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Medicina Intensiva Dec 2023To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality.
DESIGN
Systematic review and meta-analysis.
SETTING
Intensive care unit.
PATIENTS AND PARTICIPANTS
Patients with sepsis and septic shock.
INTERVENTIONS
Studies of patients with sepsis and/or septic shock that associated clinical monitoring of tissue perfusion with mortality were included. A systematic review was performed by searching the PubMed/MEDLINE, Cochrane Library, SCOPUS, and OVID databases.
MAIN VARIABLES OF INTEREST
The risk of bias was assessed with the QUADAS-2 tool. Sensitivity and specificity were calculated to evaluate the predictive accuracy for mortality. Review Manager software version 5.4 was used to draw the forest plot graphs, and Stata version 15.1 was used to build the hierarchical summary receiver operating characteristic model.
RESULTS
Thirteen studies were included, with a total of 1667 patients and 17 analyses. Two articles evaluated the temperature gradient, four evaluated the capillary refill time, and seven evaluated the mottling in the skin. In most studies, the outcome was mortality at 14 or 28 days. The pooled sensitivity of the included studies was 70%, specificity 75.9% (95% CI, 61.6%-86.2%), diagnostic odds ratio 7.41 (95% CI, 3.91-14.04), and positive and negative likelihood ratios 2.91 (95% CI, 1.80-4.72) and 0.39 (95% CI, 0.30-0.51), respectively.
CONCLUSIONS
Clinical evaluation of tissue perfusion at the bedside is a useful tool, with moderate sensitivity and specificity, to identify patients with a higher risk of death among those with sepsis and septic shock.
REGISTRATION
PROSPERO CRD42019134351.
Topics: Humans; Shock, Septic; Sepsis; Sensitivity and Specificity; Intensive Care Units; Perfusion
PubMed: 37419840
DOI: 10.1016/j.medine.2023.05.011 -
Transplantation Mar 2024Dynamic preservation methods such as normothermic, subnormothermic, and hypothermic machine perfusion circuits have emerged as viable alternatives to conventional static... (Review)
Review
Dynamic preservation methods such as normothermic, subnormothermic, and hypothermic machine perfusion circuits have emerged as viable alternatives to conventional static cold storage. These organ perfusion technologies serve as preservation methods and enable organ assessment, reconditioning, and repair before transplantation. Gene therapy is a novel strategy with the potential to transform the field of graft optimization and treatment. Thereby specific pathways involved in the transplantation process can be targeted and modified. This review aims to provide an overview of gene delivery methods during ex vivo machine perfusion of kidney and liver grafts. Recent literature on state-of-the-art gene therapy approaches during ex situ organ preservation, especially with respect to ischemia-reperfusion injury, as well as acute and chronic graft rejection have been analyzed. Additionally, potential challenges that could affect further refinement of this therapeutic modality are outlined.
Topics: Perfusion; Kidney; Organ Preservation; Kidney Transplantation; Extracorporeal Circulation
PubMed: 37482634
DOI: 10.1097/TP.0000000000004738 -
Fertility and Sterility Dec 2023To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft...
OBJECTIVE
To describe the feasibility of hypothermic machine perfusion (HMP) in uterus transplantation (UT) to potentially improve the preservation of the uterus and enhance graft preservation in the donation after brainstem death (DBD) context. Uterus transplantation is a new surgical approach to treating absolute uterine infertility; it can be performed after living donation or after DBD. In the DBD context, the uterus is typically the last organ removed after other vital organs, with the exception of the Baylor team, which removes the uterus first. This key aspect imposes an unavoidable mild temperature ischemia for >1 hour on the uterus during the removal of the vital abdominal and chest organs. In renal transplantation, the perfusion machine reduces the risk of delayed graft function; thus, we hypothesized that machine perfusion could result in a reduction of uterus graft dysfunction. The uterus graft dysfunction could be expressed by a low embryo implantation rate, pregnancy loss, or vascular pregnancy diseases such as preeclampsia or fetal growth restriction." To date, static cold storage of the uterus is the only standard method for preservation before transplantation. HMP is an emerging method that could potentially improve the preservation of the uterus to enhance graft preservation in the DBD context.
DESIGN
This video article shows all the technical details of using the HMP for uterine transplantation.
SETTING
University.
ANIMALS
Porcine model.
INTERVENTION
Porcine uterus was retrieved from a DBD domestic animal model and flushed with KPS MP (Bridge To Life Ltd in UK) at 4 °C. After vascular preparation on the back table, the uterus was perfused using KPS MP through a cannula in the aorta using the VitaSmart device (Bridge To Life Ltd in UK) for 18 hours. Then, the uterus was transplanted to the porcine recipient.
MAIN OUTCOME MEASURES
The macroscopic appearance of the uterus at the end of HMP and the assessment of the uterus vascularization after transplantation in the recipient compared with the native uterus.
RESULTS
This video shows the cannulation of the iliac vessels, cooling and removal of the uterus on a porcine model, uterus preservation using HMP during 18 hours, and then UT in a new recipient pig with the reperfusion of the transplanted uterus next to the native, intact uterus of the recipient. The macroscopic appearance of the uterus at the end of HMP appeared viable and was perfectly flushed. The assessment of the uterus vascularization after transplantation in the recipient was similar to that of the native uterus. To our knowledge, we describe here for the first time the UT procedure in DBD context on an animal model and the use of HMP for uterus preservation in UT programs; this could increase the number of uterine grafts available for a greater number of female recipients.
CONCLUSION
Hypothermic machine perfusion could allow the duration of cold ischemia to be prolonged without altering the uterine graft. Nevertheless, this assertion has to be validated in a human context.
Topics: Animals; Female; Cold Temperature; Organ Preservation; Perfusion; Swine; Uterus
PubMed: 37660880
DOI: 10.1016/j.fertnstert.2023.08.020 -
Cells Jul 2023The application of decellularized scaffolds for artificial tissue reconstruction has been an approach with great therapeutic potential in regenerative medicine....
The application of decellularized scaffolds for artificial tissue reconstruction has been an approach with great therapeutic potential in regenerative medicine. Recently, biomimetic ovarian tissue reconstruction was proposed to reestablish ovarian endocrine functions. Despite many decellularization methods proposed, there is no established protocol for whole ovaries by detergent perfusion that is able to preserve tissue macro and microstructure with higher efficiency. This generated biomaterial may have the potential to be applied for other purposes beyond reproduction and be translated to other areas in the tissue engineering field. Therefore, this study aimed to establish and standardize a protocol for porcine ovaries' decellularization based on detergent perfusion and ultrasonication to obtain functional whole-ovary scaffolds. For that, porcine ovaries ( = 5) were perfused with detergents (0.5% SDS and 1% Triton X-100) and submitted to an ultrasonication bath to produce acellular scaffolds. The decellularization efficiency was evaluated by DAPI staining and total genomic DNA quantification. ECM morphological evaluation was performed by histological, immunohistochemistry, and ultrastructural analyses. ECM physico-chemical composition was evaluated using FTIR and Raman spectroscopy. A cytocompatibility and cell adhesion assay using murine fibroblasts was performed. Results showed that the proposed method was able to remove cellular components efficiently. There was no significant ECM component loss in relation to native tissue, and the scaffolds were cytocompatible and allowed cell attachment. In conclusion, the proposed decellularization protocol produced whole-ovaries scaffolds with preserved ECM composition and great potential for application in tissue engineering.
Topics: Female; Swine; Mice; Animals; Ovary; Tissue Scaffolds; Detergents; Extracellular Matrix; Perfusion
PubMed: 37508528
DOI: 10.3390/cells12141864 -
Anesthesiology Dec 2023Bedside electrical impedance tomography could be useful to visualize evolving pulmonary perfusion distributions when acute respiratory distress syndrome worsens or in...
BACKGROUND
Bedside electrical impedance tomography could be useful to visualize evolving pulmonary perfusion distributions when acute respiratory distress syndrome worsens or in response to ventilatory and positional therapies. In experimental acute respiratory distress syndrome, this study evaluated the agreement of electrical impedance tomography and dynamic contrast-enhanced computed tomography perfusion distributions at two injury time points and in response to increased positive end-expiratory pressure (PEEP) and prone position.
METHODS
Eleven mechanically ventilated (VT 8 ml · kg-1) Yorkshire pigs (five male, six female) received bronchial hydrochloric acid (3.5 ml · kg-1) to invoke lung injury. Electrical impedance tomography and computed tomography perfusion images were obtained at 2 h (early injury) and 24 h (late injury) after injury in supine position with PEEP 5 and 10 cm H2O. In eight animals, electrical impedance tomography and computed tomography perfusion imaging were also conducted in the prone position. Electrical impedance tomography perfusion (QEIT) and computed tomography perfusion (QCT) values (as percentages of image total) were compared in eight vertical regions across injury stages, levels of PEEP, and body positions using mixed-effects linear regression. The primary outcome was agreement between QEIT and QCT, defined using limits of agreement and Pearson correlation coefficient.
RESULTS
Pao2/Fio2 decreased over the course of the experiment (healthy to early injury, -253 [95% CI, -317 to -189]; early to late injury, -88 [95% CI, -151 to -24]). The limits of agreement between QEIT and QCT were -4.66% and 4.73% for the middle 50% quantile of average regional perfusion, and the correlation coefficient was 0.88 (95% CI, 0.86 to 0.90]; P < 0.001). Electrical impedance tomography and computed tomography showed similar perfusion redistributions over injury stages and in response to increased PEEP. QEIT redistributions after positional therapy underestimated QCT in ventral regions and overestimated QCT in dorsal regions.
CONCLUSIONS
Electrical impedance tomography closely approximated computed tomography perfusion measures in experimental acute respiratory distress syndrome, in the supine position, over injury progression and with increased PEEP. Further validation is needed to determine the accuracy of electrical impedance tomography in measuring perfusion redistributions after positional changes.
Topics: Male; Female; Swine; Animals; Electric Impedance; Tomography, X-Ray Computed; Respiratory Distress Syndrome; Lung; Perfusion; Tomography
PubMed: 37566686
DOI: 10.1097/ALN.0000000000004731 -
Magnetic Resonance Imaging Clinics of... Feb 2024
Topics: Humans; Magnetic Resonance Imaging; Magnetic Resonance Angiography; Perfusion
PubMed: 38007289
DOI: 10.1016/j.mric.2023.09.008 -
Innovations (Philadelphia, Pa.) 2023Extracorporeal circulation (ECC) is generally based on standards established in the last decade. In recent years, a concept of perfusion management during ECC,... (Review)
Review
OBJECTIVE
Extracorporeal circulation (ECC) is generally based on standards established in the last decade. In recent years, a concept of perfusion management during ECC, goal-directed perfusion (GDP), has emerged to create optimal conditions for oxygen delivery and extraction, initiated by Rannuci et al. The aim of the present work was to determine whether the ECC procedure can truly be optimized with the current state of knowledge and understanding of human physiology.
METHODS
Discussed articles from 2017 to 2022 were selected from the MEDLINE (PubMed) database using the keywords "cardiopulmonary bypass" AND "cardiac surgery" AND "oxygen delivery" with the conditions of "clinical trial" OR "randomized controlled trial."
RESULTS
The concept of GDP is an attempt to reproduce the physiological conditions of tissue respiration during ECC. Published articles, also due to their retrospective nature, are based on standards and recommendations that do not fully fit the field of physiological circulation. There are still insufficient tools to assess the relationship between volemia, perfusion pressure, and pump performance. Limitations include indications for vasoactive drugs. Methodology has rarely taken into account the period of starting and stopping the heart-lung machine, the most pronounced periods of circulatory destabilization with reduced oxygen delivery.
CONCLUSIONS
Problems associated with ECC such as acute kidney injury, liver failure, vasoplegic syndrome, and others must await its resolution. The use of advanced monitoring technology and data engineering may allow the development of baseline hemodynamic models, which may make the ECC procedure more physiologic and thus improve the safety of the procedure.
Topics: Humans; Retrospective Studies; Goals; Extracorporeal Circulation; Perfusion; Oxygen
PubMed: 37997651
DOI: 10.1177/15569845231211904 -
Transplantation Jun 2024Dynamic organ preservation is a relatively old technique which has regained significant interest in the last decade. Machine perfusion (MP) techniques are applied in... (Review)
Review
Dynamic organ preservation is a relatively old technique which has regained significant interest in the last decade. Machine perfusion (MP) techniques are applied in various fields of solid organ transplantation today. The first clinical series of ex situ MP in liver transplantation was presented in 2010. Since then, the number of research and clinical applications has substantially increased. Despite the notable beneficial effect on organ quality and recipient outcome, MP is still not routinely used in liver transplantation. Based on the enormous need to better preserve organs and the subsequent demand to continuously innovate and develop perfusion equipment further, this technology is also beneficial to test and deliver future therapeutic strategies to livers before implantation. This article summarizes the various challenges observed during the current shift from static to dynamic liver preservation in the clinical setting. The different organ perfusion strategies are discussed first, together with ongoing clinical trials and future study design. The current status of research and the impact of costs and regulations is highlighted next. Factors contributing to costs and other required resources for a worldwide successful implementation and reimbursement are presented third. The impact of research on cost-utility and effectivity to guide the tailored decision-making regarding the optimal perfusion strategy is discussed next. Finally, this article provides potential solutions to the challenging field of innovation in healthcare considering the various social and economic factors and the role of clinical, regulatory, and financial stakeholders worldwide.
Topics: Liver Transplantation; Humans; Perfusion; Organ Preservation; Treatment Outcome; Cost-Benefit Analysis; Liver
PubMed: 38057969
DOI: 10.1097/TP.0000000000004872 -
Journal of Visualized Experiments : JoVE Sep 2023This protocol presents an optimized erythrocytes-free NEVLP system using mouse livers. Ex vivo preservation of mouse livers was achieved by employing modified cannulas...
This protocol presents an optimized erythrocytes-free NEVLP system using mouse livers. Ex vivo preservation of mouse livers was achieved by employing modified cannulas and techniques adapted from conventional commercial ex vivo perfusion equipment. The system was utilized to evaluate the preservation outcomes following 12 h of perfusion. C57BL/6J mice served as liver donors, and the livers were explanted by cannulating the portal vein (PV) and bile duct (BD), and subsequently flushing the organ with warm (37 °C) heparinized saline. Then, the explanted livers were transferred to the perfusion chamber and subjected to normothermic oxygenated machine perfusion (NEVLP). Inlet and outlet perfusate samples were collected at 3 h intervals for perfusate analysis. Upon completion of the perfusion, liver samples were obtained for histological analysis, with morphological integrity assessed using modified Suzuki-Score through Hematoxylin-Eosin (HE) staining. The optimization experiments yielded the following findings: (1) mice weighing over 30 g were deemed more suitable for the experiment due to the larger size of their bile duct (BD). (2) a 2 Fr (outer diameter = 0.66 mm) polyurethane cannula was better suited for cannulating the portal vein (PV) when compared to a polypropylene cannula. This was attributed to the polyurethane material's enhanced grip, resulting in reduced catheter slippage during the transfer from the body to the organ chamber. (3) for cannulation of the bile duct (BD), a 1 Fr (outer diameter = 0.33 mm) polyurethane cannula was found to be more effective compared to the polypropylene UT - 03 (outer diameter = 0.30 mm) cannula. With this optimized protocol, mouse livers were successfully preserved for a duration of 12 h without significant impact on the histological structure. Hematoxylin-Eosin (HE) staining revealed a well-preserved morphological architecture of the liver, characterized by predominantly viable hepatocytes with clearly visible nuclei and mild dilation of hepatic sinusoids.
Topics: Mice; Animals; Eosine Yellowish-(YS); Hematoxylin; Polypropylenes; Polyurethanes; Liver Transplantation; Organ Preservation; Mice, Inbred C57BL; Liver; Perfusion
PubMed: 37811934
DOI: 10.3791/65363 -
Hepatology (Baltimore, Md.) Sep 2023Acute cellular rejection (ACR) is a frequent complication after liver transplantation. By reducing ischemia and graft damage, dynamic preservation techniques may... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Acute cellular rejection (ACR) is a frequent complication after liver transplantation. By reducing ischemia and graft damage, dynamic preservation techniques may diminish ACR. We performed a systematic review to assess the effect of currently tested organ perfusion (OP) approaches versus static cold storage (SCS) on post-transplant ACR-rates.
APPROACH AND RESULTS
A systematic search of Medline, Embase, Cochrane Library, and Web of Science was conducted. Studies reporting ACR-rates between OP and SCS and comprising at least 10 liver transplants performed with either hypothermic oxygenated perfusion (HOPE), normothermic machine perfusion, or normothermic regional perfusion were included. Studies with mixed perfusion approaches were excluded. Eight studies were identified (226 patients in OP and 330 in SCS). Six studies were on HOPE, one on normothermic machine perfusion, and one on normothermic regional perfusion. At meta-analysis, OP was associated with a reduction in ACR compared with SCS [OR: 0.55 (95% CI, 0.33-0.91), p =0.02]. This effect remained significant when considering HOPE alone [OR: 0.54 (95% CI, 0.29-1), p =0.05], in a subgroup analysis of studies including only grafts from donation after cardiac death [OR: 0.43 (0.20-0.91) p =0.03], and in HOPE studies with only donation after cardiac death grafts [OR: 0.37 (0.14-1), p =0.05].
CONCLUSIONS
Dynamic OP techniques are associated with a reduction in ACR after liver transplantation compared with SCS. PROSPERO registration: CRD42022348356.
Topics: Humans; Liver Transplantation; Organ Preservation; Perfusion; Graft Rejection; Death; Liver; Graft Survival
PubMed: 36988381
DOI: 10.1097/HEP.0000000000000363