Augmented Reality Implementation in Minimally Invasive Surgery for Future Application in Pulmonary Surgery: A Systematic Review.

OBJECTIVE: This systematic review investigates of Augmented Reality (AR) systems used in minimally invasive surgery of deformable organs, focusing on initial registration, dynamic tracking, and visualization. The objective is to acquire a comprehensive understanding of the current knowledge, applications, and challenges associated with current AR-techniques, aiming to leverage these insights for developing a dedicated AR pulmonary Video or Robotic Assisted Thoracic Surgery (VATS/RATS) workflow. METHODS: A systematic search was conducted within Embase, Medline (Ovid) and Web of Science on April 16, 2024, following the Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA). The search focused on intraoperative AR applications and intraoperative navigational purposes for deformable organs. Quality assessment was performed and studies were categorized according to initial registration and dynamic tracking methods. RESULTS: 33 articles were included, of which one involved pulmonary surgery. Studies used both manual and (semi-) automatic registration methods, established through anatomical landmark-based, fiducial-based, or surface-based techniques. Diverse outcome measures were considered, including surgical outcomes and registration accuracy. The majority of studies that reached an registration accuracy below 5 mm applied surface-based registration. CONCLUSIONS: AR can potentially aid surgeons with real-time navigation and decision making during anatomically complex minimally invasive procedures. Future research for pulmonary applications should focus on exploring surface-based registration methods, considering their non-invasive, marker-less nature, and promising accuracy. Additionally, vascular-labeling-based methods are worth exploring, given the importance and relative stability of broncho-vascular anatomy in pulmonary VATS/RATS. Assessing clinical feasibility of these approaches is crucial, particularly concerning registration accuracy and potential impact on surgical outcomes.

The current status of stem cell-based therapies during ex vivo graft perfusion: An integrated review of four organs.

The use of extended criteria donor grafts is a promising strategy to increase the number of organ transplantations and reduce waitlist mortality. However, these organs are often compromised and/or damaged, are more susceptible to preservation injury, and are at risk for developing post-transplant complications. Ex vivo organ perfusion is a novel technology to preserve donor organs while providing oxygen and nutrients at distinct perfusion temperatures. This preservation method allows to resuscitate grafts and optimize function with therapeutic interventions prior to solid organ transplantation. Stem cell-based therapies are increasingly explored for their ability to promote regeneration and reduce the inflammatory response associated with in vivo reperfusion. The aim of this review is to describe the current state of stem cell-based therapies during ex vivo organ perfusion for the kidney, liver, lung, and heart. We discuss different strategies, including type of cells, route of administration, mechanisms of action, efficacy, and safety. The progress made within lung transplantation justifies the initiation of clinical trials, whereas more research is likely required for the kidney, liver, and heart to progress into clinical application. We emphasize the need for standardization of methodology to increase comparability between future (clinical) studies.

Strongly Entangled Triplet Acyl-Alkyl Radical Pairs in Crystals of Photostable Diphenylmethyl Adamantyl Ketones.

Radical pairs generated in crystalline solids by bond cleavage reactions of triplet ketones offer the unique opportunity to explore a frontier of spin dynamics where rigid radicals are highly entangled as the result of short inter-radical distances, large singlet-triplet energy gaps (ΔEST), and limited spin-lattice relaxation mechanisms. Here we report the pulsed laser generation and detection of strongly entangled triplet acyl-alkyl radical pairs generated in nanocrystalline suspensions of 1,1-diphenylmethyl 2-ketones with various 3-admantyl substituents. The sought-after triplet acyl-alkyl radical pairs could be studied for the first time in the solid state by taking advantage of the efficient triplet excited state α-cleavage reactions of 1,1-diphenylmethyl ketones and the slow rate of CO loss from the acyl radicals, which would have to generate highly unstable phenyl and primary alkyl radicals or relatively unstable secondary and tertiary alkyl radicals. With the loss of CO prevented, the lifetime of the triplet acyl-alkyl radical pair intermediates is determined by intersystem crossing to the singlet radical pair state, which is followed by immediate bond formation to the ground state starting ketone. Experimental results revealed biexponential kinetics with long-lived components that account for ca. 87-92% of the transient population and lifetimes that extend to the range of 53-63 µs, the longest reported so far for this type of radical pair. Structural information inferred from the starting ketone will make it possible to analyze the affects of proximity and orientation of the singly occupied orbitals and potentially help set a path for the use of triplet radical pairs as qubits in quantum information technologies.

Seroprevalence and risk factors for hepatitis B and C virus infection in Damietta Governorate, Egypt.

Hepatitis B and C virus (HBV and HCV) infections remain major public health problems in Egypt and data are needed on risk factors for infection. This study determined the prevalence of anti-HCV and HBV surface antigen seropositivity in Damietta Governorate, Egypt, and evaluated potential risk factors for infection and the impact of HBV vaccination on seroprevalence. A household, cross-sectional study was conducted of 2977 individuals. About 20% were vaccinated against HBV. Only 1.1% were infected with HBV and 9.3% with HCV; both infections coexisted in 12 people (0.4%) (all unvaccinated). The main risk factors for both HCV and HBV were exposure to dental procedures, surgery, stitches, schistosomiasis treatment and contact with infected person. HBV and HCV prevalences in Damietta were lower than the national rate, likely due to the routine compulsory HBV vaccination in those aged < 19 years. There is a need to educate the general population about HBV and HCV transmission routes and avoidance of risky behaviours.

Technique for surgical replacement of the ascending aorta with concomitant aortic valve and hemiarch replacement: a procedural guide.

In this video tutorial case report, we show how to perform an open surgical correction of an ascending aortic aneurysm in a 74-year-old patient requiring concomitant aortic valve and hemiarch replacements, presenting with symptomatic stenosis of the aortic valve and moderate dilatation of the ascending aorta.

Ex vivo lung perfusion: a procedural guide.

Available donor organs for lung transplantation are scarce. Ex vivo lung perfusion provides a platform to preserve, assess, and recondition donor lungs and can thereby aid in enlarging the donor pool. This video tutorial discusses the indications, preparation, and surgical technique for and the initiation, maintenance and termination of the ex vivo lung perfusion procedure.

Comparative study of male and female patients undergoing surgical aortic valve replacement.

BACKGROUND: Sex does have an effect on disease perception and outcomes after cardiac surgery. OBJECTIVES: The aim of this study was to quantify the differences in cardiovascular risk profiles within an age-matched cohort and assess the long-term survival differences in males and females who underwent surgical aortic valve replacement (SAVR) with or without concomitant coronary artery bypass surgery. METHODS: All-comers patients who underwent SAVR with or without coronary artery bypass surgery were included. Characteristics, clinical features and survival up to 30 years were compared between female and male patients. Propensity matching and age matching using propensity scores were used to compare both groups. RESULTS: During the total study period between 1987 and 2017, there were 3462 patients {mean age 66.8 [standard deviation (SD): 11.1] years, 37.1% female} who underwent SAVR with or without coronary artery bypass surgery at our institution. In general, female patients were older than male patients (69.1 (SD : 10.3) versus 65.5 (SD : 11.3), respectively). In the age-matched cohort, female patients were less likely to have multiple comorbidities and undergo concomitant coronary artery bypass surgery. Twenty-year survival following the index procedure was higher in age-matched female patients (27.1%) compared to male patients (24.4%) in the overall cohort (P = 0.018). CONCLUSIONS: Substantial sex differences in cardiovascular risk profile exist. However, when SAVR with or without coronary artery bypass surgery is performed, extended long-term mortality is comparable between males and females. More research regarding sex-dimorphic mechanisms of aortic stenosis and coronary atherosclerosis would promote more awareness in terms of sex-specific risk factors after cardiac surgery and contribute to more guided personalized surgery in the future.

Virtual Reality Simulator versus Conventional Advanced Life Support Training for Cardiopulmonary Resuscitation Post-Cardiac Surgery: A Randomized Controlled Trial.

External chest compressions are often ineffective for patients arresting after cardiac surgery, for whom emergency resternotomy may be required. A single-blinded randomized controlled trial (RCT) was performed, with participants being randomized to a virtual reality (VR) Cardiac Surgical Unit Advanced Life Support (CSU-ALS) simulator training arm or a conventional classroom CSU-ALS training arm. Twenty-eight cardiothoracic surgery (CTS) residents were included and subsequently assessed in a moulage scenario in groups of two, either participating as a leader or surgeon. The primary binary outcomes were two time targets: (1) delivering three stacked shocks within 1 min and (2) resternotomy within 5 min. Secondary outcomes were the number of protocol mistakes made and a questionnaire after the VR simulator. The conventional training group administered stacked shocks within 1 min in 43% (n = 6) of cases, and none in the VR group reached this target, missing it by an average of 25 s. The resternotomy time target was reached in 100% of the cases (n = 14) in the conventional training group and in 83% of the cases (n = 10) in the VR group. The VR group made 11 mistakes in total versus 15 for those who underwent conventional training. Participants reported that the VR simulator was useful and easy to use. The results show that the VR simulator can provide adequate CSU-ALS training. Moreover, VR training results in fewer mistakes suggesting that repetitive practice in an immersive environment improves skills.

Essential Surgical Plan Modifications After Virtual Reality Planning in 50 Consecutive Segmentectomies.

BACKGROUND: Lately, increased interest in pulmonary segmentectomy has been observed. Segmental border identification is extremely difficult on 2-dimensional computed tomography (CT). Preoperative application of virtual reality (VR) can provide better insight into patient-specific anatomy. The aim of this study was to investigate the added clinical value of 3-dimensional (3D) VR using PulmoVR for preoperative planning. METHODS: Patients with an indication for pulmonary segmentectomy were included between June 2020 and September 2021 at the Erasmus Medical Center, Rotterdam, The Netherlands. CT scans were (semi)automatically segmented to visualize lung segments, segmental arteries, veins, and bronchi. Three surgeons made a surgical plan on the basis of the conventional CT scan and subsequently analyzed the VR visualization. The primary outcome was the incidence of critical (ensuring radical resection) preoperative plan modifications. Secondarily, data on observed anatomic variation and perioperative (oncologic) outcomes were collected. RESULTS: A total of 50 patients (median age at surgery, 65 years [interquartile range, 17.25 years]) with an indication for pulmonary segmentectomy were included. After supplemental VR visualization, the surgical plan was adjusted in 52%; the tumor was localized in a different segment in 14%, more lung-sparing resection was planned in 10%, and extended segmentectomy, including 1 lobectomy, was planned in 28%. Pathologic examination confirmed radical resection in 49 patients (98%). CONCLUSIONS: This 3D VR technology showed added clinical value in the first 50 VR-guided segmentectomies because a 52% change of plan with 98% radical resection was observed. Furthermore, 3D VR visualization of the bronchovasculature, including various anatomic variations, provided better insight into patient-specific anatomy and offered lung-sparing possibilities with more certainty.

Discovery of dual-target natural antimalarial agents against DHODH and PMT of Plasmodium falciparum: pharmacophore modelling, molecular docking, quantum mechanics, and molecular dynamics simulations.

Malaria is a lethal disease that claims thousands of lives worldwide annually. The objective of this study was to identify new natural compounds that can target two P. falciparum enzymes; P. falciparum Dihydroorotate dehydrogenase (PfDHODH) and P. falciparum phosphoethanolamine methyltransferase (PfPMT). To accomplish this, e-pharmacophore modelling and molecular docking were employed against PfDHODH. Following this, 1201 natural compounds with docking scores of ≤ -7 kcal/mol were docked into the active site of the second enzyme PMT. The top nine compounds were subjected to further investigation using MM-GBSA free binding energy calculations and ADME analysis. The results revealed favourable free binding energy values better than the references, as well as acceptable pharmacokinetic properties. Compounds ZINC000013377887, ZINC000015113777, and ZINC000085595753 were scrutinized to assess their interaction stability with the PfDHODH enzyme, and chemical stability reactivity using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. These findings indicate that the three natural compounds are potential candidates for dual PfDHODH and PfPMT inhibitors for malaria treatment.

Video-assisted thoracic surgery S7 segmentectomy: use of virtual reality surgical planning and simulated reality intraoperative modelling.

Preoperative planning and perioperative guidance are crucial in anatomical sublobar pulmonary resections. Preoperative virtual reality visualization of the computed tomography scan and intraoperative guidance through a soft-tissue dynamic lung model (simulated reality) can provide better insights into patient-specific anatomy for the surgical team. Using these imaging techniques, we present a right-sided video-assisted thoracoscopic surgery segment 7 resection.

Virtual reality simulation as a training tool for perfusionists in extracorporeal circulation: Establishing face and content validity.

Objective: We conducted a prospective study to assess the face and content validity of a new virtual reality (VR) extracorporeal circulation simulator (ECC) developed for perfusionists to facilitate training and practice. We evaluated the opinions of students and staff members about the feasibility of the simulation. The 2 groups consisted of experts (qualified perfusionists) and novices (trainee perfusionists). Methods: Perfusionists (n = 12 experts and n = 11 trainees) received instructions on how to use the VR simulator and then proceeded to perform the start of cardiopulmonary bypass in the VR environment. Participants then completed a Usefulness, Satisfaction, and Ease of Use Questionnaire. The questions were rated on a 5-point Likert scale, ranging from 1 (fully disagree) to 5 (fully agree), to assess the face validity and content validity of this simulator. Results: Participants reported a predominantly positive experience with the VR-ECC simulator, with 96% (n = 22) agreeing that the simulator was a useful way of training ECC scenarios. All participants found it easy to interact with the software (100%, n = 23), and 82% of students (n = 9) believed it helped them remember the steps involved with initiating ECC. Finally, (87% [n = 20]) of participants believed the image quality and depth perception were good. Conclusions: Our next-generation simulator was valid for face and content constructs, and almost all participants found it to be a useful way of training for ECC scenarios. This simulator represents a first step toward truly blended digital learning and a new interactive, flexible, and innovative modality for perfusion training.

Preferential solubilization behaviours and stability of some phenolic-bearing essential oils formulated in different microemulsion systems.

The solubilization behaviour of a number of essential oils (EOs) containing volatile phenolic constituents was investigated in five different micellar solutions. These oils include clove bud (Eugenia caryophyllata), thyme (Thymus serpyllum) and oregano (Thymus capitatus). Ternary and pseudo-ternary phase diagrams were constructed to assess the ability for microemulsion formation and dilutability of each system using non-ionic surfactants. Results showed that Tween 20 (T20) was more suitable to solubilize these oils compared with Tween 80 (T80). Clove EO was found to be easily microemulsifiable compared with the other EOs, whereas oregano showed the least tendency to form a microemulsion. Particle sizes measured at different dilution lines ranged between 5.9 and 16.9 nm. The chemical composition of each EO was revealed by gas chromatography and was correlated with the observed solubilization behaviour. The presence of solubilization enhancers like poly-ols and short-chain alcohols improved solubilization of all EOs; however, establishment of new dilution lines was controlled by EO type. Physical stability assessment showed that all microemulsions were stable against alternate freeze/thaw cycles which extended for 1 week. On the contrary, each system showed different temperature sensitivity in the thermal stress assessment. The results of this investigation can be useful in fabrication of thermodynamically stable aqueous system carrying aromatic and bioactive phenolics for different applications in personal hygiene, cosmetic, fragrance and pharmaceutical products.

Virtual Reality in the Preoperative Planning of Adult Aortic Surgery: A Feasibility Study.

Background: Complex aortic anatomy needs careful preoperative planning in which a patient-tailored approach with novel immersive techniques could serve as a valuable addition to current preoperative imaging. This pilot study aimed to investigate the technical feasibility of virtual reality (VR) as an additional imaging tool for preoperative planning in ascending aortic surgery. Methods: Ten cardiothoracic surgeons were presented with six patients who had each undergone a recent repair of the ascending aorta. Two-dimensional computed tomography images of each patient were assessed prior to the VR session. After three-dimensional (3D) VR rendering and 3D segmentation of the ascending aorta and aortic arch, the reconstructions were analyzed by each surgeon in VR via a head-mounted display. Each cardiothoracic surgeon completed a questionnaire after each planning procedure. The results of their assessments were compared to the performed operations. The primary endpoint of the present study was a change of surgical approach from open to clamped distal anastomosis, and vice versa. Results: Compared with conventional imaging, 80% of surgeons found that VR prepared them better for surgery. In 33% of cases (two out of six), the preoperative decision was adjusted due to the 3D VR-based evaluation of the anatomy. Surgeons rated CardioVR usefulness, user-friendliness, and satisfaction with median scores of 3.8 (IQR: 3.5-4.1), 4.2 (IQR: 3.8-4.6,) and 4.1 (IQR: 3.8-4.7) on a five-point Likert scale, respectively. Conclusions: Three-dimensional VR imaging was associated with improved anatomical understanding among surgeons and could be helpful in the future preoperative planning of ascending aortic surgery.

Outcomes of surgical aortic valve replacement over three decades.

OBJECTIVE: The study objective was to analyze temporal changes in baseline and procedural characteristics and long-term survival of patients undergoing surgical aortic valve replacement over a 30-year period. METHODS: A retrospective analysis of patients undergoing surgical aortic valve replacement between 1987 and 2016 in the Erasmus Medical Center (Rotterdam, The Netherlands) was conducted. Patient baseline and procedural characteristics were analyzed in periods according to the date of surgical aortic valve replacement (period A: 1987-1996; B: 1997-2006; C: 2007-2016). Survival status was determined using the Dutch National Death Registry. Relative survival was obtained by comparing the survival after surgical aortic valve replacement with the survival of the age-, sex-, and year-matched general population. RESULTS: Between 1987 and 2016, 4404 patients underwent SAVR. From period A to C, the mean age increased from 63.9 ± 11.2 years to 66.2 ± 12.3 years (P < .001), and the prevalence of diabetes mellitus, hypertension, hypercholesterolemia, previous myocardial infarction, and previous stroke at baseline increased (P values for trend for all < .001). The prevalence of concomitant procedures increased from 42.4% in period A to 48.3% in period C (P = .004). Bioprosthesis use increased significantly (18.8% in period A vs 67.1% in period C, P < .001). Mean survival after surgical aortic valve replacement was 13.8 years. Relative survival at 20 years in the overall cohort was 60.4% (95% confidence interval, 55.9-65.2) and 73.8% (95% confidence interval, 67.1-81.1) in patients undergoing isolated primary surgical aortic valve replacement. CONCLUSIONS: Patient complexity has been continuously increasing over the last 30 years, yet long-term survival after surgical aortic valve replacement remains high compared with the age-, sex-, and year-matched general population.

Preoperative visualization of congenital lung abnormalities: hybridizing artificial intelligence and virtual reality.

OBJECTIVES: When surgical resection is indicated for a congenital lung abnormality (CLA), lobectomy is often preferred over segmentectomy, mostly because the latter is associated with more residual disease. Presumably, this occurs in children because sublobar surgery often does not adhere to anatomical borders (wedge resection instead of segmentectomy), thus increasing the risk of residual disease. This study investigated the feasibility of identifying eligible cases for anatomical segmentectomy by combining virtual reality (VR) and artificial intelligence (AI). METHODS: Semi-automated segmentation of bronchovascular structures and lesions were visualized with VR and AI technology. Two specialists independently evaluated via a questionnaire the informative value of regular computed tomography versus three-dimensional (3D) VR images. RESULTS: Five asymptomatic, non-operated cases were selected. Bronchovascular segmentation, volume calculation and image visualization in the VR environment were successful in all cases. Based on the computed tomography images, assignment of the CLA lesion to specific lung segments matched between the consulted specialists in only 1 out of the cases. Based on the three 3D VR images, however, the localization matched in 3 of the 5 cases. If the patients would have been operated, adding the 3D VR tool to the preoperative workup would have resulted in changing the surgical strategy (i.e. lobectomy versus segmentectomy) in 4 cases. CONCLUSIONS: This study demonstrated the technical feasibility of a hybridized AI-VR visualization of segment-level lung anatomy in patients with CLA. Further exploration of the value of 3D VR in identifying eligible cases for anatomical segmentectomy is therefore warranted.

Porcupine Inhibition Disrupts Mitochondrial Function and Homeostasis in WNT Ligand-Addicted Pancreatic Cancer.

WNT signaling promotes pancreatic ductal adenocarcinoma (PDAC) through diverse effects on proliferation, differentiation, survival, and stemness. A subset of PDAC with inactivating mutations in ring finger protein 43 (RNF43) show growth dependency on autocrine WNT ligand signaling and are susceptible to agents that block WNT ligand acylation by Porcupine O-acyltransferase, which is required for proper WNT ligand processing and secretion. For this study, global transcriptomic, proteomic, and metabolomic analyses were performed to explore the therapeutic response of RNF43-mutant PDAC to the Porcupine inhibitor (PORCNi) LGK974. LGK974 disrupted cellular bioenergetics and mitochondrial function through actions that included rapid mitochondrial depolarization, reduced mitochondrial content, and inhibition of oxidative phosphorylation and tricarboxylic acid cycle. LGK974 also broadly altered transcriptional activity, downregulating genes involved in cell cycle, nucleotide metabolism, and ribosomal biogenesis and upregulating genes involved in epithelial-mesenchymal transition, hypoxia, endocytosis, and lysosomes. Autophagy and lysosomal activity were augmented in response to LGK974, which synergistically inhibited tumor cell viability in combination with chloroquine. Autocrine WNT ligand signaling dictates metabolic dependencies in RNF43-mutant PDAC through a combination of transcription dependent and independent effects linked to mitochondrial health and function. Metabolic adaptations to mitochondrial damage and bioenergetic stress represent potential targetable liabilities in combination with PORCNi for the treatment of WNT ligand-addicted PDAC.

Current and Future Applications of Virtual, Augmented, and Mixed Reality in Cardiothoracic Surgery.

BACKGROUND: This review aims to examine the existing literature to address currently used virtual, augmented, and mixed reality modalities in the areas of preoperative surgical planning, intraoperative guidance, and postoperative management in the field of cardiothoracic surgery. In addition this innovative technology provides future perspectives and potential benefits for cardiothoracic surgeons, trainees, and patients. METHODS: A targeted, nonsystematic literature assessment was performed within the Medline and Google Scholar databases to help identify current trends and to provide better understanding of the current state-of-the-art extended reality (XR) modalities in cardiothoracic surgery. Related articles published up to July 2020 were included in the review. RESULTS: XR is a novel technique gaining increasing application in cardiothoracic surgery. It provides a 3-dimensional and realistic view of structures and environments and offers the user the ability to interact with digital projections of surgical targets. Recent studies showed the validity and benefits of XR applications in cardiothoracic surgery. Examples include XR-guided preoperative planning, intraoperative guidance and navigation, postoperative pain and rehabilitation management, surgical simulation, and patient education. CONCLUSIONS: XR is gaining interest in the field of cardiothoracic surgery. In particular there are promising roles for XR applications in televirtuality, surgical planning, surgical simulation, and perioperative management. However future refinement and research are needed to further implement XR in the aforementioned settings within cardiothoracic surgery.

High torque tenovirus (TTV) load before first vaccine dose is associated with poor serological response to COVID-19 vaccination in lung transplant recipients.

BACKGROUND: Serological responses to COVID-19 vaccination are diminished in recipients of solid organ transplants, especially in lung transplant recipients (LTR), probably as result of immunosuppressive treatment. There is currently no marker of immunosuppression that can be used to predict the COVID-19 vaccination response. Here, we study whether torque tenovirus (TTV), a highly prevalent virus can be used as an indicator of immunosuppression. METHODS: The humoral response to the mRNA 1273 vaccine was assessed in 103 LTR, who received a transplant between 4 and 237 months prior to vaccination, by measuring Spike (S)-specific IgG levels at baseline, 28 days after first, and 28 days after the second vaccination. TTV loads were determined by RT-PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. RESULTS: Humoral responses to COVID-19 vaccination were observed in 41 of 103 (40%) LTR at 28 days after the second vaccination. Sixty-two of 103 (60%) were non-responders. Lower TTV loads at baseline (significantly) correlated with higher S-specific antibodies and a higher percentage of responders. Lower TTV loads also strongly correlated with longer time since transplantation, indicating that participants with lower TTV loads were longer after transplantation. CONCLUSIONS: This study shows a better humoral response to the SARS-CoV-2 vaccine in subjects with a lower TTV load pre-vaccination. In addition, TTV load correlates with the time after transplantation. Further studies on the use of TTV load in vaccination efficacy studies in immunocompromised cohorts should provide leads for the potential use of this marker for optimizing vaccination response.