Biosymbiotic haptic feedback - Sustained long term human machine interfaces.

Haptic technology permeates diverse fields and is receiving renewed attention for VR and AR applications. Advances in flexible electronics, facilitate the integration of haptic technologies into soft wearable systems, however, because of small footprint requirements face challenges of operational time requiring either large batteries, wired connections or frequent recharge, restricting the utility of haptic devices to short-duration tasks or low duty cycles, prohibiting continuously assisting applications. Currently many chronic applications are not investigated because of this technological gap. Here, we address wireless power and operation challenges with a biosymbiotic approach enabling continuous operation without user intervention, facilitated by wireless power transfer, eliminating the need for large batteries, and offering long-term haptic feedback without adhesive attachment to the body. These capabilities enable haptic feedback for robotic surgery training and posture correction over weeks of use with neural net computation. The demonstrations showcase that this device class expands use beyond conventional brick and strap or epidermally attached devices enabling new fields of use for imperceptible therapeutic and assistive haptic technologies supporting care and disease management.

Noteworthy in Cardiothoracic Surgery 2023.

Noteworthy in Cardiothoracic Surgery 2023 summarizes a few of the most high-impact trials and provocative trends in cardiothoracic surgery and transplantation this past year. Transplantation using organs procured from donation after circulatory death (DCD) continues to increase, and the American Society of Transplant Surgeons released recommendations on best practices in 2023. We review a summary of data on the impact of DCD on heart and lung transplantation. There has been increased interest in extracorporeal life support (ECLS), particularly after the COVID-19 pandemic, and we review the results of the highly discussed ECLS-SHOCK trial, which randomized patients in cardiogenic shock with planned revascularization to ECLS vs usual care. With improving survival outcomes in complex aortic surgery, there is a need for higher-quality evidence to guide which cooling and cerebral perfusion strategies may optimize cognitive outcomes in these patients. We review the short-term outcomes of the GOT ICE trial (Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest), a multicenter, randomized controlled trial of three different nadir temperatures, evaluating outcomes in cognition and associated changes in functional magnetic resonance imaging. Finally, both the Society of Thoracic Surgeons (STS) and the American College of Cardiology, American Heart Association, American College of Chest Physicians and Heart Rhythm Society (ACC/AHA/ACCP/HRS) updated atrial fibrillation guidelines in 2023, and we review surgically relevant updates to the guidelines and the evidence behind them.

Association of procurement technique with organ yield and cost following donation after circulatory death.

Donation after circulatory death (DCD) could account for the largest expansion of the donor allograft pool in the contemporary era. However, the organ yield and associated costs of normothermic regional perfusion (NRP) compared to super-rapid recovery (SRR) with ex-situ normothermic machine perfusion, remain unreported. The Organ Procurement and Transplantation Network (December 2019 to June 2023) was analyzed to determine the number of organs recovered per donor. A cost analysis was performed based on our institution's experience since 2022. Of 43 502 donors, 30 646 (70%) were donors after brain death (DBD), 12 536 (29%) DCD-SRR and 320 (0.7%) DCD-NRP. The mean number of organs recovered was 3.70 for DBD, 3.71 for DCD-NRP (P < .001), and 2.45 for DCD-SRR (P < .001). Following risk adjustment, DCD-NRP (adjusted odds ratio 1.34, confidence interval 1.04-1.75) and DCD-SRR (adjusted odds ratio 2.11, confidence interval 2.01-2.21; reference: DBD) remained associated with greater odds of allograft nonuse. Including incomplete and completed procurement runs, the total average cost of DCD-NRP was $9463.22 per donor. By conservative estimates, we found that approximately 31 donor allografts could be procured using DCD-NRP for the cost equivalent of 1 allograft procured via DCD-SRR with ex-situ normothermic machine perfusion. In conclusion, DCD-SRR procurements were associated with the lowest organ yield compared to other procurement methods. To facilitate broader adoption of DCD procurement, a comprehensive understanding of the trade-offs inherent in each technique is imperative.

Post-transplant survival after normothermic regional perfusion versus direct procurement and perfusion in donation after circulatory determination of death in heart transplantation.

BACKGROUND: Since 2019, the annual transplantation rate of hearts donated following circulatory death (DCD) has increased significantly in the United States. The 2 major heart procurement techniques following circulatory death are direct procurement and perfusion (DPP) and normothermic regional perfusion (NRP). Post-transplant survival for heart recipients has not been compared between these 2 techniques. METHODS: This observational study uses data on adult heart transplants from donors after circulatory death from January 1, 2019 to December 31, 2021 in the Scientific Registry of Transplant Recipients. We identified comparable transplant cases across procurement types using propensity-score matching and measured the association between procurement technique and 1-year post-transplant survival using Kaplan-Meier and Cox proportional hazards model stratefied by matching pairs. RESULTS: Among 318 DCD heart transplants, 216 (68%) were procured via DPP, and 102 (32%) via NRP. Among 22 transplant centers that accepted circulatory-death donors, 3 used NRP exclusively, and 5 used both procurement techniques. After propensity-score matching on recipient and donor factors, there was no significant difference in 1-year post-transplant survival (93.1% for NRP vs 91.1% for DPP, p = 0.79) between procurement techniques. CONCLUSIONS: NRP and DPP procurements are associated with similar 1-year post-transplant survival. If NRP is ethically permissible and improves outcomes for abdominal organs, it should be the preferred procurement technique for DCD hearts.

The American Society of Transplant Surgeons Consensus Statement on Normothermic Regional Perfusion.

On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively. This article discusses major topics and conclusions addressed at the meeting.

Characterization of pulmonary arterial stiffness using cardiac MRI.

Pulmonary arterial stiffness (PAS) is a pathologic hallmark of all types of pulmonary hypertension (PH). Cardiac MRI (CMR), a gold-standard imaging modality for the evaluation of pulmonary flow, biventricular morphology and function has been historically reserved for the longitudinal clinical follow-up, PH phenotyping purposes, right ventricular evaluation, and research purposes. Over the last two decades, numerous indices combining invasive catheterization and non-invasive CMR have been utilized to phenotype the character and severity of PAS in different types of PH and to assess its clinically prognostic potential with encouraging results. Many recent studies have demonstrated a strong role of CMR derived PAS markers in predicting long-term clinical outcomes and improving currently gold standard risk assessment provided by the REVEAL calculator. With the utilization of a machine learning strategies, strong diagnostic and prognostic performance of CMR reported in multicenter studies, and ability to detect PH at early stages, the non-invasive assessment of PAS is on verge of routine clinical utilization. In this review, we focus on appraising important CMR studies interrogating PAS over the last 20 years, describing the benefits and limitations of different PAS indices, and their pathophysiologic relevance to pulmonary vascular remodeling. We also discuss the role of CMR and PAS in clinical surveillance and phenotyping of PH, and the long-term future goal to utilize PAS as a biomarker to aid with more targeted therapeutic management.

Prolonged travel time to transplantation center is associated with poor outcomes following heart transplantation.

BACKGROUND: This study aims to examine the impact of home-to-transplantation center travel time as a potential barrier to healthcare accessibility. METHODS: Observational study examined adult heart transplant recipients who received a graft between 2012 and 2022 in the United States. Travel time was calculated using the Google Distance Matrix API between the recipient's residence and transplantation center. A multivariable parametric survival model was fitted to minimize confounding bias. RESULTS: Among the 25,923 recipients that met the selection criteria, the median travel time was 51 â€‹min and 95 â€‹% of recipients lived within a 5-h radius of their center. White recipients experienced longer median travel times (62 â€‹min, p â€‹< â€‹0.001) compared to Black (36 â€‹min) or Hispanic (40 â€‹min) recipients. A travel time of 1-2 â€‹h (survival time ratio [STR] 0.867, p â€‹= â€‹0.035) or >2 â€‹h (STR 0.873, p â€‹= â€‹0.026) away from the transplantation center was independently associated with lower long-term survival rates. CONCLUSION: Extended travel times to transplantation centers may negatively impact long-term survival outcomes for heart transplant recipients, suggesting the need to address this potential barrier to healthcare accessibility.

Association of cardiac preservation solution with short-term outcomes after heart transplantation.

AIMS: There is wide variability in the practice of cardiac preservation for heart transplantation. Prior reports suggest that the type of solution may be linked with a reduced incidence of posttransplantation complications. METHODS: Adult (≥18 years old) heart recipients who underwent transplantation between 2015 and 2021 in the United States were examined. Recipients were stratified by solution utilized for their grafts at the time of recovery: University of Wisconsin, histidine-tryptophan-ketoglutarate (HTK), or Celsior solution. The primary endpoint was a composite of 30-day mortality, primary graft dysfunction, or re-transplantation. Risk adjustment was performed for the recipient, donor, and procedural characteristics using regression modeling. RESULTS: Among 16 884 recipients, the group distribution was University of Wisconsin solution 53%, HTK 22%, Celsior solution 15%, and other 10%. The observed incidence of the composite endpoint (University of Wisconsin solution = 3.6%, HTK = 4.0%, Celsior solution = 3.7%, P = 0.301) and 1-year survival (University of Wisconsin solution = 91.7%, HTK = 91.3%, Celsior solution = 91.7%, log-rank P = 0.777) were similar between groups. After adjustment, HTK was associated with a higher risk of the composite endpoint [odds ratio (OR) 1.249, 95% confidence interval (CI) 1.019-1.525, P = 0.030] in reference to University of Wisconsin solution. This association was substantially increased among recipients with ischemic periods of greater than 4 h (OR 1.817, 95% CI 1.188-2.730, P = 0.005). The risks were similar between University of Wisconsin solution and Celsior solution (P = 0.454). CONCLUSION: The use of the histidine-tryptophan-ketoglutarate solution during cold static storage for cardiac preservation is associated with increased rates of early mortality or primary graft dysfunction. Clinician discretion should guide its use, especially when prolonged ischemic times (>4 h) are anticipated.

Lung recovery utilizing thoracoabdominal normothermic regional perfusion during donation after circulatory death: The Colorado experience.

Objective: Donation after circulatory death (DCD) procurement and transplantation after thoracoabdominal normothermic regional perfusion (TA-NRP) remains a novel technique to improve cardiac and hepatic allograft preservation but may be complicated by lung allograft pulmonary edema. We present a single-center series on early implementation of a lung-protective protocol with strategies to mitigate posttransplant pulmonary edema in DCD lung allografts after TA-NRP procurement. Methods: Data from all lung transplantations performed using a TA-NRP procurement strategy from October 2022 to April 2023 are presented. Donor management consisted of key factors to reduce lung allograft pulmonary edema: aggressive predonation and early posttransplant diuresis, complete venous drainage at TA-NRP initiation, and early pulmonary artery venting upon initiation of systemic perfusion. Donor and recipient characteristics, procurement characteristics such as TA-NRP intervals, and 30-day postoperative outcomes were assessed. Results: During the study period, 8 lung transplants were performed utilizing TA-NRP procurement from DCD donors. Donor ages ranged from 16 to 39 years and extubation time to declaration of death ranged from 10 to 90 minutes. Time from declaration to TA-NRP initiation was 7 to 17 minutes with TA-NRP perfusion times of 49 to 111 minutes. Median left and right allograft warm ischemia times were 55.5 minutes (interquartile range, 46.5-67.5 minutes) and 41.0 minutes (interquartile range, 39.0-53.0 minutes, respectively, with 2 recipients supported with cardiopulmonary bypass or venoarterial extracorporeal membrane oxygenation during implantation. No postoperative extracorporeal membrane oxygenation was required. There were no pulmonary-related deaths; however, 1 patient died from complications of severe necrotizing pancreatitis with a normal functioning allograft. All patients were extubated within 24 hours. Index intensive care unit length of stay ranged from 3 to 11 days with a hospital length of stay of 13 to 37 days. Conclusions: Despite concern regarding quality of DCD lung allografts recovered using the TA-NRP technique, we report initial success using this procurement method. Implementation of strategies to mitigate pulmonary edema can result in acceptable outcomes following lung transplantation. Demonstration of short- and long-term safety and efficacy of this technique will become increasingly important as the use of TA-NRP for thoracic and abdominal allografts in DCD donors expands.

4D-Flow MRI intracardiac flow analysis considering different subtypes of pulmonary hypertension.

Intracardiac flow hemodynamic patterns have been considered to be an early sign of diastolic dysfunction. In this study we investigated right ventricular (RV) diastolic dysfunction between patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension with chronic lung disease (PH-CLD) via 4D-Flow cardiac MRI (CMR). Patients underwent prospective, comprehensive CMR for function and size including 4D-Flow CMR protocol for intracardiac flow visualization and analysis. RV early filling phase and peak atrial phase vorticity (E-vorticity and A-vorticity) values were calculated in all patients. Patients further underwent comprehensive Doppler and tissue Doppler evaluation for the RV diastolic dysfunction. In total 13 patients with PAH, 15 patients with PH-CLD, and 10 control subjects underwent the 4D-Flow CMR and echocardiography evaluation for RV diastolic dysfunction. Reduced E-vorticity differentiated PAH and PH-CLD from healthy controls (both p < 0.01) despite the same Doppler E values. E-vorticity was further decreased in PAH patients when compared to PH-CLD group (p < 0.05) with similar Doppler and tissue Doppler markers of diastolic dysfunction. A-vorticity was decreased in both PAH and PH-CLD groups compared to controls but with no difference between the disease groups. E-vorticity correlated with ejection fraction (R = 0.60, p < 0.001), end-systolic volume (R = 0.50, p = 0.001), stroke volume (R = 0.42, p = 0.007), and cardiac output (R = 0.30, p = 0.027). Intracardiac flow analysis using 4D-Flow CMR derived vorticity is a sensitive method to differentiate diastolic dysfunction in patients with different PH etiology and similar Doppler echocardiography profile.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era.

BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Importance of social vulnerability on long-term outcomes after heart transplantation.

The relationship between social determinants of health and outcomes after heart transplantation has not been examined. The social vulnerability index (SVI) uses United States census data to determine the social vulnerability of every census tract based on 15 factors. This retrospective study seeks to examine the impact of SVI on outcomes after heart transplantation. Adult heart recipients who received a graft between 2012 and 2021 were stratified into SVI percentiles of <75% and SVI of ≥75%. The primary endpoint was survival. The median SVI was 48% (interquartile range: 30%-67%) among 23 700 recipients. One-year survival was similar between groups (91.4 vs 90.7%, log-rank P = .169); however, 5-year survival was lower among individuals living in vulnerable communities (74.8% vs 80.0%, P < .001). This finding persisted despite risk adjustment for other factors associated with mortality (survival time ratio 0.819, 95% confidence interval: 0.755-0.890, P < .001). The incidences of 5-year hospital readmission (81.4% vs 75.4%, P < .001) and graft rejection (40.3% vs 35.7%, P = .004) were higher among individuals living in vulnerable communities. Individuals living in vulnerable communities may be at increased risk of mortality after heart transplantation. These findings suggest there is an opportunity to focus on these recipients undergoing heart transplantation to improve survival.

Variability in Heart Yield From Donation After Brain Death Between Organ Procurement Organizations: An Opportunity for Improvement.

Increasing the number of available hearts for transplantation is the best strategy to decrease waitlist mortality. This study examines organ procurement organizations (OPOs) and their role in the transplantation network to determine whether variability in performance exists across them. Adult deceased donors who met the criteria for brain death between 2010 and 2020 (inclusive) in the United States were examined. A regression model was fitted and internally validated using donor characteristics available at the time of organ recovery to predict the likelihood of heart transplantation. Subsequently, an expected heart yield was calculated for each donor using this model. Observed-to-expected (O/E) heart yield ratios for each OPO were calculated by dividing the number of hearts recovered for transplantation by the expected number of recoveries. There were 58 OPOs active during the study period, and on average, OPO activity grew over time. The mean O/E ratio among OPOs was 0.98 (standard deviation ± 0.18). Twenty-one OPOs consistently performed below the expected level (95% confidence intervals < 1.0) and generated a deficit of 1,088 expected transplantations during the study period. The proportion of hearts that were recovered for transplantation varied significantly by OPO categories: low tier 31.8%, mid tier 35.6%, and high tier 36.2% (p < 0.01), even as the expected yield was similar across tiers (p = 0.69). OPO performance accounts for 28% of the variability in successfully transplanting a heart after accounting for the role of referring hospitals, donor families, and transplantation centers. In conclusion, there is significant variability in volume and heart yield from brain-dead donors across OPOs.

Cardiac Surgeons Highlight the Need for Innovation Stewardship: Noteworthy in 2022.

Modern cardiac surgery has rapidly evolved to treat complex cardiovascular disease. This past year boasted noteworthy advances in xenotransplantation, prosthetic cardiac valves, and endovascular thoracic aortic repair. Newer devices often offer incremental design changes while demanding significant cost increases that leave surgeons to decide if the benefit to patients justifies the increased cost. As innovations are introduced, surgeons must continuously aim to harmonize short- and long-term benefits with financial costs). We must also ensure quality patient outcomes while embracing innovations that will advance equitable cardiovascular care.

The international experience of in-situ recovery of the DCD heart: a multicentre retrospective observational study.

Background: Heart transplantation is an effective treatment offering the best recovery in both quality and quantity of life in those affected by refractory, severe heart failure. However, transplantation is limited by donor organ availability. The reintroduction of heart donation after the circulatory determination of death (DCD) in 2014 offered an uplift in transplant activity by 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion of the DCD heart. The objective of this paper is to assess the clinical outcomes of DCD donor hearts recovered and transplanted from donors undergoing taNRP. Method: This was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use of mechanical support immediately following transplantation, perioperative and long-term actuarial survival and incidence of acute rejection requiring treatment. 157 taNRP DCD heart transplants, performed between February 2, 2015, and July 29, 2022, have been included from 15 major transplant centres worldwide including the UK, Spain, the USA and Belgium. 673 donations after the neurological determination of death (DBD) heart transplantations from the same centres were used as a comparison group for survival. Findings: taNRP resulted in a 23% increase in heart transplantation activity. Survival was similar in the taNRP group when compared to DBD. 30-day survival was 96.8% ([92.5%-98.6%] 95% CI, n = 156), 1-year survival was 93.2% ([87.7%-96.3%] 95% CI, n = 72) and 5-year survival was 84.3% ([69.6%-92.2%] 95% CI, n = 13). Interpretation: Our study suggests that taNRP provides a significant boost to heart transplantation activity. The survival rates of taNRP are comparable to those obtained for DBD transplantation in this study. The similar survival may in part be related to a short warm ischaemic time or through a possible selection bias of younger donors, this being an uncontrolled observational study. Therefore, our study suggests that taNRP offers an effective method of organ preservation and procurement. This early success of the technique warrants further investigation and use. Funding: None of the authors have a financial relationship with a commercial entity that has an interest in the subject.

Mitochondrial genomes in the iconic reindeer lichens: Architecture, variation, and synteny across multiple evolutionary scales.

Variation in mitochondrial genome composition across intraspecific, interspecific, and higher taxonomic scales has been little studied in lichen obligate symbioses. Cladonia is one of the most diverse and ecologically important lichen genera, with over 500 species representing an array of unique morphologies and chemical profiles. Here, we assess mitochondrial genome diversity and variation in this flagship genus, with focused sampling of two clades of the "true" reindeer lichens, Cladonia subgenus Cladina, and additional genomes from nine outgroup taxa. We describe composition and architecture at the gene and the genome scale, examining patterns in organellar genome size in larger taxonomic groups in Ascomycota. Mitochondrial genomes of Cladonia, Pilophorus, and Stereocaulon were consistently larger than those of Lepraria and contained more introns, suggesting a selective pressure in asexual morphology in Lepraria driving it toward genomic simplification. Collectively, lichen mitochondrial genomes were larger than most other fungal life strategies, reaffirming the notion that coevolutionary streamlining does not correlate to genome size reductions. Genomes from Cladonia ravenelii and Stereocaulon pileatum exhibited ATP9 duplication, bearing paralogs that may still be functional. Homing endonuclease genes (HEGs), though scarce in Lepraria, were diverse and abundant in Cladonia, exhibiting variable evolutionary histories that were sometimes independent of the mitochondrial evolutionary history. Intraspecific HEG diversity was also high, with C. rangiferina especially bearing a range of HEGs with one unique to the species. This study reveals a rich history of events that have transformed mitochondrial genomes of Cladonia and related genera, allowing future study alongside a wealth of assembled genomes.