. Surgical success defined as successful decannulation or resolution of airway symptoms was recorded as single surgery success and overall success following open surgical revision surgery. Multivariate Bayesian analysis, logistical regression, and Kaplan-Meier analysis were performed.
Results:
542 patients were identified, including 165 from the single-center study and an additional 377 patients from the multicenter group. The median age was 36 months at the time of the most recent surgery. 70.9% of the LTRs were double-staged procedures. The overall success rate was 86.4% and operation-specific success rate was 69.2%. The specific comorbidities and aerodigestive test results that impacted success based on univariate analysis included staging, bronchiectasis, pulmonary hypertension, GERD, ASD, PDA, grade of stenosis, advanced levels of stenosis, Trisomy 21, MRSA, prior open surgery at another hospital, and gross appearance on EGD. Bayesian model averaging with backward selection was used to validate and refine a predictive model for surgical success with favorable receiver operating curve characteristics - AUC values of 0.827 for single surgery success and 0.797 for overall success.
Discussion:
With over 500 patients reviewed, this was the largest multicenter study of LTR to date, which elucidated the impact of comorbidities on success with LTR and was able to improve upon the predictive modeling based on single-center data. Patient factors are most critical in the outcome of LTR. Stage and levels of stenosis, as well as pulmonary and GI conditions most strongly impact the likelihood of success. Future prospective case-control studies will be performed to further optimize the current model for outcome prediction and patient management.
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