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.

Impact of facility type and volume in locally advanced esophageal cancer.

BACKGROUND: We hypothesized that academic facilities and high-volume facilities would be independently associated with improved survival and a greater propensity for performing surgery in locally advanced esophageal cancer. METHODS: We identified patients diagnosed with stage IB-III esophageal cancer during 2004-2016 from the National Cancer Database. Facility type was categorized as academic or community, and facility volume was based on the number of times a facility's unique identification code appeared in the dataset. Each facility type was dichotomized into high- and low-volume subgroups using the cutoff of 20 esophageal cancers treated/year. We fitted multivariable regression models in order to assess differences in surgery selection and survival between facilities according to type and volume. RESULTS: Compared to patients treated at high-volume community hospitals, those at high-volume academic facilities were more likely to undergo surgery (odds ratio: 1.865, p < 0.001) and were associated with lower odds of death (odds ratio: 0.784, p = 0.004). For both academic and community hospitals, patients at high-volume facilities were more likely to undergo surgery compared to those at low-volume facilities, p < 0.05. For patients treated at academic facilities, high-volume facilities were associated with lower odds of death (odds ratio: 0.858, p = 0.02) compared to low-volume facilities, while there was no significant difference in the odds of death between high- and low-volume community hospitals (odds ratio: 1.018, p = 0.87). CONCLUSIONS: Both facility type and case volume impact surgery selection and survival in locally advanced esophageal cancer. Compared to community hospitals, academic facilities were more likely to perform surgery and were associated with improved survival.

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.

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.

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.

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.

Increasing Time-to-Treatment for Lung Cancer: Are We Going Backward?

BACKGROUND: Treatment delays in lung cancer care in the United States may be attributable to a diverse range of patient, provider, and institutional factors, the precise contributions of which remain unclear. The objective of our study was to use the National Cancer Database to investigate specific predictors of increased time-to-treatment initiation. METHODS: We identified 567 783 patients undergoing treatment for stage I to stage IV non-small cell lung cancer during 2010 to 2018. Time-to-treatment initiation was defined as the number of days from radiologic diagnosis to initiation of first treatment. We used mixed effect negative binomial regression to determine predictors of time-to-treatment initiation. RESULTS: We noted a steady rise in the overall mean time-to-treatment initiation interval from 33 days (2010) to 39 days (2018; P < .01). Black race, a later year at diagnosis, nonprivate insurance, and diagnosis and treatment at different facilities were independent predictors of increased time-to-treatment initiation, irrespective of disease stage. Compared with White race, Black race corresponded to a 15% to 20% increase in time-to-treatment initiation, depending on disease stage (P < .01). For stages I and II, radiation as first course of therapy corresponded with a 69% and 33% increase in time-to-treatment initiation, respectively, compared with surgery (P < .01). CONCLUSIONS: Lung cancer treatment initiation times have seen an upward trajectory in recent years. Black patients encountered significantly longer treatment initiation times, regardless of treatment modality or disease stage. Prolonged initiation times appear to contribute to existing health care disparities by disproportionately affecting medically underserved communities.

Anastomotic stenosis of bioengineered trachea grafts is driven by transforming growth factor ß1-induced signaling, proinflammatory macrophages, and delayed epithelialization.

Objective: Anastomotic stenosis caused by hypertrophic granulation tissue often develops in response to orthotopically implanted bioengineered tracheal grafts. To determine mechanisms responsible for the development and persistence of this granulation tissue, we looked for changes in gene expression from tissue specimens from the graft-native interface. Methods: RNA was isolated from paraffin-embedded tissue samples of the anastomotic sites of orthotopically implanted bioengineered tracheal grafts of 9 animals. Tissue samples were binned into 3 groups based on degree of stenosis: no stenosis (<5%), mild stenosis (25%-50%), and moderate and severe stenosis (≥75%). Sections of healthy trachea tissue were used as control. The expression levels of ∼200 genes related to wound healing, plus several endogenous controls, were measured with a pathway-focused predesigned primer array. Results: Expression of ARG2, IL4, RPL13 A, TGFBR3, and EGFR decreased, whereas expression of RUNX2 was increased in stenotic wounds compared with nonstenotic tissue. Based on the cell types present in the trachea and wound healing, this expression profile indicates a lack of M2 anti-inflammatory macrophages, absent epithelial cells, and transforming growth factor ß1-induced signaling. Conclusions: These findings represent a significant step for tracheal tissue engineering by identifying several key mechanisms present in stenotic granulation tissue. Further research must be conducted to determine what modifications of the graft substrate and which coadministered therapeutics can be used to prevent the development of hypertrophic granulation tissue.

A review of venous reconstruction options for the mediastinum.

Major vessels of the mediastinum such as the superior vena cava (SVC) and bilateral innominate veins can occasionally become involved with aggressive tumors or the mediastinum, including non-small cell lung cancer and thymoma. This may result in partial or complete obstruction. With presentation of these tumors symptoms can often be debilitating and would otherwise be treated with palliative therapy. A select population of patients are candidates for tumor resection. The ability to perform an adequate resection will depend on the ability to create a durable reconstruction of the SVC and bilateral innominate veins. Pre-operative and intra-operative considerations will allow for a safe surgery with few complications to the patient. Furthermore, depending on the extent of resection, there are a variety of techniques for reconstruction. These can range from a primary repair of a partial venous wall resection to a complex replacement of both the SVC and one or both innominate veins. Multiple options exist for the use of these conduits, such as polytetrafluoroethylene, homograft, autologous vein, and bovine or porcine pericardium. Depending on the type of conduit used, the post-operative outcomes will differ. In order to perform this operation safely, proper knowledge and experience is required. We review a variety of strategies used to manage these rare but complex scenarios.

Conversion to Thoracotomy in Non-Small Cell Lung Cancer: Risk Factors and Perioperative Outcomes.

Objective: We aimed to identify predictors of conversion to thoracotomy and test the hypothesis that conversion is associated with inferior perioperative outcomes in non-small cell lung cancer (NSCLC). Methods: We queried the National Cancer Database for patients with stage I to III NSCLC undergoing minimally invasive surgery (MIS) during 2010 to 2016. We compared clinicopathologic factors between patients undergoing MIS with and without conversion. We fitted multivariable regression models to identify independent predictors of conversion and compare perioperative outcomes between the 2 groups. Results: A rising trend in the use of MIS was accompanied by a declining trend in the rate of conversion to thoracotomy. A total of 11.3% of the 83,219 cases were converted. Conversion was associated with a higher Charlson-Deyo score, squamous histology, nodal involvement, high tumor grade, tumor size ≥5 cm, and a higher T stage (P < 0.05). Successful MIS without conversion was predicted by advanced age, sublobar resection, robotic approach, and treatment at an academic high-volume facility (P < 0.05). Conversion was linked to longer hospital stays, higher 30-day and 90-day mortality, and unplanned readmission (P < 0.05), irrespective of the type of MIS approach. Conclusions: Conversion rates for video-assisted and robot-assisted thoracoscopic surgery have seen a decline in recent years. Irrespective of the type of MIS approach, conversion was associated with inferior perioperative outcomes. The robotic approach and treatment at an academic high-volume facility were associated with a lower likelihood of conversion. Early recognition of the individual risk factors for conversion may help to counsel patients about the likelihood of, and detriments associated with, conversion and ultimately reduce conversion rates.

Inflammatory cytokines in robot-assisted thoracic surgery versus video-assisted thoracic surgery.

Background: Cytokines play a crucial role in the inflammatory response and are essential modulators of injury repair mechanisms. While minimally invasive operations have been shown to induce lower levels of cytokines compared to open thoracotomy, the inflammatory cytokine profile difference between video-assisted (VATS) and robotic-assisted thoracic surgery (RATS) techniques has yet to be elucidated. Methods: In this prospective observational study of 45 patients undergoing RATS (n=30) or VATS (n=15) lung resection for malignancy, plasma levels of interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon (IFN)-γ, tumor necrosis factor (TNF)-α, monocyte chemo-attractant protein (MCP)-1, and endothelial growth factor (EGF) were measured before and after surgery via immunoassay. Results: Levels of IL-6 and MCP-1 were significantly higher in patients undergoing VATS than in patients undergoing RATS (P<0.001 and P=0.005, respectively) 2 hours following surgery. MCP-1 levels were also found to be significantly higher in the VATS group (P<0.001) 24 hours following surgery. IL-1α, IL-1ß, IL-2, IL-4, IL-8, IL-10, IFN-γ, TNF-α, and EGF levels were not significantly different at any time-point comparing VATS to RATS. Conclusions: The VATS approach is associated with a more robust pro-inflammatory cytokine response through the upregulation of MCP-1 and IL-6 when compared to the RATS approach in patients undergoing anatomic lung resection. Further studies are necessary to validate the clinical significance of this finding.

Treatment quality and outcomes vary with hospital burden of uninsured and Medicaid patients with cancer in early non-small cell lung cancer.

Objectives: Safety-net hospitals deliver a significant level of care to uninsured patients, Medicaid-enrolled patients, and other vulnerable patients. Little is known about the impact of safety-net hospital status on outcomes in non-small cell lung cancer. We aimed to compare treatment characteristics and outcomes between hospitals categorized according to their relative burden of uninsured or Medicaid-enrolled patients with non-small cell lung cancer. Methods: We queried the National Cancer Database for patients with clinical stage I and II non-small cell lung cancer presenting from 2004 to 2018. We categorized hospitals on the basis of their relative burden of uninsured or Medicaid-enrolled patients with non-small cell lung cancer into low-burden (<8.2%), medium-burden (8.2%-12.0%), high-burden (12.1%-16.8%), and highest burden (>16.8%) quartiles. We investigated the impact of care at these hospitals on outcomes while controlling for sociodemographic, clinical, and facility characteristics. Results: We identified 204,189 patients treated at 1286 facilities. There were 592 low-burden, 297 medium-burden, 219 high-burden, and 178 highest burden hospitals. Patients at highest burden hospitals were more likely to be younger, male, Black, and Hispanic (P < .01), and to reside in rural, low-income, and low-educated regions (P < .01). Patients at these facilities had a greater likelihood of not receiving surgery, undergoing an open procedure, undergoing a regional lymph node examination involving less than 10 lymph nodes, having a length of stay more than 4 days, and not receiving treatment (P < .05). Conclusions: Our results indicate reduced treatment quality and higher mortality in patients undergoing surgery for early non-small cell lung cancer at hospitals with an increased burden of uninsured or Medicaid-enrolled patients with non-small cell lung cancer. There is a need to raise the standard of care to improve outcomes in vulnerable populations.