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Legal Medicine (Tokyo, Japan) Sep 2023Acute Myocardial Infarction (AMI) refers to the death of heart tissue in the absence ofperfusion. It is one of the top causes of death globally, particularly in middle... (Review)
Review
Acute Myocardial Infarction (AMI) refers to the death of heart tissue in the absence ofperfusion. It is one of the top causes of death globally, particularly in middle andhigher-age groups. However, for the pathologist, the post-mortem macroscopic andmicroscopic diagnosis of early AMI remains challenging. In the early acute stage ofAMI, no microscopic visible signs of tissue alterations like necrosis and neutrophilinfiltration can be seen. In such a scenario, immunohistochemistry (IHC) accounts forthe most suitable and safest alternative to study early diagnostic cases by selectivelydetecting changes in the cell population. This systematic review focuses on themultiple causes/changes that lead to the privation of blood flow as well as tissuechanges induced by the absence of perfusion.We performed a systematic review of the last 10-15 years' publications that focused ondetecting immunohistochemical changes that appear in the cell population in case ofacute myocardial infarction. We found around 160 articles on AMI, which we narroweddown to 50 with the use of specific filters such as: "Acute Myocardial Infarction," "Ischemia," "Hypoxia," "Forensic," "Immunohistochemistry, and "Autopsy." The presentreview comprehensively highlights the current knowledge of specific IHC markers usedas gold standards during post-mortem investigation of acute myocardial infarction. Thepresent review comprehensively highlights the current knowledge of specific IHCmarkers used as gold standards during post-mortem investigation of acute myocardialinfarction, and some new potential immunohistochemical markers that can be used inthe early detection of myocardial infarction.
Topics: Humans; Autopsy; Forensic Pathology; Myocardial Infarction; Heart; Forensic Medicine; Biomarkers
PubMed: 37392575
DOI: 10.1016/j.legalmed.2023.102293 -
Journal of Pharmaceutical Health Care... Jun 2024Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor...
BACKGROUND
Based on several case reports and observational studies, there is a growing concern regarding the potential association between roxadustat, a hypoxia-inducible factor prolyl-hydroxylase inhibitor, and suppression of thyroid function. In this systematic review and meta-analysis (PROSPERO: CRD42023471516), we aimed to evaluate the relationship between roxadustat use and suppression of thyroid function.
METHODS
We conducted a comprehensive search of MEDLINE via PubMed, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases using the search term "roxadustat" to identify all relevant studies. The study population comprised adults with renal anemia who participated in a randomized controlled trial or observational study, with roxadustat as the intervention and a placebo or erythropoiesis-stimulating agent (ESA) as the comparator. The primary outcome was suppression of thyroid function and the secondary outcome was hypothyroidism. A meta-analysis was conducted using the DerSimonian-Laird random effects model based on the size of the intention-to-treat population, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Two reviewers independently screened the articles, extracted data, and assessed studies using the ROBINS-I tool.
RESULTS
Of the six studies eligible for inclusion, a meta-analysis was performed using data from two observational studies comparing roxadustat and ESA. The meta-analysis showed that the incidence of suppression of thyroid function was significantly higher with roxadustat use than with ESA use (OR: 6.45; 95% CI: 3.39-12.27; I = 12%). Compared with ESA, roxadustat seemed to potentially increase the risk for suppression of thyroid function in patients with renal anemia.
CONCLUSIONS
Our findings highlighted the importance of monitoring thyroid function in patients treated with roxadustat. The results of this review may enhance the safety of using roxadustat to treat renal anemia through advance recognition of the risk for suppression of thyroid function.
PubMed: 38851711
DOI: 10.1186/s40780-024-00351-z -
Journal of Exercise Science and Fitness Oct 2023Enhancement in maximal oxygen consumption (VO) induced by hypoxic training is important for both athletes and non-athletes. However, the lack of comparison of multiple... (Review)
Review
BACKGROUND
Enhancement in maximal oxygen consumption (VO) induced by hypoxic training is important for both athletes and non-athletes. However, the lack of comparison of multiple paradigms and the exploration of related modulating factors leads to the inability to recommend the optimal regimen in different situations. This study aimed to investigate the efficacy of seven common hypoxic training paradigms on VO and associated moderators.
METHODS
Electronic (i.e., five databases) and manual searches were performed, and 42 studies involving 1246 healthy adults were included. Pairwise meta-analyses were conducted to compare different hypoxic training paradigms and hypoxic training and control conditions. The Bayesian network meta-analysis model was applied to calculate the standardised mean differences (SMDs) of pre-post VO alteration among hypoxic training paradigms in overall, athlete, and non-athlete populations, while meta-regression analyses were employed to explore the relationships between covariates and SMDs.
RESULTS
All seven hypoxic training paradigms were effective to varying degrees, with SMDs ranging from 1.45 to 7.10. Intermittent hypoxia interval training (IHIT) had the highest probability of being the most efficient hypoxic training paradigm in the overall population and athlete subgroup (42%, 44%), whereas intermittent hypoxic training (IHT) was the most promising hypoxic training paradigm among non-athletes (66%). Meta-regression analysis revealed that saturation hours (coefficient, 0.004; = 0.038; 95% CI [0.0002, 0.0085]) accounted for variations of VO improvement induced by IHT.
CONCLUSION
Efficient hypoxic training paradigms for VO gains differed between athletes and non-athletes, with IHIT ranking best for athletes and IHT for non-athletes. The practicability of saturation hours is confirmed with respect to dose-response issues in the future hypoxic training and associated scientific research.
REGISTRATION
This study was registered in the PROSPERO international prospective register of systematic reviews (CRD42022333548).
PubMed: 37854170
DOI: 10.1016/j.jesf.2023.09.001 -
Indian Journal of Otolaryngology and... Dec 2023Hypoxia-inducible factor-1α is a transcriptional protein that has been extensively researched in human cancers whose overexpression is found to be associated with...
Hypoxia-inducible factor-1α is a transcriptional protein that has been extensively researched in human cancers whose overexpression is found to be associated with unfavorable prognosis. Contemporary studies have proved its vital role in ameloblastoma by correlating its expression with the aggressiveness of the tumor. Therefore, an attempt was made to explore its significance in the malignant transformation and prognosis of ameloblastoma. The present systematic review aimed to understand the impact of HIF-1α in AMB which might lead to favorable outcomes in the treatment. An electronic search was carried out using PubMed, Scopus, Google scholar, Cochrane library, and EMBASE databases. Original articles from all languages involving HIF-1α in AMB were scrutinized by two independent authors. Data were compiled and tabulated in Microsoft Excel and the Risk of bias was analyzed using the JBI tool. Twelve eligible articles were included for the quantitative analysis comprising 305 cases of AMB in which HIF-1α expression was studied for various characteristics like pattern, intensity, and site of immunoexpression which were found to be increased with an increase in the aggressiveness of AMB. It was concluded that HIF-1α is proven to have a crucial role in the progression and aggressiveness of AMB. Extended research regarding the crucial role of HIF-1α in the initiation of tumors and therapies aiming at HIF-1α in AMB cases might show promising outcomes in the future.
PubMed: 37974737
DOI: 10.1007/s12070-023-03928-6 -
Clinics and Research in Hepatology and... Apr 2024This study aims to perform a meta-analysis to evaluate the safety and efficacy of dexmedetomidine versus midazolam for complex digestive endoscopy procedures, with the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aims to perform a meta-analysis to evaluate the safety and efficacy of dexmedetomidine versus midazolam for complex digestive endoscopy procedures, with the goal of offering comprehensive clinical evidence.
METHODS
Following predefined inclusion criteria, five databases were systematically searched, with a focus on identifying randomized controlled trials (RCTs) that compared the administration of dexmedetomidine and midazolam during complex digestive endoscopy procedures. The statistical software Stata 15.1 was employed for meticulous data analysis.
RESULTS
Sixteen RCTs were encompassed, involving a total of 1218 patients. In comparison to the midazolam group, dexmedetomidine administration was associated with a reduced risk of respiratory depression (RR=0.25, 95 %CI: 0.11-0.56) and hypoxemia (RR=0.22, 95 %CI: 0.12-0.39). Additionally, the dexmedetomidine group exhibited lower incidence rates of choking (RR=0.27, 95 %CI: 0.16-0.47), physical movement (RR=0.16, 95 %CI: 0.09-0.27), and postoperative nausea and vomiting (RR=0.56,95 %CI: 0.34-0.92). Patients and endoscopists in the dexmedetomidine group reported higher levels of satisfaction (patient satisfaction: SMD=0.73, 95 %CI: 0.26-1.21; endoscopist satisfaction: SMD=0.84, 95 %CI: 0.24-1.44). The incidence of hypotension and anesthesia recovery time did not significantly differ between the two groups (hypotension: RR=1.73,95 %CI:0.94-3.20; anesthesia recovery time: SMD=0.02, 95 %Cl: 0.44-0.49). It is noteworthy that the administration of dexmedetomidine was associated with a significant increase in the incidence of bradycardia in patients.
CONCLUSION
Compared to midazolam, dexmedetomidine exhibits a favorable safety profile for use in complex gastrointestinal endoscopy by significantly reducing the risk of respiratory depression and hypoxemia. Despite this, dexmedetomidine is associated with a higher incidence of bradycardia. These findings underscore the need for further research through larger, multi-center studies to thoroughly investigate dexmedetomidine's safety and efficacy.
Topics: Humans; Midazolam; Hypnotics and Sedatives; Dexmedetomidine; Bradycardia; Endoscopy, Gastrointestinal; Respiratory Insufficiency; Hypoxia; Hypotension
PubMed: 38467278
DOI: 10.1016/j.clinre.2024.102315 -
Computers in Biology and Medicine Apr 2024Uterine contractions during labour constrict maternal blood flow and oxygen delivery to the developing baby, causing transient hypoxia. While most babies are...
INTRODUCTION
Uterine contractions during labour constrict maternal blood flow and oxygen delivery to the developing baby, causing transient hypoxia. While most babies are physiologically adapted to withstand such intrapartum hypoxia, those exposed to severe hypoxia or with poor physiological reserves may experience neurological injury or death during labour. Cardiotocography (CTG) monitoring was developed to identify babies at risk of hypoxia by detecting changes in fetal heart rate (FHR) patterns. CTG monitoring is in widespread use in intrapartum care for the detection of fetal hypoxia, but the clinical utility is limited by a relatively poor positive predictive value (PPV) of an abnormal CTG and significant inter and intra observer variability in CTG interpretation. Clinical risk and human factors may impact the quality of CTG interpretation. Misclassification of CTG traces may lead to both under-treatment (with the risk of fetal injury or death) or over-treatment (which may include unnecessary operative interventions that put both mother and baby at risk of complications). Machine learning (ML) has been applied to this problem since early 2000 and has shown potential to predict fetal hypoxia more accurately than visual interpretation of CTG alone. To consider how these tools might be translated for clinical practice, we conducted a review of ML techniques already applied to CTG classification and identified research gaps requiring investigation in order to progress towards clinical implementation.
MATERIALS AND METHOD
We used identified keywords to search databases for relevant publications on PubMed, EMBASE and IEEE Xplore. We used Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews (PRISMA-ScR). Title, abstract and full text were screened according to the inclusion criteria.
RESULTS
We included 36 studies that used signal processing and ML techniques to classify CTG. Most studies used an open-access CTG database and predominantly used fetal metabolic acidosis as the benchmark for hypoxia with varying pH levels. Various methods were used to process and extract CTG signals and several ML algorithms were used to classify CTG. We identified significant concerns over the practicality of using varying pH levels as the CTG classification benchmark. Furthermore, studies needed to be more generalised as most used the same database with a low number of subjects for an ML study.
CONCLUSION
ML studies demonstrate potential in predicting fetal hypoxia from CTG. However, more diverse datasets, standardisation of hypoxia benchmarks and enhancement of algorithms and features are needed for future clinical implementation.
Topics: Female; Humans; Pregnancy; Cardiotocography; Fetal Hypoxia; Heart Rate, Fetal; Labor, Obstetric; Uterine Contraction
PubMed: 38489990
DOI: 10.1016/j.compbiomed.2024.108220 -
Indian Journal of Pediatrics Mar 2024Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however,... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however, additional neuroprotective agents are required to improve prognosis. The authors searched for all drugs in combination with HT and compared their effects using a network meta-analysis.
METHODS
The authors searched PubMed, Embase, and Cochrane Library until September 24, 2022 for articles assessing mortality, NDI, seizures, and abnormal brain imaging findings in neonates with hypoxic-ischemic encephalopathy. Direct pairwise comparisons and a network meta-analysis was performed under random effects.
RESULTS
Thirteen randomized clinical trials enroled 902 newborns treated with six combination therapies: erythropoietin magnesium sulfate, melatonin (MT), topiramate, xenon, and darbepoetin alfa. The results of all comparisons were not statistically significant, except for NDI, HT vs. MT+HT: odds ratio = 6.67, 95% confidence interval = 1.14-38.83; however, the overall evidence quality was low for the small sample size.
CONCLUSIONS
Currently, no combination therapy can reduce mortality, seizures, or abnormal brain imaging findings in neonatal hypoxic-ischemic encephalopathy. According to low quality evidence, HT combined with MT may reduce NDI.
Topics: Infant, Newborn; Humans; Hypoxia-Ischemia, Brain; Hypothermia; Network Meta-Analysis; Hypothermia, Induced; Seizures
PubMed: 37199820
DOI: 10.1007/s12098-023-04563-3 -
Archives of Oral Biology Jun 2024Oral submucous fibrosis is a frequently reported potentially malignant disorder characterized by fibrosis and a malignant transformation rate of 7-30%. The role of... (Meta-Analysis)
Meta-Analysis Review
An enigmatic pathogenetic mechanism of hypoxia inducible factor - 1/2 alpha in the progression of fibrosis of oral submucous fibrosis and its malignant transformation: A systematic review and meta-analysis.
OBJECTIVE
Oral submucous fibrosis is a frequently reported potentially malignant disorder characterized by fibrosis and a malignant transformation rate of 7-30%. The role of hypoxia-inducible factor-1/2α in malignant transformation mechanisms of oral submucous fibrosis remains uncharted territory owing to a scarcity of studies. Thus the present systematic review and meta-analysis aimed to determine the role of hypoxia-inducible factor-1/2α in the progression of fibrosis of oral submucous fibrosis and its malignant transformation.
MATERIAL AND METHODS
Using PubMed, Google Scholar, and Cochrane Library databases, full-text articles that investigated hypoxia-inducible factor-1/2α in oral submucous fibrosis were entailed for review. A modified Newcastle-Ottawa scale was employed to evaluate risk of bias in all articles and Review Manager was utilized for meta-analysis.
RESULTS
Eighteen and eight qualified articles respectively were included for qualitative and quantitative data synthesis. Progressive upregulation of hypoxia-inducible factor-1/2α in oral submucous fibrosis is associated with fibrosis-induced carcinogenesis. A Random-effects model uncloaked that oral submucous fibrosis cases with significantly increased expression of hypoxia-inducible factor-1α had an increased associated risk of malignant transformation compared with controls (combined odds ratio 523.83, 95% confidence interval 125.74- 2182.28, p < 0.00001).
CONCLUSION
The existing evidence substantiates the notion that hypoxia-inducible factor-1/2α, a fundamental pathogenetic mechanism of progression and malignant transformation of oral submucous fibrosis in the background of fibrosis.
Topics: Humans; Oral Submucous Fibrosis; Hypoxia-Inducible Factor 1, alpha Subunit; Cell Transformation, Neoplastic; Fibrosis; Hypoxia
PubMed: 38492547
DOI: 10.1016/j.archoralbio.2024.105944 -
PloS One 2024Intrahepatic cholestasis of pregnancy (ICP) is a serious liver conditions that negatively impacts obstetric and neonatal outcomes. Elevated levels of bile acid,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intrahepatic cholestasis of pregnancy (ICP) is a serious liver conditions that negatively impacts obstetric and neonatal outcomes. Elevated levels of bile acid, particularly glycine conjugate, may compromise blood flow and cause functional hypoxia-ischemia.
AIMS
This meta-analysis aims to assess the association between ICP and key pregnancy outcomes including emergency caesarian sections (C-sections), preeclampsia, hemorrhage, preterm birth, small for gestational age, admission rate to neonatal intensive care union (NICU), gestational age, and stillbirth.
MATERIALS AND METHODS
Literature search across five databases (PubMed, Embase, Web of Science) was done to detect relevant studies published up until June 2023. Meta-analysis of the identified studies was done using a random-effects model, and the results presented as Odds ratio (OR).
RESULTS
A literature search identified 662 studies. Of them, 21 met the inclusion criteria. There was a significant association between ICP and odds of C-section (OR: 1.42, p <0.001), preeclampsia (OR: 2.64, p <0.001), NICU admission (OR: 2.1, p <0.001), and pre-term birth (OR: 2.64, p <0.001). ICP was not associated with postpartum hemmorhage (OR: 1.31, p = 0.13), small for gestational age (OR: 0.87, p = 0.07), stillbirth (OR: 1.49, p = 0.29).
CONCLUSIONS
Our results confirm the adverse effects of ICP on co-existing pregnancy complications, obstetric and neonatal outcomes. ICP in associated with severe complications including increased rates of preeclampsia, emergency C-sections, preterm births, l gestational periods and higher rates of NICU admissions. These results may assist healthcare professionals in formulating comprehensive care guidelines for expectant mothers and newborns.
Topics: Humans; Pregnancy; Cholestasis, Intrahepatic; Female; Pregnancy Complications; Infant, Newborn; Pregnancy Outcome; Premature Birth; Stillbirth; Pre-Eclampsia; Cesarean Section; Gestational Age; Infant, Small for Gestational Age
PubMed: 38833446
DOI: 10.1371/journal.pone.0304604 -
Seizure Oct 2023Bumetanide, an inhibitor of the sodium-potassium-chloride cotransporter-1, has been suggested as an adjunct to phenobarbital for treating neonatal seizures.
BACKGROUND
Bumetanide, an inhibitor of the sodium-potassium-chloride cotransporter-1, has been suggested as an adjunct to phenobarbital for treating neonatal seizures.
METHODS
A systematic review of animal and human studies was conducted to evaluate the efficacy and safety of bumetanide for neonatal seizures. PubMed, Embase, CINAHL and Cochrane databases were searched in March 2023.
RESULTS
26 animal (rat or mice) studies describing 38 experiments (28 in-vivo and ten in-vitro) and two human studies (one RCT and one open-label dose-finding) were included. The study designs, methods to induce seizures, bumetanide dose, and outcome measures were heterogeneous, with only 4/38 experiments being in animal hypoxia/ischaemia models. Among 38 animal experiments, bumetanide was reported to have antiseizure effects in 21, pro-seizure in six and ineffective in 11. The two human studies (n = 57) did not show the benefits of bumetanide as an add-on agent to phenobarbital in their primary analyses, but one study reported benefit on post-hoc analysis. Overall, hearing impairment was detected in 5/37 surviving infants in the bumetanide group vs. 0/13 in controls. Four of the five infants with hearing impairment had received aminoglycosides concurrently. Other adverse effects reported were diuresis, mild-to-moderate dehydration, hypotension, and electrolyte disturbances. The studies did not report on long-term neurodevelopment. The certainty of the evidence was very low.
CONCLUSION
Animal data suggest that bumetanide has inconsistent effects as an antiseizure medication in neonates. Data from human studies are scarce and raise some concerns regarding ototoxicity when given with aminoglycosides. Well conducted studies in animal models of hypoxic-ischaemic encephalopathy are urgently needed. Future RCTs, if conducted in human neonates, should have an adequate sample size, assess neurodevelopment, minimize using aminoglycosides, be transparent about the potential ototoxicity in the parent information sheet, conduct early hearing tests and have trial-stopping rules that include hearing impairment as an outcome.
Topics: Infant, Newborn; Infant; Humans; Rats; Mice; Animals; Bumetanide; Ototoxicity; Sodium Potassium Chloride Symporter Inhibitors; Solute Carrier Family 12, Member 2; Seizures; Epilepsy; Phenobarbital; Infant, Newborn, Diseases; Aminoglycosides; Hearing Loss; Anticonvulsants
PubMed: 37690372
DOI: 10.1016/j.seizure.2023.09.007