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Cureus Aug 2023Sickle cell anemia is a hemoglobinopathy that causes complications such as Vaso-Occlusive Crisis (VOC), stroke, priapism, Acute Chest Syndromes (ACS), and bone infarcts... (Review)
Review
Sickle cell anemia is a hemoglobinopathy that causes complications such as Vaso-Occlusive Crisis (VOC), stroke, priapism, Acute Chest Syndromes (ACS), and bone infarcts due to blood vessel occlusion, resulting in hypoxia, ischemia, and inflammation. Preventing these incidents improves the quality of life and lowers mortality rates in Sickle Cell Disease (SCD) patients. This systematic review aims to describe the drugs, their mechanisms of action, dosages, changes in hemoglobin parameters, decrease in VOCs, delay the time for the next VOC, decrease in the length of hospital stay, and side effects associated with these drugs. This review adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. For this review, we searched the PubMed, Google Scholar, and Cochrane databases and screened them for full free texts published in English and studied in humans in the last five years beginning in 2018. Randomized clinical trials (RCT), observational studies, meta-analyses, systemic reviews, and traditional reviews were all included in the search. According to the type of study, quality assessment tools are used, and eight papers are chosen. Full-text articles from these papers are studied, analyzed, and tabulated. We discussed seven interventions that are used to treat sickle cell disease. Voxelotor, crizanlizumab, L-glutamate, long-term blood transfusions, Zinc (Zn), Niprisan®, and Ciklavit* were found to reduce the number and severity of VOC. We discovered that VOCs containing L -glutamate reduced the length of hospitalization. Magnesium (Mg) did not affect the number and severity of VOCs. This review includes a few articles for the study. Future papers on this subject should include a large sample size and many papers. More clinical trials are required to evaluate the dosages and outcomes of using these drugs in combination to prevent VOCs.
PubMed: 37664256
DOI: 10.7759/cureus.42785 -
Human Reproduction Open 2023What is the role of iron in the pathophysiology of endometriosis?
STUDY QUESTION
What is the role of iron in the pathophysiology of endometriosis?
SUMMARY ANSWER
Iron excess is demonstrated wherever endometriotic tissues are found and is associated with oxidative stress, an inflammatory micro-environment, and cell damage; the iron-mediated oxidative stress is independently linked to subfertility, symptom severity, and malignant transformation.
WHAT IS KNOWN ALREADY
Iron is found in excess in endometriotic tissues, and multiple mechanisms have been studied and posited to explain this. It is clear that iron excess plays a vital role in promoting oxidative stress and cell damage. The evidence base is large, but no comprehensive reviews exist to summarize our understanding and highlight the overarching themes to further our understanding and suggest future directions of study for the field.
STUDY DESIGN SIZE DURATION
This systematic review with a thematic analysis retrieved studies from the PubMed, Embase, Web of Science, and Cochrane Library databases and searches were conducted from inception through to August 2022. Human and animal studies published in the English language were included and identified using a combination of exploded MeSH terms ('Iron' and 'Endometriosis') and free-text search terms ('Iron', 'Ferric', 'Ferrous', 'Endometriosis', 'Endometrioma').
PARTICIPANTS/MATERIALS SETTING METHODS
This review was reported in accordance with the PRISMA guidelines. All studies reporting original data concerning the role of iron or iron complexes in the pathophysiology of endometriosis were included. Studies that did not report original data or provided a review of the field were excluded. Bias analysis was completed for each included study by using the Newcastle-Ottawa scoring system.
MAIN RESULTS AND THE ROLE OF CHANCE
There were 776 records identified and these were screened down to 53 studies which met the eligibility criteria, including 6 animal and 47 human studies, with 3556 individual participants. Iron excess is demonstrated in various tissues and fluids, including ovarian endometriomas, ovarian follicles, ectopic endometriotic lesions, and peritoneal fluid. Markers of oxidative stress are strongly associated with high iron levels, and aberrant expression of iron-transport proteins has been demonstrated. Abnormal resistance to ferroptosis is likely. Iron-mediated oxidative stress is responsible for a pro-inflammatory micro-environment and is linked to subfertility, symptom severity, and, possibly, malignant transformation.
LIMITATIONS REASONS FOR CAUTION
A minority of the included studies were of objectively low quality with a high risk of bias and may lead to misleading conclusions. Additionally, multiple studies failed to appropriately characterize the included patients by known confounding variables, such as menstrual cycle phase, which may introduce bias to the findings.
WIDER IMPLICATIONS OF THE FINDINGS
Current literature depicts a central role of aberrant iron mechanics and subsequent oxidative stress in endometriosis. It is likely that iron excess is at least partly responsible for the persistence and proliferation of ectopic endometriotic lesions. As such, iron mechanics represent an attractive target for novel therapeutics, including iron chelators or effectors of the iron-oxidative stress pathway. There are significant gaps in our current understanding, and this review highlights and recommends several topics for further research. These include the role of iron chelation, resistance to ferroptosis, the relationship between iron excess and localized hypoxia, systemic iron pathophysiology in endometriosis, and the role of oxidative stress in malignant transformation.
STUDY FUNDING/COMPETING INTERESTS
J.W. and S.G.P. are supported by clinical fellowships at Liverpool University Hospital NHS Foundation trust. No additional funding was requested or required for the completion of this work. C.J.H. is supported by a Wellbeing of Women project grant (RG2137). D.K.H. is supported by a Wellbeing of Women project grant (RG2137) and an MRC clinical research training fellowship (MR/V007238/1). The authors have no conflicts of interest to declare.
REGISTRATION NUMBER
A protocol was prospectively registered with the PROSPERO database in August 2021 (CRD42021272818).
PubMed: 37638130
DOI: 10.1093/hropen/hoad033 -
PloS One 2023Recovery of cognitive and physiological responses following a hypoxic exposure may not be considered in various operational and research settings. Understanding recovery...
Recovery of cognitive and physiological responses following a hypoxic exposure may not be considered in various operational and research settings. Understanding recovery profiles and influential factors can guide post-hypoxia restrictions to reduce the risk of further cognitive and physiological deterioration, and the potential for incidents and accidents. We systematically evaluated the available evidence on recovery of cognitive and basic physiological responses following an acute hypoxic exposure to improve understanding of the performance and safety implications, and to inform post-hypoxia restrictions. This systematic review summarises 30 studies that document the recovery of either a cognitive or physiological index from an acute hypoxic exposure. Titles and abstracts from PubMed (MEDLINE) and Scopus were searched from inception to July 2022, of which 22 full text articles were considered eligible. An additional 8 articles from other sources were identified and also considered eligible. The overall quality of evidence was moderate (average Rosendal score, 58%) and there was a large range of hypoxic exposures. Heart rate, peripheral blood haemoglobin-oxygen saturation and heart rate variability typically normalised within seconds-to-minutes following return to normoxia or hyperoxia. Whereas, cognitive performance, blood pressure, cerebral tissue oxygenation, ventilation and electroencephalogram indices could persist for minutes-to-hours following a hypoxic exposure, and one study suggested regional cerebral tissue oxygenation requires up to 24 hours to recover. Full recovery of most cognitive and physiological indices, however, appear much sooner and typically within ~2-4 hours. Based on these findings, there is evidence to support a 'hypoxia hangover' and a need to implement restrictions following acute hypoxic exposures. The severity and duration of these restrictions is unclear but should consider the population, subsequent requirement for safety-critical tasks and hypoxic exposure.
Topics: Humans; Hypoxia; Oximetry; Respiration; Blood Pressure; Cognition
PubMed: 37585402
DOI: 10.1371/journal.pone.0289716 -
Critical Care Research and Practice 2023This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to compare the safety and efficacy of supine vs. nonsupine positions during...
BACKGROUND
This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to compare the safety and efficacy of supine vs. nonsupine positions during intubation.
METHODS
Based on the literature from inception to October 2020, 13 studies with nonemergent intubation in supine and nonsupine positions were chosen using PRISMA and MOOSE protocols. Pooled estimates were calculated using random-effects models with 95% confidence interval (CI). The primary outcome was a successful intubation, attempt, and duration of intubation. The secondary outcome was adverse events (trauma and hypoxia). Bias was evaluated qualitatively, by visual analysis, and quantitatively through the Egger test.
RESULTS
The final analysis included 13 clinical trials with 1,916 patients. The pooled success rates in the supine vs. lateral positions were 99.21% and 98.82%. The supine vs. semierect positions were 99.21% and 98.82%. The 1st attempt success rate in the supine vs. lateral position was 85.35% and 88.56% compared to 91.38% and 90.76% for the supine vs. semierect position. The rate of total adverse events in the supine position was 3.73% vs. 6.74% in the lateral position, and the rate of total adverse events in the supine position was 0.44% vs. 0.93% in semierect position. Low to substantial heterogeneity was noted in our analysis. . There is no significant difference between total successful intubations and success from 1st intubation attempt between supine and nonsupine positions. However, there are slightly higher rates of adverse events in nonsupine position. Addition of more recent studies on supine vs. nonsupine intubations would improve this study. Given these findings, it is important to develop more studies regarding different intubation positions and techniques with the aim of improving efficacy and decreasing adverse outcomes. . This review is not registered in a public database. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
PubMed: 37457639
DOI: 10.1155/2023/5496368 -
The Journal of Clinical Endocrinology... Dec 2023Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women...
PURPOSE
Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS
We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS
Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSION
AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
Topics: Humans; Female; Adult; Polycystic Ovary Syndrome; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipose Tissue; Insulin; Cytokines; Obesity; Inflammation; Glucose
PubMed: 37329216
DOI: 10.1210/clinem/dgad356