Comparing observed and preferred instruction in robotic surgery.

BACKGROUND: The unique setup of robotic surgery challenges the traditional instructional dynamic between surgical learners and teachers. Previous studies have posited difficulties such as reliance on observational learning and ease of takeover. However, we lack understanding of how these instructional challenges manifest and are perceived by learners. Improving instruction has the potential to optimize education and performance in robotic surgery. METHODS: In this qualitative study, we conducted robotic case observations and learner interviews focusing on instruction in robotic surgery. We deductively generated codes in a theory-informed manner after review of the instructional literature in surgery, medicine, and other fields. We applied these codes in a rigorous directed content analysis of field notes and transcripts to identify themes. RESULTS: Thirty-eight faculty, fellows, and residents participated in 10 robotic cases and 20 semistructured interviews. Observed practices on the basis of case observations differed substantially from preferred practices on the basis of interview data. Using 37 codes, we identified 4 main themes related to instruction in robotic surgery: contextualization, individualization, autonomy, and multimodality. We contrasted observed and preferred instruction in each of these areas to generate instructional considerations that may better align preferences and practices. CONCLUSIONS: We observed several suboptimal instructional practices that contradicted preferred ways of learning. We suggested robotic-specific instructional considerations such as using multimodality to promote active learning and to reduce ambiguity. We also provided considerations applicable to all types of surgery, such as to include rationale to promote learning consolidation and to frame operative steps to allow trainees to plan their participation.

Anti-cancer bioactivity of sweet basil leaf derived extracellular vesicles on pancreatic cancer cells.

Most living organisms secrete tiny lipid bilayer particles encapsulating various biomolecular entities, including nucleic acids and proteins. These secreted extracellular vesicles (EVs) are shown to aid in communication between cells and their environment. EVs are mainly involved in the signalling and manipulation of physiological processes. Plant EVs display similar functional activity as seen in mammalian EVs. Medicinal plants have many bioactive constituents with potential applications in cancer treatment. Particularly, Basil (Ocimum basilicum), has wide therapeutic properties including anti-inflammatory, anti-cancer, and anti-infection, among others. In this study, we focused on using EVs purified from Apoplast Washing Fluid (AWF) of Basil plant leaves as a biological therapeutic agent against cancer. Characterization of Basil EVs revealed a size range of 100-250 nm, which were later assessed for their cell uptake and apoptosis inducing abilities in pancreatic cancer cells. Basil plant EVs (BasEVs) showed a significant cytotoxic effect on pancreatic cancer cell line MIA PaCa-2 at a concentration of 80 and 160 µg/mL in cell viability, as well as clonogenic assays. Similarly, RT-PCR and western blot analysis has shown up regulation in apoptotic gene and protein expression of Bax, respectively, in BasEV treatment groups compared to untreated controls of MIA PaCa-2. Overall, our results suggest that EVs from basil plants have potent anti-cancer effects in pancreatic cancer cells and can serve as a drug delivery system, demanding an investigation into the therapeutic potential of other medicinal plant EVs.

The link between insurance and blood pressure control in U.S. stroke survivors.

BACKGROUND: After a stroke, poorly controlled blood pressure (BP) is associated with a higher risk of recurrent vascular events. Despite the importance of controlling BP to avert recurrent vascular events, fewer than half of stroke survivors in the United States achieve BP control. It is unclear to what extent insurance status affects BP levels after stroke. METHODS: We assessed BP control among adults with a history of stroke who participated in the National Health and Nutrition Examination Surveys from 1999 through 2016. The relationship between insurance type and BP level (low normal: <120/80 mmHg and normal: <140/90 mmHg) were evaluated using logistic regression before and after adjusting for sociodemographic characteristics and medical comorbidities for those <65 years and ≥ 65 years. RESULTS: Among 1646 adult stroke survivors (weighted n = 5,586,417), 30% had BP in the low normal range while 64% had BP in the normal range. Among 613 stroke survivors <65 years (weighted n = 2,396,980), only those with other government insurance (CHAMPVA, CHAMPUS/TRICARE) had better BP control than the uninsured (adjusted HR 2.68, 95% CI 0.99-7.25). Among 1033 participants ≥65 years (weighted n = 3,189,437), those with private insurance plus Medicare trended toward better normal BP compared to Medicare alone (adjusted HR 1.34, 95% CI 0.94-1.90). CONCLUSIONS: Only stroke survivors with CHAMPVA, CHAMPUS/TRICARE government insurance in the United States have lower odds of controlled BP compared to no insurance among those <65 years. Insurance alone does not improve BP control among stroke survivors.

Reconstruction of Segmental Bone Defect in Canine Tibia Model Utilizing Bi-Phasic Scaffold: Pilot Study.

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 µm as primary pores, 40-70 µm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.

Randomized controlled trials in lung cancer surgery: How are we doing?

Objective: Randomized control trials are considered the highest level of evidence, yet the scalability and practicality of implementing randomized control trials in the thoracic surgical oncology space are not well described. The aim of this study is to understand what types of randomized control trials have been conducted in thoracic surgical oncology and ascertain their success rate in completing them as originally planned. Methods: The ClinicalTrials.gov database was queried in April 2023 to identify registered randomized control trials performed in patients with lung cancer who underwent surgery (by any technique) as part of their treatment. Results: There were 68 eligible randomized control trials; 33 (48.5%) were intended to examine different perioperative patient management strategies (eg, analgesia, ventilation, drainage) or to examine different intraoperative technical aspects (eg, stapling, number of ports, port placement, ligation). The number of randomized control trials was relatively stable over time until a large increase in randomized control trials starting in 2016. Forty-four of the randomized control trials (64.7%) were open-label studies, 43 (63.2%) were conducted in a single facility, 66 (97.1%) had 2 arms, and the mean number of patients enrolled per randomized control trial was 236 (SD, 187). Of 21 completed randomized control trials (31%), the average time to complete accrual was 1605 days (4.4 years) and average time to complete primary/secondary outcomes and adverse events collection was 2125 days (5.82 years). Conclusions: Given the immense investment of resources that randomized control trials require, these findings suggest the need to scrutinize future randomized control trial proposals to assess the likelihood of successful completion. Future study is needed to understand the various contributing factors to randomized control trial success or failure.

Differences Between Attending and Trainee Surgeon Performance Using Objective Performance Indicators During Robot-Assisted Lobectomy.

OBJECTIVE: Existing approaches for assessing surgical performance are subjective and prone to bias. In contrast, utilizing digital kinematic and system data from the surgical robot allows the calculation of objective performance indicators (OPIs) that may differentiate technical skill and competency. This study compared OPIs of trainees and attending surgeons to assess differences during robotic lobectomy (RL). METHODS: There were 50 cardiothoracic surgery residents and 7 attending surgeons who performed RL on a left upper lobectomy of an ex vivo perfused model. A novel recorder simultaneously captured video and data from the system and instruments. The lobectomy was annotated into discrete tasks, and OPIs were analyzed for both hands during 6 tasks: exposure of the superior pulmonary vein, upper division of the pulmonary artery and bronchus, and the stapling of these structures. RESULTS: There were significant differences between attendings and trainees in all tasks. Among 20 OPIs during exposure tasks, significant differences were observed for the left hand in 31 of 60 (52%) of OPIs and for the right hand in 42 of 60 (70%). During stapling tasks, significant differences were observed for the stapling hand in 28 of 60 (47%) of OPIs and for the nonstapling hand in 14 of 60 (25%). CONCLUSIONS: Use of a novel data and video recorder to generate OPIs for both hands revealed significant differences in the operative gestures performed by trainees compared to attendings during RL. This method of assessing performance has potential for establishing objective competency benchmarks and use for tracking progress.

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.

Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery.

Over the past 5 years, our laboratory has systematically developed a structure-guided library approach to evolve new adeno-associated virus (AAV) capsids with altered tissue tropism, higher transduction efficiency and the ability to evade pre-existing humoral immunity. Here, we provide a detailed protocol describing two distinct evolution strategies using structurally divergent AAV serotypes as templates, exemplified by improving CNS gene transfer efficiency in vivo. We outline four major components of our strategy: (i) structure-guided design of AAV capsid libraries, (ii) AAV library production, (iii) library cycling in single versus multiple animal models, followed by (iv) evaluation of lead AAV vector candidates in vivo. The protocol spans ~95 d, excluding gene expression analysis in vivo, and can vary depending on user experience, resources and experimental design. A distinguishing attribute of the current protocol is the focus on providing biomedical researchers with 3D structural information to guide evolution of precise 'hotspots' on AAV capsids. Furthermore, the protocol outlines two distinct methods for AAV library evolution consisting of adenovirus-enabled infectious cycling in a single species and noninfectious cycling in a cross-species manner. Notably, our workflow can be seamlessly merged with other RNA transcript-based library strategies and tailored for tissue-specific capsid selection. Overall, the procedures outlined herein can be adapted to expand the AAV vector toolkit for genetic manipulation of animal models and development of human gene therapies.

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.

CUSUM learning curves: what they can and can't tell us.

INTRODUCTION: There has been increased interest in assessing the surgeon learning curve for new skill acquisition. While there is no consensus around the best methodology, one of the most frequently used learning curve assessments in the surgical literature is the cumulative sum curve (CUSUM) of operative time. To demonstrate the limitations of this methodology, we assessed the CUSUM of console time across cohorts of surgeons with differing case acquisition rates while varying the total number of cases used to calculate the CUSUM. METHODS: We compared the CUSUM curves of the average console times of surgeons who completed their first 20 robotic-assisted (RAS) cases in 13, 26, 39, and 52 weeks, respectively, for their first 50 and 100 cases, respectively. This analysis was performed for prostatectomy (1094 surgeons), malignant hysterectomy (737 surgeons), and inguinal hernia (1486 surgeons). RESULTS: In all procedures, the CUSUM curve of the cohort of surgeons who completed their first 20 procedures in 13 weeks demonstrated a lower slope than cohorts of surgeons with slower case acquisition rates. The case number at which the peak of the CUSUM curve occurs uniformly increases when the total number of cases used in generation of the CUSUM chart changes from 50 to 100 cases. CONCLUSION: The CUSUM analyses of these three procedures suggests that surgeons with fast initial case acquisition rates have less variability in their operative times over the course of their learning curve. The peak of the CUSUM curve, which is often used in surgical learning curve literature to denote "proficiency" is predictably influenced by the total number of procedures evaluated, suggesting that defining the peak as the point at which a surgeon has overcome the learning curve is subject to routine bias. The CUSUM peak, by itself, is an insufficient measure of "conquering the learning curve."

Experience matters for robotic assistance: an analysis of case data.

Many robotic procedures require active participation by assistants. Most prior work on assistants' effect on outcomes has been limited in procedural focus and scope, with studies reporting differing results. Knowing how assistant experience affects operating room time could inform operating room case scheduling and provide an impetus for additional assistant training. As such, this retrospective cohort study aimed to determine the association between assistant experience and operating room time for 2291 robotic-assisted operations performed from 2016 to 2022 at our institution. Linear regression showed a significant association between the presence of a junior resident and increased case length differential with an increase of 26.9 min (p = 0.01). There were no significant associations between the presence of a senior resident (p = 0.52), presence of a fellow (p = 0.20), or presence of a physician assistant (p = 0.43) and case length differential. The finding of increased operating room time in the presence of a junior resident during robotic cases supports consideration of the adoption of formal assistant training programs for residents to improve efficiency.

Initial Real-World Experience with Faricimab in Treatment-Resistant Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the initial efficacy and safety of intravitreal faricimab in eyes previously treated for neovascular age-related macular degeneration (nARMD). Patients and methods: A retrospective review of all patients with nARMD previously treated with anti-vascular endothelial growth factor (anti-VEGF) injections who received at least 3 intravitreal faricimab injections with at least 3 months of follow-up. Results: A total of 190 eyes were included. Patients received a mean of 34.2±23 anti-VEGF injections over 182.41±128 weeks prior to switching to faricimab. Patients then received a mean of 6.99±2.3 faricimab injections with an average 34.88±8.2 weeks of follow-up. The mean best corrected visual acuities improved from 0.33±0.32 logMAR ≈20/43 to 0.27±0.32 logMAR ≈20/37 (P=0.0022). The central subfield thickness (CST) improved from 312±87µm to 287±71µm (P<0.0001). At the last clinical visit, 24% had no subretinal fluid or intraretinal fluid on optical coherence tomography. The mean dosing interval between the last two consecutive faricimab injections (7.64±6.2 weeks) was significantly longer than that for ranibizumab (5.16±2.0 weeks, P<0.001) or aflibercept (5.57±3.6 weeks, P<0.001). No patients developed idiopathic intraocular inflammation. Conclusion: Intravitreal faricimab was associated with improved vision and CSTs, even in treatment-resistant nARMD eyes. The mean last dosing interval for faricimab was longer than for ranibizumab or aflibercept. No significant adverse events were directly attributed to faricimab during the study.

Race, Ethnic, Sex, and Socioeconomic Inequities in Interhospital Transfer for Acute Ischemic Stroke in the United States.

BACKGROUND: Patients with stroke in the United States can be transferred for higher level of care. Little is known about possible inequities in interhospital transfers (IHTs) for acute ischemic stroke. We hypothesized that historically marginalized populations would have lower odds of IHT. METHODS: A cross-sectional analysis was done for adults with a primary diagnosis of acute ischemic stroke in 2010 to 2017; n=747 982 were identified in the National Inpatient Sample. Yearly rates for IHT were assessed and adjusted odds ratios (aORs) of IHT in 2014 to 2017 were compared with that of 2010 to 2013. Multinomial logistic regression was used to determine the aOR of IHT, adjusting for sociodemographic variables (model 1), sociodemographic and medical variables such as comorbidity and mortality risk (model 2), and sociodemographic, medical, and hospital variables (model 3). RESULTS: After adjusting for sociodemographic, medical, and hospital characteristics, there were no significant temporal differences in IHT from 2010 to 2017. Overall, women were less likely than men to be transferred in all models (model 3: aOR, 0.89 [0.86-0.92]). Compared with those who were White, individuals who were Black (aOR, 0.93 [0.88-0.99]), Hispanic (aOR, 0.90 [0.83-0.97]), other (aOR, 0.90 [0.82-0.99]), or of unknown race, ethnicity (aOR, 0.89 [0.80-1.00]) were less likely to be transferred (model 2), but these differences dissipated when further adjusting for hospital-level characteristics (model 3). Compared with those with private insurance, those with Medicaid (aOR, 0.86 [0.80-0.91]), self-pay (aOR, 0.64 [0.59-0.70]), and no charge (aOR, 0.64 [0.46-0.88]) were less likely to be transferred (model 3). Individuals with lower income were less likely to be transferred compared with those with higher income (model 3: aOR, 0.85 [0.80-0.90], third versus fourth quartile). CONCLUSIONS: Adjusted odds of IHT for acute ischemic stroke remained stable from 2010 to 2017. There are numerous inequities in the rates of IHT by race, ethnicity, sex, insurance, and income. Further studies are needed to understand these inequities and develop policies and interventions to mitigate them.

A virus-induced circular RNA maintains latent infection of Kaposi's sarcoma herpesvirus.

Non-coding RNAs (ncRNAs) play important roles in host-pathogen interactions; oncogenic viruses like Kaposi's sarcoma herpesvirus (KSHV) employ ncRNAs to establish a latent reservoir and persist for the life of the host. We previously reported that KSHV infection alters a novel class of RNA, circular RNAs (circRNAs). CircRNAs are alternative splicing isoforms and regulate gene expression, but their importance in infection is largely unknown. Here, we showed that a human circRNA, hsa_circ_0001400, is induced by various pathogenic viruses, namely KSHV, Epstein-Barr virus, and human cytomegalovirus. The induction of circRNAs including circ_0001400 by KSHV is co-transcriptionally regulated, likely at splicing. Consistently, screening for circ_0001400-interacting proteins identified a splicing factor, PNISR. Functional studies using infected primary endothelial cells revealed that circ_0001400 inhibits KSHV lytic transcription and virus production. Simultaneously, the circRNA promoted cell cycle, inhibited apoptosis, and induced immune genes. RNA-pull down assays identified transcripts interacting with circ_0001400, including TTI1, which is a component of the pro-growth mTOR complexes. We thus identified a circRNA that is pro-growth and anti-lytic replication. These results support a model in which KSHV induces circ_0001400 expression to maintain latency. Since circ_0001400 is induced by multiple viruses, this novel viral strategy may be widely employed by other viruses.

Association Between Hyperacute Blood Pressure Variability and Hematoma Expansion After Intracerebral Hemorrhage: Secondary Analysis of the FAST-MAG Database.

BACKGROUND: Blood pressure variability (BPV) has emerged as a significant factor associated with clinical outcomes after intracerebral hemorrhage (ICH). Although hematoma expansion (HE) is associated with clinical outcomes, the relationship between BPV that encompasses prehospital data and HE is unknown. We hypothesized that BPV was positively associated with HE. METHODS: We analyzed 268 patients with primary ICH enrolled in the National Institutes of Health-funded Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study who received head computed tomography or magnetic resonance imaging on arrival to the emergency department (ED) and repeat imaging within 6-48 h. BPV was calculated by standard deviation (SD) and coefficient of variation (CV) from prehospital data as well as systolic blood pressure (SBP) measurements taken on ED arrival, 15 min post antihypertensive infusion start, 1 h post maintenance infusion start, and 4 h after ED arrival. HE was defined by hematoma volume expansion increase > 6 mL or by 33%. Univariate logistic regression was used for presence of HE in quintiles of SD and CV of SBP for demographics and clinical characteristics. RESULTS: Of the 268 patients analyzed from the FAST-MAG study, 116 (43%) had HE. Proportions of patients with HE were not statistically significant in the higher quintiles of the SD and CV of SBP for either the hyperacute or the acute period. Presence of HE was significantly more common in patients on anticoagulation. CONCLUSIONS: Higher BPV was not found to be associated with occurrence of HE in the hyperacute or the acute period of spontaneous ICH. Further study is needed to determine the relationship.

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.