Liver transplantation can be performed with deceased or living donor allografts. Deceased liver grafts are donated from brain- or circulation-death patients, and they have usually suffered from a certain degree of damage. Post-transplant graft function and patient survival are closely related to liver allograft recovery. How to define the damage of liver grafts is unclear. A total of 47 liver donors, 23 deceased and 24 living, were enrolled in this study. All deceased donors had suffered from severe brain damage, and six of them had experienced cardio-pulmonary-cerebral resuscitation (CPR). The exploration of liver graft metabolomics was conducted by liquid chromatography coupled with mass spectrometry. Compared with living donor grafts, the deceased liver grafts expressed higher levels of various diacylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, oleoylcarnitine and linoleylcarnitine; and lower levels of cardiolipin and phosphatidylcholine. The liver grafts from the donors with CPR had higher levels of cardiolipin, phosphatidic acid, phosphatidylcholine, phatidylethanolamine and amiodarone than the donors without CPR. When focusing on amino acids, the deceased livers had higher levels of histidine, taurine and tryptophan than the living donor livers. In conclusion, the deceased donors had suffered from cardio-circulation instability, and their lipid metabolites were increased. The elevation of lipid metabolites can be employed as an indicator of liver graft suffering.

Aim: Patients receiving oral anticoagulants with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) have an increased risk of gastrointestinal bleeding (GIB). We compared cases of GIB associated with VKAs and DOACs in terms of risk factors, scores, timing, location, severity, and outcome. Methods: Data from patients treated at a university hospital in Switzerland for GIB under VKA and DOACs between 2012 and 2018 were analyzed in this investigator-driven, retrospective, single-center study. Results: A total of 248 patients (110 males; median age, 80 years; 134 VKA, 114 DOAC) were included. No significant differences in age, weight or sex were observed. The propensity of the VKA group for risk factors such as comorbidities, interacting medications, or a high risk for bleeding (HAS-BLED score) was higher than that of the DOAC group. 56% of the VKA-treated patients had a supratherapeutic INR, and 25% in the DOAC group received an unlicensed dose. Significantly more patients in the DOAC group were not formally overdosed with OAC whilst receiving amiodarone compared to the VKA group (57% vs. 18%, respectively, p = 0.03). Latency between the documented start of oral anticoagulation and GIB was shorter in the DOAC group (median 3 months) than in the VKA group (median 23.5 months, p¡0.001). There were no differences in terms of location and severity of the GIB, length of hospitalization, or mortality. Conclusion: Patients taking VKAs displayed more risk factors for GIB than those taking DOACs. Treatment with DOACs was associated with early GIB and calls for increased vigilance during the first months after commencement. Co-medication with amiodarone appeared to be a risk factor for GIB in patients taking DOACs.

This review of 19 studies (39,783 patients) of atrial fibrillation after thoracic surgery addresses the pathophysiology, incidence, and consequences of atrial fibrillation in this population, as well as its prevention and management. Interestingly, atrial fibrillation was most often identified in patients not previously known to have the disease. Rhythm control with amiodarone was the most commonly used treatment and nearly all patients were discharged in sinus rhythm. Major predictors were age; male sex; history of atrial fibrillation; congestive heart failure; left atrial enlargement; elevated brain natriuretic peptide level; and the invasiveness of procedures. Overall, patients with atrial fibrillation stayed 3 days longer in hospital. We also discuss the importance of standardising research on this subject and provide recommendations that might mitigate the impact postoperative atrial fibrillation on hospital resources.

Consider amiodarone pneumonitis as an important differential diagnosis of ARDS, especially in clinically ill patients who recently received Intravenous amiodarone.

Atrial fibrillation (AF) is the most common type of supraventricular tachyarrhythmia. Nifekalant is a new class III antiarrhythmic drug approved for the treatment of ventricular tachyarrhythmias, but its effectiveness in converting AF to sinus rhythm remains unclear. The present analysis aimed to investigate the effect of nifekalant in the conversion of AF. PubMed, Cochrane Library and China National Knowledge Infrastructure databases were systematically used to search relevant studies published between 1999 (data at which the drug was first approved for marketing in Japan) and 2022. Randomized clinical trials, prospective studies and retrospective studies on the use of nifekalant for AF were screened. The study metrics included the success rate of the conversion of AF, the mean time to conversion, the success rate of 12 months after a single AF catheter ablation procedure and the incidence of adverse events. The eligible studies screened included six randomized clinical trials, three prospective studies and three retrospective studies, totalling 12 studies with 1,162 patients. The risk ratio (RR) for successful conversion in the nifekalant and control groups was 1.95 [95% confidence interval (CI), 1.23-3.08; P=0.005] and the mean difference for the mean time to conversion was -1.73 [95% CI, -2.69-(-0.77); P=0.0004]. Statistically significant differences were observed between nifekalant and control groups. Subgroup analysis revealed a statistically significant difference in the success rate of conversion following catheter ablation in the nifekalant group compared with the amiodarone group and the RR value was 1.95 (95% CI, 1.37-2.77; P=0.0002). Statistically significant difference was observed compared with the electrical cardioversion group and the RR value was 0.90 (95% CI, 0.84-0.98; P=0.01). However, the combined RR values for the two groups were 1.18 (95% CI, 0.85-1.65; P<0.0002). The RR value for adverse events was 0.85 (95% CI, 0.51-1.43; P=0.55), with no statistically significant differences between nifekalant and control groups. In conclusion, the results demonstrated that the success rate and time to conversion in the nifekalant group were improved compared with those in the control group, particularly after catheter ablation, and the conversion effect with nifekalant was significantly improved compared with that in the control group.

Transcriptomic analysis is a powerful method in the utilization of New Approach Methods (NAMs) for identifying mechanisms of toxicity and application to hazard characterization. With this regard, mapping toxicological events to time of exposure would be helpful to characterize early events. Here, we investigated time-dependent changes in gene expression levels in iPSC-derived renal proximal tubular-like cells (PTL) treated with five diverse compounds using TempO-Seq transcriptomics with the aims to evaluate the application of PTL for toxicity prediction and to report on temporal effects for the activation of cellular stress response pathways. PTL were treated with either 50 μM amiodarone, 10 μM sodium arsenate, 5 nM rotenone, or 300 nM tunicamycin over a temporal time course between 1 and 24 h. The TGFβ-type I receptor kinase inhibitor GW788388 (1 μM) was used as a negative control. Pathway analysis revealed the induction of key stress-response pathways, including Nrf2 oxidative stress response, unfolding protein response, and metal stress response. Early response genes per pathway were identified much earlier than 24 h and included HMOX1, ATF3, DDIT3, and several MT1 isotypes. GW788388 did not induce any genes within the stress response pathways above, but showed deregulation of genes involved in TGFβ inhibition, including downregulation of CYP24A1 and SERPINE1 and upregulation of WT1. This study highlights the application of iPSC-derived renal cells for prediction of cellular toxicity and sheds new light on the temporal and early effects of key genes that are involved in cellular stress response pathways.

Cardiac amyloidosis (CA) is a restrictive disease that results from intramyocardial amyloid deposition due to immunoglobulin light chain or transthyretin proteins. Up to two-third of CA patients have atrial fibrillation (AF) due to electromechanical, autonomic, and hemodynamic disturbances. AF in CA carries particularly increased risk of thromboembolism, prompting anticoagulation therapy irrespective of CHA2DS2VASc score. However, CA is also associated with enhanced bleeding risk that warrants thorough assessment of bleeding profile before initiation of anticoagulation. Management of AF in CA is challenging because these patients poorly tolerate rate control agents, while cardiomyopathy precludes most antiarrhythmic agents, leaving amiodarone as the preferred antiarrhythmic drug. The effectiveness of direct current cardioversion in restoring sinus rhythm in CA is comparable with that in the general population, although intraprocedural complication rates could be higher. Transesophageal echocardiogram should be performed prior to direct current cardioversion, given high incidence of intracardiac thrombus in these patients. Finally, the data on catheter ablation is limited.

The prophylactic use of amiodarone to reduce the incidence of postoperative arrhythmias is effective for patients undergoing general cardiac surgeries; however, no data exists for the use of prophylactic amiodarone to prevent postoperative arrhythmias after CF-LVAD. This single-center, retrospective analysis compared patients with CF-LVADs placed between April 2014 and June 2020 who received prophylactic postoperative amiodarone to those who did not. Based on institution practice at the respective times, patients with a CF-LVAD placed between April 2014 and June 2018 were included in the group receiving postoperative amiodarone arrhythmia prophylaxis and patients with a CF-LVAD placed July 2018 to June 2020 were included in the group not receiving arrhythmia prophylaxis. The primary outcome was the incidence of first occurring atrial or ventricular arrhythmia from CF-LVAD placement to 21 days or hospital discharge. Sixty patients received amiodarone for arrhythmia prophylaxis and 27 patients did not receive prophylaxis. The primary outcome occurred in 40% of the prophylaxis group and 66.7% in the no prophylaxis group (RR, 0.60; 95% CI, 0.40-0.90; p = 0.038). In patients receiving CF-LVADs, the use of prophylactic amiodarone was associated with a reduction in the incidence of postoperative arrhythmias, which was driven primarily by a reduction in postoperative atrial arrhythmias, without significantly increasing the rate of amiodarone-related adverse events.

Although both stellate ganglion blockade and nifekalant are effective treatment options for electrical storm, the clinical effect of their combination is uncertain.

Caffeine (1,3,7-trimethylxantine), a structural analog of adenosine, is widely used as a central nervous system stimulant in beverages and drugs. Caffeine overdose induces hypokalemia, fatal ventricular fibrillation, and cardiac arrest, resulting in death. We describe a case of caffeine overdose that presented with refractory ventricular fibrillation that was treated with supportive care because invasive care for severely ill patients was limited due to the COVID-19 pandemic. A 20-year-old woman with no underlying medical history ingested 90,200-mg caffeine tablets (total dose 18 g) in a suicide attempt. She was transported to the emergency department 45 min after ingestion with dizziness, palpitations, nausea, and vomiting. She developed cardiac arrest 80 min after ingesting the caffeine, with refractory ventricular tachycardia that recurred for about 2.5 h. Advanced life support including defibrillation was started immediately and we gave intravenous Intralipid emulsion, potassium chloride, amiodarone, and esmolol, without hemodialysis or extracorporeal membrane oxygenation (ECMO). The ventricular fibrillation was stopped 4 h after ingestion. As supportive care, mechanical ventilation, sedatives, and neuromuscular blockade were continued until 12 h after ingestion. Although she suffered from prolonged, refractory ventricular tachycardia, she recovered without complications. This case report describes the clinical course of severe caffeine intoxication without an active elimination method, such as hemodialysis or ECMO and explores the treatment of caffeine intoxication with a literature review.

Loss of CDH1/Cadherin-1 is a common step towards the acquisition of an abnormal epithelial phenotype. In gastric cancer (GC), mutation and/or downregulation of CDH1/Cadherin-1 is recurrent in sporadic and hereditary diffuse GC type. To approach the molecular events downstream of CDH1/Cadherin-1 alterations and their relevance in gastric carcinogenesis, we queried public databases for genetic and DNA methylation data in search of molecular signatures with a still-uncertain role in the pathological mechanism of GC. In all GC subtypes, modulated genes correlating with CDH1/Cadherin-1 aberrations are associated with stem cell and epithelial-to-mesenchymal transition pathways. A higher level of genes upregulated in CDH1-mutated GC cases is associated with reduced overall survival. In the diffuse GC (DGC) subtype, genes downregulated in CDH1-mutated compared to cases with wild type CDH1/Cadherin-1 resulted in being strongly intertwined with the DREAM complex. The inverse correlation between hypermethylated CpGs and CDH1/Cadherin-1 transcription in diverse subtypes implies a common epigenetic program. We identified nonredundant protein-encoding isoforms of 22 genes among those differentially expressed in GC compared to normal stomach. These unique proteins represent potential agents involved in cell transformation and candidate therapeutic targets. Meanwhile, drug-induced and CDH1/Cadherin-1 mutation-related gene expression comparison predicts FIT, GR-127935 hydrochloride, amiodarone hydrochloride in GC and BRD-K55722623, BRD-K13169950, and AY 9944 in DGC as the most effective treatments, providing cues for the design of combined pharmacological treatments. By integrating genetic and epigenetic aspects with their expected functional outcome, we unveiled promising targets for combinatorial pharmacological treatments of GC.

(1) Background: Catheter ablation (CA) is an accepted treatment option for drug-refractory ventricular tachycardia (VT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study investigates the effect of amiodarone on ablation outcomes in ARVC. (2) Methods: The study enrolled patients with ARVC undergoing CA of sustained VT. In all patients, substrate modification was performed to achieve non-inducible VT. The patients were categorized into two groups according to whether they had used amiodarone before CA. Baseline and electrophysiological characteristics, substrate, and outcomes were compared. (3) Results: A total of 72 ARVC patients were studied, including 29 (40.3%) "off" amiodarone and 43 (56.7%) "on" amiodarone. The scar area was similar between the two groups. Patients "off" amiodarone had smaller endocardial and epicardial areas with abnormal electrograms. Twenty of 43 patients (47.5%) "on" amiodarone discontinued it within 3 months after CA. During a mean follow-up period of 43.2 ± 29.5 months, higher VT recurrence was observed in patients "on" amiodarone. Patients "on" amiodarone who discontinued amiodarone after CA had a lower recurrence than those without. (4) Conclusions: Patients with ARVC "on" amiodarone before CA had distinct substrate characteristics and worse ablation outcomes than patients "off" amiodarone, especially in those who had used amiodarone continuously.