Comparing Robotic, Thoracoscopic, and Open Segmentectomy: A National Cancer Database Analysis.

INTRODUCTION: Minimally invasive approaches to lung resection have become widely acceptable and more recently, segmentectomy has demonstrated equivalent oncologic outcomes when compared to lobectomy for early-stage non-small cell lung cancer (NSCLC). However, studies comparing outcomes following segmentectomy by different surgical approaches are lacking. Our objective was to investigate the outcomes of patients undergoing robotic, video-assisted thoracoscopic surgery (VATS), or open segmentectomy for NSCLC using the National Cancer Database. METHODS: NSCLC patients with clinical stage I who underwent segmentectomy from 2010 to 2016 were identified. After propensity-score matching (1:4:1), multivariate logistic regression analyses were performed to determine predictors of 30-d readmissions, 90-d mortality, and overall survival. RESULTS: 22,792 patients met study inclusion. After matching, approaches included robotic (n = 2493; 17%), VATS (n = 9972; 66%), and open (n = 2493; 17%). An open approach was associated with higher 30-d readmissions (7% open versus 5.5% VATS versus 5.6% robot, P = 0.033) and 90-d mortality (4.4% open versus 2.2% VATS versus 2.5% robot, P < 0.001). A robotic approach was associated with improved 5-y survival (50% open versus 58% VATS versus 63% robot, P < 0.001). CONCLUSIONS: For patients with clinical stage I NSCLC undergoing segmentectomy, compared to the open approach, a VATS approach was associated with lower 30-d readmission and 90-d mortality. A robotic approach was associated with improved 5-y survival compared to open and VATS approaches when matched. Additional studies are necessary to determine if unrecognized covariates contribute to these differences.

Comparison of Global Evaluative Assessment of Robotic Surgery with objective performance indicators for the assessment of skill during robotic-assisted thoracic surgery.

BACKGROUND: The Global Evaluative Assessment of Robotic Skills is a popular but ultimately subjective assessment tool in robotic-assisted surgery. An alternative approach is to record system or console events or calculate instrument kinematics to derive objective performance indicators. The aim of this study was to compare these 2 approaches and correlate the Global Evaluative Assessment of Robotic Skills with different types of objective performance indicators during robotic-assisted lobectomy. METHODS: Video, system event, and kinematic data were recorded from the robotic surgical system during left upper lobectomy on a standardized perfused and pulsatile ex vivo porcine heart-lung model. Videos were segmented into steps, and the superior vein dissection was graded independently by 2 blinded expert surgeons with Global Evaluative Assessment of Robotic Skills. Objective performance indicators representing categories for energy use, event data, movement, smoothness, time, and wrist articulation were calculated for the same task and compared to Global Evaluative Assessment of Robotic Skills scores. RESULTS: Video and data from 51 cases were analyzed (44 fellows, 7 attendings). Global Evaluative Assessment of Robotic Skills scores were significantly higher for attendings (P < .05), but there was a significant difference in raters' scores of 31.4% (defined as >20% difference in total score). The interclass correlation was 0.44 for 1 rater and 0.61 for 2 raters. Objective performance indicators correlated with Global Evaluative Assessment of Robotic Skills to varying degrees. The most highly correlated Global Evaluative Assessment of Robotic Skills domain was efficiency. Instrument movement and smoothness were highly correlated among objective performance indicator categories. Of individual objective performance indicators, right-hand median jerk, an objective performance indicator of change of acceleration, had the highest correlation coefficient (0.55). CONCLUSION: There was a relatively poor overall correlation between the Global Evaluative Assessment of Robotic Skills and objective performance indicators. However, both appear strongly correlated for certain metrics such as efficiency and smoothness. Objective performance indicators may be a potentially more quantitative and granular approach to assessing skill, given that they can be calculated mathematically and automatically without subjective interpretation.

A novel approach to quantifying surgical workflow in robotic-assisted lobectomy.

INTRODUCTION: Understanding surgical workflow is critical for optimizing efficiencies and outcomes; however, most research evaluating workflow is impacted by observer subjectivity, limiting its reproducibility, scalability, and actionability. To address this, we developed a novel approach to quantitatively describe workflow within robotic-assisted lobectomy (RL). We demonstrate the utility of this approach by analysing features of surgical workflow that correlate with procedure duration. METHODS: RL was deconstructed into 12 tasks by expert thoracic surgeons. Task start and stop times were annotated across videos of 10 upper RLs (5 right and 5 left). Markov Networks were used to estimate both the likelihood of transitioning from one task to another and each task-transition entropy (i.e. complexity). Associations between the frequency with which each task was revisited intraoperatively and procedure duration were assessed using Pearson's correlation coefficient. RESULTS: Entropy calculations identified fissure dissection and hilar node dissection as tasks with especially complex transitions, while mediastinal lymph node dissection and division of pulmonary veins were less complex. The number of transitions to three tasks significantly correlated with case duration (fissure dissection (R = 0.69, p = 0.01), dissect arteries (R = 0.59, p = 0.03), and divide arteries (R = 0.63, p = 0.03)). CONCLUSION: This pilot demonstrates the feasibility of objectively quantifying workflow between RL tasks and introduces entropy as a new metric of task-transition complexity. These innovative measures of surgical workflow enable detailed characterization of a given surgery and might indicate behaviour that impacts case progression. We discuss how these measures can serve as a foundation and be combined with relevant clinical information to better understand factors influencing surgical inefficiency.

Task-Based Objective Performance Indicators in Robotic Lobectomy Offer a Novel Avenue for Case Assessments.

This article discusses a task-based assessment of thoracic performance during robotic lobectomies that obviates the inherent limitations or bias that persist in existing approaches.

Objective performance indicators of cardiothoracic residents are associated with vascular injury during robotic-assisted lobectomy on porcine models.

Surgical training relies on subjective feedback on resident technical performance by attending surgeons. A novel data recorder connected to a robotic-assisted surgical platform captures synchronized kinematic and video data during an operation to calculate quantitative, objective performance indicators (OPIs). The aim of this study was to determine if OPIs during initial task of a resident's robotic-assisted lobectomy (RL) correlated with bleeding during the procedure. Forty-six residents from the 2019 Thoracic Surgery Directors Association Resident Boot Camp completed RL on an ex vivo perfused porcine model while continuous video and kinematic data were recorded. For this pilot study, RL was segmented into 12 tasks and OPIs were calculated for the initial major task. Cases were reviewed for major bleeding events and OPIs of bleeding cases were compared to those who did not. Data from 42 residents were complete and included in the analysis. 10/42 residents (23.8%) encountered bleeding: 10/40 residents who started with superior pulmonary vein exposure and 0/2 residents who started with pulmonary artery exposure. Twenty OPIs for both hands were assessed during the initial task. Six OPIs related to instrument usage or smoothness of motion were significant for bleeding. Differences were statistically significant for both hands (p < 0.05). OPIs showing bimanual asymmetry indicated lower proficiency. This study demonstrates that kinematic and video analytics can establish a correlation between objective performance metrics and bleeding events in an ex vivo perfused lobectomy. Further study could assist in the development of focused exercises and simulation on objective domains to help improve overall performance and reducing complications during RL.

A Review of Robotic Thoracic Surgery Adoption and Future Innovations.

The embracing of new technology and surgical innovation has been one of the hallmarks of cardiothoracic surgery. The adoption of video-assisted thoracoscopic surgery was the paradigm-changing perspective shift that has enabled an entire culture of minimally invasive cardiothoracic surgery. From this foundation robotically assisted thoracic surgery has developed into mainstream practice. The aim of this review is to recount the technological and academic milestones of the past as well as describe future technological innovations that will shape the future of thoracic robotic surgery.

The Scan, the Needle, or the Knife? National Trends in Diagnosing Stage I Lung Cancer.

OBJECTIVE: Indeterminate lung nodules have been increasingly discovered since the expansion of lung cancer screening programs. The diagnostic approach for suspicious nodules varies based on institutional resources and preferences. The aim of this study is to analyze factors associated with diagnostic modalities used for early-stage non-small cell lung cancer (NSCLC). METHODS: The National Cancer Database was queried for all patients with stage I NSCLC from 2004 to 2015. Four diagnostic modalities were identified, including clinical radiography alone (CRA), bronchial cytology (BC), procedural biopsy (PB), and surgical biopsy (SB). A multivariable multinomial logistic regression was used to assess associations of patient demographics, cancer characteristics, and facility characteristics with these modalities. RESULTS: Of 250,614 patients, 4,233 (1.7%) had CRA, 5,226 (2.1%) had BC, 147,621 (59.9%) had PB, and 93,534 (37.3%) had SB. Older patients were more likely to receive CRA (adjusted odds ratio [ORadj] = 5.3) and less likely to receive SB (ORadj = 0.73). Black patients were less likely to receive SB (ORadj = 0.83) and more likely to receive BC (ORadj = 1.31). Private insurance was associated with SB (ORadj = 1.11), whereas Medicaid was associated with BC (ORadj = 1.21). Patients more than 50 miles from the facility were more likely to undergo SB (ORadj = 1.25 vs PB; ORadj = 1.30 vs CRA; ORadj = 1.38 vs BC). Patients receiving SB had shorter days from diagnosis to treatment (23.0 vs 53.5 to 64.7 for other modalities, P < 0.001). CONCLUSIONS: Diagnostic SB to confirm early-stage NSCLC was associated with younger age, greater travel distance, and shorter time to treatment in comparison with other modalities. Black race and non-private insurance were less likely to be associated with SB.

Bacterial two-component systems as sensors for synthetic biology applications.

Two-component systems (TCSs) are a ubiquitous family of signal transduction pathways that enable bacteria to sense and respond to diverse physical, chemical, and biological stimuli outside and inside the cell. Synthetic biologists have begun to repurpose TCSs for applications in optogenetics, materials science, gut microbiome engineering, and soil nutrient biosensing, among others. New engineering methods including genetic refactoring, DNA-binding domain swapping, detection threshold tuning, and phosphorylation cross-talk insulation are being used to increase the reliability of TCS sensor performance and tailor TCS signaling properties to the requirements of specific applications. There is now potential to combine these methods with large-scale gene synthesis and laboratory screening to discover the inputs sensed by many uncharacterized TCSs and develop a large new family of genetically-encoded sensors that respond to an unrivaled breadth of stimuli.

Short and long-term outcomes of surgical intervention for empyema in the post-fibrinolytic era.

BACKGROUND: Open window thoracostomy (OWT) is indicated for patients with bronchopleural fistula (BPF) or trapped lung in the setting of empyema refractory to non-surgical interventions. We investigated the role of OWT in the era of minimally invasive surgeries, endobronchial valves and fibrinolytic therapy. METHODS: A retrospective chart review of all patients who underwent OWT at a single institution from 2010 to 2020 was performed. Indications for the procedure as well as operative details and morbidity and mortality were evaluated to determine patient outcomes for OWT. RESULTS: Eighteen patients were identified for the study. The most common indication for OWT was post-resectional BPF (n = 9). Prior to OWT, n = 11 patients failed other surgical or minimally invasive interventions. Patient comorbidities were quantified with the Charlson Comorbidity index (n = 11 score ≥ 5, 10-year survival ≤21%). Three (16.7%) patients died < 30 days post-operatively and 12 (66%) patients were deceased by the study's end (overall survival 24.0 ± 32.2 months). Mean number of ribs resected were 2.5 ± 1.2 (range 1-6) with one patient having 6 ribs removed. Patients were managed with negative pressure wound therapy (n = 9) or Kerlix packing (n = 9). Eleven patients (61.6%) underwent delayed closure (mean time from index surgery to closure 4.8 ± 6.7 months). CONCLUSIONS: Our study illustrates the significant comorbidities of patients undergoing OWT, the poor outcomes therein, and pitfalls associated with this procedure. We show that negative pressure wound therapy can be utilized as potential way to obliterate the pleural space and manage an open chest in the absence of an airleak; however, OWT procedures continue to be extremely morbid.

Vulnerability of cholecystokinin-expressing GABAergic interneurons in the unilateral intrahippocampal kainate mouse model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is characterized by recurrent spontaneous seizures and behavioral comorbidities. Reduced hippocampal theta oscillations and hyperexcitability that contribute to cognitive deficits and spontaneous seizures are present beyond the sclerotic hippocampus in TLE. However, the mechanisms underlying compromised network oscillations and hyperexcitability observed in circuits remote from the sclerotic hippocampus are largely unknown. Cholecystokinin (CCK)-expressing basket cells (CCKBCs) critically participate in hippocampal theta rhythmogenesis, and regulate neuronal excitability. Thus, we examined whether CCKBCs were vulnerable in nonsclerotic regions of the ventral hippocampus remote from dorsal sclerotic hippocampus using the intrahippocampal kainate (IHK) mouse model of TLE, targeting unilateral dorsal hippocampus. We found a decrease in the number of CCK+ interneurons in ipsilateral ventral CA1 regions from epileptic mice compared to those from sham controls. We also found that the number of boutons from CCK+ interneurons was reduced in the stratum pyramidale, but not in other CA1 layers, of ipsilateral hippocampus in epileptic mice, suggesting that CCKBCs are vulnerable. Electrical recordings showed that synaptic connectivity and strength from surviving CCKBCs to CA1 pyramidal cells (PCs) were similar between epileptic mice and sham controls. In agreement with reduced CCKBC number in TLE, electrical recordings revealed a significant reduction in amplitude and frequency of IPSCs in CA1 PCs evoked by carbachol (commonly used to excite CCK+ interneurons) in ventral CA1 regions from epileptic mice versus sham controls. These findings suggest that loss of CCKBCs beyond the hippocampal lesion may contribute to hyperexcitability and compromised network oscillations in TLE.

Dynamic Control of Gene Expression with Riboregulated Switchable Feedback Promoters.

One major challenge in synthetic biology is the deleterious impacts of cellular stress caused by expression of heterologous pathways, sensors, and circuits. Feedback control and dynamic regulation are broadly proposed strategies to mitigate this cellular stress by optimizing gene expression levels temporally and in response to biological cues. While a variety of approaches for feedback implementation exist, they are often complex and cannot be easily manipulated. Here, we report a strategy that uses RNA transcriptional regulators to integrate additional layers of control over the output of natural and engineered feedback responsive circuits. Called riboregulated switchable feedback promoters (rSFPs), these gene expression cassettes can be modularly activated using multiple mechanisms, from manual induction to autonomous quorum sensing, allowing control over the timing, magnitude, and autonomy of expression. We develop rSFPs in Escherichia coli to regulate multiple feedback networks and apply them to control the output of two metabolic pathways. We envision that rSFPs will become a valuable tool for flexible and dynamic control of gene expression in metabolic engineering, biological therapeutic production, and many other applications.

How We Do It: Implementing a Virtual, Multi-Institutional Collaborative Education Model for the COVID-19 Pandemic and Beyond.

OBJECTIVE: To describe the implementation of a virtual, multi-institutional educational collaboration involving over 50 general surgery residency programs during the COVID-19 pandemic that enabled enhanced learning for surgical residents despite social-distancing requirements. DESIGN: Description of Virginia Commonwealth University's virtual educational augmentation program and the development of a collaborative teaching network during the coronavirus pandemic. SETTING: This collaboration was initiated by Virginia Commonwealth University's Department of Surgery, Richmond, VA, and grew to include general surgery residency programs from across the nation. PARTICIPANTS: General surgery residents and faculty from Departments of General Surgery were recruited locally via direct emails and nationally via the Association of Program Directors' listserv and Twitter. In total, 52 institutions participated from every part of the country. RESULTS: A virtual, multi-institutional collaborative lecture series was initiated that grew to involve over 50 general surgery residency programs, allowing for daily didactics by experts in their fields during the initial surge of the COVID-19 pandemic, while maintaining social distancing and the provision of essential clinical care. CONCLUSION: A multi-institutional collaboration enabled continued didactic education during the coronavirus pandemic, vastly broadening the expertise, scope and variety available to residents, while decreasing burden on faculty. We believe this can serve as a framework for future multi-institutional collaborations that extend beyond the COVID-19 era.

Optogenetic control of gut bacterial metabolism to promote longevity.

Gut microbial metabolism is associated with host longevity. However, because it requires direct manipulation of microbial metabolism in situ, establishing a causal link between these two processes remains challenging. We demonstrate an optogenetic method to control gene expression and metabolite production from bacteria residing in the host gut. We genetically engineer an Escherichia coli strain that secretes colanic acid (CA) under the quantitative control of light. Using this optogenetically-controlled strain to induce CA production directly in the Caenorhabditis elegans gut, we reveal the local effect of CA in protecting intestinal mitochondria from stress-induced hyper-fragmentation. We also demonstrate that the lifespan-extending effect of this strain is positively correlated with the intensity of green light, indicating a dose-dependent CA benefit on the host. Thus, optogenetics can be used to achieve quantitative and temporal control of gut bacterial metabolism in order to reveal its local and systemic effects on host health and aging.

Global reference mapping of human transcription factor footprints.

Combinatorial binding of transcription factors to regulatory DNA underpins gene regulation in all organisms. Genetic variation in regulatory regions has been connected with diseases and diverse phenotypic traits1, but it remains challenging to distinguish variants that affect regulatory function2. Genomic DNase I footprinting enables the quantitative, nucleotide-resolution delineation of sites of transcription factor occupancy within native chromatin3-6. However, only a small fraction of such sites have been precisely resolved on the human genome sequence6. Here, to enable comprehensive mapping of transcription factor footprints, we produced high-density DNase I cleavage maps from 243 human cell and tissue types and states and integrated these data to delineate about 4.5 million compact genomic elements that encode transcription factor occupancy at nucleotide resolution. We map the fine-scale structure within about 1.6 million DNase I-hypersensitive sites and show that the overwhelming majority are populated by well-spaced sites of single transcription factor-DNA interaction. Cell-context-dependent cis-regulation is chiefly executed by wholesale modulation of accessibility at regulatory DNA rather than by differential transcription factor occupancy within accessible elements. We also show that the enrichment of genetic variants associated with diseases or phenotypic traits in regulatory regions1,7 is almost entirely attributable to variants within footprints, and that functional variants that affect transcription factor occupancy are nearly evenly partitioned between loss- and gain-of-function alleles. Unexpectedly, we find increased density of human genetic variation within transcription factor footprints, revealing an unappreciated driver of cis-regulatory evolution. Our results provide a framework for both global and nucleotide-precision analyses of gene regulatory mechanisms and functional genetic variation.