BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.
- MeSH
- dárci tkání statistika a číselné údaje MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- perfuze * metody přístrojové vybavení MeSH
- přežívání štěpu * MeSH
- senioři MeSH
- terapeutická hypotermie metody MeSH
- transplantace jater * metody škodlivé účinky MeSH
- uchovávání orgánů * metody MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
Ischemic stroke is a common and serious condition. Timely restoration of cerebral perfusion is crucial for improving patient outcomes and reducing economic impacts. For three decades, alteplase has been the only established pharmacological treatment, often combined with endovascular therapy. Tenecteplase, a newer generation of fibrinolytic therapy, is recommended by the ESO 2023 guidelines as a suitable alternative to alteplase, particularly if treatment is initiated within 4.5 hours of symptom onset. Tenecteplase offers higher fibrin specificity, lower binding to PAI-1, and a longer plasma half-life compared to alteplase, allowing for single bolus administration. Clinical studies have shown that tenecteplase 0.25 mg/kg achieves better recanalization and clinical improvement without increased risk of bleeding. It is equally effective and safe as alteplase, with meta-analyses indicating improved recanalization and clinical outcomes at a lower risk of bleeding. Tenecteplase is a suitable alternative for treating iNCMP, especially within 4.5 hours of symptom onset. Its single bolus administration simplifies hospital management and improves the logistics of transporting patients to specialized centers.
- MeSH
- fibrinolýza účinky léků MeSH
- ischemická cévní mozková příhoda * diagnóza farmakoterapie MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- reperfuze klasifikace metody MeSH
- tenektepláza * aplikace a dávkování farmakologie terapeutické užití MeSH
- tkáňový aktivátor plazminogenu farmakologie terapeutické užití MeSH
- trombolytická terapie klasifikace metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Cardiovascular diseases represent an economic burden for health systems accounting for substantial morbidity and mortality worldwide. Despite timely and costly efforts in drug development, the cardiovascular safety and efficacy of the drugs are not always fully achieved. These lead to the drugs' withdrawal with adverse cardiac effects from the market or in the late stages of drug development. There is a growing need for a cost-effective drug screening assay to rapidly detect potential acute drug cardiotoxicity. The Langendorff isolated heart perfusion technique, which provides cardiac hemodynamic parameters (e.g., contractile function and heart rate), has become a powerful approach in the early drug discovery phase to overcome drawbacks in the drug candidate's identification. However, traditional ex vivo retrograde heart perfusion methods consume a large volume of perfusate, which increases the cost and limits compound screening. An elegant and cost-effective alternative mode for ex vivo retrograde heart perfusion is the constant-flow with a recirculating circuit (CFCC), which allows assessment of cardiac function using a reduced perfusion volume while limiting adverse effects on the heart. Here, we provide evidence for cardiac parameters stability over time in this mode. Next, we demonstrate that our recycled ex vivo perfusion system and the traditional open one yield similar outputs on cardiac function under basal conditions and upon ?-adrenergic stimulation with isoproterenol. Subsequently, we validate the proof of concept of therapeutic agent screening using this efficient method. ?-blocker (i.e., propranolol) infusion in closed circulation countered the positive effects induced by isoproterenol stimulation on cardiac function. Keywords: Drug development, Drug screening, Cardiovascular safety, Langendorff method, Closed circulation.
BACKGROUND: We evaluated the association of reperfusion quality and different patterns of achieved reperfusion with clinical and radiological outcomes in the ESCAPE NA1 trial. METHODS: Data are from the ESCAPE-NA1 trial. Good clinical outcome [90-day modified Rankin Scale (mRS) 0-2], excellent outcome (90-day mRS0-1), isolated subarachnoid hemorrhage, symptomatic hemorrhage (sICH) on follow-up imaging, and death were compared across different levels of reperfusion defined by expanded Treatment in Cerebral Infarction (eTICI) Scale. Comparisons were also made between patients with (a) first-pass eTICI 2c3 reperfusion vs multiple-pass eTICI 2c3; (b) final eTICI 2b reperfusion vs eTICI 2b converted-to-eTICI 2c3; (c) sudden reperfusion vs gradual reperfusion if >1 pass was required. Multivariable logistic regression was used to test associations of reperfusion grade and clinical outcomes. RESULTS: Of 1037 included patients, final eTICI 0-1 was achieved in 46 (4.4%), eTICI 2a in 76 (7.3%), eTICI 2b in 424 (40.9%), eTICI 2c in 284 (27.4%), and eTICI 3 in 207 (20%) patients. The odds for good and excellent clinical outcome gradually increased with improved reperfusion grades (adjOR ranging from 5.7-29.3 and 4.3-17.6) and decreased for sICH and death. No differences in outcomes between first-pass versus multiple-pass eTICI 2c3, eTICI 2b converted-to-eTICI 2c3 versus unchanged eTICI 2b and between sudden versus gradual eTICI 2c3 reperfusion were observed. CONCLUSION: Better reperfusion degrees significantly improved clinical outcomes and reduced mortality, independent of the number of passes and whether eTICI 2c3 was achieved suddenly or gradually.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- reperfuze * metody MeSH
- senioři MeSH
- subarachnoidální krvácení terapie diagnostické zobrazování mortalita MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.
- MeSH
- arteria femoralis * MeSH
- dospělí MeSH
- ischemie prevence a kontrola etiologie MeSH
- katetrizace metody MeSH
- končetiny krevní zásobení MeSH
- lidé MeSH
- mimotělní membránová oxygenace * metody MeSH
- perfuze metody MeSH
- periferní katetrizace metody škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Atrioventricular (AV) accessory pathways (APs) provide additional electrical connections between the atria and ventricles, resulting in severe electrical disturbances. It is generally accepted that APs originate in the altered annulus fibrosus maturation in the late prenatal and perinatal period. However, current experimental methods cannot address their development in specific locations around the annulus fibrosus because of the inaccessibility of late fetal hearts for electrophysiological investigation under physiological conditions. In this study, we describe an approach for optical mapping of the retrogradely perfused chick heart in the last third of the incubation period. This system showed stability for electrophysiological measurement for several hours. This feature allowed analysis of the number and functionality of the APs separately in each clinically relevant position. Under physiological conditions, we also recorded the shortening of the AV delay with annulus fibrosus maturation and analyzed ventricular activation patterns after conduction through APs at specific locations. We observed a gradual regression of AP with an area-specific rate (left-sided APs disappeared first). The results also revealed a sudden drop in the number of active APs between embryonic days 16 and 18. Accessory myocardial AV connections were histologically documented in all positions around the annulus fibrosus even after hatching. The fact that no electrically active AP was present at this stage highlights the necessity of electrophysiological evaluation of accessory atrioventricular connections in studying AP formation.NEW & NOTEWORTHY We present the use of retrograde perfusion and optical mapping to investigate, for the first time, the regression of accessory pathways during annulus fibrosus maturation, separately examining each clinically relevant location. The system enables measurements under physiological conditions and demonstrates long-lasting stability compared with other approaches. This study offers applications of the model to investigate electrical and/or functional development in late embryonic development without concern about heart viability.
- MeSH
- akční potenciály * MeSH
- kuřecí embryo MeSH
- nodus atrioventricularis embryologie patofyziologie MeSH
- perfuze MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Incomplete reperfusion (IR) after mechanical thrombectomy (MT) can be a consequence of residual occlusion, no-reflow phenomenon, or collateral counterpressure. Data on the impact of these phenomena on clinical outcome are limited. METHODS: Patients from the ESCAPE-NA1 trial with IR (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b) were compared with those with complete or near-complete reperfusion (eTICI 2c-3) on the final angiography run. Final runs were assessed for (a) an MT-accessible occlusion, or (b) a non-MT-accessible occlusion pattern. The primary clinical outcome was modified Rankin Scale (mRS) 0-2 at 90 days. Our imaging outcome was infarction in IR territory on follow-up imaging. Unadjusted and adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95% CI) were obtained. RESULTS: Of 1105 patients, 443 (40.1%) with IR and 506 (46.1%) with complete or near-complete reperfusion were included. An MT-accessible occlusion was identified in 147/443 patients (33.2%) and a non-MT-accessible occlusion in 296/443 (66.8%). As compared with patients with near-complete/complete reperfusion, patients with IR had significantly lower chances of achieving mRS 0-2 at 90 days (aIRR 0.82, 95% CI 0.74 to 0.91). Rates of mRS 0-2 were lower in the MT-accessible occlusion group as compared with the non-MT-accessible occlusion pattern group (aIRR 0.71, 95% CI 0.60 to 0.83, and aIRR 0.89, 95% CI 0.81 to 0.98, respectively). More patients with MT-accessible occlusion patterns developed infarcts in the non-reperfused territory as compared with patients with non-MT occlusion patterns (68.7% vs 46.3%). CONCLUSION: IR was associated with worse clinical outcomes than near-complete/complete reperfusion. Two-thirds of our patients with IR had non-MT-accessible occlusion patterns which were associated with better clinical and imaging outcomes compared with those with MT-accessible occlusion patterns.
- MeSH
- cerebrální infarkt diagnostické zobrazování terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- reperfuze * metody MeSH
- senioři MeSH
- trombektomie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
PURPOSE: Dynamic Contrast-Enhanced (DCE) MRI with 2nd generation pharmacokinetic models provides estimates of plasma flow and permeability surface-area product in contrast to the broadly used 1st generation models (e.g. the Tofts models). However, the use of 2nd generation models requires higher frequency with which the dynamic images are acquired (around 1.5 s per image). Blind deconvolution can decrease the demands on temporal resolution as shown previously for one of the 1st generation models. Here, the temporal-resolution requirements achievable for blind deconvolution with a 2nd generation model are studied. METHODS: The 2nd generation model is formulated as the distributed-capillary adiabatic-tissue-homogeneity (DCATH) model. Blind deconvolution is based on Parker's model of the arterial input function. The accuracy and precision of the estimated arterial input functions and the perfusion parameters is evaluated on synthetic and real clinical datasets with different levels of the temporal resolution. RESULTS: The estimated arterial input functions remained unchanged from their reference high-temporal-resolution estimates (obtained with the sampling interval around 1 s) when increasing the sampling interval up to about 5 s for synthetic data and up to 3.6-4.8 s for real data. Further increasing of the sampling intervals led to systematic distortions, such as lowering and broadening of the 1st pass peak. The resulting perfusion-parameter estimation error was below 10% for the sampling intervals up to 3 s (synthetic data), in line with the real data perfusion-parameter boxplots which remained unchanged up to the sampling interval 3.6 s. CONCLUSION: We show that use of blind deconvolution decreases the demands on temporal resolution in DCE-MRI from about 1.5 s (in case of measured arterial input functions) to 3-4 s. This can be exploited in increased spatial resolution or larger organ coverage.
BACKGROUND: While 4 randomized controlled clinical trials confirmed the early benefits of hypothermic oxygenated machine perfusion (HOPE), high-level evidence regarding long-term clinical outcomes is lacking. The aim of this follow-up study from the HOPE-ECD-DBD trial was to compare long-term outcomes in patients who underwent liver transplantation using extended criteria donor allografts from donation after brain death (ECD-DBD), randomized to either HOPE or static cold storage (SCS). METHODS: Between September 2017 and September 2020, recipients of liver transplantation from 4 European centers receiving extended criteria donor-donation after brain death allografts were randomly assigned to HOPE or SCS (1:1). Follow-up data were available for all patients. Analyzed endpoints included the incidence of late-onset complications (occurring later than 6 months and graded according to the Clavien-Dindo Classification and the Comprehensive Complication Index) and long-term graft survival and patient survival. RESULTS: A total of 46 patients were randomized, 23 in both arms. The median follow-up was 48 months (95% CI: 41-55). After excluding early perioperative morbidity, a significant reduction in late-onset morbidity was observed in the HOPE group (median reduction of 23 Comprehensive Complication Index-points [p=0.003] and lower incidence of major complications [Clavien-Dindo ≥3, 43% vs. 85%, p=0.009]). Primary graft loss occurred in 13 patients (HOPE n=3 vs. SCS n=10), resulting in a significantly lower overall graft survival (p=0.029) and adverse 1-, 3-, and 5-year survival probabilities in the SCS group, which did not reach the level of significance (HOPE 0.913, 0.869, 0.869 vs. SCS 0.783, 0.606, 0.519, respectively). CONCLUSIONS: Our exploratory findings indicate that HOPE reduces late-onset morbidity and improves long-term graft survival providing clinical evidence to further support the broad implementation of HOPE in human liver transplantation.
BACKGROUND: Disparities in the availability of reperfusion services for acute ischemic stroke are considerable globally and require urgent attention. Contemporary data on the availability of reperfusion services in different countries are used to provide the necessary evidence to prioritize where access to acute stroke treatment is needed. AIMS: To provide a snapshot of published literature on the provision of reperfusion services globally, including when facilitated by telemedicine or mobile stroke unit services. METHODS: We searched PubMed to identify original articles, published up to January 2023 for the most recent, representative, and relevant patient-level data for each country. Keywords included thrombolysis, endovascular thrombectomy and telemedicine. We also screened reference lists of review articles, citation history of articles, and the gray literature. The information is provided as a narrative summary. RESULTS: Of 11,222 potentially eligible articles retrieved, 148 were included for review following de-duplications and full-text review. Data were also obtained from national stroke clinical registry reports, Registry of Stroke Care Quality (RES-Q) and PRE-hospital Stroke Treatment Organization (PRESTO) repositories, and other national sources. Overall, we found evidence of the provision of intravenous thrombolysis services in 70 countries (63% high-income countries (HICs)) and endovascular thrombectomy services in 33 countries (68% HICs), corresponding to far less than half of the countries in the world. Recent data (from 2019 or later) were lacking for 35 of 67 countries with known year of data (52%). We found published data on 74 different stroke telemedicine programs (93% in HICs) and 14 active mobile stroke unit pre-hospital ambulance services (80% in HICs) around the world. CONCLUSION: Despite remarkable advancements in reperfusion therapies for stroke, it is evident from available patient-level data that their availability remains unevenly distributed globally. Contemporary published data on availability of reperfusion services remain scarce, even in HICs, thereby making it difficult to reliably ascertain current gaps in the provision of this vital acute stroke treatment around the world.
- MeSH
- cévní mozková příhoda * epidemiologie terapie MeSH
- ischemická cévní mozková příhoda * MeSH
- lidé MeSH
- reperfuze MeSH
- sanitky MeSH
- trombektomie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
