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ASAIO Journal (American Society For... Aug 2022Thrombosis in extracorporeal membrane oxygenation (ECMO) circuits remains a frequent complication. We characterize the location, extent, structure, and clinical...
Thrombosis in extracorporeal membrane oxygenation (ECMO) circuits remains a frequent complication. We characterize the location, extent, structure, and clinical implications of thrombi in 53 ECMO circuits from 46 pediatric patients. The tubing, pump, and oxygenator were examined for visible thrombi. Representative samples of thrombi were collected for histologic, immunofluorescence, and immunohistochemical analysis. Thrombi were found in 81% of ECMO circuits. The most clinically significant were inflow oxygenator membrane surface thrombi (11% of circuits), arterial tubing thrombi (30%), and venous tubing (26%) or connector thrombi (26%). Oxygenator membrane surface thrombi resulted in rapidly increasing delta pressure across the oxygenator over 1-2 days, oxygenator failure, and circuit replacement. Oxygenator membrane surface thrombi were associated with intravascular venous thrombosis and bacterial infection before starting ECMO. Arterial cannula/tubing thrombi led in one case to aortic and mesenteric artery thrombosis followed by bowel infarction. In 11% of cases, venous tubing thrombi grew large enough to break off and embolize to the pump, resulting in increased hemolysis. Antifibrinolytic therapy during ECMO was associated with an increased risk of pump thromboembolism. Other less clinically significant thrombi included pump axle thrombi with thrombus fragments trapped in the oxygenator (45%), and deep oxygenator membrane thrombi (15%). Examination of ECMO circuits after removal is a useful quality improvement tool that can elucidate the cause of circuit problems, indicate patients at increased risk of thrombosis, and suggest areas for possible improvements.
Topics: Child; Extracorporeal Membrane Oxygenation; Humans; Oxygenators; Oxygenators, Membrane; Thrombosis
PubMed: 34860711
DOI: 10.1097/MAT.0000000000001605 -
Experimental Biology and Medicine... Jul 2020Hypoxia contributes to tumor aggressiveness and promotes growth of many solid tumors that are often resistant to conventional therapies. In order to achieve successful... (Review)
Review
Hypoxia contributes to tumor aggressiveness and promotes growth of many solid tumors that are often resistant to conventional therapies. In order to achieve successful therapeutic strategies targeting different cancer types, it is necessary to understand the molecular mechanisms and signaling pathways that are induced by hypoxia. Aberrant tumor vasculature and alterations in cellular metabolism and drug resistance due to hypoxia further confound this problem. This review focuses on the implications of hypoxia in an inflammatory TME and its impact on the signaling and metabolic pathways regulating growth and progression of cancer, along with changes in lymphangiogenic and angiogenic mechanisms. Finally, the overarching role of hypoxia in mediating therapeutic resistance in cancers is discussed.
Topics: Cell Hypoxia; Cell Respiration; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mitochondria; Neoplasms; Tumor Microenvironment
PubMed: 32594767
DOI: 10.1177/1535370220934038 -
The Journal of Thoracic and... Jul 2020
Topics: Lung Transplantation; Oxygenators, Membrane
PubMed: 31672391
DOI: 10.1016/j.jtcvs.2019.09.124 -
European Heart Journal. Acute... Dec 2022
Topics: Humans; Oxygenators, Membrane; Shock, Cardiogenic
PubMed: 36306402
DOI: 10.1093/ehjacc/zuac140 -
ACS Nano Nov 2023Cancer with a complex pathological process is a major disease to human welfare. Due to the imbalance between oxygen (O) supply and consumption, hypoxia is a natural... (Review)
Review
Cancer with a complex pathological process is a major disease to human welfare. Due to the imbalance between oxygen (O) supply and consumption, hypoxia is a natural characteristic of most solid tumors and an important obstacle for cancer therapy, which is closely related to tumor proliferation, metastasis, and invasion. Various strategies to exploit the feature of tumor hypoxia have been developed in the past decade, which can be used to alleviate tumor hypoxia, or utilize the hypoxia for targeted delivery and diagnostic imaging. The strategies to alleviate tumor hypoxia include delivering O, in situ O generation, reprogramming the tumor vascular system, decreasing O consumption, and inhibiting HIF-1 related pathways. On the other side, hypoxia can also be utilized for hypoxia-responsive chemical construction and hypoxia-active prodrug-based strategies. Taking advantage of hypoxia in the tumor region, a number of methods have been applied to identify and keep track of changes in tumor hypoxia. Herein, we thoroughly review the recent progress of nanomedicine strategies in both conquering and utilizing hypoxia to combat cancer and put forward the prospect of emerging nanomaterials for future clinical transformation, which hopes to provide perspectives in nanomaterials design.
Topics: Humans; Nanomedicine; Neoplasms; Hypoxia; Tumor Hypoxia; Cell Hypoxia; Oxygen; Cell Line, Tumor
PubMed: 37871328
DOI: 10.1021/acsnano.3c07763 -
Nature Reviews. Clinical Oncology Dec 2021Hypoxia is prevalent in human tumours and contributes to microenvironments that shape cancer evolution and adversely affect therapeutic outcomes. Historically, two... (Review)
Review
Hypoxia is prevalent in human tumours and contributes to microenvironments that shape cancer evolution and adversely affect therapeutic outcomes. Historically, two different tumour microenvironment (TME) research communities have been discernible. One has focused on physicochemical gradients of oxygen, pH and nutrients in the tumour interstitium, motivated in part by the barrier that hypoxia poses to effective radiotherapy. The other has focused on cellular interactions involving tumour and non-tumour cells within the TME. Over the past decade, strong links have been established between these two themes, providing new insights into fundamental aspects of tumour biology and presenting new strategies for addressing the effects of hypoxia and other microenvironmental features that arise from the inefficient microvascular system in solid tumours. This Review provides a perspective on advances at the interface between these two aspects of the TME, with a focus on translational therapeutic opportunities relating to the elimination and/or exploitation of tumour hypoxia.
Topics: Cell Hypoxia; Humans; Neoplasms; Oxygen; Signal Transduction; Tumor Microenvironment
PubMed: 34326502
DOI: 10.1038/s41571-021-00539-4 -
PloS One 2022Current methods for identification of oxygenator clotting during prolonged extracorporeal life support include visual inspection, evaluation of oxygenator resistance and...
Current methods for identification of oxygenator clotting during prolonged extracorporeal life support include visual inspection, evaluation of oxygenator resistance and oxygen exchange performance, and assessment of clotting-related laboratory parameters. However, these observations do not provide a quantitative assessment of oxygenator clot formation. By measuring changes in the dynamic oxygenator blood volume this study aimed to evaluate the relation to oxygenator resistance and oxygen transfer performance. Sixty-seven oxygenators were studied during adult extracorporeal life support. Oxygenator blood volume, oxygenator resistance, and oxygen transfer efficiency were monitored. Oxygenator blood volume decreased with increasing runtime (r = -0.462; p <0.001). There was a statistically significant, fair negative correlation between oxygenator blood volume and oxygenator resistance (r = -0.476; p<0.001) in all oxygenators, which became stronger analyzing only exchanged oxygenators (r = -0.680; p<0.001) and oxygenators with an oxygenator blood volume <187 mL (r = 0.831; p<0.001). No relevant correlation between oxygenator blood volume and O2 transfer was found. Oxygenator blood volume declined over time and was clearly associated with an increasing oxygenator resistance during prolonged extracorporeal life support, though O2 transfer was less affected.
Topics: Adult; Blood Volume; Carbon Dioxide; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Middle Aged; Monitoring, Physiologic; Oxygen; Oxygenators; Regional Blood Flow
PubMed: 35108345
DOI: 10.1371/journal.pone.0263360 -
Current Molecular Pharmacology 2021Hypoxia is an integral part of the tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major... (Review)
Review
Hypoxia is an integral part of the tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1β (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mechanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.
Topics: Aryl Hydrocarbon Receptor Nuclear Translocator; Cell Hypoxia; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; Oxygen; Tumor Microenvironment
PubMed: 33494692
DOI: 10.2174/1874467214666210120154929 -
Experimental & Molecular Medicine Mar 2024Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response... (Review)
Review
Oxygen is crucial for life and acts as the final electron acceptor in mitochondrial energy production. Cells adapt to varying oxygen levels through intricate response systems. Hypoxia-inducible factors (HIFs), including HIF-1α and HIF-2α, orchestrate the cellular hypoxic response, activating genes to increase the oxygen supply and reduce expenditure. Under conditions of excess oxygen and resulting oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2) activates hundreds of genes for oxidant removal and adaptive cell survival. Hypoxia and oxidative stress are core hallmarks of solid tumors and activated HIFs and NRF2 play pivotal roles in tumor growth and progression. The complex interplay between hypoxia and oxidative stress within the tumor microenvironment adds another layer of intricacy to the HIF and NRF2 signaling systems. This review aimed to elucidate the dynamic changes and functions of the HIF and NRF2 signaling pathways in response to conditions of hypoxia and oxidative stress, emphasizing their implications within the tumor milieu. Additionally, this review explored the elaborate interplay between HIFs and NRF2, providing insights into the significance of these interactions for the development of novel cancer treatment strategies.
Topics: Humans; Cell Hypoxia; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; NF-E2-Related Factor 2; Oxidative Stress; Oxygen; Tumor Microenvironment
PubMed: 38424190
DOI: 10.1038/s12276-024-01180-8 -
Science Advances Nov 2023Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity... (Review)
Review
Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity of oxygen-dependent enzymes. The affinity of these enzymes for oxygen positions them along a continuum of oxygen sensing that defines their roles in launching reactive and adaptive cellular responses. These responses encompass regulation of all steps in the central dogma, with rapid perturbation of the metabolome and proteome followed by more persistent reprogramming of the transcriptome and epigenome. Core hypoxia response genes and pathways are commonly regulated at multiple inflection points, fine-tuning the dependencies on oxygen concentration and hypoxia duration. Ultimately, shifts in the activity of oxygen-sensing enzymes directly or indirectly endow cells with intrinsic hypoxia tolerance and drive processes that are associated with aggressive phenotypes in cancer including angiogenesis, migration, invasion, immune evasion, epithelial mesenchymal transition, and stemness.
Topics: Humans; Tumor Hypoxia; Neoplasms; Hypoxia; Oxygen; Phenotype
PubMed: 37992163
DOI: 10.1126/sciadv.adj6409