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BMJ Clinical Evidence Jul 2008Carbon monoxide is an odourless, colourless gas, and poisoning causes hypoxia, cell damage, and death. Exposure to carbon monoxide is measured either directly from blood... (Review)
Review
INTRODUCTION
Carbon monoxide is an odourless, colourless gas, and poisoning causes hypoxia, cell damage, and death. Exposure to carbon monoxide is measured either directly from blood samples and expressed as a percentage of carboxyhaemoglobin, or indirectly using the carbon monoxide in expired breath. Carboxyhaemoglobin percentage is the most frequently used biomarker of carbon monoxide exposure. Although the diagnosis of carbon monoxide poisoning can be confirmed by detecting elevated levels of carboxyhaemoglobin in the blood, the presence of clinical signs and symptoms after known exposure to carbon monoxide should not be ignored.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of oxygen treatments for acute carbon monoxide poisoning? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: 100% hyperbaric oxygen, oxygen 28%, and oxygen 100% by non-re-breather mask.
Topics: Carbon Monoxide; Carbon Monoxide Poisoning; Carboxyhemoglobin; Humans; Oxygen; Respiration
PubMed: 19445736
DOI: No ID Found -
Effect of Ketamine on Postoperative Neurocognitive Disorders: A Systematic Review and Meta-Analysis.Journal of Clinical Medicine Jun 2023Neurocognitive alterations in the perioperative period might be caused by a wide variety of factors including pain, blood loss, hypotension, hypoxia, micro- and... (Review)
Review
BACKGROUND
Neurocognitive alterations in the perioperative period might be caused by a wide variety of factors including pain, blood loss, hypotension, hypoxia, micro- and macroemboli, cardiopulmonary bypass (CPB), reperfusion damage, and surgery itself, and all are risk factors for developing postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). The objective of this study was to evaluate the effect of ketamine on neurocognitive dysfunction after anesthesia.
METHODS
We conducted a meta-analysis of randomized controlled trials (RCTs) comparing ketamine use (experimental group) with placebo (controls).
RESULTS
The model favors the control group over the experimental group in terms of frequency of hallucinations (the risk ratio with 95% CI is 1.54 [1.09, 2.19], -value = 0.02), the number of patients readmitted within 30 days (RR with 95% CI is 0.25 [0.09, 0.70]), and the number of adverse events (overall RR with 95% CI is 1.31 [1.06, 1.62]). In terms of morphine consumption, the model favors the experimental group.
CONCLUSION
There was no statistically significant difference in incidences of postoperative delirium, vasopressor requirement, and fentanyl consumption between the ketamine and control groups. However, hallucinations were more frequently reported in the ketamine group.
PubMed: 37445346
DOI: 10.3390/jcm12134314 -
Cells Jun 2023Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating... (Review)
Review
Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.
Topics: Humans; MicroRNAs; Endothelial Cells; Vascular Endothelial Growth Factor A; Phosphatidylinositol 3-Kinases; Neoplasms; Mitogen-Activated Protein Kinase Kinases; Receptors, Vascular Endothelial Growth Factor; Tumor Microenvironment
PubMed: 37443725
DOI: 10.3390/cells12131692 -
Frontiers in Medicine 2023Obstructive sleep apnea syndrome (OSAS) is a chronic disorder characterized by recurring episode obstruction and collapse of upper airways during sleep, leading to...
INTRODUCTION
Obstructive sleep apnea syndrome (OSAS) is a chronic disorder characterized by recurring episode obstruction and collapse of upper airways during sleep, leading to hypoxia and sleep disruption. OSAS is commonly associated with an increased prevalence of hypertension. The underlying mechanism in OSA with hypertension is related to intermittent hypoxia. This hypoxia induces endothelial dysfunction, overactivity of sympathetic effects, oxidative stress, and systemic inflammation. Hypoxemia triggers the sympathetic process's overactivity, leading to the development of resistant hypertension in OSA. Thus, we hypothesize to evaluate the association between resistant hypertension and OSA.
METHODS
The PubMed, ClinicalTrails.gov, CINAHL, Google Scholar, Cochrane Library, and Science Direct databases were searched from 2000 to January 2022 for studies demonstrating the association between resistant hypertension and OSA. The eligible articles underwent quality appraisal, meta-analysis, and heterogeneity assessment.
RESULTS
This study comprises seven studies, including 2,541 patients ranged from 20 to 70 years. The pooled analysis of six studies demonstrated that OSAS patients with a history of increased age, gender, obesity, and smoking status are at an increased risk for resistant hypertension (OR: 4.16 [3.07, 5.64], :0%) than the non-OSAS patients. Similarly, the pooled effect demonstrated that patients with OSAS were at an increased risk of resistant hypertension (OR: 3.34 [2.44, 4.58]; :0%) than the non-OSAS patients when all associated risk factors were adjusted using multivariate analysis.
CONCLUSION
This study concludes that OSAS patients with or without related risk factors demonstrated increased risk for resistant hypertension.
PubMed: 37332747
DOI: 10.3389/fmed.2023.1200952 -
Association Between Obstructive Sleep Apnea and Osteoporosis: A Systematic Review and Meta-Analysis.International Journal of Endocrinology... Jul 2016Hypoxia reduces osteoblast growth resulting in bone thinning and osteoporosis. Although obstructive sleep apnea (OSA) with recurrent hypoxia might be a contributing... (Review)
Review
CONTEXT
Hypoxia reduces osteoblast growth resulting in bone thinning and osteoporosis. Although obstructive sleep apnea (OSA) with recurrent hypoxia might be a contributing factor for osteoporosis development, whether OSA is a risk or protective factor for osteoporosis has not been demonstrated.
OBJECTIVES
This systematic review and meta-analysis evaluated the association between OSA and osteoporosis using published observational studies.
DATA SOURCES
PubMed/MEDLINE and EMBASE databases.
STUDY SELECTION
We completed a systematic review and meta-analysis of published observational studies that evaluated incidence or prevalence of osteoporosis or bone mineral density in obstructive sleep apnea compared with controls. Severity of OSA was characterized using the apnea-hypopnea index (AHI).
DATA EXTRACTION
Primary outcomes were incidence, prevalence, or odds ratio of having osteoporosis, defined as bone mineral density T-score < -2.5 SD.
RESULTS
Of 353 articles, 344 articles were excluded, 9 underwent full-length review and data were extracted from 7 studies consisting of 113,558 patients. Finally, 3 extracted studies were included in the meta-analysis of osteoporosis. Among cohort studies, the pooled odds ratio of osteoporosis in patients with OSA was 1.92 (95% confidence interval [CI]: 1.24 - 2.97) compared with controls. Among cross-sectional studies, odds of osteoporosis was higher in controls compared with patients with OSA (OR = 0.60, 95% CI: 0.42 - 0.87). In subgroup analysis by gender and study design, in both sexes, only cohort studies had higher odds of osteoporosis compared with controls.
CONCLUSIONS
There was significant association between OSA and osteoporosis in studies with cohort design. Further prospective studies with large numbers of patients adjusted for the effects of age, sex, or BMI are required to comprehensively determine whether OSA is a risk factor for osteoporosis.
PubMed: 27942262
DOI: 10.5812/ijem.36317 -
Brain Sciences Nov 2023Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of... (Review)
Review
Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of studies investigating hypoxia (10-16% O) for ≥14 days in humans, as well as the neurobiological mechanisms triggered by hypoxia in animals, and suggests optimal treatment protocols to guide future studies. We followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020. Searches were performed on PubMed/MEDLINE, PsycInfo, EMBASE, and the Cochrane Library, in May-September 2023. Two authors independently reviewed the human studies with the following tools: (1) revised Cochrane collaboration's risk of bias for randomized trials 2.0; (2) the risk of bias in nonrandomized studies of interventions. We identified 58 eligible studies (k = 8 human studies with N = 274 individuals; k = 48 animal studies) reporting the effects of hypoxia on cognition, motor function, neuroimaging, neuronal/synaptic morphology, inflammation, oxidative stress, erythropoietin, neurotrophins, and Alzheimer's disease markers. A total of 75% of human studies indicated cognitive and/or neurological benefits, although all studies were evaluated ashigh risk of bias due to a lack of randomization and assessor blinding. Low-dose intermittent or continuous hypoxia repeated for 30-240 min sessions, preferably in combination with motor-cognitive training, produced beneficial effects, and high-dose hypoxia with longer (≥6 h) durations and chronic exposure produced more adverse effects. Larger and methodologically stronger translational studies are warranted.
PubMed: 38137096
DOI: 10.3390/brainsci13121648 -
The Cochrane Database of Systematic... Oct 2018Peripheral arterial disease (PAD), caused by narrowing of the arteries in the limbs, is increasing in incidence and prevalence as our population is ageing and as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD), caused by narrowing of the arteries in the limbs, is increasing in incidence and prevalence as our population is ageing and as diabetes is becoming more prevalent. PAD can cause pain in the limbs while walking, known as intermittent claudication, or can be more severe and cause pain while at rest, ulceration, and ultimately gangrene and limb loss. This more severe stage of PAD is known as 'critical limb ischaemia'. Treatments for PAD include medications that help to reduce the increased risk of cardiovascular events and help improve blood flow, as well as endovascular or surgical repair or bypass of the blocked arteries. However, many people are unresponsive to medications and are not suited to surgical or endovascular treatment, leaving amputation as the last option. Gene therapy is a novel approach in which genetic material encoding for proteins that may help increase revascularisation is injected into the affected limbs of patients. This type of treatment has been shown to be safe, but its efficacy, especially regarding ulcer healing, effects on quality of life, and other symptomatic outcomes remain unknown.
OBJECTIVES
To assess the effects of gene therapy for symptomatic peripheral arterial disease.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched Cochrane CENTRAL, the Cochrane Vascular Specialised Register, MEDLINE Ovid, Embase Ovid, CINAHL, and AMED, along with trials registries (all searched 27 November 2017). We also checked reference lists of included studies and systematic reviews for further studies.
SELECTION CRITERIA
We included randomised and quasi-randomised studies that evaluated gene therapy versus no gene therapy in people with PAD. We excluded studies that evaluated direct growth hormone treatment or cell-based treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, performed quality assessment, and extracted data from the included studies. We collected pertinent information on each study, as well as data for the outcomes of amputation-free survival, ulcer healing, quality of life, amputation, all-cause mortality, ankle brachial index, symptom scores, and claudication distance.
MAIN RESULTS
We included in this review a total of 17 studies with 1988 participants (evidence current until November 2017). Three studies limited their inclusion to people with intermittent claudication, 12 limited inclusion to people with varying levels of critical limb ischaemia, and two included people with either condition. Study investigators evaluated many different types of gene therapies, using different protocols. Most studies evaluated growth factor-encoding gene therapy, with six studies using vascular endothelial growth factor (VEGF)-encoding genes, four using hepatocyte growth factor (HGF)-encoding genes, and three using fibroblast growth factor (FGF)-encoded genes. Two studies evaluated hypoxia-inducible factor 1-alpha (HIF-1α) gene therapy, one study used a developmental endothelial locus-1 gene therapy, and the final study evaluated a stromal cell-derived factor-1 (SDF-1) gene therapy. Most studies reported outcomes after 12 months of follow-up, but follow-up ranged from three months to two years.Overall risk of bias varied between studies, with many studies not providing sufficient detail for adequate determination of low risk of bias for many domains. Two studies did not utilise a placebo control, leading to risk of performance bias. Several studies reported in previous protocols or in their Methods sections that they would report on certain outcomes for which no data were then reported, increasing risk of reporting bias. All included studies reported sponsorships from corporate entities that led to unclear risk of other bias. The overall quality of evidence ranged from moderate to very low, generally as the result of heterogeneity and imprecision, with few or no studies reporting on outcomes.Evidence suggests no clear differences for the outcomes of amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving this treatment (all moderate-quality evidence). Low-quality evidence suggests improvement in complete ulcer healing with gene therapy (odds ratio (OR) 2.16, 95% confidence interval (CI) 1.02 to 4.59; P = 0.04). We could not combine data on quality of life and can draw no conclusions at this time regarding this outcome (very low-quality evidence). We included one study in the meta-analysis for ankle brachial index, which showed no clear differences between treatments, but we can draw no overall association (low-quality evidence). We combined in a meta-analysis pain symptom scores as assessed by visual analogue scales from two studies and found no clear differences between treatment groups (very low-quality evidence). We carried out extensive subgroup analyses by PAD classification, dosage schedule, vector type, and gene used but identified no substantial differences.
AUTHORS' CONCLUSIONS
Moderate-quality evidence shows no clear differences in amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving gene therapy. Some evidence suggests that gene therapy may lead to improved complete ulcer healing, but this outcome needs to be explored with improved reporting of the measure, such as decreased ulcer area in cm², and better description of ulcer types and healing. Further standardised data that are amenable to meta-analysis are needed to evaluate other outcomes such as quality of life, ankle brachial index, symptom scores, and claudication distance.
Topics: Amputation, Surgical; Chemokine CXCL12; Extremities; Fibroblast Growth Factors; Genetic Therapy; Hepatocyte Growth Factor; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intermittent Claudication; Ischemia; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A
PubMed: 30380135
DOI: 10.1002/14651858.CD012058.pub2 -
Brain and Behavior Nov 2023Obstructive sleep apnea (OSA) is a common sleep disorder that causes intermittent hypoxia and sleep fragmentation, leading to attention impairment and other cognitive... (Review)
Review
BACKGROUND AND OBJECTIVE
Obstructive sleep apnea (OSA) is a common sleep disorder that causes intermittent hypoxia and sleep fragmentation, leading to attention impairment and other cognitive deficits. Magnetic resonance imaging (MRI) is a powerful modality that can reveal the structural and functional brain alterations associated with attention impairment in OSA patients. The objective of this systematic review is to identify and synthesize the evidence on MRI biomarkers and neuropsychological assessments of attention deficits in OSA patients.
METHODS
We searched the Scopus and PubMed databases for studies that used MRI to measure biomarkers related to attention alteration in OSA patients and reported qualitative and quantitative data on the association between MRI biomarkers and attention outcomes. We also included studies that found an association between neuropsychological assessments and MRI findings in OSA patients with attention deficits.
RESULTS
We included 19 studies that met our inclusion criteria and extracted the relevant data from each study. We categorized the studies into three groups based on the MRI modality and the cognitive domain they used: structural and diffusion tensor imaging MRI findings, functional, perfusion, and metabolic MRI findings, and neuropsychological assessment findings.
CONCLUSIONS
We found that OSA is associated with structural, functional, and metabolic brain alterations in multiple regions and networks that are involved in attention processing. Treatment with continuous positive airway pressure can partially reverse some of the brain changes and improve cognitive function in some domains and in some studies. This review suggests that MRI techniques and neuropsychological assessments can be useful tools for monitoring the progression and response to treatment of OSA patients.
Topics: Humans; Diffusion Tensor Imaging; Sleep Apnea, Obstructive; Brain; Magnetic Resonance Imaging; Biomarkers; Neuropsychological Tests
PubMed: 37743582
DOI: 10.1002/brb3.3262 -
Frontiers in Aging 2021The effects of short-term hyperoxia on age-related diseases and aging biomarkers have been reported in animal and human experiments using different protocols; however,... (Review)
Review
The effects of short-term hyperoxia on age-related diseases and aging biomarkers have been reported in animal and human experiments using different protocols; however, the findings of the studies remain conflicting. In this systematic review, we summarized the existing reports in the effects of short-term hyperoxia on age-related diseases, hypoxia-inducible factor 1α (HIF-1α), and other oxygen-sensitive transcription factors relevant to aging, telomere length, cellular senescence, and its side effects. This review was done as described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A systematic search was done in PubMed, Google Scholar, and Cochrane Library and from the references of selected articles to identify relevant studies until May 2021. Of the total 1,699 identified studies, 17 were included in this review. Most of the studies have shown significant effects of short-term hyperoxia on age-related diseases and aging biomarkers. The findings of the studies suggest the potential benefits of short-term hyperoxia in several clinical applications such as for patients undergoing stressful operations, restoration of cognitive function, and the treatment of severe traumatic brain injury. Short-term hyperoxia has significant effects in upregulation or downregulation of transcription factors relevant to aging such as HIF-1α, nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB), and nuclear factor (erythroid-derived 2)-like 2 (NRF2) among others. Short-term hyperoxia also has significant effects to increase antioxidant enzymes, and increase telomere length and clearance of senescent cells. Some of the studies have also reported adverse consequences including mitochondrial DNA damage and nuclear cataract formation depending on the dose and duration of oxygen exposure. In conclusion, short-term hyperoxia could be a feasible treatment option to treat age-related disease and to slow aging because of its ability to increase antioxidant enzymes, significantly increase telomere length and clearance of senescent cells, and improve cognitive function, among others. The reported side effects of hyperoxia vary depending on the dose and duration of exposure. Therefore, it seems that additional studies for better understanding the beneficial effects of short-term hyperoxia and for minimizing side effects are necessary for optimal clinical application.
PubMed: 35822043
DOI: 10.3389/fragi.2021.783144 -
Clinical and Molecular Hepatology Apr 2023Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1 and NRP2 are the receptors of multiple proteins involved in key signaling pathways associated with tumor progression. We aimed to systematically review all the available findings on their role in HCC. We searched the Scopus, Web of Science (WOS), PubMed, Cochrane and Embase databases for articles evaluating NRPs in preclinical or clinical HCC models. This study was registered in PROSPERO (CRD42022349774) and include 49 studies. Multiple cellular and molecular processes have been associated with one or both NRPs, indicating that they are potential diagnostic and prognostic biomarkers in HCC patients. Mainly NRP1 has been shown to promote tumor cell survival and progression by modulating several signaling pathways. NRPs mainly regulate angiogenesis, invasion and migration and have shown to induce invasion and metastasis. They also regulate the immune response and tumor microenvironment, showing a crucial interplay with the hypoxia response and microRNAs in HCC. Altogether, NRP1 and NRP2 are potential biomarkers and therapeutic targets, providing novel insight into the clinical landscape of HCC patients.
Topics: Humans; Carcinoma, Hepatocellular; Neuropilins; Liver Neoplasms; Signal Transduction; Biomarkers; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 36726054
DOI: 10.3350/cmh.2022.0425