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AbstractObjectiveTo conduct a randomised, open label comparison of the effectiveness and safety of intravenous vernakalant and intravenous procainamide for the management of acute atrial fibrillation in the emergency department.DesignRandomised clinical trial (RAFF4 trial).Setting12 tertiary care emergency departments in Canada.ParticipantsPatients with acute atrial fibrillation for whom acute rhythm control was a safe option.InterventionsPatients were randomised (1:1) to an intravenous infusion of vernakalant or procainamide; when rapid conversion did not occur, patients were offered electrical cardioversion.Main outcomes and measuresThe primary outcome was conversion to sinus rhythm within 30 minutes of drug infusion completion. Secondary outcomes included time to conversion to sinus rhythm and whether the patient required electrical cardioversion.ResultsOf the 350 enrolled eligible patients, baseline characteristics were similar in the procainamide (n=172) and vernakalant (n=178) groups. For the primary outcome of conversion success, vernakalant was more effective (62.4% v 48.3%; adjusted absolute difference 15.0%, 95% confidence interval 4.6% to 25.0%, P=0.005; adjusted odds ratio 1.87, 95% confidence interval 1.2 to 2.9, P=0.006). With vernakalant, time to conversion was faster (21.8 v 44.7 minutes; mean difference −22.9, 95% confidence interval −29.9 to −16.0, P<0.001), and fewer patients underwent attempted electrical cardioversion (33.7% v 44.2%; odds ratio 0.62, 95% confidence interval 0.39 to 0.96, P=0.033). Adverse events were similar in both groups, were generally mild and brief, and most patients were discharged home. Subgroup analysis strongly favoured vernakalant for conversion in patients younger than 70 years (73.3% v 47.2%; adjusted odds ratio 3.1, 95% confidence interval 1.7 to 5.5, P=0.001, interaction P=0.005).ConclusionsIn this head-to-head comparison, vernakalant was superior to procainamide for patients with higher conversion rates and faster times to conversion. Therefore, vernakalant is a safe and highly effective intravenous alternative for the rapid cardioversion and discharge home of patients with acute atrial fibrillation.Trial registrationClinicalTrials.gov NCT04485195

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non-coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resistance in cancer. The present review describes central epigenetic aberrations during malignant transformation and explains how epidrugs target DNA methylation, histone modifications and ncRNAs. Furthermore, clinical trials focused on evaluating the effect of these epidrugs alone or in combination with other anticancer therapies and other ncRNA-based therapies are discussed. The use of epidrugs promises to be an effective tool for reversing drug resistance in some patients with cancer.

The 4-amino-N-[2 (diethylamino) ethyl] benzamide (procainamide)-tetraphenylborate complex was synthesized by reacting sodium tetraphenyl borate with 4-amino-N-[2 (diethylamino) ethyl] benzamide, chloride salt, and procainamide in deionized water at room temperature through an ion-associate reaction (green chemistry) at room temperature, and characterized by several physicochemical methods. The formation of ion-associate complex between bio-active molecules and/or organic molecules is crucial to comprehending the relationships between bioactive molecules and receptor interactions. The solid complex was characterized by infrared spectra, NMR, elemental analysis, and mass spectrometry, indicating the formation of ion-associate or ion-pair complex. The complex under study was examined for antibacterial activity. The ground state electronic characteristics of the S1 and S2 complex configurations were computed using the density functional theory (DFT) approach, using B3LYP level 6-311 G(d,p) basis sets. R[sup.2] = 0.9765 and 0.9556, respectively, indicate a strong correlation between the observed and theoretical [sup.1] H-NMR, and the relative error of vibrational frequencies for both configurations was acceptable, as well. HOMO and LUMO frontier molecular orbitals and molecular electrostatics using the optimized were used to obtain a potential map of the chemical. The n → π* UV absorption peak of the UV cutoff edge was detected for both configurations of the complex. Spectroscopic methods were structures used to characterize the structure (FT-IR and 1HNMR). In the ground state, DFT/B3LYP/6-311G(d,p) basis sets were used to determine the electrical and geometric properties of the S1 and S2 configurations of the title complex. Comparing the observed and calculated values for the S1 and S2 forms, the HOMO-LUMO energy gap of compounds was 3182 and 3231 eV, respectively. The small energy gap between HOMO and LUMO indicated that the compound was stable. In addition, the MEP reveals that positive potential sites were around the PR molecule, whereas negative potential sites were surrounding the TPB site of atoms. The UV absorption of both arrangements is comparable to the experimental UV spectrum.

Rhabdomyosarcomas have been described in association with thyroid disease, dermatomyositis, Duchenne muscular dystrophy, and in muscular dystrophy models but not in patients with ryanodine receptor-1 gene (RYR1) pathogenic variants. We described here an 18-year-old male who reported a cervical nodule. Magnetic resonance images revealed a mass in the ethmoidal sinus corresponding to rhabdomyosarcoma. As his father died from malignant hyperthermia (MH), an in vitro contracture test was conducted and was positive for MH susceptibility. Muscle histopathological analysis in the biopsy showed the presence of cores. Molecular analysis using NGS sequencing identified germline variants in the RYR1 and ASPSCR1 (alveolar soft part sarcoma) genes. This report expands the spectrum of diseases associated with rhabdomyosarcomas and a possible differential diagnosis of soft tissue tumors in patients with RYR1 variants.

Epigenetics play a crucial role in gene regulation and cellular processes. Most importantly, its dysregulation can contribute to the development of tumors. Epigenetic modifications, such as DNA methylation and histone acetylation, are reversible processes that can be utilized as targets for therapeutic intervention. DNA methylation inhibitors disrupt DNA methylation patterns by inhibiting DNA methyltransferases. Such inhibitors can restore normal gene expression patterns, and they can be effective against various forms of cancer. Histone deacetylase inhibitors increase histone acetylation levels, leading to altered gene expressions. Like DNA methylation inhibitors, histone methyltransferase inhibitors target molecules involved in histone methylation. Bromodomain and extra-terminal domain inhibitors target proteins involved in gene expression. They can be effective by inhibiting oncogene expression and inducing anti-proliferative effects seen in cancer. Understanding epigenetic modifications and utilizing epigenetic inhibitors will offer new possibilities for cancer research.

With recent negative studies of amiodarone and lidocaine for cardiac arrest, research into other antiarrhythmics is warranted. Literature on procainamide in cardiac arrest is limited. We evaluated procainamide for out-of-hospital cardiac arrests (OHCA) from the Resuscitation Outcomes Consortium (ROC). We included all ROC Epistry 3 OHCAs with an initial shockable rhythm that received an antiarrhythmic. We stratified cases by antiarrhythmic: procainamide, amiodarone, or lidocaine. The outcomes were prehospital return of spontaneous circulation (ROSC), ROSC in the ED, and survival to hospital discharge. We defined propensity scores based on possible confounders utilizing 1:1 propensity score matching to compare procainamide to amiodarone and lidocaine. We analyzed the matched data using logistic regression. We also used multivariable logistic regression to evaluate the association between antiarrhythmic and outcomes. 3087 subjects met inclusion criteria; 51 patients received only procainamide, 1776 received amiodarone, and 1418 received lidocaine. On propensity score analysis and compared to procainamide, amiodarone had similar prehospital ROSC (OR 0.7, 95% CI 0.3–1.8), ED ROSC (OR 0.6, 95% CI 0.3–1.3), and survival (OR 1.0, 95% CI 0.3–3.1). Lidocaine also had a similar prehospital ROSC (OR 0.9, 95% CI 0.4–2.2), ED ROSC (OR 1.2, 95% CI 0.5–2.7), and survival (OR 1.4, 95% CI 0.5–4.0). However, using multivariable regression, amiodarone had lower prehospital ROSC than procainamide (aOR 0.3, 95% CI 0.1–0.6). While associated with increased prehospital ROSC when compared with amiodarone using multivariable regression, procainamide otherwise had similar prehospital ROSC, ED ROSC, and survival. The role of procainamide in OHCA remains unclear.