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Future Science OA Dec 2024We developed a machine learning model using EuroScore assumptions and preoperative and intraoperative risk factors to predict mortality after coronary artery bypass...
We developed a machine learning model using EuroScore assumptions and preoperative and intraoperative risk factors to predict mortality after coronary artery bypass graft (CABG). We retrospectively examined data from 108 CABG patients at King Abdullah University Hospital, classifying them into risk groups via EuroScore and predicting mortality through random forest classification. High-risk patients displayed longer surgical times and significant factors such as age and surgery choice. The median EuroScore was 0.95 (0.5-6.4). The model yielded high AUC scores (0.98, 0.95) indicating strong predictive accuracy. Our findings showed that the machine learning models combined with the EuroScore significantly improve post-CABG mortality prediction. For further validation, larger datasets are needed.
PubMed: 38884372
DOI: 10.2144/fsoa-2023-0152 -
Progress in Neuro-psychopharmacology &... Jun 2024The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic... (Review)
Review
BACKGROUND
The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD.
METHODS
PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected.
RESULTS
Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1β, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients.
CONCLUSION
Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.
PubMed: 38879067
DOI: 10.1016/j.pnpbp.2024.111056 -
The American Journal of Clinical... Jun 2024A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated...
Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n-3 fatty acid eicosapentaenoic acid: A secondary analysis of the seAFOod polyp prevention trial.
BACKGROUND
A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for pro-inflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs.
OBJECTIVE
We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2 x 2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 months (ISRCTN05926847).
METHODS
Participant Indel genotype was determined by PCR blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention versus placebo. Presence of at least one Indel I allele and an interaction term (I allele x active intervention) were co-variates.
RESULTS
In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR] 0.92, 95% confidence interval 0.74, 1.16), mirroring original seAFOod trial analysis. However, presence of at least one I allele identified EPA users with a significant reduction in colorectal polyp number (IRR 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR.
CONCLUSIONS
The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted.
TRIAL REGISTRATION
The seAFOod polyp prevention trial and STOP-ADENOMA study are registered with https://www.isrctn.com as ISRCTN05926847.
PubMed: 38879016
DOI: 10.1016/j.ajcnut.2024.06.004 -
European Journal of Pharmaceutical... Jun 2024Dual antiplatelet therapy with aspirin and clopidogrel has reduced ischemic vascular events significantly. Genetics influence, especially those in clopidogrel...
Dual antiplatelet therapy with aspirin and clopidogrel has reduced ischemic vascular events significantly. Genetics influence, especially those in clopidogrel pharmacokinetic-relevant genes partially accounts for interindividual pharmacodynamic variability of clopidogrel. However, most studies have concentrated on the genetic variations in introns, exons, or promoters of the candidate genes, and the association between genetic variations in 3'-UTR in clopidogrel pharmacokinetic-relevant genes and clopidogrel response is unknown. In our study, ten different algorithms were applied to pick potential miRNAs targeting the clopidogrel pharmacokinetic-relevant genes. Furthermore, the correlation between miRNA expression profiles and mRNA expression of corresponding clopidogrel pharmacokinetic-relevant genes were analyzed. Through comprehensive analysis, including bioinformatics prediction and correlation analysis of miRNA and mRNA expression profiles, miR-218-5p and miR-506-5p were supposed to regulate the expression of PON1 via binding with its 3'-UTR. Moreover, PON1 rs854551 and rs854552 were located in miRNA recognizing sequences and may serve as potential miRSNPs possibly affecting PON1 expression. The rs854552 polymorphism was genotyped and platelet reactivity index (PRI) indicative of clopidogrel response was measured in 341 Chinese coronary artery disease (CAD) patients 24h after administration of 300 mg clopidogrel. Our results showed that PON1 rs854552 had a significant influence on PRI in CAD patients, especially in patients with CYP2C19 extensive metabolic phenotype. In conclusion, PON1 rs854552 polymorphisms may affect clopidogrel response. Bioinformatics prediction followed by functional validation could aid in decoding the contribution of unexplained variations in the 3'-UTR in drug-metabolizing enzymes on clopidogrel response.
PubMed: 38878906
DOI: 10.1016/j.ejps.2024.106830 -
Frontiers in Veterinary Science 2024The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on ileal immune function in broilers under lipopolysaccharide (LPS)-induced immune...
AIMS
The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on ileal immune function in broilers under lipopolysaccharide (LPS)-induced immune stress.
METHODS
Two hundred and forty one-day-old male Arbor Acres chicks were randomly divided into four groups (saline, LPS, saline + AEE and LPS + AEE) with six replicates of ten broilers each. The saline group and LPS group were fed the normal diet, while the other two groups received normal diet plus 0.1 g/kg AEE. Broilers in the LPS and LPS + AEE groups were injected intraperitoneally with 0.5 mg/kg B.W LPS in saline for seven consecutive days beginning at 14 days of age, while broilers in the saline and saline + AEE groups were injected with saline only.
RESULTS
The results showed that AEE improved the ileal morphology and increased the ratio of villus height to crypt depth of immune-stressed broilers. LPS-induced immune stress significantly reduced the expression of the genes for the tight junction proteins , zonula occludens-1 (), and , in the ileum, while AEE significantly up-regulated the expression of these genes. Compared with the saline group, the LPS-treated chickens showed significantly increased mRNA expression of the inflammatory factors tumor necrosis factor-α (), interleukin-1β (), interleukin-6 (), interleukin-10 (), cyclooxygenase-2 (), and microsomal Prostaglandin E Synthesase-1 () in the ileum, while they were significantly decreased by AEE supplementation. In addition, analysis of the ileal bacterial composition showed that compared with saline and LPS + AEE groups, the proportion of Firmicutes and in the LPS group was lower, while the proportion of Proteobacteria and was higher. Similarly, Line Discriminant Analysis Effect Size (LEfSe) analysis showed that compared with the LPS group, was dominant in the saline group, while the LPS + AEE group was rich in , , Ruminococcaceae, , , Oscillospiraceae, and .
CONCLUSION
These results indicate that dietary supplementation with 0.1 g/kg AEE could protect the intestinal health by improving the intestinal villus morphology, enhancing the expression of tight junction genes and alleviating inflammation to resist the immune stress caused by LPS stimulation in broilers, and the mechanism may involve -related signal transduction and improved intestinal microbiota composition.
PubMed: 38872795
DOI: 10.3389/fvets.2024.1401909 -
Clinical and Applied... 2024Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk...
BACKGROUND
Aspirin is a widely used antiplatelet medication to prevent blood clots, reducing the risk of cardiovascular event. Healthcare providers need to be mindful of the risk of aspirin-induced bleeding and carefully balancing its benefits against potential risks. The objective of this study was to create a practical nomogram for predicting bleeding risk in patients with a history of myocardial infarction treating with aspirin.
METHODS
A total of 2099 myocardial infarction patients with aspirin were enrolled. The patients were randomly divided into two groups, with a 7:3 ratio, for model development and internal validation. Boruta analysis was utilized to identify clinically significant features associated with bleeding. Logistic regression model based on independent bleeding risk factors was constructed and presented as a nomogram. Model performance was assessed from three aspects: identification, calibration, and clinical utility.
RESULTS
Boruta analysis identified eight clinical features from 25, and further multivariate logistic regression analysis selected four independent risk factors: hemoglobin, platelet count, previous bleeding, and sex. A visual nomogram was created based on these variables. The model achieved an area under the curve of 0.888 (95% CI: 0.845-0.931) in the training dataset and 0.888 (95% CI: 0.808-0.968) in the test dataset. Calibration curve analysis showed close approximation to the ideal curve. Decision curve analysis demonstrated favorable clinical net benefit for the model.
CONCLUSIONS
Our study focused on creating and validating a model to evaluate bleeding risk in patients with a history of myocardial infarction treated with aspirin, which demonstrated outstanding performance in discrimination, calibration, and net clinical benefit.
Topics: Humans; Nomograms; Myocardial Infarction; Aspirin; Hemorrhage; Female; Male; Middle Aged; Aged; Risk Factors; Platelet Aggregation Inhibitors; Risk Assessment
PubMed: 38870349
DOI: 10.1177/10760296241262789 -
Revue Medicale de Liege Jun 2024Preeclampsia is a pregnancy-specific condition characterized by gestational hypertension associated with proteinuria or organ dysfunction after 20 weeks of gestation. It... (Review)
Review
Preeclampsia is a pregnancy-specific condition characterized by gestational hypertension associated with proteinuria or organ dysfunction after 20 weeks of gestation. It complicates 2 to 8 % of pregnancies worldwide and represents the leading cause of maternal and fetal mortality in developed countries. The only definitive treatment remains termination of pregnancy and delivery of the placenta. Prompt assessment of maternal and fetal status should be held in search of severity criteria and adequate management of this condition according to gestational age. Foremost concerns for pregnant patients are impending eclampsia or placental abruption, while fetal complications arise from placental insufficiency and risks associated with premature pregnancy termination. The sole efficient prophylaxis of preeclampsia in current state of evidence is aspirin at a dosage of 160 mg per day in high risk patients. Preeclampsia is now recognized as a high-risk factor for cardiovascular, renal, and neurological diseases and should therefore be considered as an opportunity for screening and prevention.
Topics: Humans; Pregnancy; Pre-Eclampsia; Female; Risk Factors
PubMed: 38869138
DOI: No ID Found -
European Stroke Journal Jun 2024Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk...
BACKGROUND AND PURPOSE
Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs.
METHODS
READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment.
RESULTS
We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding.
CONCLUSIONS
In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start.
PubMed: 38869034
DOI: 10.1177/23969873241255250 -
Cureus May 2024Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an uncommon genetic disorder that affects small blood vessels in...
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an uncommon genetic disorder that affects small blood vessels in the brain. It leads to neurological symptoms, disability-adjusted life years, and difficult emotional and physical situations for patients and their families. As unusual brain symptoms appear, it becomes important to understand the different clinical manifestations of CADASIL. Our case report and review examine several cases to demonstrate different presentations and management strategies of CADASIL. A 52-year-old male with a family history of strokes at a young age from his father and paternal grandfather presented to a neurology clinic for left facial droop and drooling. Brain magnetic resonance imaging showed extensive periventricular and subcortical white matter disease, including the external capsule and subcortical white matter of the temporal lobe. Findings were suggestive of small vessel vasculopathy. A cerebral angiogram showed that all large extra- and intracranial vessels were patent without evidence of aneurysm formation. There was no obvious evidence of beading of the distal intracranial vessels. Cerebrospinal fluid studies were normal. The NOTCH3 mutation was sent to test for CADASIL, which came back positive. The patient was started on aspirin (81 mg) and atorvastatin (20 mg) daily. The patient was counseled on the possibility of having an ischemic or hemorrhagic stroke. Aspirin and atorvastatin were continued, a neuropsychological evaluation was ordered, and CADASIL genetic counseling and testing were offered to him and his children. Over several years, patients developed several strokes and seizures due to infarcts. He also developed intraparenchymal hemorrhage complicated by dysphagia, requiring a feeding tube. Due to his severe physical debility, he was discharged to a nursing home for rehabilitation, where he did not improve with therapy and remained bedbound. He was discharged and sent home with his family. CADASIL can present as a diagnostic challenge due to its common presentation with migraines, transient ischemic attacks, and strokes, with or without risk factors. This unique presentation of CADASIL with facial palsy highlights the importance of emerging atypical presentations and the need for a detailed history of neuroimaging, family history, and personal history of neurovascular events. By accurately diagnosing the condition, patients and families can be counseled on the disease course and genetics. Management requires a multidisciplinary approach with neurology, genetic counseling, physical therapy, psychology, and psychiatry if depression or anxiety is present, with the aim of improving the patient's quality of life.
PubMed: 38868233
DOI: 10.7759/cureus.60165 -
European Heart Journal Supplements :... Apr 2024Venous thromboembolism (VTE) is a serious complication that can arise during and after hospitalization, particularly following surgery under general anaesthesia....
Venous thromboembolism (VTE) is a serious complication that can arise during and after hospitalization, particularly following surgery under general anaesthesia. Particularly at risk are major orthopaedic surgical procedures such as elective knee or hip replacement and the treatment of hip fractures. In these patients, current guidelines recommend (low or low-moderate level of evidence) aspirin as a possible alternative to anticoagulant therapy for the prophylaxis of long-term venous thromboembolism after an initial period with anticoagulant drugs. Several randomized trials and meta-analyses demonstrate no significant differences in the risk of VTE when comparing aspirin with anticoagulants. However, it must be considered that most recommendations are based on elective orthopaedic surgery and that trials after fractures have excluded patients at high thrombotic risk. Consequently, the overall incidence of major clinical events (death and pulmonary embolism) was ∼1% with wide confidence margins in even large non-inferiority studies. The incidence of asymptomatic VTE, especially distal, appears to be higher with aspirin. Patient preference and lower costs could play an important role in the choice in favour of aspirin.
PubMed: 38867879
DOI: 10.1093/eurheartjsupp/suae025