Comparing immediate postoperative outcomes of different VATS approaches for anatomical lung resection: a single-centre retrospective study.

BACKGROUND: Video-assisted thoracic surgery (VATS) can be performed through 1 or more intercostal or subxiphoid ports. The aim of this study was to evaluate whether number and location of ports had an impact on early perioperative outcomes and postoperative pain after anatomical lung resection (ALR). METHODS: A search of the departmental electronic database identified all patients who underwent VATS ALR between June 2018 and June 2019. We stratified patients according to the surgical approach: 2-port VATS, 3-port VATS, and subxiphoid VATS. We extracted demographic and clinicopathologic data. We used univariate analysis with unpaired t tests and χ2 tests to compare these variables between the subgroups. RESULTS: We included 201 patients in the analysis. When patients were stratified by surgical approach, there was no difference in terms of age, disease load, length of surgery, postoperative complications, duration of pleural drainage, and length of hospital stay. Postoperative pain and morphine equivalent usage were also comparable between the groups. According to these results, number and location of VATS ports seemingly has no clinical impact on early postoperative outcomes. Limitations of the study include its retrospective nature, small sample size, and short follow-up interval. CONCLUSION: Our results suggest that incision location and the number of VATS ports is not associated with differences in the incidence of perioperative complications or postoperative pain. Given the limitations described above, further studies with longer follow-up intervals are required to explore the lasting impact of this surgical approach on quality of life.

Psychological Impact of the COVID-19 Pandemic on Canadian Surgical Residents: A Province-Wide Study.

OBJECTIVES: The objective of this study was to evaluate the psychological impact of the COVID-19 pandemic on surgical residents. DESIGN: An online survey was distributed evaluating multiple domains: demographics, health and socioeconomic factors, clinical experience, educational experience, and psychological outcomes. The Mayo Clinic Resident Well-Being Index (RWBI) was used as a validated measure of resident mental health. SETTING AND PARTICIPANTS: Surgical residents from University of British Columbia's surgical residency programs. RESULTS: A total of 31/86 surgical residents responded to the survey. Of which, 57% and 46% reported feeling burned out or depressed, respectively. Residents who were concerned about personal protective equipment supply and who lived with family members with comorbidities had a higher risk of depression (p = 0.03, p = 0.04). The median Mayo Clinic Resident Well-Being Index was 2.5, higher than the median of 2 observed in the United States national survey of residents. CONCLUSIONS: The pandemic had a considerable negative impact on the psychological well-being of surgical residents.

Next-generation sequencing of non-small cell lung cancer at a Quebec health care cancer centre.

BACKGROUND: Lung cancer is the leading cause of cancer death in both men and women. Quebec has the highest lung cancer mortality out of all provinces in Canada, believed to be caused by higher smoking rates. Molecular testing for lung cancer is standard of care due to the discovery of actionable driver mutations that can be targeted with tyrosine kinase inhibitors. To date, no detailed molecular testing characterization of Quebec patients with lung cancer using next generation sequencing (NGS) has been performed. MATERIALS AND METHODS: The aim of this study was to describe the genomic landscape of patients with lung cancer (n = 997) who underwent NGS molecular testing at a tertiary care center in Quebec and to correlate it with clinical and pathology variables. RESULTS: Compared to 10 other NGS studies found through a structured search strategy, our cohort had a higher prevalence of KRAS mutations (39.2%) compared to most geographical locations. Additionally, we observed a significant positive association between decreasing age and a higher proportion of KRAS G12C mutations. CONCLUSION: Overall, it remains important to assess institutional rates of actionable driver mutations to help guide governing bodies, fuel clinical trials and create benchmarks for expected rates as quality metrics.

Tm4sf1-marked Endothelial Subpopulation Is Dysregulated in Pulmonary Arterial Hypertension.

The identification and role of endothelial progenitor cells in pulmonary arterial hypertension (PAH) remain controversial. Single-cell omics analysis can shed light on endothelial progenitor cells and their potential contribution to PAH pathobiology. We aim to identify endothelial cells that may have stem/progenitor potential in rat lungs and assess their relevance to PAH. Differential expression, gene set enrichment, cell-cell communication, and trajectory reconstruction analyses were performed on lung endothelial cells from single-cell RNA sequencing of Sugen-hypoxia, monocrotaline, and control rats. Relevance to human PAH was assessed in multiple independent blood and lung transcriptomic data sets. Rat lung endothelial cells were visualized by immunofluorescence in situ, analyzed by flow cytometry, and assessed for tubulogenesis in vitro. A subpopulation of endothelial cells (endothelial arterial type 2 [EA2]) marked by Tm4sf1 (transmembrane 4 L six family member 1), a gene strongly implicated in cancer, harbored a distinct transcriptomic signature enriched for angiogenesis and CXCL12 signaling. Trajectory analysis predicted that EA2 has a less differentiated state compared with other endothelial subpopulations. Analysis of independent data sets revealed that TM4SF1 is downregulated in lungs and endothelial cells from patients and PAH models, is a marker for hematopoietic stem cells, and is upregulated in PAH circulation. TM4SF1+CD31+ rat lung endothelial cells were visualized in distal pulmonary arteries, expressed hematopoietic marker CD45, and formed tubules in coculture with lung fibroblasts. Our study uncovered a novel Tm4sf1-marked subpopulation of rat lung endothelial cells that may have stem/progenitor potential and demonstrated its relevance to PAH. Future studies are warranted to further elucidate the role of EA2 and Tm4sf1 in PAH.

Laparoscopic versus open resection in patients with locally advanced colon cancer.

BACKGROUND: Surgical resection of locally advanced colon cancer (LACC) is challenging due to tumor size and the frequent need for multivisceral resection. The role of laparoscopic resection in LACC is controversial. This study aims to compare outcomes for laparoscopic versus open surgery in LACC. METHODS: A population-based retrospective review was conducted of patients treated at a Provincial Cancer Center for LACC from 2005 to 2015. Patients with non-metastatic T4 colon cancers were included. Descriptive, survival, and recurrence analyses were used. RESULTS: In all, 1,328 patients were reviewed, 23% of whom had laparoscopic surgery. A greater number of T4b tumors were removed via an open approach (35.9% vs 12.7%, P < .001). Positive resection margins occurred in 7.5% of laparoscopic and 16.5% of open cases (P < .001), and multivisceral resection was required in 11.0% and 27.7% (P < .001), respectively. Median follow-up was 37 months (interquartile range [IQR] 17-64) during which 48.6% patients died and 42.1% developed recurrence: locoregional (15.0%), distant (35.3%), peritoneal (11.4%). Age, right-sided tumors, nodal status, and laparoscopic approach were independent predictors of peritoneal recurrence. Overall survival (OS) (73 vs 61 months, P = .188) and recurrence-free survival (RFS) (39 vs 31 months, P = .288) were similar with both approaches. Age, nodal, and margin status were predictive of OS and RFS. CONCLUSION: Open surgical approach is used more frequently when tumors invade adjacent organs or require multivisceral resections. When employed, laparoscopic approach had similar rates of survival and recurrence compared with open approach, but was an independent predictor of peritoneal recurrence. Careful patient selection in operative approach is suggested.

Surgery after neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer.

Surgery is the standard of care for patients with operable non-small cell lung cancer (NSCLC). However, as a single modality, surgery for early stage or locally advanced NSCLC remains associated with high rates of local and distant recurrence. The addition of neoadjuvant or adjuvant chemotherapy has modestly improved outcomes. While systemic therapy paired with surgery for other malignancies such as breast cancer have resulted in far better outcomes for equivalent stage designations, outcome improvements for operable NSCLC have lagged in part as a result of trials where adjuvant chemotherapy seemed to incur harm for stage IA patients and only modest survival benefit for stage IB-IIIA patients (AJCC 7th ed.). In recent years, immunotherapy for NSCLC has emerged as a systemic therapy with significant benefit over traditional chemotherapy regimens. These advances with immune checkpoint inhibitors (ICIs) have opened the door to administering peri-operative immunotherapy for operable NSCLC. As a result, a great multitude of studies investigating the use of immunotherapy in combination with surgery for NSCLC as well as several other malignancies have emerged. In this review, we outline the rationale for neoadjuvant immunotherapy in the treatment of operable NSCLC and summarize the available evidence that include preoperative ICI as a single modality or in combination with systemic agents and/or radiotherapy. Further, we summarize how such treatment trajectories open multiple unique windows of opportunity for scientific discovery and potential therapeutic gains for these vulnerable patients.

Optimizing Resident Wellness During a Pandemic: University of British Columbia's General Surgery Program's COVID-19 Experience.

OBJECTIVE: The University of British Columbia's General Surgery Program delineates a unique and systematic approach to wellness for surgical residents during a pandemic. SUMMARY BACKGROUND DATA: During the COVID-19 pandemic, health care workers are suffering from increased rates of mental health disturbances. Residents' duty obligations put them at increased physical and mental health risk. It is only by prioritizing their well-being that we can better serve the patients and prepare for a surge. Therefore, it is imperative that measures are put in place to protect them. METHODS: Resident wellness was optimized by targeting 3 domains: efficiency of practice, culture of wellness and personal resilience. RESULTS: Efficiency in delivering information and patient care minimizes additional stress to residents that is caused by the pandemic. By having a reserve team, prioritizing the safety of residents and taking burnout seriously, the culture of wellness and sense of community in our program are emphasized. All of the residents' personal resilience was further optimized by the regular and mandatory measures put in place by the program. CONCLUSIONS: The new challenges brought on by a pandemic puts increased pressure on residents. Measures must be put in place to protect resident from the increased physical and mental health stress in order to best serve patients during this difficult time.

Single-Cell Study of Two Rat Models of Pulmonary Arterial Hypertension Reveals Connections to Human Pathobiology and Drug Repositioning.

Rationale: The cellular and molecular landscape and translational value of commonly used models of pulmonary arterial hypertension (PAH) are poorly understood. Single-cell transcriptomics can enhance molecular understanding of preclinical models and facilitate their rational use and interpretation.Objectives: To determine and prioritize dysregulated genes, pathways, and cell types in lungs of PAH rat models to assess relevance to human PAH and identify drug repositioning candidates.Methods: Single-cell RNA sequencing was performed on the lungs of monocrotaline (MCT), Sugen-hypoxia (SuHx), and control rats to identify altered genes and cell types, followed by validation using flow-sorted cells, RNA in situ hybridization, and immunofluorescence. Relevance to human PAH was assessed by histology of lungs from patients and via integration with human PAH genetic loci and known disease genes. Candidate drugs were predicted using Connectivity Map.Measurements and Main Results: Distinct changes in genes and pathways in numerous cell types were identified in SuHx and MCT lungs. Widespread upregulation of NF-κB signaling and downregulation of IFN signaling was observed across cell types. SuHx nonclassical monocytes and MCT conventional dendritic cells showed particularly strong NF-κB pathway activation. Genes altered in SuHx nonclassical monocytes were significantly enriched for PAH-associated genes and genetic variants, and candidate drugs predicted to reverse the changes were identified. An open-access online platform was developed to share single-cell data and drug candidates (http://mergeomics.research.idre.ucla.edu/PVDSingleCell/).Conclusions: Our study revealed the distinct and shared dysregulation of genes and pathways in two commonly used PAH models for the first time at single-cell resolution and demonstrated their relevance to human PAH and utility for drug repositioning.

Targeting potential drivers of COVID-19: Neutrophil extracellular traps.

Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10-15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils-the ability to form neutrophil extracellular traps (NETs)-may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.

The future of general surgery training: A Canadian resident nationwide Delphi consensus statement.

BACKGROUND: Several models have been introduced to improve and restructure surgical training, but continued barriers exist. Residents are uniquely positioned to offer perspective on practical challenges and needs of reformatting surgical education. This study aimed to establish a nationwide, Delphi consensus statement on the perceptions of Canadian residents regarding the future of general surgery training. METHODS: Canadian general surgery residents participated in a moderated focus group using the Nominal Group Technique to discuss early subspecialization, competency-based medical education, and transition to practice. Qualitative verbal data were transcribed, categorized into themes, and synthesized into recommendation statements. During an iterative Delphi survey, resident leaders ranked each statement on a 5-point Likert scale of agreement. The survey was terminated once consensus was achieved (≥2 survey rounds and Cronbach's α ≥ 0.80). RESULTS: A total of 66 statements were synthesized by 16 members of the Canadian Association of General Surgeons Resident Committee. A total of 49 residents participated in the Delphi consensus, which was achieved after 2 voting rounds (Cronbach's α = 0.93). Participants agreed that (1) residency should focus on achieving standardized competencies and milestones based on resident ability to meet specific measurable metrics, (2) early streaming should be offered after "core" milestones and competencies have been achieved, and (3) an explicit period should allow transition-to-independent practice with tailored rotations, greater autonomy, and resident-run clinics. We identified 10 barriers to competency-based medical education implementation. CONCLUSION: A nationwide consensus regarding the future of surgical training was established among current residents. These findings can inform and help implement guidelines and national curricula that meet the needs of the trainee and address the many challenges they face during their training.

Association of Depression With Mortality in Older Adults Undergoing Transcatheter or Surgical Aortic Valve Replacement.

Importance: Depression is increasingly recognized as a risk factor for adverse outcomes in cardiovascular disease. However, little is known about depression in older adults undergoing transcatheter (TAVR) or surgical (SAVR) aortic valve replacement. Objective: To determine the prevalence of depression and its association with all-cause mortality in older adults undergoing TAVR or SAVR. Design, Setting, and Participants: This preplanned analysis of the Frailty Aortic Valve Replacement (FRAILTY-AVR) prospective cohort study included 14 centers in 3 countries from November 15, 2011, through April 7, 2016. Individuals 70 years or older who underwent TAVR or SAVR were enrolled. Depressive symptoms were evaluated using the Geriatric Depression Scale Short Form at baseline and follow-up. Main Outcomes and Measures: All-cause mortality at 1 and 12 months after TAVR or SAVR. Logistic regression was used to determine the association of depression with mortality after adjusting for confounders such as frailty and cognitive impairment. Results: Among 1035 older adults (427 men [41.3%] and 608 women [58.7%]) with a mean (SD) age of 81.4 (6.1) years, 326 (31.5%) had a positive result of screening for depression, whereas only 89 (8.6%) had depression documented in their clinical record. After adjusting for clinical and geriatric confounders, baseline depression was found to be associated with mortality at 1 month (odds ratio [OR], 2.20; 95% CI, 1.18-4.10) and at 12 months (OR, 1.532; 95% CI, 1.03-2.24). Persistent depression, defined as baseline depression that was still present 6 months after the procedure, was associated with a 3-fold increase in mortality at 12 months (OR, 2.98; 95% CI, 1.08-8.20). Conclusions and Relevance: One in 3 older adults undergoing TAVR or SAVR had depressive symptoms at baseline and a higher risk of short-term and midterm mortality. Patients with persistent depressive symptoms at follow-up had the highest risk of mortality.