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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 -
BMC Pulmonary Medicine Nov 2023Acute heart failure (AHF) is often associated with diffuse insufficiency and arterial hypoxemia, requiring respiratory support for rapid and effective correction. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute heart failure (AHF) is often associated with diffuse insufficiency and arterial hypoxemia, requiring respiratory support for rapid and effective correction. We aimed to compare the effects of high-flow nasal cannula(HFNC) with those of conventional oxygen therapy(COT) or non-invasive ventilation(NIV) on the prognosis of patients with AHF.
METHODS
We performed the search using PubMed, Embase, Web of Science, MEDLINE, the Cochrane Library, CNKI, Wanfang, and VIP databases from the inception to August 31, 2023 for relevant studies in English and Chinese. We included controlled studies comparing HFNC with COT or NIV in patients with AHF. Primary outcomes included the intubation rate, respiratory rate (RR), heart rate (HR), and oxygenation status.
RESULTS
From the 1288 original papers identified, 16 studies met the inclusion criteria, and 1333 patients were included. Compared with COT, HFNC reduced the intubation rate (odds ratio [OR]: 0.29, 95% CI: 0.14-0.58, P = 0.0005), RR (standardized mean difference [SMD]: -0.73 95% CI: -0.99 - -0.47, P < 0.00001) and HR (SMD: -0.88, 95% CI: -1.07 - -0.69, P < 0.00001), and hospital stay (SMD: -0.94, 95% CI: -1.76 - -0.12, P = 0.03), and increase arterial oxygen partial pressure (PaO), (SMD: 0.88, 95% CI: 0.70-1.06, P < 0.00001) and oxygen saturation (SpO [%], SMD: 0.70, 95% CI: 0.34-1.06, P = 0.0001).
CONCLUSIONS
There were no significant differences in intubation rate, RR, HR, arterial blood gas parameters, and dyspnea scores between the HFNC and NIV groups. Compared with COT, HFNC effectively reduced the intubation rate and provided greater clinical benefits to patients with AHF. However, there was no significant difference in the clinical prognosis of patients with AHF between the HFNC and NIV groups.
TRIAL REGISTRATION
PROSPERO (identifier: CRD42022365611).
Topics: Humans; Cannula; Oxygen; Oxygen Inhalation Therapy; Hypoxia; Noninvasive Ventilation; Heart Failure; Respiratory Insufficiency
PubMed: 38017474
DOI: 10.1186/s12890-023-02782-0 -
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 -
Cureus Sep 2023The goal of the present systematic review was to investigate the occurrence patterns of intermittent hypoxemia in newborns throughout the early postnatal period as well... (Review)
Review
The goal of the present systematic review was to investigate the occurrence patterns of intermittent hypoxemia in newborns throughout the early postnatal period as well as the link between neonatal intermittent hypoxemia exposure and harmful consequences such as neonatal morbidity and death. We collected data from 2014 to 2023 using several abstracting, referencing, and indexing database libraries in the field of medical sciences. A total of 715 papers were evaluated by both authors, and only seven articles met the specified review criteria after a thorough analysis. In preterm neonates with intermittent hypoxia (IH), severe morbidities such as bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), motor impairment, and cognitive delay were found. Only one study that extended to 18 months noted mortality. The length and occurrence of intermittent hypoxemia and the stage of premature neonates at the time of delivery are all closely associated with these morbidities. Therefore, it becomes important to continuously measure the patterns of occurrence of intermittent hypoxemia during early postnatal life to avoid its long-term morbidity and mortality impact.
PubMed: 37868466
DOI: 10.7759/cureus.45561 -
Obesity Reviews : An Official Journal... Aug 2023By 2030, it is expected that a billion people will have suffer from obesity. Adipose tissue synthesizes leptin, an adipokine that affects cardiovascular risk. Leptin... (Review)
Review
By 2030, it is expected that a billion people will have suffer from obesity. Adipose tissue synthesizes leptin, an adipokine that affects cardiovascular risk. Leptin intensifies the synthesis of vascular endothelial growth factor (VEGF). Our study reviews recent reports on leptin-VEGF crosstalk in obesity and related disorders. PubMed, Web of Science, Scopus, and Google Scholar were searched. One hundred and one articles involving human, animal, and in vitro research were included. In vitro studies show the crucial role of interaction between endothelial cells and adipocytes and hypoxia as a factor that intensifies leptin's effects on VEGF. Leptin-VEGF crosstalk promotes the progression of cancer. The animal research reveal that a high-fat diet enhances leptin and VEGF crosstalk. Genetic and epigenetic mechanisms and procreator-offspring programming may be involved in leptin-VEGF crosstalk. Some female-specific characteristics of leptin-VEGF relation in obesity were observed. The human studies have shown that increased leptin and VEGF synthesis and leptin-VEGF crosstalk are factors linking obesity with elevated cardiovascular risk. The studies of the last 10 years documented a range of significant aspects of leptin-VEGF crosstalk specific for obesity and related disorders, shedding new light on the link between obesity and increased cardiovascular risk.
Topics: Animals; Female; Humans; Leptin; Vascular Endothelial Growth Factor A; Endothelial Cells; Vascular Endothelial Growth Factors; Obesity
PubMed: 37230803
DOI: 10.1111/obr.13575 -
Renal Failure Dec 2024This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular and renal safety outcomes of hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat for anemia patients with chronic kidney disease: a systematic review and meta-analysis.
This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD patients. 18 trials with a total of 8806 participants were identified for analysis. We employed a fixed-effects model for analysis. The pooled result revealed no significant difference in the risk of occurrence of cardiac disorders when comparing CKD patients receiving roxadustat with the placebo (RR = 1.049; CI [0.918 to 1.200]) or ESA (RR = 1.066; CI [0.919 to 1.235]), in both dialysis-dependent (DD) (RR = 1.094; CI [0.925 to 1.293]) or non-dialysis-dependent (NDD) (RR = 1.036; CI [0.916 to 1.171]) CKD patients. No significant difference was observed in the risk of kidney-related adverse events when comparing roxadustat with the placebo (RR = 1.088; CI [0.980 to 1.209]) or ESA (RR = 0.968; CI [0.831 to 1.152]), in DD (RR = 2.649; CI [0.201 to 34.981]) or NDD (RR = 1.053; CI [0.965 to 1.149]) CKD patients. A high risk of hyperkalemia was observed in the roxadustat group in DD (RR = 0.939; CI [0.898 to 0.981]). Incidence of hypertension was higher in the roxadustat for NDD patients (RR = 1.198; CI [1.042 to 1.377]), or compared to the placebo (RR = 1.374; CI [1.153 to 1.638]). In summary, the risk of cardiac or kidney-related events observed in the roxadustat was not significantly increase whether in DD or NDD patients. However, attention must be paid to the occurrence of hyperkalemia for DD patients and hypertension in NDD patients using roxadustat.
Topics: Humans; Prolyl-Hydroxylase Inhibitors; Prolyl Hydroxylases; Hyperkalemia; Anemia; Renal Insufficiency, Chronic; Hypertension; Kidney; Hypoxia
PubMed: 38345037
DOI: 10.1080/0886022X.2024.2313864 -
Journal of Clinical Anesthesia Dec 2023Obesity is associated with an increased risk of sleep-disordered breathing (SDB) and postoperative pulmonary complications (PPCs). Postoperative noninvasive respiratory... (Meta-Analysis)
Meta-Analysis Review
STUDY OBJECTIVE
Obesity is associated with an increased risk of sleep-disordered breathing (SDB) and postoperative pulmonary complications (PPCs). Postoperative noninvasive respiratory support (NRS) has been recommended to obese patients despite the controversy about its benefit. The network meta-analysis (NMA) was used in this study to compare the effect of different methods of NRS on preventing PPCs in obese patients.
DESIGN
This study is a network meta-analysis.
SETTING
Post-anesthesia care unit and inpatient ward.
PATIENTS
20 randomized controlled trials involving 1184 obese patients were included in the final analysis.
INTERVENTIONS
One of the four NRS techniques, which include continuous positive airway pressure (CPAP), bi-level positive airway pressure (BiPAP), high-flow nasal cannula (HFNC), or conventional oxygen therapy (COT), was performed after general anesthesia.
MEASUREMENTS
The primary outcome was the incidence of PPCs, e.g., atelectasis, pneumonia, hypoxemia, and respiratory failure. The secondary outcomes included the incidence of oxygen treatment failure and anastomotic leakage, oxygenation index, and length of hospital stay (LOS). RevMan 5.3 and STATA 16.0 were used to analyze the results and any potential bias.
MAIN RESULTS
Compared with COT, BiPAP and HFNC were both effective in reducing the occurrence of postoperative atelectasis. There were no significant differences in the occurrence of other PPCs including pneumonia, hypoxemia and respiratory failure between the four NRS techniques. CPAP and HFNC were superior to other techniques in improving oxygenation and shortening LOS respectively. No differences were found in oxygen treatment failure and anastomotic leakage between the patients with different NRS. HFNC ranked the first in five of the eight outcomes (hypoxemia, respiratory failure, treatment failure, anastomotic leakage, LOS) in this review by the surface under the cumulative ranking curve (SUCRA).
CONCLUSION
Among the four postoperative NRS techniques, HFNC seems to be the optimal choice for obese patients which shows certain advantages in reducing the risk of PPCs and shortening LOS.
Topics: Humans; Anastomotic Leak; Airway Extubation; Network Meta-Analysis; Oxygen Inhalation Therapy; Oxygen; Cannula; Respiratory Insufficiency; Obesity; Hypoxia; Pulmonary Atelectasis; Postoperative Complications; Pneumonia; Noninvasive Ventilation; Randomized Controlled Trials as Topic
PubMed: 37801822
DOI: 10.1016/j.jclinane.2023.111280 -
High Altitude Medicine & Biology Dec 2023Guo, Hai, Linjie Cheng, Dilihumaier Duolikun, and Qiaoling Yao. Aerobic exercise training under normobaric hypoxic conditions to improve glucose and lipid metabolism in... (Meta-Analysis)
Meta-Analysis
Aerobic Exercise Training Under Normobaric Hypoxic Conditions to Improve Glucose and Lipid Metabolism in Overweight and Obese Individuals: A Systematic Review and Meta-Analysis.
Guo, Hai, Linjie Cheng, Dilihumaier Duolikun, and Qiaoling Yao. Aerobic exercise training under normobaric hypoxic conditions to improve glucose and lipid metabolism in overweight and obese individuals: a systematic review and meta-analysis. 24:312-320, 2023. Obesity is a critical public health issue around the world, reaching epidemic proportions in some countries. However, only a few studies have examined the effects of hypoxic training on metabolic parameters in an obese population. This systematic review and meta-analysis aimed to determine the effects of aerobic exercise training under normobaric hypoxic conditions versus normoxic training in improving glucose and lipid metabolism in obese individuals. A systematic search of PubMed, EMBASE, Web of Science, and Wan Fang databases (up to August 2021) was performed to identify randomized controlled trials (RCTs) of overweight or obese human subjects eligible for inclusion. Main study endpoints were changes in body mass index (BMI), waist/hip (W/H) ratio, leptin, blood glucose and insulin levels, as well as blood lipids between hypoxic and normoxic conditioning. Fourteen RCTs with a total of 413 subjects qualified for inclusion. Pooled analyses revealed that BMI ( = 0.38), W/H ratio ( = 0), blood glucose ( = 0.01), and triglyceride ( = -2.27) were not significantly different between aerobic exercise training under hypoxic and normoxic conditions. However, significant differences were found in heart rate at rest ( = -4.50) between aerobic exercise training under hypoxic versus normoxic conditions. In conclusion, no significant benefits were noted in aerobic exercise training under hypoxic conditions over normoxic conditions in overweight or obese individuals. However, the maximum training heart rate mm was significantly higher under hypoxic conditions than under normoxic conditions. Future studies with larger samples controlling for exercise-related parameters, and addressing the potential modifying effects of level of hypoxia, sex, or age on the role of hypoxic exercise training are warranted. PROSPERO registration number: CRD42020221680.
Topics: Humans; Overweight; Glucose; Blood Glucose; Obesity; Exercise; Hypoxia; Lipid Metabolism
PubMed: 38127802
DOI: 10.1089/ham.2022.0099 -
Neurological Research and Practice Jun 2024This review specifically investigates ketamine's role in SRSE management. (Review)
Review
OBJECTIVE
This review specifically investigates ketamine's role in SRSE management.
METHODS
PubMed, EMBASE, and Google Scholar databases were searched from inception to May 1st, 2023, for English-language literature. Inclusion criteria encompassed studies on SRSE in humans of all ages and genders treated with ketamine.
RESULTS
In this systematic review encompassing 19 studies with 336 participants, age ranged from 9 months to 86 years. Infections, anoxia, and metabolic issues emerged as the common causes of SRSE, while some cases had unknown origins, termed as NORSE (New Onset RSE) or FIRESs (Febrile Infection-Related Epilepsy Syndrome). Most studies categorized SRSE cases into convulsive (N = 105) and non-convulsive (N = 197). Ketamine was used after failed antiepileptics and anesthetics in 17 studies, while in others, it was a first or second line of treatment. Dosages varied from 0.5 mg/kg (bolus) and 0.2-15 mg/kg/hour (maintenance) in adults and 1-3 mg/kg (bolus) and 0.5-3 mg/kg/hour (maintenance) in pediatrics, lasting one to 30 days. Ketamine was concurrently used with other drugs in 40-100% of cases, most frequently propofol and midazolam. Seizure resolution rate varied from 53.3 to 91% and 40-100% in larger (N = 42-68) and smaller case series (N = 5-20) respectively. Seizure resolution occurred in every case of case report except in one in which the patient died. Burst suppression in EEG was reported in 12 patients from two case series and two case reports. Recurrence was reported in 11 patients from five studies. The reported all-cause mortality varied from 38.8 to 59.5% and 0-36.4% in larger and smaller case series., unrelated directly to ketamine dosage or duration.
SIGNIFICANCE
Ketamine demonstrates safety and effectiveness in SRSE, offering advantages over GABAergic drugs by acting on NMDA receptors, providing neuroprotection, and reducing vasopressor requirement.
PubMed: 38926769
DOI: 10.1186/s42466-024-00322-7 -
The Journal of Pediatrics Nov 2023To assess magnesium sulfate (MgSO) as a neuroprotective agent in hypoxic-ischemic encephalopathy. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess magnesium sulfate (MgSO) as a neuroprotective agent in hypoxic-ischemic encephalopathy.
STUDY DESIGN
For this systematic review, PubMed, EMBASE, the Cochrane Library, EMCARE, and MedNar were searched in November 2022 for randomized controlled trials (RCTs). Meta-analysis was conducted using Stata 16.0 and RevMan 5.3.
RESULTS
Twenty RCTs with a total sample size of 1485 were included, of which 16 were from settings where therapeutic hypothermia (TH) was not offered. Regarding MgSO in settings where TH was not offered, only 1 study evaluated composite outcome of death or disability at ≥18 months and reported such poor outcome in 8 of 14 control infants and 4 of 8 in the MgSO group. MgSO was not associated with mortality (RR, 0.86; 95% CI, 0.72-1.03; 13 RCTs) or hypotension (RR, 1.02; 95% CI, 0.88-1.18; 5 RCTs). Thirteen studies reported that MgSO improved in-hospital outcomes, such as reduced seizure burden and improved neurological status at discharge. MgSO reduced the risk of poor suck feeds (RR, 0.52; 95% CI, 0.40-0.68; 6RCTs) and abnormal electroencephalogram (RR, 0.64; 95% CI, 0.45-0.93; 5 RCTs). Certainty of evidence was moderate for mortality and low or very low for other outcomes. For studies with MgSO as an adjunct to TH, none reported on death or neurodevelopmental disability at ≥18 months. MgSO was not associated with mortality (RR, 0.65; 95% CI, 0.34-1.27; 3 RCTs) or hypotension (RR, 1.0; 95% CI, 0.71-1.40; 3 RCTs).
CONCLUSIONS
Evidence around long-term outcomes of MgSO when used with or without TH was scant. MgSO therapy may improve in-hospital neurological outcomes without affecting mortality in settings where TH is not offered. Well-designed RCTs for neuroprotection are needed, especially in low-resource settings.
TRIAL REGISTRATION
"Open Science Forum" (https://doi.org/10.17605/OSF.IO/FRM4D).
Topics: Infant, Newborn; Infant; Humans; Magnesium Sulfate; Hypoxia-Ischemia, Brain; Seizures; Hypotension
PubMed: 37468038
DOI: 10.1016/j.jpeds.2023.113610