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.

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.

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.

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.

Virtual Reality Simulation Training for Cardiopulmonary Resuscitation After Cardiac Surgery: Face and Content Validity Study.

BACKGROUND: Cardiac arrest after cardiac surgery commonly has a reversible cause, where emergency resternotomy is often required for treatment, as recommended by international guidelines. We have developed a virtual reality (VR) simulation for training of cardiopulmonary resuscitation (CPR) and emergency resternotomy procedures after cardiac surgery, the Cardiopulmonary Resuscitation Virtual Reality Simulator (CPVR-sim). Two fictive clinical scenarios were used: one case of pulseless electrical activity (PEA) and a combined case of PEA and ventricular fibrillation. In this prospective study, we researched the face validity and content validity of the CPVR-sim. OBJECTIVE: We designed a prospective study to assess the feasibility and to establish the face and content validity of two clinical scenarios (shockable and nonshockable cardiac arrest) of the CPVR-sim partly divided into a group of novices and experts in performing CPR and emergency resternotomies in patients after cardiac surgery. METHODS: Clinicians (staff cardiothoracic surgeons, physicians, surgical residents, nurse practitioners, and medical students) participated in this study and performed two different scenarios, either PEA or combined PEA and ventricular fibrillation. All participants (N=41) performed a simulation and completed the questionnaire rating the simulator's usefulness, satisfaction, ease of use, effectiveness, and immersiveness to assess face validity and content validity. RESULTS: Responses toward face validity and content validity were predominantly positive in both groups. Most participants in the PEA scenario (n=26, 87%) felt actively involved in the simulation, and 23 (77%) participants felt in charge of the situation. The participants thought it was easy to learn how to interact with the software (n=24, 80%) and thought that the software responded adequately (n=21, 70%). All 15 (100%) expert participants preferred VR training as an addition to conventional training. Moreover, 13 (87%) of the expert participants would recommend VR training to other colleagues, and 14 (93%) of the expert participants thought the CPVR-sim was a useful method to train for infrequent post-cardiac surgery emergencies requiring CPR. Additionally, 10 (91%) of the participants thought it was easy to move in the VR environment, and that the CPVR-sim responded adequately in this scenario. CONCLUSIONS: We developed a proof-of-concept VR simulation for CPR training with two scenarios of a patient after cardiac surgery, which participants found was immersive and useful. By proving the face validity and content validity of the CPVR-sim, we present the first step toward a cardiothoracic surgery VR training platform.

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.

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.

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.

Long-term outcome and bridging success of patients evaluated and bridged to lung transplantation on the ICU.

BACKGROUND: Evaluating and bridging patients to lung transplantation (LTx) on the intensive care unit (ICU) remains controversial, especially without a previous waitlist status. Long term outcome data after LTx from ICU remains scarce. We compared long-term survival and development of chronic lung allograft dysfunction (CLAD) in elective and LTx from ICU, with or without previous waitlist status. METHODS: Patients transplanted between 2004 and 2018 in 2 large academic Dutch institutes were included. Long-term survival and development of CLAD was compared in patients who received an elective LTx (ELTx), those bridged and transplanted from the ICU with a previous listing status (BTT), and in patients urgently evaluated and bridged on ICU (EBTT). RESULTS: A total of 582 patients underwent a LTx, 70 (12%) from ICU, 39 BTT and 31 EBTT. Patients transplanted from ICU were younger than ELTx (46 vs 51 years) and were bridged with mechanical ventilation (n = 42 (60%)), extra corporeal membrane oxygenation (n = 28 (40%)), or both (n = 21/28). Bridging success was 48% in the BTT group and 72% in the EBTT group. Patients bridged to LTx on ICU had similar 1 and 5 year survival (86.8% and 78.4%) compared to elective LTx (86.8% and 71.9%). This was not different between the BTT and EBTT group. 5 year CLAD free survival was not different in patients transplanted from ICU vs ELTx. CONCLUSION: Patients bridged to LTx on the ICU with and without prior listing status had excellent short and long-term patient and graft outcomes, and was similar to patients electively transplanted.

Cardiac malformations in Pdgfralpha mutant embryos are associated with increased expression of WT1 and Nkx2.5 in the second heart field.

Platelet-derived growth factor receptor alpha (Pdgfralpha) identifies cardiac progenitor cells in the posterior part of the second heart field. We aim to elucidate the role of Pdgfralpha in this region. Hearts of Pdgfralpha-deficient mouse embryos (E9.5-E14.5) showed cardiac malformations consisting of atrial and sinus venosus myocardium hypoplasia, including venous valves and sinoatrial node. In vivo staining for Nkx2.5 showed increased myocardial expression in Pdgfralpha mutants, confirmed by Western blot analysis. Due to hypoplasia of the primary atrial septum, mesenchymal cap, and dorsal mesenchymal protrusion, the atrioventricular septal complex failed to fuse. Impaired epicardial development and severe blebbing coincided with diminished migration of epicardium-derived cells and myocardial thinning, which could be linked to increased WT1 and altered alpha4-integrin expression. Our data provide novel insight for a possible role for Pdgfralpha in transduction pathways that lead to repression of Nkx2.5 and WT1 during development of posterior heart field-derived cardiac structures.

Weaning from cardiopulmonary bypass, decannulation, and closure.

In 1952, John Gibbon performed the first successful cardiac procedure using cardiopulmonary bypass, which turned out to be one of the most important clinical advances of that year. Cardiopulmonary bypass has also been described as "One of the most impressive evidences of the role of investigative surgery in the history of medicine in the persevering efforts of Dr. Gibbon for more than 20 years, which finally culminated in a practical heart-lung machine," at the first John H. Gibbon, Jr, Lecture at the annual meeting of the American College of Surgeons [1]. Due to the subsequent advancement of cardiopulmonary bypass, many patients with complex heart disease requiring surgical care undergo cardiac surgery while the other organs remain adequately oxygenated and perfused.

Surgical Aortic Valve Replacement with Concomitant Aortic Surgery in Patients with Purely Bicuspid Aortic Valve and Associated Aortopathy.

The bicuspid aortic valve (BAV) is the most common congenital cardiac malformation associated with aortopathy. The current study provides surgical clinical data on the patient characteristics and long-term survival of this less common adult purely BAV population undergoing surgical aortic valve replacement (SAVR) with concomitant aortic surgery. Adult patients with purely BAV who underwent SAVR and concomitant aortic surgery were included. Prevalence, predictors of survival, and outcomes for this patient population were analyzed. A total of 48 patients (mean age 58.7 ± 13.2 years, 33% female) with purely BAV underwent SAVR and concomitant aortic surgery between 1987 and 2016. The majority (62%) of the patients had pure aortic stenosis (AS). A total of 12 patients died. Survival was 92%, 73%, and 69% at 1, 5, and 20 years of follow-up. At 15 years of follow-up, the survival was close to that of the Dutch population, with a relative survival of 77%. Adult patients with a purely bicuspid aortic valve morphology undergoing SAVR and concomitant aortic root and/or ascending aorta present with excellent survival.

Conventional open harvesting of the radial artery as a conduit for coronary artery bypass grafting.

This video tutorial summarizes the main steps of the conventional open surgical technique for harvesting the radial artery as a coronary artery bypass graft, taking anatomic and surgical aspects into account.

Surgical setup for cardiopulmonary bypass through central cannulation.

The introduction of cardiopulmonary bypass was one of the most important clinical advances of 1952. In that year, John Gibbon performed the first successful cardiac surgery using cardiopulmonary bypass. The procedure has been described as "One of the most impressive evidences of the role of investigative surgery in the history of medicine in the persevering efforts of Dr. Gibbon for more than 20 years, which finally culminated in a practical heart-lung machine", at the first John H. Gibbon, Jr. Lecture at the annual meeting of the American College of Surgeons. Due to on-going advancements in cardiopulmonary bypass, many patients with complex heart disease requiring surgical care undergo cardiac surgery while the other organs remain adequately oxygenated and perfused. This tutorial discusses the access, surgical technique, and initiation of cardiopulmonary bypass through central cannulation and describes the safeguards and pitfalls.