Identifying Molecular Pathophysiology and Potential Therapeutic Options in Iatrogenic Tracheal Stenosis.

INTRODUCTION: While most patients with iatrogenic tracheal stenosis (ITS) respond to endoscopic ablative procedures, approximately 15% experience a recalcitrant, recurring disease course that is resistant to conventional management. We aimed to explore genetic profiles of patients with recalcitrant ITS to understand underlying pathophysiology and identify novel therapeutic options. METHODS: We collected 11 samples of granulation tissue from patients with ITS and performed RNA sequencing. We identified the top 10 most highly up- and down-regulated genes and cellular processes that these genes corresponded to. For the most highly dysregulated genes, we identified potential therapeutic options that favorably regulate their expression. RESULTS: The dysregulations in gene expression corresponded to hyperkeratinization (upregulation of genes involved in keratin production and keratinocyte differentiation) and cellular proliferation (downregulation of cell cycle regulating and pro-apoptotic genes). Genes involved in retinoic acid (RA) metabolism and signaling were dysregulated in a pattern suggesting local cellular RA deficiency. Consequently, RA also emerged as the most promising potential therapeutic option for ITS, as it favorably regulated seven of the ten most highly dysregulated genes. CONCLUSION: This is the first study to characterize the role of hyperkeratinization and dysregulations in RA metabolism and signaling in the disease pathophysiology. Given the ability of RA to favorably regulate key genes involved in ITS, future studies must explore its efficacy as a potential therapeutic option for patients with recalcitrant ITS.

Gene expression profiles in COVID-19-associated tracheal stenosis indicate persistent anti-viral response and dysregulated retinol metabolism.

INTRODUCTION: Coronavirus disease 2019 (COVID-19)-associated tracheal stenosis (COATS) may occur as a result of prolonged intubation during COVID-19 infection. We aimed to investigate patterns of gene expression in the tracheal granulation tissue of patients with COATS, leverage gene expression data to identify dysregulated cellular pathways and processes, and discuss potential therapeutic options based on the identified gene expression profiles. METHODS: Adult patients (age ≥ 18 years) presenting to clinics for management of severe, recalcitrant COATS were included in this study. RNA sequencing and differential gene expression analysis was performed with transcriptomic data for normal tracheal tissue being used as a control. The top ten most highly upregulated and downregulated genes were identified. For each of these pathologically dysregulated genes, we identified key cellular pathways and processes they are involved in using Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) applied via Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: Two women, aged 36 years and 37 years, were included. The profile of dysregulated genes indicated a cellular response consistent with viral infection (CXCL11, PI15, CCL8, DEFB103A, IFI6, ACOD1, and DEFB4A) and hyperproliferation/hypergranulation (MMP3, CASP14 and HAS1), while downregulated pathways included retinol metabolism (ALDH1A2, RBP1, RBP4, CRABP1 and CRABP2). CONCLUSION: Gene expression changes consistent with persistent viral infection and dysregulated retinol metabolism may promote tracheal hypergranulation and hyperproliferation leading to COATS. Given the presence of existing literature highlighting retinoic acid's ability to favorably regulate these genes, improve cell-cell adhesion, and decrease overall disease severity in COVID-19, future studies must evaluate its utility for adjunctive management of COATS in animal models and clinical settings.

Factors associated with safe and successful postoperative day 1 discharge after lung operations: a systematic review and meta-analysis.

BACKGROUND: A shorter length of stay (LOS) is associated with fewer hospital-acquired adverse conditions and decreased utilization of hospital resources. While modern perioperative care protocols have enabled some ambitious surgical teams to achieve discharge as early as within postoperative day 1 (POD1), most other teams remain cautious about such an approach due to the perceived risk of missing postoperative complications and increased readmission rates. We aimed to identify factors that would help guide surgical teams aiming for safe and successful POD1 discharge after lung resection. METHODS: We searched the PubMed, Embase, Scopus, Web of Science and CENTRAL databases for articles comparing perioperative characteristics in patients discharged within POD1 (DWPOD1) and after POD1 (DAPOD1) following lung resection. Meta-analysis was performed using a random-effects model. RESULTS: We included eight retrospective cohort studies with a total of 216,887 patients, of which 22,250 (10.3%) patients were DWPOD1. Our meta-analysis showed that younger patients, those without cardiovascular and respiratory comorbidities, and those with better preoperative pulmonary function are more likely to qualify for DWPOD1. Certain operative factors, such as a minimally invasive approach, shorter operations, and sublobar resections, also favor DWPOD1. DWPOD1 appears to be safe, with comparable 30-day mortality and readmission rates, and significantly less postoperative morbidity than DAPOD1. CONCLUSIONS: In select patients with a favorable preoperative profile, DWPOD1 after lung resection can be achieved successfully and without increased risk of adverse outcomes such as postoperative morbidity, mortality, or readmissions.

Novel Journal Metrics in Cardiothoracic Surgery: How Different Are Contemporary Metrics From the Impact Factor?

OBJECTIVE: Despite shortcomings, impact factor (IF) remains the "gold standard" metric for journal quality. However, novel metrics including the h-index, g-index, and Altmetric Attention Score (AAS; mentions in mainstream/social media) are gaining traction. We assessed correlations between these metrics among cardiothoracic surgery journals. METHODS: For all cardiothoracic surgery journals with a 2021 Clarivate IF (N = 20), the 2-year IF (2019 to 2020) and 5-year IF (2016 to 2020), h-index, and g-index were obtained. Two-year journal-level AAS (2019 to 2020) was also calculated. Journal Twitter presence and activity was sourced from Twitter and the Twitter application programming interface. Correlations were assessed using Spearman correlation, and coefficients of determination were calculated. RESULTS: IF demonstrated a moderate-strong positive correlation with the h-index (rs = 0.48 to 0.77) and g-index (rs = 0.49 to 0.79) and a moderate correlation with AAS (rs = 0.53 to 0.58). The 2-year IF accounted for 25% to 49% of variability in the h-index, 27% to 55% of variability in the g-index, and 32% of variability in the AAS. Among journals with a Twitter account (N = 10), IF was strongly correlated with Twitter following (rs = 0.81 to 0.86), which was in turn strongly correlated with journal AAS (rs = 0.79). Article-level AAS was moderately correlated with citation count (rs = 0.47). CONCLUSIONS: IF accounted for only between 25% and 55% of variability in the h-index and g-index, indicating that these newer metrics measure unique dimensions of citation-based impact. Thus, the academic community must familiarize itself with these newer journal metrics. Social media attention may be associated with scholarly impact, although further work is needed to understand these relationships.

Neoadjuvant vs Adjuvant Chemoimmunotherapy for Stage II-IIIB Non-Small Cell Lung Cancer.

BACKGROUND: In patients with resectable non-small cell lung cancer (NSCLC), recent trials demonstrate survival benefit of chemoimmunotherapy over chemotherapy alone in both the neoadjuvant and adjuvant settings. To date, there is no direct comparison between neoadjuvant and adjuvant protocols. We compared neoadjuvant vs adjuvant chemoimmunotherapy for resectable stage II-IIIB NSCLC. METHODS: We queried the National Cancer Database for patients who had undergone an operation for stage II-IIIB NSCLC and who had received neoadjuvant or adjuvant chemoimmunotherapy between 2015 and 2020. We used inverse probability weighting to adjust for confounding variables and used Kaplan-Meier survival curves and Cox regression to explore the relationship between treatment groups and overall survival (OS) at 3 years postoperatively. RESULTS: The inverse probability-weighted cohort represented 2119 weighted patient cases (neoadjuvant, 1034; adjuvant, 1085). Kaplan-Meier analysis demonstrated a significant OS benefit for neoadjuvant chemoimmunotherapy compared with adjuvant chemoimmunotherapy in the weighted cohort (3-year OS: 77% [95% CI, 71%-83%] vs 68% [95% CI, 64%-72%]; P = .035). On adjusted Cox regression, neoadjuvant chemoimmunotherapy was associated with a significant OS benefit (hazard ratio, 0.70; 95% CI, 0.50-0.96; P = .027). Among patients for whom pathologic stage data were available, 25% of patients receiving neoadjuvant chemoimmunotherapy had a pathologic complete response, with an additional 32.5% being downstaged. CONCLUSIONS: Neoadjuvant chemoimmunotherapy confers a significant OS benefit over adjuvant chemoimmunotherapy for patients with resectable stage II-IIIB NSCLC. Although randomized trials are needed to confirm our findings, strong consideration should be given to administering neoadjuvant chemoimmunotherapy to patients who are predetermined to receive systemic treatment.

From emissions to incisions and beyond: the repercussions of climate change on surgical disease in low- and-middle-income countries.

Climate change has far-reaching repercussions for surgical healthcare in low- and middle-income countries. Natural disasters cause injuries and infrastructural damage, while air pollution and global warming may increase surgical disease and predispose to worse outcomes. Socioeconomic ramifications further strain healthcare systems, highlighting the need for integrated climate and healthcare policies.

Endoscopic tracheoplasty: segmental tracheal ring resection in a porcine model.

Endoscopic tracheoplasty is used for the relief of airway obstruction because of several benign conditions such as postintubation stenosis, inflammatory disorders such as Wegener granulomatosis, and benign neoplastic processes. Several endoscopic treatment modalities exist for these conditions, all with good initial results. However, recurrence is common and often requires frequent reintervention. Endoscopic segmental tracheal ring resection is a novel therapeutic approach that could potentially provide a durable solution. Endoscopic segmental tracheal ring resection was performed in 3 Yorkshire pigs under general anesthesia. A combination of bipolar cautery and sharp dissection was used to resect 25% to 33% of the circumference of a single tracheal ring. Technical success was achieved in all 3 animals with no intraoperative complications. Full-thickness excision, including the anterior perichondrium, was performed in 1 animal without violation of the pretracheal fascia, with no subcutaneous emphysema or clinically apparent pneumothorax. Average operative time was 31 minutes and estimated blood loss was minimal. Heart rate, oxygen saturation, and peak airway pressures were maintained within normal ranges during the procedure and for the 60-minute postoperative period. Histologic analysis of the resected specimen confirmed complete thickness excision of the segment of tracheal cartilage. Endoscopic tracheoplasty by segmental tracheal ring resection is a safe and feasible technique in a porcine model. Long-term durability could potentially outlast other endoscopic techniques for the treatment of bening tracheal stenosis. Survival studies in a porcine model of tracheal stenosis must be performed to assess the long-term outcomes of this approach.