Chondrocytes are a primary cell type used in articular cartilage tissue engineering due to their ability to be applied autologously, minimizing the risk of immune rejection. However, isolated chondrocytes often exhibit h...Chondrocytes are a primary cell type used in articular cartilage tissue engineering due to their ability to be applied autologously, minimizing the risk of immune rejection. However, isolated chondrocytes often exhibit heterogeneity, including mixtures of viable, dead, and dedifferentiated cells, which may impact their functional properties. In this study, the hydrophobicity and surface tension components of chondrocytes isolated from healthy and osteoarthritis (OA) donors were explored using a drop shape analyzer and Young's-Dupré equation over a 21 day culture period. The results indicate that OA-derived chondrocytes consistently exhibited higher water contact angles than healthy chondrocytes, with statistically significant differences observed on days 0, 7, and 14 of culture. The amounts of all three components of surface tension in healthy chondrocytes were significantly higher than those in OA-derived chondrocytes, except for van der Waals forces on day 0. Additionally, the observed modulation of chondrocyte hydrophobicity over the 21 day culture period indicates a potential functional phenotype shift from OA state toward a healthier phenotype under standard culture conditions. These results not only highlight hydrophobicity and surface tension as potential biomarkers for distinguishing OA and healthy chondrocytes, but also suggest possible therapeutic strategies aimed at restoring OA chondrocytes to a healthy state.
To examine the global epidemiology of extracorporeal membrane oxygenation discontinuation due to resource limitation (EDRL), assessing differences across geographic regions and between pre- and post-coronavirus disease 2...To examine the global epidemiology of extracorporeal membrane oxygenation discontinuation due to resource limitation (EDRL), assessing differences across geographic regions and between pre- and post-coronavirus disease 2019 (COVID-19) periods. Retrospective cohort analysis of all children and adults from international ECMO centers (2013-2023) in which ECMO was discontinued due to resource limitations. Of the 161,851 ECMO runs, 312 (0.19%) underwent EDRL. Of those, 25% occurred in children. Leading diagnoses were cardiogenic shock (n = 62, 20%) and COVID-19 (n = 33, 11%). Twelve percent survived post-EDRL and 29% were transported on ECMO for resource reallocation. Extracorporeal membrane oxygenation discontinuation due to resource limitations increased worldwide over time, particularly following COVID-19 (1.44 EDRLs per 1,000 ECMO runs vs. 2.44 EDRLs per 1,000 ECMO runs, p < 0.001), disproportionately to the overall increase in ECMO utilization ( p = 0.019), especially in Europe ( p < 0.001) and North America ( p = 0.003). Latin America and Southwest Asia/Africa exhibited high proportions of EDRLs relative to ECMO runs (12.8 and 4.8 per 1,000 cannulations, respectively) and low post-EDRL survival rates (6.7% and 0%, respectively). Resource limitation remains a rare indication for ECMO decannulation, differs across global regions, and has grown over time disproportionately to the overall increase in ECMO use, particularly in Europe and North America and with the onset of the COVID-19 pandemic.
Delays in mechanical circulatory support (MCS) for cardiogenic shock can be critical. However, timely access to a hybrid operating room or C-arm fluoroscopy for urgent axillary Impella 5.5 (Abiomed, Danvers, MA) implanta...Delays in mechanical circulatory support (MCS) for cardiogenic shock can be critical. However, timely access to a hybrid operating room or C-arm fluoroscopy for urgent axillary Impella 5.5 (Abiomed, Danvers, MA) implantation remains a barrier. To address this, we developed a fluoroscopy-free axillary Impella 5.5 implantation technique using transesophageal echocardiography (TEE) guidance. From January 2023 to November 2024, 19 adults underwent the procedure. A preoperative flowchart ensured appropriate selection, with the right axillary artery as the preferred access. Transesophageal echocardiography-guided pigtail advancement, valve crossing, and device positioning. All implantations (100%) were successful without conversion to fluoroscopy-guided or ECMO. There were no strokes or major complications. All patients had optimal positioning and rapid hemodynamic improvement. These findings support the feasibility and safety of TEE-guided, fluoroscopy-free Impella 5.5 implantation. It offers a significant benefit for earlier implantation of MCS in patients with cardiogenic shock, especially in settings where limited or delayed access to fluoroscopic imaging resources is a barrier to timely intervention.
Gandini L, Liu K, Passmore MR
… +12 more, Chan CHH, Wilson ES, Ijuin S, Milani A, Hyslop K, White N, Perera B, Obonyo N, Bouquet M, Li Bassi G, Fraser JF, Suen JY
Hydrogen has emerged as a therapeutic agent in inflammatory critical illnesses due to its potential to modulate inflammation and oxidative stress. However, its role in extracorporeal membrane oxygenation (ECMO), a life-s...Hydrogen has emerged as a therapeutic agent in inflammatory critical illnesses due to its potential to modulate inflammation and oxidative stress. However, its role in extracorporeal membrane oxygenation (ECMO), a life-saving intervention for severe cardiorespiratory failure associated with pronounced inflammation and oxidative stress, remains largely unexplored. This ex vivo study investigated whether ECMO could serve as an effective vehicle for hydrogen delivery. It also evaluated hydrogen's effects on oxidative stress, inflammation, and coagulation responses arising from the interaction between human blood and non-biological ECMO surfaces. Four healthy male volunteers each provided two blood donations, 6 months apart. We assigned human blood-filled ECMO circuits to two different sweep gas formulations: a CO₂-enriched gas mixture (n = 4) or a mixture of 2% hydrogen in CO₂-enriched gas (n = 4). At T0, stable hydrogen concentrations (9.82 ± 1.97 μmol/L) were achieved and maintained for 6 hours, confirming the reliability of the hydrogen delivery method. Hydrogen exposure significantly reduced collagen (p = 0.01), TRAP-6 (p = 0.04), and ADP-induced (p = 0.04) platelet aggregation and showed a trend toward reduction in oxidative stress markers. In conclusion, this preliminary ex vivo study demonstrates the feasibility of delivering hydrogen gas via the sweep gas of a clinically established ECMO machine and its initial effects on blood, warranting further investigation in larger preclinical animal models.
Computational fluid dynamics (CFD) is increasingly important in biomedical engineering; however, its use in medical device design remains constrained by regulatory requirements for model validation and verification. To a...Computational fluid dynamics (CFD) is increasingly important in biomedical engineering; however, its use in medical device design remains constrained by regulatory requirements for model validation and verification. To address this, the Food and Drug Administration (FDA) proposed a benchmark nozzle geometry for standardized validation. This study employs a turbulence-based hemolysis model-the Ozturk-Papavassiliou-O'Rear (OPO) model-to investigate the FDA nozzle and identify red blood cell (RBC) damage caused by eddy structures similar in size to RBCs. Flow simulations were conducted for sudden contraction (SC) and gradual cone (GC) nozzle configurations at inlet velocities of 0.46 and 0.6 m/s (throat Reynolds of 3,500 and 6,500). Regions where eddies fall within the damaging Kolmogorov length scale were identified and analyzed. Hemolysis predictions were made using the eddy surface area distribution and validated against experimental hemolysis index (HI) data. For SC, a qualitative indicator, the cumulative eddy surface area of 6-20 μm, was provided; a numerical HI was postponed until a recalibration specific to SC and independent verification. For GC, the OPO model reproduced experimental trends in hemolysis risk localization but underpredicted absolute HI. These findings suggest that the OPO model offers a viable approach to predicting turbulence-resolved hemolysis in medical device design.
Del Nido Cardioplegia (DNC) is widely used in nontransplant cardiac surgery, but its role as a preservation solution in cardiac transplantation is unclear. We conducted a retrospective observational study of 61 patients...Del Nido Cardioplegia (DNC) is widely used in nontransplant cardiac surgery, but its role as a preservation solution in cardiac transplantation is unclear. We conducted a retrospective observational study of 61 patients undergoing heart transplant between January 2015 and December 2023. Only recipients with locally procured donor hearts were included. Recipients were grouped according to the type of preservative solution: DNC (n = 33) versus control (crystalloid + cold blood cardioplegia; n = 28). Patients in the DNC group were older and more frequently received hearts from donation after circulatory death. The Del Nido Cardioplegia group had lower troponin-T release at 48 hours (median [interquartile range {IQR}]: 1,062 [820] vs. 700 [345]; p = 0.03). Compared with the DNC, control group was related with longer ischemic (median [IQR]: 65 [55-83] vs. 80 [70.2-92.7] minutes; p = 0.002) and bypass times (median [IQR]: 90 [73.5-112] vs. 108 [97-118] minutes; p = 0.001). On-pump blood glucose levels and need for electrical defibrillation were lower with DNC. In heart transplantation using locally procured grafts, DNC appears to be a feasible preservation strategy. Del Nido Cardioplegia was associated with shorter operative times and lower troponin release in our initial experience. Further studies should be performed to confirm these promising results.
Carey G, Antonini MV, McCauley M
… +13 more, Tonna J, Furlong-Dillard J, Hutin A, Swol J, Cho SM, Sandhu H, Zaaqoq A, Davidson M, Hermsen J, Desai A, Bělohlávek J, McCarthy D, Glazer JM
Although the goal of extracorporeal cardiopulmonary resuscitation (ECPR) remains survival with meaningful neurologic recovery, secondary contribution to organ donation is increasingly recognized. We identified standardiz...Although the goal of extracorporeal cardiopulmonary resuscitation (ECPR) remains survival with meaningful neurologic recovery, secondary contribution to organ donation is increasingly recognized. We identified standardized outcome metrics for quality improvement and reporting and explored the feasibility of developing an ECPR Cumulative Impact Index. Fourteen international ECPR experts completed a modified Delphi process to achieve these aims. Qualitative analysis of free-text responses further informed framework development. Consensus was not reached on a unified scoring index. However, participants endorsed several reporting domains with greater than 75% agreement, including cerebral performance categorization and modified Rankin score with organ donation as outcomes, and specific metric tracking pertaining to organ donation. Similarly, there was greater than 75% agreement not to stratify organ donation into neurological versus circulatory determination of death. Qualitative analysis explored five themes: death without donation, non-neurologically intact survival, organ donation benefit, score implementation, and ethical principles. Particular emphasis was placed on avoiding incentivization of cannulation solely for organ donation and understanding that the lived patient and family experience cannot be so simply summarized through numeric quantification. Ultimately, the panel agreed that while a unified ECPR beneficence score remains elusive, consensus-based outcome metrics offer a practical and ethically grounded framework for program evaluation.
Patients with continuous-flow ventricular assist devices (CF-VADs) face an elevated risk of nonsurgical bleeding. One hypothetical cause is that the loss of pulsatility promotes unraveling and enzymatic degradation of vo...Patients with continuous-flow ventricular assist devices (CF-VADs) face an elevated risk of nonsurgical bleeding. One hypothetical cause is that the loss of pulsatility promotes unraveling and enzymatic degradation of von Willebrand factor (VWF), a key clotting protein. Artificial pulsatility has been proposed to counter this effect, but the role of pulse frequency in VWF unraveling remains unclear. This study investigates VWF conformational changes in response to varying pulse frequencies. Membrane-bound VWF on human aortic endothelial cells (HAECs) exposed to pulsatile in vitro conditions exhibited significantly less unraveling than under continuous flow ( p < 0.005). To enable real-time observation of VWF conformation, VWF was immobilized in a microfluidic device and exposed to continuous or pulsatile flows (20, 40, or 60 pulses/min) to model HAEC-bound unraveling. Results showed that frequencies greater than or equal to 40 pulses/min significantly reduced maximum extension compared with continuous flow and low-frequency conditions (≤ 20 pulses/min), whereas minimum extension was greatest under continuous flow and declined as frequency increased. Step-change flow experiments revealed a time constant of 0.19 ± 0.04 seconds for extension and ~1 second for recoiling. These findings support optimizing pulsatile flow frequency as a strategy to minimize VWF unfolding and mitigate nonsurgical bleeding in CF-VAD patients.
Severe respiratory failure is frequently complicated by right ventricular dysfunction (RVD), which occurs in 20-50% of cases. In patients on venovenous extracorporeal membrane oxygenation (VV ECMO) with refractory RVD, c...Severe respiratory failure is frequently complicated by right ventricular dysfunction (RVD), which occurs in 20-50% of cases. In patients on venovenous extracorporeal membrane oxygenation (VV ECMO) with refractory RVD, conversion to venopulmonary (VP) ECMO can provide additional mechanical support. This study evaluates the impact of VV to VP ECMO conversion on mortality and end-organ dysfunction in severe respiratory failure. A retrospective cohort study of 19 adult patients on VV ECMO who were converted to VP ECMO was performed. Outcomes included in-hospital mortality, resolution of acute kidney injury (AKI), pressor requirements, ventilator and ECMO parameters, and ECMO support duration. Venopulmonary ECMO conversion facilitated AKI resolution in 62.5% of patients with pre-conversion AKI (5/8) and was associated with liberation from continuous renal replacement therapy in 40% of patients (2/5). Conversion resulted in reduced pressor requirements (7/9, 78%), ECMO flows (15/19, 79%), sweep gas flow (12/19, 63%), ECMO fraction of inspired oxygen (FiO2; 5/19, 26%), and ventilator FiO2 (3/19, 16%). Venopulmonary ECMO conversion facilitated sedation weaning in 10 patients (53%) which was previously not tolerated due to desaturation events on VV ECMO. Overall, VP ECMO conversion was associated with improved oxygenation, hemodynamic stability, and end-organ function in the majority of patients.
The University of Wisconsin (UW) solution is widely used for cardiac allograft preservation. In early 2021, our center transitioned to Del Nido (DN) cardioplegia for all donors. This study evaluated whether this shift af...The University of Wisconsin (UW) solution is widely used for cardiac allograft preservation. In early 2021, our center transitioned to Del Nido (DN) cardioplegia for all donors. This study evaluated whether this shift affected post-transplant outcomes. Adult, single-organ, donation after brain death heart transplants from January 2020 to December 2023 were included; congenital cases and non-ice storage techniques were excluded. Recipients were grouped by preservation solution. Interrupted time series (ITS) regression accounted for temporal bias and baseline differences, while exponential decay analysis evaluated lactate clearance. Of 203 transplants, 71 used UW and 132 used DN. Baseline characteristics were similar aside from longer ischemic times in the DN group. Unadjusted outcomes showed no significant differences in severe primary graft dysfunction (PGD), early mortality, cardiac index, or 24 hour vasoactive inotrope score (VIS). Intensive care unit and hospital stays were longer in the DN group. Lactate clearance was faster with DN (half-life 11.3 vs. 18.6 hours; p = 0.07). Interrupted time series regression showed no significant impact of DN on PGD, mortality, or morbidity scores, though VIS modestly increased (p = 0.048), and peak lactate levels decreased (p = 0.004). Del Nido provides comparable preservation to UW, supporting its use based on logistics and availability.
This study aimed to explore the effect of trimethoprim on the antibacterial efficacy and cell viability of vancomycin- and gentamicin-containing bone cement, aiming to establish a basis for its clinical application. Bone...This study aimed to explore the effect of trimethoprim on the antibacterial efficacy and cell viability of vancomycin- and gentamicin-containing bone cement, aiming to establish a basis for its clinical application. Bone cement was grouped by antibiotic combinations: vancomycin with trimethoprim (groups I-III), gentamicin with trimethoprim (groups IV-VI), vancomycin alone (group VII), gentamicin alone (group VIII), and trimethoprim alone (group IX). Antibacterial efficacy against Staphylococcus aureus (n = 5) was assessed using the plate diffusion method, and cell viability was evaluated using CCK8 assays for cytotoxicity and proliferation (n = 5). Increasing trimethoprim content significantly enhanced antibacterial zones for vancomycin- and gentamicin-based groups ( p < 0.05). Vancomycin-trimethoprim groups showed moderate cytotoxicity by day 5, while other groups demonstrated robust cell proliferation with minimal cytotoxicity ( p < 0.05). Trimethoprim improves the antibacterial efficacy of vancomycin and gentamicin bone cement while maintaining cell viability.
Right ventricular failure (RVF) is an important complication following implantation of a left ventricular assist device (LVAD) in patients with advanced heart failure. This study aims to identify perioperative hemodynami...Right ventricular failure (RVF) is an important complication following implantation of a left ventricular assist device (LVAD) in patients with advanced heart failure. This study aims to identify perioperative hemodynamic predictors of RVF following LVAD implantation and develop an internally validated predictive model. Patients who underwent LVAD implantations between March 2013 and March 2023 at a large-volume tertiary center were retrospectively analyzed. The primary outcome was early post-implant RVF, defined by need for right ventricular assist device (RVAD), prolonged inotrope dependence (> 14 days), or death within 14 days while on inotropes. Perioperative hemodynamic variables were analyzed using univariate logistic regression. A prediction model was then developed using stepwise multivariate logistic regression, and internally validated using k-fold cross-validation. Among 210 patients, 73 patients (34.8%) developed early post-implant RVF. Decreased post-implant cardiac index (odds ratio [OR]: 0.0122, p = 0.001), decreased mean arterial pressure (OR: 0.932, p = 0.008), and simultaneously increased cardiac index and pulmonary pulse pressure (OR: 1.13, p = 0.021) independently predicted RVF. Preimplantation IV inotrope therapy was a significant confounder (OR: 3.96, p = 0.021). Our proposed predictive model achieved strong discriminatory power (area under the curve [AUC] of 0.830) and stable cross-validation performance. External validation with multicenter cohorts is warranted to confirm predictive accuracy and clinical applicability.
Patients who undergo left ventricular assist device (LVAD) implantation may present with severe tricuspid regurgitation (TR), revealing underlying right heart failure. This study aims to evaluate the impact of concurrent...Patients who undergo left ventricular assist device (LVAD) implantation may present with severe tricuspid regurgitation (TR), revealing underlying right heart failure. This study aims to evaluate the impact of concurrent tricuspid valve surgery (TVS) on LVAD implantation outcomes. Online electronic databases were systematically reviewed for studies including patients with advanced heart failure and TR treated by isolated LVAD implantation versus concomitant TVS and LVAD implantation. In-hospital outcomes were analyzed, and Kaplan-Meier (KM) curves presenting late survival by reconstruction of individual patient data. Sixteen studies were identified, comprising 2,206 patients who underwent either isolated LVAD or LVAD implant with concomitant TVS. There was no significant difference in early mortality between the two groups (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 0.85-1.65, p = 0.3, I2: 0%). The odds of right ventricular assist device (RVAD) implant were significantly higher in the LVAD + TVS group: (OR: 1.36 [95% CI: 1.0-1.86], p = 0.05). Analysis of late all-cause mortality showed a significantly higher risk of mortality in the LVAD + TVS group, hazard ratio (HR): 0.82 (0.69-0.98, p = 0.032) at each time-point. Tricuspid valve surgery at the same time as LVAD implant showed no difference in early operative mortality but jeopardized long-term survival. Future studies should aim to identify distinct patient subsets that could significantly benefit from TVS during the implantation of LVAD.
Anticoagulation is mandatory during venoarterial extracorporeal membrane oxygenation (V-A ECMO) flow reduction trials with very low blood flow. Anticoagulation in the ECMO circuit might be intensified with less effect in...Anticoagulation is mandatory during venoarterial extracorporeal membrane oxygenation (V-A ECMO) flow reduction trials with very low blood flow. Anticoagulation in the ECMO circuit might be intensified with less effect in the patient by temporarily increasing the heparin dose directly connected to the oxygenator. We performed a prospective observational study in 16 patients on V-A ECMO, measuring anticoagulation parameters before and at the end of flow reduction trials in both the patients' circulation and the ECMO circuit, while having increased the heparin infusion rate during the flow reduction trial. The heparin infusion rate was doubled in eight patients for 30 [25-30] minutes, which resulted in an increase in activated partial thromboplastin time (APTT) of 5 seconds [2-6] in the patient and 13 seconds [5-20] in the ECMO circuit (p = 0.03). Heparin was tripled in eight patients for 22 [18-27] minutes, which resulted in an increase in APTT with 5 seconds [3-9] in the patient and 10 seconds [5-22] in the ECMO circuit (p = 0.02). In conclusion, increased APTT levels in the ECMO circuit during flow reduction trials can be achieved by increasing heparin infusion rates via the ECMO circuit, with minor effects in the patient. This can be helpful in patients with high bleeding risk.
There are limited data regarding heart retransplantation (re-HT) using donors after circulatory death (DCD). We analyzed outcomes of adult re-HT using the United Network for Organ Sharing (UNOS) registry. We identified 6...There are limited data regarding heart retransplantation (re-HT) using donors after circulatory death (DCD). We analyzed outcomes of adult re-HT using the United Network for Organ Sharing (UNOS) registry. We identified 630 adult recipients who underwent isolated re-HT or re-HT with simultaneous kidney transplantation between 2018 and 2024. Recipient and donor characteristics, as well as clinical outcomes, were compared between brain death (DBD) (n = 578) and DCD (n = 52) groups. The proportion of re-HTs using DCD donors increased from 1.9% in 2020 to 24.1% in 2024 (95% confidence interval [CI], 48.2-110.9; p = 0.013). Before matching, the DBD group had a higher acuity of illness, with a significantly greater proportion listed as UNOS statuses 1-2 (57.0% vs. 15.0%; p < 0.001). After matching, the DCD group had significantly longer ischemic time (3.3 [2.6-3.9] vs. 4.0 [3.0-5.9] hours; p < 0.001), and a higher incidence of early post-transplant graft dysfunction at 24 hours (1.0% vs. 5.9%; p < 0.001). However, rates of acute rejection before discharge (19% vs. 14%, p = 0.63) and 180 day survival (95.0% [90.9-99.4] vs. 88.0% [79.4-97.5], p = 0.12) were comparable between groups. The use of DCD donors in re-HT has grown significantly and shows similar early outcomes to DBD donors. Our findings support the clinical utility of DCD for re-HT.