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EuroIntervention : Journal of EuroPCR... Jun 2024
Topics: Humans; Platelet Aggregation Inhibitors; Clopidogrel; Percutaneous Coronary Intervention; Treatment Outcome
PubMed: 38887879
DOI: 10.4244/EIJ-E-24-00009 -
Trials Jun 2024A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of...
BACKGROUND
A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC.
METHODS
This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activity measured with accelerometry, and blood biomarkers for endothelial health, inflammation, coagulation, platelet function, and oxidative stress. Investigators, study participants, outcome assessors, and data analysts are blinded regarding the intervention assignment. Individuals with PCC were involved in the design of this study.
DISCUSSION
This is the first trial to investigate the effects of Pycnogenol® versus placebo on patient-reported health status in people with PCC. Should the trial proof clinical effectiveness, Pycnogenol® may serve as a therapeutic approach to mitigate symptoms associated with PCC.
TRIAL REGISTRATION
The study is registered at ClinicalTrials.gov. :NCT05890534, June 6, 2023.
Topics: Humans; Plant Extracts; Flavonoids; Randomized Controlled Trials as Topic; Quality of Life; COVID-19; Treatment Outcome; SARS-CoV-2; Health Status; COVID-19 Drug Treatment; Post-Acute COVID-19 Syndrome; Adult; Female; Male; Antioxidants; Anti-Inflammatory Agents
PubMed: 38879571
DOI: 10.1186/s13063-024-08187-6 -
Clinical and Translational Science Jun 2024This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral...
This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.
Topics: Humans; Cytochrome P-450 CYP2C19; Atrial Fibrillation; Male; Female; Aged; Coronary Artery Bypass; Middle Aged; Clopidogrel; Postoperative Complications; Genotype; Platelet Aggregation Inhibitors; Platelet Aggregation; Incidence; Aspirin
PubMed: 38877696
DOI: 10.1111/cts.13862 -
Biomedicine & Pharmacotherapy =... Jul 2024Enterovirus 71 (EV71), a prominent pathogen associated with hand, foot, and mouth disease (HFMD), has been reported worldwide. To date, the advancement of effective...
Enterovirus 71 (EV71), a prominent pathogen associated with hand, foot, and mouth disease (HFMD), has been reported worldwide. To date, the advancement of effective drugs targeting EV71 remains in the preliminary experimental stage. In this study, magnolol demonstrated a significant dose-dependent inhibition of EV71 replication in vitro. It upregulated the overall expression level of nuclear factor erythroid 2 - related factor 2 (Nrf2) and facilitated its nucleus translocation, resulting in the increased expression of various ferroptosis inhibitory genes. This process led to a reduction in reactive oxygen species (ROS) accumulation induced by viral infection. Additionally, magnolol exhibited a broad-spectrum antiviral effect against enteroviruses. Notably, treatment with magnolol substantially enhanced the survival rate of EV71-infected mice, attenuated viral load in heart, liver, brain, and limb tissues, and mitigated tissue inflammation. Taken together, magnolol emerges as a promising candidate for the development of anti-EV71 drugs.
Topics: Animals; Biphenyl Compounds; NF-E2-Related Factor 2; Lignans; Enterovirus A, Human; Antiviral Agents; Mice; Humans; Glutathione; Virus Replication; Reactive Oxygen Species; Enterovirus Infections; Signal Transduction; Chlorocebus aethiops; Vero Cells; Ferroptosis
PubMed: 38876045
DOI: 10.1016/j.biopha.2024.116866 -
Medicine Jun 2024Diabetes nephropathy (DN), as one of the common complications of diabetes, is characterized by persistent albuminuria, decreased glomerular filtration rate, and elevated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetes nephropathy (DN), as one of the common complications of diabetes, is characterized by persistent albuminuria, decreased glomerular filtration rate, and elevated arterial blood pressure. At present, Xuebijing injection is widely used in the treatment of DN. However, few systematic reviews and meta-analysis related to Xuebijing injection intervention in DN were published. In order to more systematically and objectively evaluate the clinical efficacy of Xuebijing injection intervention in DN, we conducted systematic reviews and meta-analysis to verify it.
OBJECTIVE
The purpose of the research was to systematically evaluate the clinical efficacy of Xuebijing injection combined with alprostadil in the treatment of diabetic nephropathy.
METHODS
We searched the China National Knowledge Infrastructure (CNKI), China Biomedical Database (SinoMed), Weipu Database (VIP), Wanfang Database, PubMed, The Cochrane Library, Embase, Web of Science and other databases by computer, and searched the randomized controlled trials of Xuebijing injection combined with alprostadil in the treatment of DN at home and abroad from the establishment of the database to 2022. The main outcome indicators included blood glucose, and the secondary outcome indicators included blood lipid, renal function, urinary protein, and safety. Two evaluators independently screened the literature, extracted the data and evaluated the risk of bias in the included studies. RevMan 5.3 software was used to analyze the data.
RESULTS
A total of 14 randomized controlled trials were included, including 1233 cases, 618 cases in the treatment group and 615 cases in the control group. The results of meta-analysis demonstrated that compared with the control group, the treatment group could effectively reduce fasting plasma glucose [mean difference [MD] = -1.90, 95% CI (-2.40, -1.40), P < .00001], glycosylated hemoglobin A1c [MD = -2.38, 95% CI (-2.51, -2.25), P < .00001], 2h postprandial blood glucose [MD = -2.92, 95% CI (-3.95, -1.89), P < .00001], triacylglycerol [MD = -1.08, 95% CI (-1.66, -0.50), P = .0003], total cholesterol [MD = -1.17, 95% CI (-1.39, -0.95), P < .00001], low-density lipoprotein cholesterol [MD = -1.19, 95% CI (-1.60, -0.78), P < .00001], high-density lipoprotein cholesterol [MD = 0.32, 95% CI (0.23, 0.42), P < .00001], serum creatinine [MD = -42.95, 95% CI (-57.46, -28.43), P < .00001], blood urea nitrogen [MD = -2.24, 95%CI (-2.62,-1.86), P < .00001], blood β2 microglobulin [SMD = -1.49, 95% CI (-1.70, -1.28), P < .00001], urine β2 microglobulin [SMD = -0.81, 95% CI (-1.04, -0.58), P < .00001], 24-hour urinary protein quantification [MD = -0.20, 95% CI (-0.26, -0.14), P < .00001], urinary albumin excretion rate [SMD = -1.15, 95% CI (-1.38, -0.93), P < .00001].
CONCLUSION
Xuebijing injection combined with alprostadil has more advantages in treating DN compared to routine Western medicine.
Topics: Humans; Drugs, Chinese Herbal; Diabetic Nephropathies; Alprostadil; Drug Therapy, Combination; Injections; Randomized Controlled Trials as Topic; Blood Glucose; Treatment Outcome; Lipids
PubMed: 38875385
DOI: 10.1097/MD.0000000000032095 -
Journal of the American Heart... Jun 2024Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention...
BACKGROUND
Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.
METHODS AND RESULTS
Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of <0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], =0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups.
CONCLUSIONS
Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
Topics: Aged; Female; Humans; Male; Middle Aged; Acute Coronary Syndrome; Black or African American; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Genotype; Hemorrhage; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 38874073
DOI: 10.1161/JAHA.123.033791 -
Antiviral Therapy Jun 2024Angiotensin-converting enzyme 2 (ACE2) is the receptor that enables SARS-CoV-2 to invade host cells. Previous studies have reported that reducing ACE2 expression may...
Angiotensin-converting enzyme 2 (ACE2) is the receptor that enables SARS-CoV-2 to invade host cells. Previous studies have reported that reducing ACE2 expression may have an anti-SARS-CoV-2 effect. In this study, we constructed a pGL4.10-F2-ACE2 vector with double luciferase genes (firefly and Renilla luciferase) under the control of the ACE2 promoter and used it to screen compounds from Chinese traditional medicinal herbs (CTMHs) that can inhibit ACE2 transcription in human cells. We transfected HEK293T cells with pGL4.10-F2-ACE2 and treated them with CTMH compounds and then measured fluorescence to evaluate the indirect inhibition of ACE2 transcription. Out of 37 compounds tested, andrographolide demonstrated a dose-dependent inhibition of ACE2 transcription. We further confirmed by RT-qPCR and Western blot assays that andrographolide also reduced ACE2 expression in BEAS-2B cells in a dose-dependent manner. Moreover, pseudovirus infection assays in BEAS-2B cells demonstrated that andrographolide can inhibit SARS-CoV-2 infection in a dose-dependent manner. These results suggest that andrographolide has potential anti-SARS-CoV-2 activity and could be a candidate drug for COVID-19 prevention and treatment.
Topics: Humans; Diterpenes; Angiotensin-Converting Enzyme 2; SARS-CoV-2; HEK293 Cells; Down-Regulation; COVID-19 Drug Treatment; COVID-19; Antiviral Agents; Drugs, Chinese Herbal
PubMed: 38873947
DOI: 10.1177/13596535241259952 -
BMC Anesthesiology Jun 2024Intra-operative anaesthesia management should be optimised to reduce the occurrence of postoperative nausea and vomiting in high-risk patients; however, a single... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Intra-operative anaesthesia management should be optimised to reduce the occurrence of postoperative nausea and vomiting in high-risk patients; however, a single intervention may not effectively reduce postoperative nausea and vomiting in such patients. This study assessed the effect of an optimised anaesthetic protocol versus a conventional one on postoperative nausea and vomiting in patients who underwent laparoscopic sleeve gastrectomy.
METHODS
A single-centre randomised trial was conducted at Peking University Shenzhen Hospital from June 2021 to December 2022. Among 168 patients who underwent laparoscopic sleeve gastrectomy, 116 qualified, and 103 completed the study with available data. Patients were categorized into the conventional group (received sevoflurane and standard fluids) and the optimised group (underwent propofol-based anaesthesia and was administered goal-directed fluids). The primary endpoints were postoperative nausea and vomiting incidence and severity within 24 h.
RESULTS
Postoperative nausea and vomiting assessment at 0-3 h post-surgery revealed no significant differences between groups. However, at 3-24 h, the optimised anaesthetic protocol group showed lower postoperative nausea and vomiting incidence and severity than those of the conventional group (P = 0.005). In the conventional group, 20 (37.04%) patients experienced moderate-to-severe postoperative nausea and vomiting, compared to six (12.25%) patients in the optimised group (odds ratio = 0.237; 95% CI = 0.086, 0.656; P = 0.006). No significant differences were noted in antiemetic treatment, moderate-to-severe pain incidence, anaesthesia recovery, post-anaesthetic care unit stay, or postoperative duration between the groups. While the total intra-operative infusion volumes were comparable, the optimised group had a significantly higher colloidal infusion volume (500 mL vs. 0 mL, P = 0.014) than that of the conventional group.
CONCLUSIONS
The incidence and severity of postoperative nausea and vomiting 3-24 h postoperatively in patients who underwent laparoscopic sleeve gastrectomy were significantly lower with propofol-based total intravenous anaesthesia and goal-directed fluid therapy than with sevoflurane anaesthesia and traditional fluid management. Total intravenous anaesthesia is an effective multimodal antiemetic strategy for bariatric surgery.
TRIAL REGISTRATION
This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC- 2,100,046,534, registration date: 21 May 2021).
Topics: Humans; Postoperative Nausea and Vomiting; Male; Female; Laparoscopy; Gastrectomy; Adult; Propofol; Sevoflurane; Middle Aged; Anesthetics, Intravenous; Anesthetics, Inhalation; Anesthesia
PubMed: 38872117
DOI: 10.1186/s12871-024-02577-8 -
Nature Communications Jun 2024People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces... (Randomized Controlled Trial)
Randomized Controlled Trial
People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. -10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed.
Topics: Humans; Peripheral Arterial Disease; Niacinamide; Male; Female; Aged; Pyridinium Compounds; Double-Blind Method; Resveratrol; Middle Aged; Walking; Treatment Outcome; Oxidative Stress
PubMed: 38871717
DOI: 10.1038/s41467-024-49092-5 -
Biomedicine & Pharmacotherapy =... Jul 2024The advent of general anesthesia (GA) has significant implications for clinical practice. However, the exact mechanisms underlying GA-induced transitions in...
The advent of general anesthesia (GA) has significant implications for clinical practice. However, the exact mechanisms underlying GA-induced transitions in consciousness remain elusive. Given some similarities between GA and sleep, the sleep-arousal neural nuclei and circuits involved in sleep-arousal, including the 5-HTergic system, could be implicated in GA. Herein, we utilized pharmacology, optogenetics, chemogenetics, fiber photometry, and retrograde tracing to demonstrate that both endogenous and exogenous activation of the 5-HTergic neural circuit between the dorsal raphe nucleus (DR) and basolateral amygdala (BLA) promotes arousal and facilitates recovery of consciousness from sevoflurane anesthesia. Notably, the 5-HT1A receptor within this pathway holds a pivotal role. Our findings will be conducive to substantially expanding our comprehension of the neural circuit mechanisms underlying sevoflurane anesthesia and provide a potential target for modulating consciousness, ultimately leading to a reduction in anesthetic dose requirements and side effects.
Topics: Sevoflurane; Animals; Dorsal Raphe Nucleus; Consciousness; Anesthetics, Inhalation; Basolateral Nuclear Complex; Male; Mice; Mice, Inbred C57BL; Serotonin; Neural Pathways; Receptor, Serotonin, 5-HT1A; Optogenetics
PubMed: 38870632
DOI: 10.1016/j.biopha.2024.116937