scholarly journals Ex vivo Approach to Treat Failing Organs: Expanding the Limits

2014 ◽  
Vol 54 (1-2) ◽  
pp. 64-74 ◽  
Author(s):  
Anatol Ciubotaru ◽  
Axel Haverich
Keyword(s):  
Medical Treatment ◽  
Life Support ◽  
Ex Vivo ◽  
Treatment Options ◽  
Diagnostic Methods ◽  
Organ Shortage ◽  
Organ Perfusion ◽  
Stage Disease ◽  
Number Of Patients ◽  
End Stage

Background: Advanced organ failure is often classified as an end-stage disease where the treatment options are limited only to transplantation. As an alternative, different attempts have been undertaken to improve the outcome of the treatment of failing organs by using targeted ex vivo approaches. This may solve the issue of organ shortage by treating the donor organs before transplantation and the number of patients requiring transplantation may also be reduced by applying extensive ex vivo treatment followed by autotransplantation. Methods: We performed a literature review of PubMed and included articles published between 1962 and 2013. The following keywords were used (and; or): ex vivo, therapy, surgery, organ perfusion and autotransplantation. This review includes specific methods and attempts related to ex vivo organ perfusion and preservation, temporary life support systems, surgical and other therapeutic approaches, and diagnostic methods applied ex vivo to an isolated organ. Results: For the practical clinical use of ex vivo therapies, we could identify three major directions: (1) ex vivo pretransplant organ reconditioning, (2) ex vivo surgery and (3) ex vivo medical treatment. Different attempts have been made worldwide in the above-mentioned areas focusing on ex vivo organ preservation and treatment. We summarize in the present review the developments in the field of ex vivo organ recovery and evaluate the possibilities of combining and applying different technologies such as organ perfusion and storage, ex vivo exact topographical diagnosis, ex vivo locoregional medical treatment and ex vivo surgical correction. Conclusion: Ex vivo therapies open new horizons in the treatment of end-stage organ pathologies.

Coronary sinus catalase and ceruloplasmin levels predict all-cause mortality in patients with end-stage heart failure awaiting heart transplantation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Szczurek ◽  
M Gasior ◽  
M Skrzypek ◽  
G Kubiak ◽  
A Kuczaj ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Transplantation ◽  
Coronary Sinus ◽  
Public Institution ◽  
Funding Source ◽  
Organ Shortage ◽  
Number Of Patients ◽  
End Stage ◽  
Medical University

Abstract   Background, As a consequence of the worldwide increase in life expectancy and due to significant progress in the pharmacological and interventional treatment of heart failure (HF), the proportion of patients that reach an advanced phase of disease is steadily growing. Hence, more and more numerous group of patients is qualified to the heart transplantation (HT), whereas the number of potential heart donors has remained invariable since years. It contributes to deepening in disproportion between the demand for organs which can possibly be transplanted and number of patients awaiting on the HT list. Therefore, accurate identification of patients who are most likely to benefit from HT is imperative due to an organ shortage and perioperative complications. Purpose The aim of this study was to identify the factors associated with reduced survival during a 1.5-year follow-up in patients with end-stage HF awating HT. Method We propectively analysed 85 adult patients with end-stage HF, who were accepted for HT at our institution between 2015 and 2016. During right heart catheterization, 10 ml of coronary sinus blood was additionally collected to determine the panel of oxidative stress markers. Oxidative-antioxidant balance markers included glutathione reductase (GR), glutathione peroxidase (GPx), glutathione transferase (GST), superoxide dismutase (SOD) and its mitochondrial isoenzyme (MnSOD) and cytoplasmic (Cu/ZnSOD), catalase (CAT), malondialdehyde (MDA), hydroperoxides lipid (LPH), lipofuscin (LPS), sulfhydryl groups (SH-), ceruloplasmin (CR). The study protocol was approved by the ethics committee of the Medical University of Silesia in Katowice. The endpoint of the study was mortality from any cause during a 1.5 years follow-up. Results The median age of the patients was 53.0 (43.0–56.0) years and 90.6% of them were male. All included patients were treated optimally in accordance with the guidelines of the European Society of Cardiology. Mortality rate during the follow-up period was 40%. Multivariate logistic regression analysis showed that ceruloplasmin (odds ratio [OR] = 0.745 [0.565–0.981], p=0.0363), catalase (OR = 0.950 [0.915–0.98], p=0.0076), as well as high creatinine levels (OR = 1.071 [1.002–1.144], p=0.0422) were risk factors for death during 1.5 year follow-up. Conclusions Coronary sinus lower ceruloplasmin and catalase levels, as well as higher creatinine level are independently associated with death during 1.5 year follow-up. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of SIlesia, Katowice, POland

scholarly journals Evaluation of the efficacy of a novel perfusion solution for normothermic ex vivo lung perfusion compared with Steen solution™ (animal experimental study)

2021 ◽  
Vol 23 (3) ◽  
pp. 82-89
Author(s):  
S. V. Gautier ◽  
O. M. Tsirulnikova ◽  
I. V. Pashkov ◽  
N. V. Grudinin ◽  
D. O. Oleshkevich ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Lung Diseases ◽  
Ex Vivo ◽  
Infectious Complications ◽  
Lung Perfusion ◽  
Ex Vivo Lung Perfusion ◽  
Perfusion Solution ◽  
Number Of Patients ◽  
Donor Lung ◽  
End Stage

Respiratory diseases, together with infectious complications and hereditary lung diseases, rank third in international mortality statistics. Today, lung transplantation is a recognized method of treating end-stage lung diseases. However, the number of transplant surgeries performed is not much. This is down to the high requirements on the condition of a potential lung donor and directly on the quality of the donor lung. This has significantly limited the number of optimal donors. Rehabilitation of donor lungs to optimal gas exchange indicators can be achieved and objectively assessed in the course of ex vivo lung perfusion (EVLP). The EVLP procedure is widespread in leading transplantation centers in Europe and North America. It allows to significantly expand the pool of donor lungs, thereby serving a greater number of patients in need of lung transplantation. The possibility of EVLP procedure using publicly available perfusion equipment was demonstrated. The optimized protocol fully demonstrated its reliability and efficiency. The developed perfusion solution had no statistically significant differences in comparison with the Steen SolutionTM, which in the future will serve as an alternative for EVLP procedure.

scholarly journals Cell-Based Regeneration and Treatment of Liver Diseases

2021 ◽  
Vol 22 (19) ◽  
pp. 10276
Author(s):  
Julia Hofmann ◽  
Verena Hackl ◽  
Hannah Esser ◽  
Andras T. Meszaros ◽  
Margot Fodor ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Ex Vivo ◽  
Organ Shortage ◽  
Clinical Implementation ◽  
Organ Function ◽  
Novel Technologies ◽  
Recent Developments ◽  
Underlying Mechanisms ◽  
The Moment ◽  
End Stage

The liver, in combination with a functional biliary system, is responsible for maintaining a great number of vital body functions. However, acute and chronic liver diseases may lead to irreversible liver damage and, ultimately, liver failure. At the moment, the best curative option for patients suffering from end-stage liver disease is liver transplantation. However, the number of donor livers required by far surpasses the supply, leading to a significant organ shortage. Cellular therapies play an increasing role in the restoration of organ function and can be integrated into organ transplantation protocols. Different types and sources of stem cells are considered for this purpose, but highly specific immune cells are also the focus of attention when developing individualized therapies. In-depth knowledge of the underlying mechanisms governing cell differentiation and engraftment is crucial for clinical implementation. Additionally, novel technologies such as ex vivo machine perfusion and recent developments in tissue engineering may hold promising potential for the implementation of cell-based therapies to restore proper organ function.

scholarly journals Engineering a microcirculation for perfusion control of ex vivo–assembled organ systems: Challenges and opportunities

2018 ◽  
Vol 9 ◽  
pp. 204173141877294 ◽  
Author(s):  
Pavan Kottamasu ◽  
Ira Herman
Keyword(s):  
Tissue Engineering ◽  
Ex Vivo ◽  
Organ Shortage ◽  
Donor Organ ◽  
Donor Pool ◽  
Organ Rejection ◽  
Organ Systems ◽  
Number Of Patients ◽  
Challenges And Opportunities ◽  
Donor Organs

Donor organ shortage remains a clear problem for many end-stage organ patients around the world. The number of available donor organs pales in comparison with the number of patients in need of these organs. The field of tissue engineering proposes a plausible solution. Using stem cells, a patient’s autologous cells, or allografted cells to seed-engineered scaffolds, tissue-engineered constructs can effectively supplement the donor pool and bypass other problems that arise when using donor organs, such as who receives the organ first and whether donor organ rejection may occur. However, current research methods and technologies have been unable to successfully engineer and vascularize large volume tissue constructs. This review examines the current perfusion methods for ex vivo organ systems, defines the different types of vascularization in organs, explores various strategies to vascularize ex vivo organ systems, and discusses challenges and opportunities for the field of tissue engineering.

Ex vivo lung perfusion for donor lung assessment and repair: a review of translational interspecies models

2020 ◽  
Vol 319 (6) ◽  
pp. L932-L940
Author(s):  
Aizhou Wang ◽  
Aadil Ali ◽  
Shaf Keshavjee ◽  
Mingyao Liu ◽  
Marcelo Cypel
Keyword(s):  
Therapeutic Potential ◽  
Ex Vivo ◽  
Small Animal ◽  
Lung Perfusion ◽  
Contributing Factors ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Advantages And Disadvantages ◽  
Number Of Patients ◽  
End Stage

For patients with end-stage lung disease, lung transplantation is a lifesaving therapy. Currently however, the number of patients who require a transplant exceeds the number of donor lungs available. One of the contributing factors to this is the conservative mindset of physicians who are concerned about transplanting marginal lungs due to the potential risk of primary graft dysfunction. Ex vivo lung perfusion (EVLP) technology has allowed for the expansion of donor pool of organs by enabling assessment and reconditioning of these marginal grafts before transplant. Ongoing efforts to optimize the therapeutic potential of EVLP are underway. Researchers have adopted the use of different large and small animal models to generate translational preclinical data. This includes the use of rejected human lungs, pig lungs, and rat lungs. In this review, we summarize some of the key current literature studies relevant to each of the major EVLP model platforms and identify the advantages and disadvantages of each platform. The review aims to guide investigators in choosing an appropriate species model to suit their specific goals of study, and ultimately aid in translation of therapy to meet the growing needs of the patient population.

Treatment of Severe Non-Neonatal ARDS in Children with Surfactant and Nitric Oxide in a “PRE-ECMO”-Situation

1995 ◽  
Vol 18 (10) ◽  
pp. 598-602 ◽  
Author(s):  
J.C. Möller ◽  
T.F. Schaible ◽  
I. Reiss ◽  
A. Artlich ◽  
L Gortner
Keyword(s):  
Nitric Oxide ◽  
Life Support ◽  
Treatment Options ◽  
Treatment Algorithm ◽  
Underlying Disease ◽  
Exogenous Surfactant ◽  
Natural Surfactant ◽  
Mixed Venous Saturation ◽  
Number Of Patients ◽  
Therapeutic Tools

The use of exogenous surfactant and nitric oxide in neonates has reduced the number of infants requiring ECMO. The purpose of this study was to demonstrate whether these two therapeutic options might reduce the number of over 28 days old children with severe ARDS requiring ECMO, without reducing changes of survival and morbidity. Over a 30 month period all non-neonatal ARDS patients transferred to our institution for ECMO evaluation were treated based on a study-algorithm. If they did not fulfill “fast entry criteria” (paO2< 40 for more than 3 hrs.) we first tried different ventilation, vasodilatation, and hemodynamic strategies for max. 4 hrs. (inv. I/E ratio, HFOV, epoprostenol, high doses norepinephrine. If the 01 did not decrease by< 10, 30-280 mg natural surfactant or 1-20 ppm nitric oxide were treatment options depending on the degree of pulmonary hypertension measured by echocardiography and by mixed venous saturation measurements. It was possible to use NO and surfactant sequentially. The patients had different etiologies of ARDS as near drowning, pneumonia, immunosuppression, and sepsis. If their 01 did not decrease by 10 in 8 hrs. ECMO was installed. Nineteen patients were evaluated, 6 improved with conventional therapy, their 01 decreased without a relapse (mean 01 at begin of the study: 38). Six patients improved with surfactant therapy alone (mean 01: 54), 4 patients improved after surfactant and sequential NO-treatment, 3 patients were initially treated with NO, 1 sequentially with surfactant. One patient did not show any benefit from NO or surfactant and was put on ECMO. Three patients died (withdrawal of life support because of severe brain damage caused by the underlying disease). We could not observe any respiratory related failure. No patient had to be discharged on oxygen. A sophisticated treatment algorithm integrating different modern ARDS treatment options can reduce the number of patients requiring ECMO. We speculate however that these options can only be used effectively in centers involved in ARDS treatment quite frequently and that these centers have to provide ECMO as one of their therapeutic tools.

scholarly journals Renal Delivery of Pharmacologic Agents During Machine Perfusion to Prevent Ischaemia-Reperfusion Injury: From Murine Model to Clinical Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Rossana Franzin ◽  
Alessandra Stasi ◽  
Marco Fiorentino ◽  
Simona Simone ◽  
Rainer Oberbauer ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Ex Vivo ◽  
Graft Function ◽  
Organ Donor ◽  
Pharmacological Intervention ◽  
Organ Shortage ◽  
Ischaemia Reperfusion Injury ◽  
Complement Inhibitors ◽  
End Stage ◽  
Pharmacologic Agents

Donor organ shortage still remains a serious obstacle for the access of wait-list patients to kidney transplantation, the best treatment for End-Stage Kidney Disease (ESKD). To expand the number of transplants, the use of lower quality organs from older ECD or DCD donors has become an established routine but at the price of increased incidence of Primary Non-Function, Delay Graft Function and lower-long term graft survival. In the last years, several improvements have been made in the field of renal transplantation from surgical procedure to preservation strategies. To improve renal outcomes, research has focused on development of innovative and dynamic preservation techniques, in order to assess graft function and promote regeneration by pharmacological intervention before transplantation. This review provides an overview of the current knowledge of these new preservation strategies by machine perfusions and pharmacological interventions at different timing possibilities: in the organ donor, ex-vivo during perfusion machine reconditioning or after implementation in the recipient. We will report therapies as anti-oxidant and anti-inflammatory agents, senolytics agents, complement inhibitors, HDL, siRNA and H2S supplementation. Renal delivery of pharmacologic agents during preservation state provides a window of opportunity to treat the organ in an isolated manner and a crucial route of administration. Even if few studies have been reported of transplantation after ex-vivo drugs administration, targeting the biological pathway associated to kidney failure (i.e. oxidative stress, complement system, fibrosis) might be a promising therapeutic strategy to improve the quality of various donor organs and expand organ availability.

Ex Vivo Lung Perfusion: A Review of Research and Clinical Practices

2020 ◽  
Vol 24 (1) ◽  
pp. 34-44 ◽  
Author(s):  
Patrick G. Chan ◽  
Akshay Kumar ◽  
Kathirvel Subramaniam ◽  
Pablo G. Sanchez
Keyword(s):  
Lung Disease ◽  
Ex Vivo ◽  
Conventional Technique ◽  
Lung Perfusion ◽  
Clinical Practices ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Number Of Patients ◽  
End Stage ◽  
Potential Tool

End-stage lung disease is ultimately treated with lung transplantation. However, there is a paucity of organs with an increasing number of patients being diagnosed with end-stage lung disease. Ex vivo lung perfusion has emerged as a potential tool to assess the quality and to recondition marginal donor lungs prior to transplantation with the goal of increasing the donor pool. This technology has shown promise with similar results compared with the conventional technique of cold static preservation in terms of primary graft dysfunction and overall outcomes. This review provides an update on the results and uses of this technology. The review will also summarize clinical studies and techniques in reconditioning and assessing lungs on ex vivo lung perfusion. Last, we discuss how this technology can be applied to fields outside of transplantation such as thoracic oncology and bioengineering.

scholarly journals Review of Extraosseous Applications of Thermal Ablation in the Treatment of Moderate to Severe Large Joint Osteoarthritis

2021 ◽  
Vol 25 (06) ◽  
pp. 745-755
Author(s):  
Andrew Tran ◽  
David A. Reiter ◽  
J. David Prologo ◽  
Mircea Cristescu ◽  
Felix M. Gonzalez
Keyword(s):  
Treatment Options ◽  
Additional Treatment ◽  
Joint Disease ◽  
Restricted Range ◽  
Pharmacologic Agent ◽  
Stage Disease ◽  
Large Joint ◽  
Short And Long Term ◽  
End Stage

AbstractOsteoarthritis (OA) is the most common joint disease worldwide, leading to significant pain, restricted range of motion, and disability. A gap exists between short- and long-term symptom-relieving therapies. Although arthroplasty is an effective treatment for symptomatic end-stage disease, most patients ultimately do not receive a joint replacement due to suboptimal surgical qualifications, comorbidities, or an aversion to surgery. The lack of additional treatment options in this setting makes opioid agonists a commonly used pharmacologic agent, contributing to the addiction epidemic that greatly afflicts our communities. Cooled radiofrequency ablation (CRFA) has arisen as a treatment modality in the setting of moderate to severe OA among patients refractory to conservative management, generally showing greater efficacy compared with other existing strategies. This review focuses on the benefits of CRFA and its technical feasibility as a management option among patients experiencing debilitating large joint OA with limited clinical options.

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