Successful clinical transplantation of hearts donated after circulatory death using direct procurement followed by hypothermic oxygenated perfusion: A report of the first 3 cases.

Transplantation of hearts donated after circulatory death (DCD) is emerging. Currently applied techniques (thoraco-abdominal normothermic regional perfusion and direct procurement followed by normothermic machine perfusion) face financial, ethical, and logistical challenges. We report the first three clinical cases of successful direct procurement followed by hypothermic oxygenated perfusion (DP-HOPE) with good 30-day outcome. DP-HOPE is a promising strategy to improve and simplify DCD heart procurement and preservation.

Complications related to extracorporeal life support in lung transplantation: single-center analysis.

Background: Extracorporeal life support (ECLS) is not routinely used at our center during sequential single-lung transplantation (LTx), but is restricted to anticipate and overcome hemodynamic and respiratory problems occurring peri-operatively. In this retrospective descriptive cohort study, we aim to describe our single-center experience with ECLS in LTx, analyzing ECLS-related complications. Methods: All transplantations with peri-operative ECLS use [2010-2020] were retrospectively analyzed. Multi-organ and heart-lung transplantation were excluded. Demographics, support type and indications are described. Complications are categorized according to the underlying nature and type. Data are presented as median [interquartile range (IQR)]. Kaplan-Meier was used for survival analysis. Results: The overall use of ECLS was 22% (156/703 patients) with a mean age of 52 years (IQR, 36-59 years). Transplant indications in ECLS cohort were interstitial lung disease (38%; n=60), chronic obstructive pulmonary disease (COPD) (19%; n=29), cystic fibrosis (17%; n=26) and others (26%; n=41). Per indication, 94% (15/16) of pulmonary arterial hypertension patients required ECLS, whereas only 8% (29/382) of COPD patients did. In 16% (25/156) of supported patients, veno-venous extracorporeal membrane oxygenation was initiated, while 77% (120/156) required veno-arterial support, and 7% (11/156) cardiopulmonary bypass. Thirty-day mortality was 6% (9/156). Sixteen percent (25/156) of patients were bridged to transplantation on ECLS and 24% (37/156) required post-operative support. Main reasons to use ECLS were intra-operative hemodynamic instability (53%; n=82), ventilation/oxygenation problems (22%; n=34) and reperfusion edema (17%; n=26). Overall incidence of patients with at least one ECLS-related complication was 67% (n=104). Most common complications were hemothorax (25%; n=39), need for continuous renal replacement therapy (19%; n=30), and thromboembolism (14%; n=22). Conclusions: ECLS was required in 22% of LTxs, with a reported ECLS-related complication rate of 67%, of which the most common was hemothorax. Larger databases are needed to further analyze complications and develop tailored deployment strategies for ECLS-use in LTx.

Isavuconazole Exposure in Critically Ill Patients Treated with Extracorporeal Membrane Oxygenation: Two Case Reports and a Narrative Literature Review.

Effective dosing of isavuconazole in patients supported by extracorporeal membrane oxygenation (ECMO) is important due to the role of isavuconazole as a first-line treatment in patients with influenza- and COVID-19-associated pulmonary aspergillosis. To date, robust pharmacokinetic data in patients supported by ECMO are limited. Therefore, it is unknown whether ECMO independently impacts isavuconazole exposure. We measured isavuconazole plasma concentrations in two patients supported by ECMO and estimated individual pharmacokinetic parameters using non-compartmental analysis and two previously published population pharmacokinetic models. Furthermore, a narrative literature review on isavuconazole exposure in adult patients receiving ECMO was performed. The 24 h areas under the concentration-time curve and trough concentrations of isavuconazole were lower in both patients compared with exposure values published before. In the literature, highly variable isavuconazole concentrations have been documented in patients with ECMO support. The independent effect of ECMO versus critical illness itself on isavuconazole exposure cannot be deduced from our and previously published (case) reports. Pending additional data, therapeutic drug monitoring is recommended in critically ill patients, regardless of ECMO support.

Clinical evaluation of the novel Capiox NX19 adult oxygenator-a multicenter study.

INTRODUCTION: The novel Capiox NX19 adult oxygenator is, compared to its predecessors, improved with enhanced air removal technology, a polymer heat exchanger and smaller, innovative hollow fibers resulting in a surface area reduction and a lower priming volume. The aim of this study was to evaluate the NX19 oxygenator performance in a clinical setting. METHODS: A prospective multicenter study was performed involving three large European university hospitals. The Capiox NX19 (n = 150) performance was assessed during adult cardiopulmonary bypass and involved gaseous microemboli handling and gas transfer efficiency. The heat exchanger performance was evaluated separately in vitro. RESULTS: The heat exchanger performance factors were 0.80 ± 0.03 and 0.58 ± 0.04 at pump flow rates of 3 L/min and 6 L/min, respectively. After priming, residual post-oxygenator gaseous microemboli count and volume were decreased by 91% and 93.7%, respectively. The gas compartment pressure was 6.0 ± 2.5 mmHg, while the O2 transfer was 69 ± 30 mL/min/m2 and the CO2 transfer 73 ± 34 mL/min/m2. The O2 gradient was 44 ± 19 mmHg/LPM and the O2 diffusing capacity 0.38 ± 0.14 mL/min/mmHg. The shunt fraction was 0.19 ± 0.13, whereas oxygenator resistance and shear stress were 10.5 ± 3.7 mmHg/LPM and 5.1 ± 3.1 dyn/cm2, respectively. CONCLUSION: This multicenter study displayed good clinical safety and performance of the NX19 oxygenator.

CytoSorb haemoadsorption for removal of apixaban-A proof-of-concept pilot case for a randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Emergent cardiac surgery in patients under anticoagulant therapy is still a major point of concern. Recently approved reversal agents are often not available or not suitable in the cardiac surgery setting, and timely discontinuation of the drug is not always feasible. CytoSorb® haemoadsorption therapy has been approved in Europe for intraoperative ticagrelor and rivaroxaban removal during cardiopulmonary bypass (CPB), but thus far the efficacy of CytoSorb® haemoadsorber on other anticoagulants (apixaban, dabigatran, edoxaban) has only been tested in vitro, and some signals of clinical benefits have reported in a few case reports. CASE SUMMARY: We describe a case of CPB implementation with CytoSorb® in a haemodynamic unstable patient with prosthetic aortic valve endocarditis on apixaban therapy. WHAT IS NEW AND CONCLUSION: CytoSorb® proved to be effective for removal of apixaban in emergency surgery setting by direct measurements of drug levels before and during CPB circulation.

Pleural decortication and hyperthermic intrathoracic chemotherapy for pseudomyxoma.

Aim: Pleural dissemination of pseudomyxoma peritonei (PMP) is an extremely rare diagnosis, for which no standard therapy is available.Methods: We describe the successful treatment of a 67-year-old male diagnosed with left-sided intrapleural dissemination of PMP (low-grade appendiceal mucinous neoplasm), 2 years after treatment of abdominal PMP with cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy. Treatment consisted of extended pleural decortication (ePD) and oxaliplatin-based hyperthermic intrathoracic chemotherapy (HITHOC). The patient is doing well without complications or signs of recurrence, 26 months after thoracic surgery.Conclusion: ePD in combination with HITHOC is a valuable treatment for thoracic PMP.

Transplantation of donor hearts after circulatory death using normothermic regional perfusion and cold storage preservation.

OBJECTIVES: Hearts donated after circulatory determination of death are usually preserved with normothermic machine perfusion prior to transplantation. This type of preservation is costly, requires bench time adding to warm ischaemia, and does not provide a reliable evaluation of the unloaded donor heart. We report on 4 successful donation after circulatory death (category III) hearts transplanted after thoraco-abdominal normothermic regional perfusion (NRP) and static cold storage. METHODS: After life sustaining therapy was withdrawn and death was declared, perfusion to thoraco-abdominal organs was restored using extracorporeal circulation via cannulas in the femoral artery and vein and clamping of supra-aortic vessels. After weaning from extracorporeal circulation, cardiac function was assessed. Once approved, the heart was retrieved and stored using classic static cold storage. Data are expressed as median [min-max]. RESULTS: Donor and recipient ages were 44 years [12-60] (n = 4) and 53 years [14-64] (n = 4), respectively. Time from the withdrawal of life sustaining therapy to start of NRP was 22 min [18-31]. Cold storage time was 72 min [35-129]. Thirty-day survival was 100% with a left ventricle ejection fraction of 60% [50-60]. CONCLUSIONS: Donation after circulatory death heart transplantation using thoraco-abdominal NRP and subsequent cold storage preservation for up to 129 min was safe for 4 procedures and could be a way to expand the donor heart pool while avoiding costs of machine preservation.

Successful resuscitation after hyperkalemic cardiac arrest during liver transplantation by converting veno-venous bypass to veno-arterial ECMO.

INTRODUCTION: Intraoperative cardiac arrest (ICA) is a feared complication during liver transplantation (LTx), typically occurring during reperfusion. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been used for post-reperfusion cardiac arrest. CASE REPORT: We present a case of successful resuscitation after hyperkalemic ICA during the pre-anhepatic phase of a second liver transplantation by converting veno-venous bypass (VVB) to VA-ECMO. DISCUSSION: While this technique has been recommended for ICA during reperfusion, it has never been reported during the pre-anhepatic phase. VA-ECMO can be a lifesaving extension to cardiopulmonary resuscitation for ICA during LTx with beneficial neurological outcome by providing perfusion while the cause of ICA is reversed. CONCLUSION: Conversion of VVB to VA-ECMO should be considered in all patients who suffer from ICA during LTx with use of VVB. With VVB installed, conversion to VA-ECMO is fast and effective. If VVB is not used, early VA-ECMO should be considered for ICA.

A retrospective database analysis to evaluate the potential of ex vivo lung perfusion to recruit declined lung donors.

Ex vivo lung perfusion (EVLP) is currently used for both standard and extended-criteria donor (ECD) lungs. To enlarge the donor pool, we might have to extend the threshold for ECD donation. The purpose of this study was to estimate how many additional ECD lungs could be recruited by EVLP. We reviewed all multi-organ donors (MODs) from our collaborative donor hospitals (January 2010-June 2015). All unused lung donors were categorized using registered donor data and evaluated by two independent investigators to identify which lungs could be transplanted after EVLP. 584 MODs were registered at our transplant center. 268 (45.9%) were declined as lung donor at the moment of registration, and 316 (54.1%) were considered as a donor for lung transplantation. In the latter, lungs from 220 (37.7%) donors were transplanted and 96 donors (16.4%) were not. We identified 78 of 364 declined donors (21.4%) whose lungs could potentially become transplantable after EVLP. With this retrospective database analysis of unused lung donors, we identified a large potential for EVLP to further increase the donor pool in transplant centers where the majority of donor lungs are already extended.

First-in-man observation of Talaromyces marneffei-transmission by organ transplantation.

A lung transplant recipient was diagnosed with penicilliosis due to Talaromyces marneffei, a fungus endemic in South-East Asia, which was acquired by donor transmission. This first case of Talaromyces marneffei-transmission by transplantation underscores that current globalisation of travelling necessitates increased vigilance for transmission of unusual pathogens in organ recipients.

A plasma-based biomatrix mixed with endothelial progenitor cells and keratinocytes promotes matrix formation, angiogenesis, and reepithelialization in full-thickness wounds.

In search of an autologous vascularized skin substitute, we treated full-thickness wounds (FTWs) with autologous platelet-rich plasma gel (APG) in which we embedded endothelial progenitor cells (EPCs) and basal cell keratinocytes (KCs). We cultivated autologous KCs in low-serum conditions and expanded autologous EPCs from venous blood. FTWs (n = 55) were created on the backs of four pigs, covered with wound chambers, and randomly assigned to the following treatments: (1) APG, (2) APG + KCs, (3) APG + EPCs, (4) APG + KCs + EPCs, and (5) saline. All wounds were biopsied to measure neovascularization (lectin Bandeiraea Simplicifolia-1 (BS-1), alpha smooth muscle actin [alphaSMA], and membrane type 1 matrix metalloproteinase (MT1-MMP)), matrix deposition (fibronectin, collagen type I/III, and alphavbeta3), and reepithelialization. Wound fluids were analyzed for protein expression. All APG-treated wounds showed more vascular structures (p < 0.001), and the addition of EPCs further improved neovascularization, as confirmed by higher lectin, alphaSMA, and MT1-MMP. APG groups had higher collagen I/III (p < 0.05), alphavbeta3, and fibronectin content (p < 0.001), and they exhibited higher concentrations of platelet-derived growth factor subunit bb, basic fibroblast growth factor, hepatocyte growth factor, insulin growth factor-1, transforming growth factor-beta1 and -beta3, matrix metalloproteinase-1 and -z9, and tissue-inhibiting matrix metalloproteinase-1 and -2. Applying APG + KCs resulted in the highest reepithelialization rates (p < 0.001). No differences were found for wound contraction by planimetry. In this porcine FTW model, APG acts as a supportive biomatrix that, along with the embedded cells, improves extracellular matrix organization, promotes angiogenesis, and accelerates reepithelialization.