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Scientific Reports May 2024Human liver organoids are in vitro three dimensionally (3D) cultured cells that have a bipotent stem cell phenotype. Translational research of human liver organoids for...
Efficient hepatocyte differentiation of primary human hepatocyte-derived organoids using three dimensional nanofibers (HYDROX) and their possible application in hepatotoxicity research.
Human liver organoids are in vitro three dimensionally (3D) cultured cells that have a bipotent stem cell phenotype. Translational research of human liver organoids for drug discovery has been limited by the challenge of their low hepatic function compared to primary human hepatocytes (PHHs). Various attempts have been made to develop functional hepatocyte-like cells from human liver organoids. However, none have achieved the same level of hepatic functions as PHHs. We here attempted to culture human liver organoids established from cryopreserved PHHs (PHH-derived organoids), using HYDROX, a chemically defined 3D nanofiber. While the proliferative capacity of PHH-derived organoids was lost by HYDROX-culture, the gene expression levels of drug-metabolizing enzymes were significantly improved. Enzymatic activities of cytochrome P450 3A4 (CYP3A4), CYP2C19, and CYP1A2 in HYDROX-cultured PHH-derived organoids (Org-HYDROX) were comparable to those in PHHs. When treated with hepatotoxic drugs such as troglitazone, amiodarone and acetaminophen, Org-HYDROX showed similar cell viability to PHHs, suggesting that Org-HYDROX could be applied to drug-induced hepatotoxicity tests. Furthermore, Org-HYDROX maintained its functions for up to 35 days and could be applied to chronic drug-induced hepatotoxicity tests using fialuridine. Our findings demonstrated that HYDROX could possibly be a novel biomaterial for differentiating human liver organoids towards hepatocytes applicable to pharmaceutical research.
Topics: Humans; Hepatocytes; Organoids; Cell Differentiation; Nanofibers; Cells, Cultured; Liver; Chemical and Drug Induced Liver Injury; Cell Survival; Cytochrome P-450 CYP3A
PubMed: 38736008
DOI: 10.1038/s41598-024-61544-y -
Endocrinologia, Diabetes Y Nutricion Apr 2024Thyrotoxicosis is the clinical condition resulting from an excess of thyroid hormones for any reason. The main causes are Graves-Basedow disease, toxic multinodular... (Review)
Review
Thyrotoxicosis is the clinical condition resulting from an excess of thyroid hormones for any reason. The main causes are Graves-Basedow disease, toxic multinodular goitre and toxic adenoma. The medical treatment to control thyroid function includes antithyroid drugs, beta blockers, iodine solutions, corticosteroids and cholestyramine. Although therapeutic plasma exchange is not generally part of the therapy, it is an alternative as a preliminary stage before the definitive treatment. This procedure makes it possible to eliminate T4, T3, TSI, cytokines and amiodarone. In most cases, more than one cycle is necessary, either daily or every three days, until clinical improvement is observed. The effect on thyrotoxicosis is temporary, with an approximate duration of 24-48h. This approach has been proposed as a safe and effective alternative when the medical treatment is contraindicated or not effective, and when there is multiple organ failure or emergency surgery is required.
Topics: Humans; Thyrotoxicosis; Plasma Exchange; Female; Middle Aged; Male
PubMed: 38735679
DOI: 10.1016/j.endien.2024.01.009 -
European Journal of Nuclear Medicine... May 2024[I]I-FP-CIT SPECT is an imaging tool to support the diagnosis of parkinsonian syndromes characterized by nigrostriatal dopaminergic degeneration. After intravenous...
PURPOSE
[I]I-FP-CIT SPECT is an imaging tool to support the diagnosis of parkinsonian syndromes characterized by nigrostriatal dopaminergic degeneration. After intravenous injection, [I]I-FP-CIT is metabolized for a small part by the enzyme CYP3A4, leading to the formation of [I]I-nor-β-CIT. [I]I-nor-β-CIT passes the blood-brain barrier and has a very high affinity for the serotonin transporter (SERT). The SERT is expressed in the striatum and cortical areas. So, at least theoretical, the use of frequently used CYP3A4 inhibitors (like amiodarone) may influence the specific to non-specific striatal [I]I-FP-CIT ratio. Here we tested this novel hypothesis.
METHODS
Using a retrospective design, we determined the specific to non-specific striatal [I]I-FP-CIT ratio (using BRASS software) in 6 subjects that were using an CYP3A4 inhibitor and 18 matched controls. Only subjects were included with a normal rated [I]I-FP-CIT SPECT scan, and all participants were scanned on the same brain-dedicated SPECT system.
RESULTS
The specific to non-specific (assessed in the occipital cortex) striatal [I]I-FP-CIT binding ratio was significantly higher in CYP3A4 users than in the control group (3.52 ± 0.33 vs. 2.90 ± 0.78, p < 0.001).
CONCLUSION
Our preliminary data suggest that the use of CYP3A4 inhibitors may influence striatal [I]I-FP-CIT binding ratios. This information, when reproduced in larger studies, may be relevant for studies in which quantification of [I]I-FP-CIT SPECT imaging is used for diagnostic or research purposes.
PubMed: 38730086
DOI: 10.1007/s00259-024-06748-0 -
World Journal For Pediatric &... May 2024A nine-year old boy presented following a chest x-ray for COVID-19 infection that showed cardiomegaly. Transthoracic echocardiogram revealed a large atrial septal...
A nine-year old boy presented following a chest x-ray for COVID-19 infection that showed cardiomegaly. Transthoracic echocardiogram revealed a large atrial septal defect, dilated right heart, and normal function. Surgical repair was performed eight weeks after his COVID diagnosis. After weaning from cardiopulmonary bypass, pulmonary artery pressures were 2/3 systemic and ectopy was seen, requiring inotropes, nitric oxide, lidocaine, and amiodarone. He was discharged on postoperative day (POD) 5. On POD 6, he presented with acute right foot ischemia. Computed tomography showed a large aortic thrombus, requiring emergent thrombectomy. Coagulopathy workup was negative. Cardiac magnetic resonance imaging (CMR) and catheterization showed reduced biventricular function and diastolic dysfunction. Diuretics and β blockers were started, with gradual improvement in left ventricular systolic function.
PubMed: 38706197
DOI: 10.1177/21501351241240753 -
Journal of Cardiothoracic Surgery May 2024To evaluate the clinical efficacy and safety of intraoperative intravenous amiodarone for arrhythmia prevention in on-pump coronary artery bypass grafting (CABG)... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of intraoperative intravenous amiodarone in patients undergoing on-pump coronary artery bypass grafting surgery: a systemic review and PRISMA-compliant meta-analysis.
BACKGROUND
To evaluate the clinical efficacy and safety of intraoperative intravenous amiodarone for arrhythmia prevention in on-pump coronary artery bypass grafting (CABG) patients.
METHODS
A meta-analysis of randomized controlled trials was conducted. Pubmed, Embase, Cochrane Library, Ovid, China National Knowledge Infrastructure, and the Wan Fang database until July 1th, 2023. The primary outcomes of interest included the incidences of intra- and post-operative atrial fibrillation (POAF), ventricular fibrillation, or any arrhythmia, including atrial fibrillation, ventricular fibrillation, ventricular tachycardia, premature ventricular contraction, and sinus bradycardia. For continuous and dichotomous variables, treatment effects were calculated as the weighted mean difference (WMD)/risk ratio (RR) and 95% confidence interval (CI).
RESULTS
A database search yielded 7 randomized controlled trials including 608 patients, where three studies, including three treatments (amiodarone, lidocaine, and saline), contributed to the clinical outcome of atrial fibrillation, ventricular fibrillation, or any arrhythmia. Meta-analysis demonstrated that amiodarone can significantly reduce the incidence of POAF (RR, 0.39; 95%CI: 0.20, 0.77; P = 0.007, I = 0%) in patients undergoing on-pump CABG; there was no statistically significant influence on intra-operative atrial fibrillation, intra- and post-operative ventricular fibrillation, or any arrhythmia.
CONCLUSIONS
The current study suggests that intraoperative administration of intravenous amiodarone may be safe and effective in preventing POAF in patients undergoing on-pump CABG. More well-designed clinical trials are needed to validate this result.
Topics: Humans; Amiodarone; Coronary Artery Bypass; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Intraoperative Care; Administration, Intravenous; Postoperative Complications; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38702789
DOI: 10.1186/s13019-024-02732-9 -
Journal of Medical Case Reports May 2024Amiodarone-induced thyroid dysfunction (AIT) is a side-effect associated with the use of Amiodarone for the treatment of refractory arrythmias. Resulting hyperthyroidism... (Review)
Review
BACKGROUND
Amiodarone-induced thyroid dysfunction (AIT) is a side-effect associated with the use of Amiodarone for the treatment of refractory arrythmias. Resulting hyperthyroidism can precipitate cardiac complications, including cardiac ischemia and myocardial infarction, although this has only been described in a few case reports.
CASE PRESENTATION
We present here a clinical scenario involving a 66-year-old male Caucasian patient under Amiodarone for atrial fibrillation, who developed AIT. In the presence of dyspnea, multiple cardiovascular risk factors and ECG abnormalities, a transthoracic echocardiogram was performed, showing inferobasal hypokinesia. This led to further investigations through a cardiac PET-CT, where cardiac ischemia was suspected. Ultimately, the coronary angiography revealed no abnormalities. Nonetheless, these extensive cardiologic investigations led to a delay in initiating an emergency endovascular revascularization for acute-on-chronic left limb ischemia. Although initial treatment using Carbimazole was not successful after three weeks, the patient reached euthyroidism after completion of the treatment with Prednisone so that eventually thyroidectomy was not performed. Endovascular revascularization was finally performed after more than one month.
CONCLUSIONS
We discuss here cardiac abnormalities in patients with AIT, which may be due to relative ischemia secondary to increased metabolic demand during hyperthyroidism. Improvement of cardiac complications is expected through an optimal AIT therapy including medical therapy as the primary approach and, when necessary, thyroidectomy. Cardiac investigations in the context of AIT should be carefully considered and may not justify delaying other crucial interventions. If considered mandatory, diagnostic procedures such as coronary angiography should be preferred to functional testing.
Topics: Humans; Amiodarone; Male; Aged; Anti-Arrhythmia Agents; Myocardial Ischemia; Atrial Fibrillation; Positron Emission Tomography Computed Tomography; Hyperthyroidism; Echocardiography
PubMed: 38698496
DOI: 10.1186/s13256-024-04552-w -
JTCVS Open Apr 2024Postoperative atrial fibrillation (POAF) is a prevalent complication following cardiac surgery that is associated with increased adverse events. Several guidelines and...
Enhanced Recovery After Surgery Cardiac Society turnkey order set for prevention and management of postoperative atrial fibrillation after cardiac surgery: Proceedings from the American Association for Thoracic Surgery ERAS Conclave 2023.
BACKGROUND
Postoperative atrial fibrillation (POAF) is a prevalent complication following cardiac surgery that is associated with increased adverse events. Several guidelines and expert consensus documents have been published addressing the prevention and management of POAF. We aimed to develop an order set to facilitate widespread implementation and adoption of evidence-based practices for POAF following cardiac surgery.
METHODS
Subject matter experts were consulted to translate existing guidelines and literature into a sample turnkey order set (TKO) for POAF. Orders derived from consistent class I or IIA or equivalent recommendations across referenced guidelines and consensus manuscripts appear in the TKO in bold type. Selected orders that were inconsistently class I or IIA, class IIB, or supported by published evidence appear in italic type.
RESULTS
Preoperatively, the recommendation is to screen patients for paroxysmal or chronic atrial fibrillation and initiate appropriate treatment based on individual risk stratification for the development of POAF. This may include the administration of beta-blockers or amiodarone, tailored to the patient's specific risk profile. Intraoperatively, surgical interventions such as posterior pericardiotomy should be considered in selected patients. Postoperatively, it is crucial to focus on electrolyte normalization, implementation strategies for rate or rhythm control, and anticoagulation management. These comprehensive measures aim to optimize patient outcomes and reduce the occurrence of POAF following cardiac surgery.
CONCLUSIONS
Despite the well-established benefits of implementing a multidisciplinary care pathway for POAF in cardiac surgery, its adoption and implementation remain inconsistent. We have developed a readily applicable order set that incorporates recommendations from existing guidelines.
PubMed: 38690434
DOI: 10.1016/j.xjon.2024.02.008 -
Texas Heart Institute Journal Apr 2024Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart...
BACKGROUND
Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart disease, but data are limited about its use in adults with congenital heart disease of moderate to great complexity.
METHODS
A single-center, retrospective chart review of 21 adults with congenital heart disease of moderate to great complexity who were treated with dronedarone for atrial tachyarrhythmias was performed.
RESULTS
The median (IQR) age at dronedarone initiation was 35 (27.5-39) years. Eleven patients (52%) were male. Ten patients (48%) had New York Heart Association class I disease, 10 (48%) had class II disease, and 1 (5%) had class III disease. Ejection fraction at initiation was greater than 55% in 11 patients (52%), 35% to 55% in 9 patients (43%), and less than 35% in 1 patient (5%). Prior treatments included β-blockers (71%), sotalol (38%), amiodarone (24%), digoxin (24%), and catheter ablation (38%). Rhythm control was complete in 5 patients (24%), partial in 6 (29%), and inadequate in 10 (48%). Two patients (10%) experienced adverse events, including nausea in 1 (5%) and cardiac arrest in 1 (5%), which occurred 48 months after initiation of treatment. There were no deaths during the follow-up period. The median (IQR) follow-up time for patients with complete or partial rhythm control was 20 (1-54) months.
CONCLUSION
Dronedarone can be effective for adult patients with congenital heart disease and atrial arrhythmias for whom more established therapies have failed, and with close monitoring it can be safely tolerated.
Topics: Humans; Dronedarone; Male; Retrospective Studies; Female; Adult; Heart Defects, Congenital; Anti-Arrhythmia Agents; Treatment Outcome; Heart Rate; Atrial Fibrillation; Amiodarone; Time Factors
PubMed: 38686681
DOI: 10.14503/THIJ-22-7993 -
Toxicological Sciences : An Official... Apr 2024Drug-induced liver injury (DILI) represents a major issue for pharmaceutical companies, being a potential cause of black-box warnings on marketed pharmaceuticals, or...
Drug-induced liver injury (DILI) represents a major issue for pharmaceutical companies, being a potential cause of black-box warnings on marketed pharmaceuticals, or drug withdrawal from the market. Lipid accumulation in the liver also referred to as steatosis, may be secondary to impaired mitochondrial fatty acid oxidation (mtFAO). However, an overall causal relationship between drug-induced mtFAO inhibition and the occurrence of steatosis in patients has not yet been established with a high number of pharmaceuticals. Hence, 32 steatogenic and 13 non-steatogenic drugs were tested for their ability to inhibit mtFAO in isolated mouse liver mitochondria. To this end, mitochondrial respiration was measured with palmitoyl-L-carnitine, palmitoyl-CoA + L-carnitine, or octanoyl-L-carnitine. This mtFAO tri-parametric assay was able to predict the occurrence of steatosis in patients with a sensitivity and positive predictive value above 88%. To get further information regarding the mechanism of drug-induced mtFAO impairment, mitochondrial respiration was also measured with malate/glutamate or succinate. Drugs such as diclofenac, methotrexate and troglitazone could inhibit mtFAO secondary to an impairment of the mitochondrial respiratory chain, while dexamethasone, olanzapine and zidovudine appeared to impair mtFAO directly. Mitochondrial swelling, transmembrane potential and production of reactive oxygen species were also assessed for all compounds. Only the steatogenic drugs amiodarone, ketoconazole, lovastatin and toremifene altered all these 3 mitochondrial parameters. In conclusion, our tri-parametric mtFAO assay could be useful in predicting the occurrence of steatosis in patients. The combination of this assay with other mitochondrial parameters could also help to better understand the mechanism of drug-induced mtFAO inhibition.
PubMed: 38676573
DOI: 10.1093/toxsci/kfae055 -
Nursing in Critical Care Apr 2024Amiodarone is a prophylactic rhythm-regulating drug used to prevent arrhythmia; However, especially during infusion, it has the potential to cause a number of...
BACKGROUND
Amiodarone is a prophylactic rhythm-regulating drug used to prevent arrhythmia; However, especially during infusion, it has the potential to cause a number of complications, especially phlebitis.
AIM
The aim of the study is to determine the effects of sesame oil, which has the potential to prevent phlebitis that may occur during amiodarone infusion administered to patients after cardiac surgery.
DESIGN
This prospective, two-arm (1:1), block randomized controlled interventional study.
METHODS
This study was conducted with 44 patients treated in the coronary intensive care unit of a university hospital, who received parenteral infusion of amiodarone. Sesame oil was applied superficially by applying 10 drops to a 10 cm perimeter of the cannula for 10 min. This application was repeated every 8 h during the 24-h amiodarone infusion. No intervention was made to the patients in the control group. However, standard nursing care measures and a standard transparent dressing were applied to the patients in both groups during the peripheral catheter application phase. Patients in the intervention and control groups were evaluated in terms of phlebitis at the end of every 24 h using the Visual Infusion Phlebitis Scale. The study was reported according to the CONSORT declaration.
RESULTS
Phlebitis symptoms occurred in 15/22 (68.2%) of the patients in the intervention group on the first day, 3/22 (13.6%) on the second day and 2/22 (9.1%) of the patients on the third day, while in the control group, 20/22 (90.9%) of the patients had phlebitis on the first day and 2/22 (9.1%) on the second day. The incidence of phlebitis was 20/22 (90.9%) in the intervention group and 22/22 (100%) in the control group. There was no statistically significant difference in phlebitis symptoms between groups.
CONCLUSION
The research results showed that the application of sesame oil did not significantly reduce the frequency of phlebitis. However, a trend indicating delayed onset of phlebitis symptoms was observed in the sesame oil group. Nevertheless, larger sample studies are needed. These studies are expected to assist in determining the effects of sesame oil on phlebitis more precisely and provide stronger support for the results.
RELEVANCE TO CLINICAL PRACTICE
Training of nurses on non-pharmacological methods should be supported and opportunities should be given for their application.
PubMed: 38676381
DOI: 10.1111/nicc.13085