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

OBJECTIVE: The aim of this study was to evaluate peak serum alanine aminotransferase (ALT) and postoperative clinical outcomes after hypothermic oxygenated machine perfusion (HOPE) versus static cold storage (SCS) in extended criteria donation (ECD) liver transplantation (LT) from donation after brain death (DBD). BACKGROUND: HOPE might improve outcomes in LT, particularly in high-risk settings such as ECD organs after DBD, but this hypothesis has not yet been tested in a randomized controlled clinical trial (RCT). METHODS: Between September 2017 and September 2020, 46 patients undergoing ECD-DBD LT from four centers were randomly assigned to HOPE (n = 23) or SCS (n = 23). Peak-ALT levels within 7 days following LT constituted the primary endpoint. Secondary endpoints included incidence of postoperative complications [Clavien-Dindo classification (CD), Comprehensive Complication Index (CCI)], length of intensive care- (ICU) and hospital-stay, and incidence of early allograft dysfunction (EAD). RESULTS: Demographics were equally distributed between both groups [donor age: 72 (IQR: 59-78) years, recipient age: 62 (IQR: 55-65) years, labMELD: 15 (IQR: 9-25), 38 male and 8 female recipients]. HOPE resulted in a 47% decrease in serum peak ALT [418 (IQR: 221-828) vs 796 (IQR: 477-1195) IU/L, P = 0.030], a significant reduction in 90-day complications [44% vs 74% CD grade ≥3, P = 0.036; 32 (IQR: 12-56) vs 52 (IQR: 35-98) CCI, P = 0.021], and shorter ICU- and hospital-stays [5 (IQR: 4-8) vs 8 (IQR: 5-18) days, P = 0.045; 20 (IQR: 16-27) vs 36 (IQR: 23-62) days, P = 0.002] compared to SCS. A trend toward reduced EAD was observed for HOPE (17% vs 35%; P = 0.314). CONCLUSION: This multicenter RCT demonstrates that HOPE, in comparison to SCS, significantly reduces early allograft injury and improves post-transplant outcomes in ECD-DBD liver transplantation.

• MeSH
• alografty MeSH
• dárci tkání zásobování a distribuce   MeSH
• design vybavení MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• perfuze přístrojové vybavení   MeSH
• pooperační komplikace epidemiologie   prevence a kontrola   MeSH
• přežívání štěpu MeSH
• senioři MeSH
• terapeutická hypotermie přístrojové vybavení   MeSH
• transplantace jater metody   MeSH
• uchovávání orgánů přístrojové vybavení   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
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Evropa MeSH

The purpose of calculating the capillary filtration coefficient is to experimentally evaluate edema formation in models of pulmonary ischemia-reperfusion injury. For many years, the obtaining of this coefficient implies a series of manual maneuvers during ex-vivo reperfusion of pulmonary arterial pressure, venous pressure and weight, as well as the calculation of the Kfc formula. Through automation, the calculation of capillary filtration coefficient could be easier and more efficient. To describe an automatic method designed in our laboratory to calculating the capillary filtration coefficient and compare with traditional determination of capillary filtration coefficient as gold standard method. An automatic three valve perfusion system was constructed, commanded by a mastery module connected to a graphical user interface. To test its accuracy, cardiopulmonary blocks of Wistar rats were harvested and distributed in manual (n=8) and automated (n=8) capillary filtration coefficient determination groups. Physiological parameters as pulmonary arterial pressure, pulmonary venous pressure, weight and capillary filtration coefficient were obtained. Results: Capillary filtration coefficient, pulmonary arterial pressure, venous arterial pressure shown no statistical significance difference between the groups. The automated perfusion system for obtaining Kfc was standardized and validated, giving reliable results without biases and making the process more efficient in terms of time and personal staff.

• MeSH
• arteria pulmonalis fyziologie   MeSH
• kapilární permeabilita fyziologie   MeSH
• kapiláry fyziologie   MeSH
• krysa rodu rattus MeSH
• orgánové kultury - kultivační techniky MeSH
• perfuze přístrojové vybavení   metody   MeSH
• plicní tlak v zaklínění fyziologie   MeSH
• potkani Wistar MeSH
• venae pulmonales fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Mammalian cell perfusion cultures are gaining renewed interest as an alternative to traditional fed-batch processes for the production of therapeutic proteins, such as monoclonal antibodies (mAb). The steady state operation at high viable cell density allows the continuous delivery of antibody product with increased space-time yield and reduced in-process variability of critical product quality attributes (CQA). In particular, the production of a confined mAb N-linked glycosylation pattern has the potential to increase therapeutic efficacy and bioactivity. In this study, we show that accurate control of flow rates, media composition and cell density of a Chinese hamster ovary (CHO) cell perfusion bioreactor allowed the production of a constant glycosylation profile for over 20 days. Steady state was reached after an initial transition phase of 6 days required for the stabilization of extra- and intracellular processes. The possibility to modulate the glycosylation profile was further investigated in a Design of Experiment (DoE), at different viable cell density and media supplement concentrations. This strategy was implemented in a sequential screening approach, where various steady states were achieved sequentially during one culture. It was found that, whereas high ammonia levels reached at high viable cell densities (VCD) values inhibited the processing to complex glycan structures, the supplementation of either galactose, or manganese as well as their synergy significantly increased the proportion of complex forms. The obtained experimental data set was used to compare the reliability of a statistical response surface model (RSM) to a mechanistic model of N-linked glycosylation. The latter outperformed the response surface predictions with respect to its capability and reliability in predicting the system behavior (i.e., glycosylation pattern) outside the experimental space covered by the DoE design used for the model parameter estimation. Therefore, we can conclude that the modulation of glycosylation in a sequential steady state approach in combination with mechanistic model represents an efficient and rational strategy to develop continuous processes with desired N-linked glycosylation patterns. Biotechnol. Bioeng. 2017;114: 1978-1990. © 2017 Wiley Periodicals, Inc.

• MeSH
• analýza selhání vybavení MeSH
• biologické modely * MeSH
• bioreaktory * MeSH
• CHO buňky MeSH
• Cricetulus MeSH
• design s pomocí počítače MeSH
• design vybavení MeSH
• glykosylace MeSH
• monoklonální protilátky izolace a purifikace   metabolismus   MeSH
• perfuze přístrojové vybavení   metody   MeSH
• počítačová simulace MeSH
• polysacharidy metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• elektroencefalografie metody   přístrojové vybavení   MeSH
• intrakraniální tlak fyziologie   MeSH
• lidé MeSH
• mozek fyziologie   MeSH
• nemoci mozku diagnostické zobrazování   MeSH
• neurofyziologický monitoring * metody   přístrojové vybavení   MeSH
• oxymetrie metody   přístrojové vybavení   MeSH
• perfuze metody   přístrojové vybavení   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• Klíčová slova
• klinický perfuziolog,
• MeSH
• kardiochirurgické výkony MeSH
• lidé MeSH
• mimotělní oběh * metody   ošetřování   přístrojové vybavení   škodlivé účinky   MeSH
• perfuze * metody   ošetřování   přístrojové vybavení   využití   MeSH
• popis práce normy   MeSH
• přístroj pro mimotělní oběh * normy   škodlivé účinky   využití   MeSH
• specializace MeSH
• Check Tag
• lidé MeSH

Mikrodialýza je dynamicky se rozvíjející technika využívaná k monitorování tkáňového metabolizmu, bariérové funkce a k farmakologickým studiím a odhadům lokální krevní perfuze in situ. Předkládaný souhrnný článek přibližuje čtenáři poslední z uvedených aplikací, přičemž popisuje a srovnává 2 využívané přístupy – mikrodialyzační diluční techniky s využitím průtokových indikátorů a kontinuální metabolické sledování. V současné době je upřednostňováno využití metabolických indikátorů, pomocí nichž lze citlivěji a komplexněji hodnotit perfuzí navozené změny ve tkáních. Přes mnohé výhody zůstává měření tkáňové perfuze pomocí mikrodialýzy zatím soustředěno v oblasti klinického výzkumu. Pro širší přijetí a uplatnění v rutinních klinických postupech bude nutné provést více validačních studií a identifikovat situace, kde by mikrodialýza mohla nahradit stávající metody.

Microdialysis is a dynamically evolving method utilized for monitoring of tissue metabolism and barrier function, pharmacological studies and to estimate local blood perfusion in situ. The present review summarizes current knowledge of the last of the aforementioned applications on a characterization and comparison of two approaches used – microdialysis flow-indicator dilution technique and continuous metabolic monitoring. Currently, the use of metabolic indicators, which enable sensitive and complex evaluation of perfusioninduced changes in the tissue, is preferred. Despite the method’s numerous advantages the measurement of tissue blood perfusion by microdialysis remains centralized in the area of clinical research, for the present. For wider acceptance and exercise in the routine clinical practice, more validating studies ought to be conducted and situations identified, where microdialysis could replace the current methods.

• Klíčová slova
• tkáňový metabolizmus, lokální krevní perfuze, diluční techniky, průtokové indikátory, kontinuální metabolické sledování,
• MeSH
• biologické markery analýza   krev   metabolismus   MeSH
• financování organizované MeSH
• lidé MeSH
• mikrodialýza metody   přístrojové vybavení   využití   MeSH
• octan sodný diagnostické užití   MeSH
• perfuze metody   přístrojové vybavení   využití   MeSH
• prognóza MeSH
• průtokoměry využití   MeSH
• tkáně krevní zásobení   metabolismus   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Regional hypoperfusion has been associated with the development of postoperative organ dysfunction in cardiac surgery involving cardiopulmonary bypass (CPB). Direct tissue oxymetry is a potentially new method for monitoring the quality of the peripheral tissue perfusion during CPB. The aim of this study was to assess the effects of CPB in skeletal muscle oxygenation when measured in the deltoid muscle by direct oxymetry during perioperative period. METHOD: Seven patients underwent on-pump coronary artery bypass grafting. Direct oxymetry was performed by an optical cathether introduced into the deltoid muscle. Continuous measurement was made during the surgical procedure and the postoperative period. Mean arterial blood pressure, blood flow during CPB, laboratory markers of tissue hypoperfusion, blood gases and body temperature were also recorded. RESULTS: Interstitial muscle tissue oxygen tension (pO(2)) decreased after the introduction to anaesthesia and, more significantly, during CPB. After the disconnection from CPB at the end of the operation, the pO(2) returned to pre-anaesthetic values. During the first hours after admission of the patients to the intensive care unit, the pO(2) progressively decreased, reached a minimum value after four hours, and increased slowly thereafter. There was a significant correlation of pO(2) with mean arterial blood pressure and blood flow during that time. CONCLUSION: The result of this first measurement seems to demonstrate that the standard technique of conducting cardiopulmonary bypass produces low muscle oxygen tension and, thus, little perfusion of skeletal muscle. The data also indicate that both high mean arterial blood pressure and high flow are necessary during CPB to ensure skeletal muscle perfusion. The investigation is continuing.

• MeSH
• analýza krevních plynů MeSH
• kardiopulmonální bypass přístrojové vybavení   metody   MeSH
• koronární bypass přístrojové vybavení   metody   MeSH
• krevní tlak MeSH
• kyslík metabolismus   MeSH
• lidé MeSH
• musculus deltoideus metabolismus   MeSH
• oxymetrie přístrojové vybavení   metody   MeSH
• perfuze přístrojové vybavení   metody   MeSH
• předoperační období MeSH
• regionální krevní průtok MeSH
• senioři MeSH
• tělesná teplota MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Bylo prokázáno, že u hypervaskularizovaných tumorů, jako je osteosarkom, je použití CT body perfuze jednou z metod volby ke stanovení účinku podané terapie v čase. Zvláště je sledování účinné, pokud tumor roste v měkkých tkáních mimo kost. CT body perfuze jednoznačně nastartovala nový směr ve sledování účinků onkologické léčby. Výsledné perfuzní mapy lze hodnotit kvalitativně i přesněji kvantitativně.

It has been proven, that CT Body Perfusion, which has proven to be one of the method to use for the impact of the therapy in time, can monitor hypervascular tumors like osteosarcoma. Observation is useful especially with the tumors growing in the soft tissues around the bone. CT Body Perfusion shows the started new direction in monitoring of effect of oncology treatment. Resulting perfusion maps can be evaluated qualitatively or even more precise quantitatively.

• MeSH
• angiografie metody   využití   MeSH
• financování organizované MeSH
• magnetická rezonanční tomografie metody   využití   MeSH
• osteosarkom diagnóza   farmakoterapie   MeSH
• perfuze metody   přístrojové vybavení   využití   MeSH
• počítačová rentgenová tomografie metody   přístrojové vybavení   využití   MeSH
• protinádorové látky aplikace a dávkování   terapeutické užití   MeSH
• radiografie metody   využití   MeSH
• vaskulární nádory MeSH
• Publikační typ
• kazuistiky MeSH

We have developed an improved technique for fast cooling and heating of solutions superfusing isolated cells under patch-clamp or calcium imaging conditions. The system meets the requirements for studying temperature dependency of all kinds of ion channels, in particular temperature-gated ion channels. It allows the application of temperature changes within a range of 5-60 degrees C at maximum rates of -40 degrees C/s to 60 degrees C/s. Barrels filled with different solutions are connected to a manifold consisting of seven silica capillaries (320 microm inner diameter, i.d.). A common outlet consists of a glass capillary through which the solutions are applied onto the cell surface. The upper part of this capillary is embedded in a temperature exchanger driven by a miniature Peltier device which preconditions the temperature of the passing solution. The lower part of the capillary carries an insulated copper wire, densely coiled over a length of 7 mm, and connected to a dc current source for resistive heating. The Peltier device and the heating element are electrically connected to the headstage probe which is fixed on to a micromanipulator for positioning of the manifold. The temperature of the flowing solution is measured by a miniature thermocouple inserted into the common outlet capillary near to its orifice which is placed at a distance of less than 100 microm from the surface of the examined cell. The temperature is either manually controlled by voltage commands or adjusted via the digital-to-analog converter of a conventional data acquisition interface. Examples are given of using the device in patch-clamp studies on heterologously expressed TRPV1, TRPM8, and on cultured rat sensory neurons.

• MeSH
• akční potenciály fyziologie   MeSH
• analýza selhání vybavení MeSH
• buněčné kultury metody   přístrojové vybavení   MeSH
• design vybavení MeSH
• financování organizované MeSH
• kultivované buňky MeSH
• lidé MeSH
• membránové potenciály fyziologie   MeSH
• metoda terčíkového zámku metody   přístrojové vybavení   MeSH
• neurony aferentní fyziologie   MeSH
• nízká teplota MeSH
• perfuze přístrojové vybavení   MeSH
• prostředí kontrolované MeSH
• vysoká teplota MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• hodnotící studie MeSH