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Journal of Biomedical Optics Jun 2024Photoacoustic imaging (PAI) promises to measure spatially resolved blood oxygen saturation but suffers from a lack of accurate and robust spectral unmixing methods to...
SIGNIFICANCE
Photoacoustic imaging (PAI) promises to measure spatially resolved blood oxygen saturation but suffers from a lack of accurate and robust spectral unmixing methods to deliver on this promise. Accurate blood oxygenation estimation could have important clinical applications from cancer detection to quantifying inflammation.
AIM
We address the inflexibility of existing data-driven methods for estimating blood oxygenation in PAI by introducing a recurrent neural network architecture.
APPROACH
We created 25 simulated training dataset variations to assess neural network performance. We used a long short-term memory network to implement a wavelength-flexible network architecture and proposed the Jensen-Shannon divergence to predict the most suitable training dataset.
RESULTS
The network architecture can flexibly handle the input wavelengths and outperforms linear unmixing and the previously proposed learned spectral decoloring method. Small changes in the training data significantly affect the accuracy of our method, but we find that the Jensen-Shannon divergence correlates with the estimation error and is thus suitable for predicting the most appropriate training datasets for any given application.
CONCLUSIONS
A flexible data-driven network architecture combined with the Jensen-Shannon divergence to predict the best training data set provides a promising direction that might enable robust data-driven photoacoustic oximetry for clinical use cases.
Topics: Photoacoustic Techniques; Oximetry; Humans; Neural Networks, Computer; Oxygen; Oxygen Saturation; Algorithms
PubMed: 38841431
DOI: 10.1117/1.JBO.29.S3.S33303 -
The Cochrane Database of Systematic... Sep 2023This is an updated review concerning 'Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated review concerning 'Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit'. Supplementary oxygen is provided to most patients in intensive care units (ICUs) to prevent global and organ hypoxia (inadequate oxygen levels). Oxygen has been administered liberally, resulting in high proportions of patients with hyperoxemia (exposure of tissues to abnormally high concentrations of oxygen). This has been associated with increased mortality and morbidity in some settings, but not in others. Thus far, only limited data have been available to inform clinical practice guidelines, and the optimum oxygenation target for ICU patients is uncertain. Because of the publication of new trial evidence, we have updated this review.
OBJECTIVES
To update the assessment of benefits and harms of higher versus lower fractions of inspired oxygen (FiO) or targets of arterial oxygenation for adults admitted to the ICU.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, BIOSIS Previews, and LILACS. We searched for ongoing or unpublished trials in clinical trial registers and scanned the reference lists and citations of included trials. Literature searches for this updated review were conducted in November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared higher versus lower FiO or targets of arterial oxygenation (partial pressure of oxygen (PaO), peripheral or arterial oxygen saturation (SpO or SaO)) for adults admitted to the ICU. We included trials irrespective of publication type, publication status, and language. We excluded trials randomising participants to hypoxaemia (FiO below 0.21, SaO/SpO below 80%, or PaO below 6 kPa) or to hyperbaric oxygen, and cross-over trials and quasi-randomised trials.
DATA COLLECTION AND ANALYSIS
Four review authors independently, and in pairs, screened the references identified in the literature searches and extracted the data. Our primary outcomes were all-cause mortality, the proportion of participants with one or more serious adverse events (SAEs), and quality of life. We analysed all outcomes at maximum follow-up. Only three trials reported the proportion of participants with one or more SAEs as a composite outcome. However, most trials reported on events categorised as SAEs according to the International Conference on Harmonisation Good Clinical Practice (ICH-GCP) criteria. We, therefore, conducted two analyses of the effect of higher versus lower oxygenation strategies using 1) the single SAE with the highest reported proportion in each trial, and 2) the cumulated proportion of participants with an SAE in each trial. Two trials reported on quality of life. Secondary outcomes were lung injury, myocardial infarction, stroke, and sepsis. No trial reported on lung injury as a composite outcome, but four trials reported on the occurrence of acute respiratory distress syndrome (ARDS) and five on pneumonia. We, therefore, conducted two analyses of the effect of higher versus lower oxygenation strategies using 1) the single lung injury event with the highest reported proportion in each trial, and 2) the cumulated proportion of participants with ARDS or pneumonia in each trial. We assessed the risk of systematic errors by evaluating the risk of bias in the included trials using the Risk of Bias 2 tool. We used the GRADEpro tool to assess the overall certainty of the evidence. We also evaluated the risk of publication bias for outcomes reported by 10b or more trials.
MAIN RESULTS
We included 19 RCTs (10,385 participants), of which 17 reported relevant outcomes for this review (10,248 participants). For all-cause mortality, 10 trials were judged to be at overall low risk of bias, and six at overall high risk of bias. For the reported SAEs, 10 trials were judged to be at overall low risk of bias, and seven at overall high risk of bias. Two trials reported on quality of life, of which one was judged to be at overall low risk of bias and one at high risk of bias for this outcome. Meta-analysis of all trials, regardless of risk of bias, indicated no significant difference from higher or lower oxygenation strategies at maximum follow-up with regard to mortality (risk ratio (RR) 1.01, 95% confidence interval (C)I 0.96 to 1.06; I = 14%; 16 trials; 9408 participants; very low-certainty evidence); occurrence of SAEs: the highest proportion of any specific SAE in each trial RR 1.01 (95% CI 0.96 to 1.06; I = 36%; 9466 participants; 17 trials; very low-certainty evidence), or quality of life (mean difference (MD) 0.5 points in participants assigned to higher oxygenation strategies (95% CI -2.75 to 1.75; I = 34%, 1649 participants; 2 trials; very low-certainty evidence)). Meta-analysis of the cumulated number of SAEs suggested benefit of a lower oxygenation strategy (RR 1.04 (95% CI 1.02 to 1.07; I = 74%; 9489 participants; 17 trials; very low certainty evidence)). However, trial sequential analyses, with correction for sparse data and repetitive testing, could reject a relative risk increase or reduction of 10% for mortality and the highest proportion of SAEs, and 20% for both the cumulated number of SAEs and quality of life. Given the very low-certainty of evidence, it is necessary to interpret these findings with caution. Meta-analysis of all trials indicated no statistically significant evidence of a difference between higher or lower oxygenation strategies on the occurrence of lung injuries at maximum follow-up (the highest reported proportion of lung injury RR 1.08, 95% CI 0.85 to 1.38; I = 0%; 2048 participants; 8 trials; very low-certainty evidence). Meta-analysis of all trials indicated harm from higher oxygenation strategies as compared with lower on the occurrence of sepsis at maximum follow-up (RR 1.85, 95% CI 1.17 to 2.93; I = 0%; 752 participants; 3 trials; very low-certainty evidence). Meta-analysis indicated no differences regarding the occurrences of myocardial infarction or stroke.
AUTHORS' CONCLUSIONS
In adult ICU patients, it is still not possible to draw clear conclusions about the effects of higher versus lower oxygenation strategies on all-cause mortality, SAEs, quality of life, lung injuries, myocardial infarction, stroke, and sepsis at maximum follow-up. This is due to low or very low-certainty evidence.
Topics: Adult; Humans; Oxygen; Lung Injury; Arteries; Respiratory Distress Syndrome; Intensive Care Units
PubMed: 37700687
DOI: 10.1002/14651858.CD012631.pub3 -
Nature Metabolism Jun 2024Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing...
Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5'-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation.
Topics: Lysosomes; Macrophages; Animals; Mice; Pyridoxal Phosphate; Hypoxia; Cell Hypoxia; Vitamin B 6; Oxygen; Inflammation
PubMed: 38822028
DOI: 10.1038/s42255-024-01053-4 -
Experimental Cell Research Nov 2023Aerobic cellular respiration requires oxygen, which is an essential part of cardiomyocyte metabolism. Thus, oxygen is required for the physiologic metabolic activities... (Review)
Review
Aerobic cellular respiration requires oxygen, which is an essential part of cardiomyocyte metabolism. Thus, oxygen is required for the physiologic metabolic activities and development of adult hearts. However, the activities of metabolic pathways associated with hypoxia in cardiomyocytes (CMs) have not been conclusively described. In this review, we discuss the role of hypoxia in the development of the hearts metabolic system, and the metabolic remodeling associated with the hypoxic adult heart. Hypoxia-inducible factors (HIFs), the signature transcription factors in hypoxic environments, is also investigated for their potential to modulate hypoxia-induced metabolic changes. Metabolic remodeling existing in hypoxic hearts have also been shown to occur in chronic failing hearts, implying that novel therapeutic options for heart failure (HF) may exist from the hypoxic perspective. The pressure overload-induced HF and diabetes-induced HF are also discussed to demonstrate the effects of HIF factor-related pathways to control the metabolic remodeling of failing hearts.
Topics: Humans; Adult; Hypoxia; Myocytes, Cardiac; Heart Failure; Cell Respiration; Oxygen; Hypoxia-Inducible Factor 1, alpha Subunit; Cell Hypoxia
PubMed: 37726046
DOI: 10.1016/j.yexcr.2023.113763 -
BMJ Open Nov 2023Vascular cognitive impairment (VCI) has an increasing prevalence worldwide, accounting for at least 20%-40% of all diagnoses of dementia. The decline in cognitive...
INTRODUCTION
Vascular cognitive impairment (VCI) has an increasing prevalence worldwide, accounting for at least 20%-40% of all diagnoses of dementia. The decline in cognitive function seriously impairs patients' activities of daily living and social participation and reduces their quality of life. However, there is still a lack of advanced, definitive rehabilitation programmes for VCI. Hyperbaric oxygen therapy (HBOT) and repetitive transcranial magnetic stimulation (rTMS) are recognised treatments for improving cognitive impairment. The former can restore oxygen supply in the brain by increasing oxygen partial pressure in brain tissue, while the latter can enhance neuronal excitability and promote synaptic plasticity. However, no studies have explored the effect of HBO combined with rTMS on VCI.
METHODS AND ANALYSIS
This study is designed as a single-centre, assessor-blind, randomised controlled clinical trial with four parallel arms. A total of 72 participants will be recruited and randomly assigned to the control group, HBOT group, rTMS group and HBOT combined with rTMS group at a ratio of 1:1:1:1. All enrolled participants will receive conventional treatment. The entire intervention period is 4 weeks, with a 3-week follow-up. Outcomes will be measured at baseline (T0), after a 4-week intervention (T1) and after an additional 3-week follow-up period (T2). The primary endpoint is the Montreal Cognitive Assessment score. The secondary endpoints are Mini-Mental State Examination score, Modified Barthel Index score, latency and amplitude of P300, cerebral cortical oxygenated haemoglobin (HbO) and deoxygenated haemoglobin (HbR) concentrations as measured by task-state functional near-infrared spectroscopy.
ETHICS AND DISSEMINATION
Ethics approval was obtained from the West China Hospital Clinical Trials and Biomedical Ethics Committee of Sichuan University (ethics reference: 2022 (1972)). The findings will be published in peer-reviewed journals and disseminated through scientific conferences and seminars.
TRIAL REGISTRATION NUMBER
ChiCTR2300068242.
Topics: Humans; Transcranial Magnetic Stimulation; Activities of Daily Living; Hyperbaric Oxygenation; Quality of Life; Cognitive Dysfunction; Hemoglobins; Oxygen; Randomized Controlled Trials as Topic
PubMed: 37963686
DOI: 10.1136/bmjopen-2023-073532 -
Wiley Interdisciplinary Reviews.... 2024The oxygen level in the tumor is a critical marker that determines response to different treatments. Cancerous cells can adapt to hypoxia and low pH conditions within... (Review)
Review
The oxygen level in the tumor is a critical marker that determines response to different treatments. Cancerous cells can adapt to hypoxia and low pH conditions within the tumor microenvironment (TME) to regulate tumor metabolism, proliferation, and promote tumor metastasis as well as angiogenesis, consequently leading to treatment failure and recurrence. In recent years, widespread attempts have been made to overcome tumor hypoxia through different methods, such as hyperbaric oxygen therapy (HBOT), hyperthermia, O carriers, artificial hemoglobin, oxygen generator hydrogels, and peroxide materials. While oxygen is found to be an essential agent to improve the treatment response of photodynamic therapy (PDT) and other cancer treatment modalities, the development of hypoxia within the tumor is highly associated with PDT failure. Recently, the use of nanoparticles has been a hot topic for researchers and exploited to overcome hypoxia through Oxygen-generating hydrogels, O nanocarriers, and O -generating nanoparticles. This review aimed to discuss the role of nanotechnology in tumor oxygenation and highlight the challenges, prospective, and recent advances in this area to improve PDT outcomes. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.
Topics: Humans; Photosensitizing Agents; Photochemotherapy; Tumor Hypoxia; Prospective Studies; Nanotechnology; Oxygen; Neoplasms; Nanoparticles; Hypoxia; Hydrogels; Tumor Microenvironment; Cell Line, Tumor
PubMed: 38072393
DOI: 10.1002/wnan.1937 -
World Journal of Surgical Oncology Jan 2024Head and neck cancer (HNC) is one of the most frequent malignancies in Asian males with a poor prognosis. Apart from well-known prognostic indicators, markers of tumor... (Review)
Review
BACKGROUND
Head and neck cancer (HNC) is one of the most frequent malignancies in Asian males with a poor prognosis. Apart from well-known prognostic indicators, markers of tumor hypoxia can help us predict response to treatment and survival.
METHODS
A review of the literature on the present evidence and potential clinical importance of tumor hypoxia in head and neck cancer was carried out. The data obtained from the literature search is presented as a narrative review.
RESULTS
The literature shows possible associations between prognosis and low tumor oxygenation. Intermediate hypoxia biomarkers like HIF-1, GLUT-1, miRNA, and lactate, can help in predicting the response to therapy and survival as their altered expression is related to prognosis.
CONCLUSIONS
Hypoxia is common in HNC and can be detected by use of biomarkers. The tumors that show expression of hypoxia biomarkers have poor prognosis except for patients with human papilloma virus-associated or VHL-associated cancers. Therapeutic targeting of hypoxia is emerging; however, it is still in its nascent stage, with increasing clinical trials hypoxia is set to emerge as an attractive therapeutic target in HNC.
Topics: Male; Humans; Tumor Hypoxia; Mouth Neoplasms; Hypoxia; Lactic Acid; Biomarkers
PubMed: 38200568
DOI: 10.1186/s12957-023-03284-3 -
Experimental Physiology Apr 2024An adequate supply of O is essential for the maintenance of cellular activity. Systemic or local hypoxia can be experienced during decreased O availability or associated... (Review)
Review
An adequate supply of O is essential for the maintenance of cellular activity. Systemic or local hypoxia can be experienced during decreased O availability or associated with diseases, or a combination of both. Exposure to hypoxia triggers adjustments in multiple physiological systems in the body to generate appropriate homeostatic responses. However, with significant reductions in the arterial partial pressure of O, hypoxia can be life-threatening and cause maladaptive changes or cell damage and death. To mitigate the impact of limited O availability on cellular activity, O chemoreceptors rapidly detect and respond to reductions in the arterial partial pressure of O, triggering orchestrated responses of increased ventilation and cardiac output, blood flow redistribution and metabolic adjustments. In mammals, the peripheral chemoreceptors of the carotid body are considered to be the main hypoxic sensors and the primary source of excitatory feedback driving respiratory, cardiovascular and autonomic responses. However, current evidence indicates that the CNS contains specialized brainstem and spinal cord regions that can also sense hypoxia and stimulate brain networks independently of the carotid body inputs. In this manuscript, we review the discoveries about the functioning of the O chemoreceptors and their contribution to the monitoring of O levels in the blood and brain parenchyma and mounting cardiorespiratory responses to maintain O homeostasis. We also discuss the implications of the chemoreflex-related mechanisms in paediatric and adult pathologies.
Topics: Animals; Humans; Child; Hypoxia; Chemoreceptor Cells; Carotid Body; Respiration; Lung; Mammals; Oxygen
PubMed: 38031809
DOI: 10.1113/EP091206 -
Nitric Oxide : Biology and Chemistry Sep 2023Several nitric oxide (NO) generating devices have been developed to deliver NO between 1 part per million (ppm) and 80 ppm. Although inhalation of high-dose NO may...
BACKGROUND
Several nitric oxide (NO) generating devices have been developed to deliver NO between 1 part per million (ppm) and 80 ppm. Although inhalation of high-dose NO may exert antimicrobial effects, the feasibility and safety of producing high-dose (more than 100 ppm) NO remains to be established. In the current study, we designed, developed, and tested three high-dose NO generating devices.
METHODS
We constructed three NO generating devices: a double spark plug NO generator, a high-pressure single spark plug NO generator, and a gliding arc NO generator. The NO and NO concentrations were measured at different gas flows and under various atmospheric pressures. The double spark plug NO generator was designed to deliver gas through an oxygenator and mixing with pure oxygen. The high-pressure and gliding arc NO generators were used to deliver gas through a ventilator into artificial lungs to mimic delivering high-dose NO in the clinical settings. The energy consumption was measured and compared among the three NO generators.
RESULTS
The double spark plug NO generator produced 200 ± 2 ppm (mean ± SD) of NO at gas flow of 8 L/min (or 320 ± 3 ppm at gas flow of 5 L/min) with electrode gap of 3 mm. The nitrogen dioxide (NO) levels were below 3.0 ± 0.1 ppm when mixing with various volumes of pure oxygen. The addition of a second generator increased the delivered NO from 80 (with one spark plug) to 200 ppm. With the high-pressure chamber, the NO concentration reached 407 ± 3 ppm with continuous air flow at 5 L/min when employing the 3 mm electrode gap under 2.0 atmospheric pressure (ATA). When compared to 1 ATA, NO production was increased 22% at 1.5 ATA and 34% at 2 ATA. The NO level was 180 ± 1 ppm when connecting the device to a ventilator with a constant inspiratory airflow of 15 L/min, and NO levels were below 1 (0.93 ± 0.02) ppm. The gliding arc NO generator produced up to 180 ± 4 ppm of NO when connecting the device to a ventilator, and the NO level was below 1 (0.91 ± 0.02) ppm in all testing conditions. The gliding arc device required more power (in watts) to generate the same concentrations of NO when compared to double spark plug or high-pressure NO generators.
CONCLUSIONS
Our results demonstrated that it is feasible to enhance NO production (more than 100 ppm) while maintaining NO level relatively low (less than 3 ppm) with the three recently developed NO generating devices. Future studies might include these novel designs to deliver high doses of inhaled NO as an antimicrobial used to treat upper and lower respiratory tract infections.
Topics: Nitric Oxide; Nitrogen Dioxide; Respiratory Therapy; Lung; Administration, Inhalation; Oxygen
PubMed: 37277062
DOI: 10.1016/j.niox.2023.05.007 -
Critical Care (London, England) Aug 2023The primary aim was to explore the association of global cerebral physiological variables including intracranial pressure (ICP), cerebrovascular reactivity (PRx),...
BACKGROUND
The primary aim was to explore the association of global cerebral physiological variables including intracranial pressure (ICP), cerebrovascular reactivity (PRx), cerebral perfusion pressure (CPP), and deviation from the PRx-based optimal CPP value (∆CPPopt; actual CPP-CPPopt) in relation to brain tissue oxygenation (pbtO) in traumatic brain injury (TBI).
METHODS
A total of 425 TBI patients with ICP- and pbtO monitoring for at least 12 h, who had been treated at the neurocritical care unit, Addenbrooke's Hospital, Cambridge, UK, between 2002 and 2022 were included. Generalized additive models (GAMs) and linear mixed effect models were used to explore the association of ICP, PRx, CPP, and CPPopt in relation to pbtO. PbtO < 20 mmHg, ICP > 20 mmHg, PRx > 0.30, CPP < 60 mmHg, and ∆CPPopt < - 5 mmHg were considered as cerebral insults.
RESULTS
PbtO < 20 mmHg occurred in median during 17% of the monitoring time and in less than 5% in combination with ICP > 20 mmHg, PRx > 0.30, CPP < 60 mmHg, or ∆CPPopt < - 5 mmHg. In GAM analyses, pbtO remained around 25 mmHg over a large range of ICP ([0;50] mmHg) and PRx [- 1;1], but deteriorated below 20 mmHg for extremely low CPP below 30 mmHg and ∆CPPopt below - 30 mmHg. In linear mixed effect models, ICP, CPP, PRx, and ∆CPPopt were significantly associated with pbtO, but the fixed effects could only explain a very small extent of the pbtO variation.
CONCLUSIONS
PbtO below 20 mmHg was relatively frequent and often occurred in the absence of disturbances in ICP, PRx, CPP, and ∆CPPopt. There were significant, but weak associations between the global cerebral physiological variables and pbtO, suggesting that hypoxic pbtO is often a complex and independent pathophysiological event. Thus, other variables may be more crucial to explain pbtO and, likewise, pbtO may not be a suitable outcome measure to determine whether global cerebral blood flow optimization such as CPPopt therapy is successful.
Topics: Humans; Oxygen; Brain; Brain Injuries, Traumatic; Hypoxia; Cerebrovascular Circulation
PubMed: 37653526
DOI: 10.1186/s13054-023-04627-y