Significant Systemic Side Effects Research Articles

LINC02535 + miR-30a-5p combination enhances proliferation and inhibits apoptosis in metastatic breast Cancer cells

Current clinical therapies for metastatic breast cancer (MBC) have limited therapeutic efficacy and induce significant systemic side effects, leading to poor patient compliance. To address this challenge, this investigation focuses on the design of LINC02535 + miR-30a-5p for treating breast cancer. In vitro cytotoxicity studies confirmed that LINC02535 + miR-30a-5p was more effective in 4 T1 cells, with reduced toxicity in NIH3T3 cells. Further verification of cellular morphology was achieved through various biochemical staining methods. Additionally, the antimetastatic attributes of LINC02535 + miR-30a-5p have been evaluated using both migration scratch and Transwell migration assays, which have collectively revealed excellent antimetastatic potential. The DNA fragmentation of the 4 T1 cells was assessed using a comet assay. LINC02535 + miR-30a-5p improved ROS levels and caused mitochondrial membrane potential alterations and DNA damage, which resulted in apoptosis. Therefore, we propose that LINC02535 + miR-30a-5p could be an alternative therapeutic strategy for breast cancer therapy.

Different Targeting Ligands-Mediated Drug Delivery Systems for Tumor Therapy.

Traditional tumor treatments have the drawback of harming both tumor cells and normal cells, leading to significant systemic toxic side effects. As a result, there is a pressing need for targeted drug delivery methods that can specifically target cells or tissues. Currently, researchers have made significant progress in developing targeted drug delivery systems for tumor therapy using various targeting ligands. This review aims to summarize recent advancements in targeted drug delivery systems for tumor therapy, focusing on different targeting ligands such as folic acid, carbohydrates, peptides, aptamers, and antibodies. The review also discusses the advantages, challenges, and future prospects of these targeted drug delivery systems.

A recombinant signalling-selective activated protein C that lacks anticoagulant activity is efficacious and safe in cutaneous wound preclinical models.

Various preclinical and clinical studies have demonstrated the robust wound healing capacity of the natural anticoagulant activated protein C (APC). A bioengineered APC variant designated 3K3A-APC retains APC's cytoprotective cell signalling actions with <10% anticoagulant activity. This study was aimed to provide preclinical evidence that 3K3A-APC is efficacious and safe as a wound healing agent. 3K3A-APC, like wild-type APC, demonstrated positive effects on proliferation of human skin cells (keratinocytes, endothelial cells and fibroblasts). Similarly it also increased matrix metollaproteinase-2 activation in keratinocytes and fibroblasts. Topical 3K3A-APC treatment at 10 or 30 μg both accelerated mouse wound healing when culled on Day 11. And at 10 μg, it was superior to APC and had half the dermal wound gape compared to control. Further testing was conducted in excisional porcine wounds due to their congruence to human skin. Here, 3K3A-APC advanced macroscopic healing in a dose-dependent manner (100, 250 and 500 μg) when culled on Day 21. This was histologically corroborated by greater collagen maturity, suggesting more advanced remodelling. A non-interference arm of this study found no evidence that topical 3K3A-APC caused either any significant systemic side-effects or any significant leakage into the circulation. However the female pigs exhibited transient and mild local reactions after treatments in week three, which did not impact healing. Overall these preclinical studies support the hypothesis that 3K3A-APC merits future human wound studies.

Electrosprayed Chitosan Nanoparticles for Drug Carriers in Cancer Treatment - A Mini Review

Nanoparticles have emerged as promising tools for cancer treatment due to their ability to selectively deliver drugs to the tumor site while avoiding significant systemic side effects. Chitosan nanoparticles, among various types of nanoparticles, have gained significant attention due to their biocompatibility, biodegradability, and local drug delivery capacity. The electrospray technique is an efficient method for preparing chitosan nanoparticles, offering reproducibility, scalability, and high drug encapsulation efficiency. This technique has gained popularity due to its ease of use and flexibility in meeting various demands of nanoparticle production. Recent studies have investigated the potential of chitosan nanoparticles prepared by electrospray technique to encapsulate a range of drugs. The method leverages active surface absorption, binding, or complexation with drugs. For example, chitosan-based nanoparticles loaded with DOX and QUE achieved high encapsulation efficiency of 83% and effectively inhibited the growth of HCT-116 cancer cells. Similarly, SNP-CH-DOX-CM nanoparticles showed significant anti-cancer activity against HepG2 tumors. However, it should be noted that the toxicity of nanoparticles is directly related to the concentration of the active substance. Therefore, careful optimization of drug dosing is necessary to minimize any potential toxicity.

A “biomimetic bone-magnet” with suitable mechanical properties concurrently performs accurate target collection of nanoparticles for magnetothermally driven osteosarcoma thermo-chemotherapy

Osteolytic lesions of bone tumors lead to stress-induced loss of load-bearing bones, making it difficult to treat tumors and repair bone tissue structures. Magnetic hyperthermia has become an effective minimally invasive treatment for malignant bone tumors without depth limitations. However, the effectiveness of magnetic heat therapy alone is not satisfactory, and if combined with chemotherapy, it can lead to significant systemic side effects. It is important to efficiently target chemotherapy substances to the correct area for combined therapy. We have developed a biomimetic bone magnet (BBM) that uses polymethyl methacrylate (PMMA) bone cement-loaded permanent magnet materials with good support performance to create an intrinsic tumor magnetic field. This magnetic field has magnetothermal properties and collects drug-loaded magnetic phase change nanoparticles (mCNPs) circulating in the blood for magnetothermally triggered chemotherapy. Moreover, PMMA has good mechanical properties, providing potential stress support for bone reconstruction after bone tumor treatment. Importantly, both in vivo and in vitro experimental results demonstrated the effectiveness of magnetic hyperthermia through minimally invasive injection of BBM phase transition. This new method achieves magnetic targeting by manufacturing tumor biomagnets to generate strong magnetic fields within the tumor, which opens up new avenues for treatment strategies for malignant bone tumors.

A CSF-1R-blocking antibody/IL-10 fusion protein increases anti-tumor immunity by effectuating tumor-resident CD8+ T cells

Strategies to increase intratumoral concentrations of an anticancer agent are desirable to optimize its therapeutic potential when said agent is efficacious primarily within a tumor but also have significant systemic side effects. Here, we generate a bifunctional protein by fusing interleukin-10 (IL-10) to a colony-stimulating factor-1 receptor (CSF-1R)-blocking antibody. The fusion protein demonstrates significant antitumor activity in multiple cancer models, especially head and neck cancer. Moreover, this bifunctional protein not only leads to the anticipated reduction in tumor-associated macrophages but also triggers proliferation, activation, and metabolic reprogramming of CD8+ Tcells. Furthermore, it extends the clonotype diversity of tumor-infiltrated Tcells and shifts the tumor microenvironment (TME) to an immune-active state. This study suggests an efficient strategy for designing immunotherapeutic agents by fusing a potent immunostimulatory molecule to an antibody targeting TME-enriched factors.

Subcutaneous immunoglobulin therapy for adult patients with primary immunodeficiency disease: Qatar experience.

Subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) are used for the treatment of primary immunodeficiency (PIDD). SCIG is as effective as IVIG in preventing infections.1 However, SCIG has advantages over IVIG as it causes fewer systemic reactions and can be infused at home by the patient leading to improved quality of life.2 Methods: We retrospectively analyzed adult patients with PIDD who received SCIG in an Adult Allergy Clinic in Qatar. Patients who received IVIG before SCIG and are naïve to IgG replacement were included. We compared Serum IgG levels, the number of antibiotic courses received, and the number of hospital admissions one year before and one year after starting SCIG. SF36 score was used to compare health-related quality of life scores before SCIG and after one year of SCIG. Twenty patients were included in the study, of which 17 were on prior IVIG replacement, and three were naive to replacement. SCIG replacement resulted in the maintenance of serum IgG levels in those who received IVIG prior. SCIG resulted in a statistically significant reduction in the number of antibiotics prescribed and hospitalization in the naïve subgroup but no substantial change in the prior IVIG group. 6/20 patients developed side effects like injection site pain, swelling, and headache. No patients developed significant systemic side effects. 10/20 patients discontinued the SCIG therapy, four patients due to side effects, and others due to noncompliance and financial reasons. SF36 Score was compared for the five patients in IVIG prior group and showed no significant improvement in individual score but improvement in the overall score (p=0.003) Conclusions: In our experience, SCIG therapy effectively prevents recurrent infection in PIDD patients, and patients did not experience any significant systemic side effects. There is a substantial improvement in the quality of life. However, compliance continues to be a problem.

Effects of SGLT2 (Sodium-Dependent Type 2 Glucose Transporters) on Different Systems

SGLT2 inhibitors are a class of drugs commonly used in the treatment of type 2 diabetes. Although these drugs are effective in controlling blood sugar, they also have significant systemic side effects that must be considered. The most common side effects of SGLT2 inhibitors include urinary tract infections, euglycemic ketoacidosis, orthostatic hypotension, dehydration, and cardiovascular adverse events. In addition, an increased incidence of bone fractures and decreased bone mineral density has been observed in patients taking these drugs. It is important that physicians consider these side effects when prescribing SGLT2 inhibitors and monitor patients regularly for any complications. Individual benefit-risk assessment is critical before deciding to prescribe these drugs. In summary, although SGLT2 inhibitors are an effective treatment option for type 2 diabetes, their use should be carefully evaluated and monitored to minimize systemic side effects.

A Selenium-Substituted Heptamethine Cyanine Photosensitizer for Near-Infrared Photodynamic Therapy.

Photodynamic therapy (PDT) is a relatively safe approach to cancer treatment without significant systemic side effects or drug resistance. However, the current PDT efficiency is unsatisfactory due to the lack of near-infrared (NIR) photosensitizers. Heptamethine cyanine (Cy7) dyes are well-known NIR fluorophores and are also used as photosensitizers. But their singlet oxygen quantum yields (ΦΔ ) are not ideal. Herein, we developed an NIR photosensitizer with a long-lived excited triplet state (τ=4.3 μs) by introducing a selenium atom into the structure of a Cy7 dye. The new NIR photosensitizer exhibits a significantly high singlet oxygen quantum yield (ΦΔ =0.11). Its good PDT effect was demonstrated in the living cells. Considering that the selenium-substituted photosensitizer has a very low dark cytotoxicity and good chemical stability, we conclude that it will have a promising future in biomedical and clinical applications.

Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL)

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.

Optimized metal-organic-framework based magnetic nanocomposites for efficient drug delivery and controlled release

Metal organic framework (MOF) has attracted wide attention as a promising biological platform due to its distinctive characteristics such as large surface areas, tunable pore sizes, and high selectivity in small molecule uptake. The incorporation of other guest materials into MOFs has resulted in additional functionalities of the conjugated MOF-composites. In this work, we have successfully conjugated Fe3O4 magnetic nanoparticles with MIL-88B–NH2 MOF structures using optimized synthetic media containing acetic acid as a modulating agent and F127 co-polymer as a stabilizing agent, which result in a well-controlled hybrid magnetic nanocomposite with an average size of 117 nm. This unique hybrid material has been further utilized as a nanocarrier for efficient drug delivery with the capability of on-demand controlled drug release. Glioblastoma drugs, including Carmustine (BCNU) and Mertansine (DM1), have been successfully loaded into the pores of the MOF structure to minimize their significant systemic toxic side effects that limit their clinical applications. Additionally, the controlled drug release was achieved through a localized heating effect produced by the magnetic nanodomains incorporated in the MOF structure after the application of an alternating magnetic field (AMF) on the DM1-loaded magnetic nanocomposites. In vitro cytotoxicity studies on U251 glioblastoma cells have been conducted to demonstrate the therapeutic efficacy of the drug delivery system and its capability of achieving on-demand drug release with the AMF as an external stimulus. Our results suggested that the fabricated magnetic nanocomposites are efficient for the controlled DM1 delivery, which exhibit superior cancer cell killing effects.

Bioorthogonal Equipping CAR-T Cells with Hyaluronidase and Checkpoint Blocking Antibody for Enhanced Solid Tumor Immunotherapy.

Adoptive cellular therapy utilizing chimeric antigen receptor redirected T (CAR-T) cells has shown impressive therapeutic effects on hematological malignancies. In contrast, the efficacy of CAR-T therapies in treating solid tumors is still poor, which is largely due to inefficient penetration into solid tumors and the immunosuppressive tumor microenvironment. Herein, we engineered hyaluronidase (HAase) and the checkpoint blocking antibody α-PDL1 on the CAR-T cell surface via highly efficient and biocompatible bioorthogonal click chemistry to improve their therapeutic effects on solid tumors. The modified HAase degrades hyaluronic acid and destroys the tumor extracellular matrix, allowing CAR-T cells to penetrate deeply into solid tumors, as evidenced by in vitro infiltration experiments and in vivo biodistribution studies. In addition, in vitro cytotoxicity studies showed stronger antitumor activity of α-PDL1-decorated cells than traditional CAR-T cells. Importantly, HAase- and α-PDL1-engineered CAR-T cells showed better therapeutic efficacy on two solid tumor models and did not cause significant systemic side effects. In this work, we provide a simple, efficient, and biologically safe chemical strategy to engineer traditional CAR-T cells for enhanced therapeutic efficacy on solid tumors, which can be extended to other adoptive cellular immunotherapies and holds great potential for clinical application.

Effectiveness of the Thermal Genicular Nerve Radiofrequency Ablation Therapy Under Fluoroscopy in Patients with Non-operative Advanced Stage Knee Osteoarthritis: 1-Year Follow-Up Results.

In this study, our aim was to present the 1-year results of the effect of thermal genicular nerve radiofrequency ablation (GNRFA) therapy on pain and functional outcomes in patients with advanced knee osteoarthritis. After retrospectively examining the hospital records, 49 knees of 35 patients who had undergone thermal RFA of the superior medial, superior lateral, and inferior medial branches of the genicular nerve under fluoroscopic guidance between July 2019 and December 2020 were included in the study. The visual analog scale (VAS) scores of the patients were recorded before RFA, on the day of RFA, and at the first, sixth, and 12th months postoperatively, as well as their Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores before RFA and at the 12th month postoperatively. Complications developed after the procedure and during the follow-up period were screened. Twenty-five of the patients were females and 10 males, with a mean age of 77.3 ± 7.9years (range 61-92years). The mean VAS score was 8.4 ± 0.9 before RFA, and as 1.7 ± 1.0 right after the procedure, 2.4 ± 1.7 at the first month, 3.4 ± 1.8 at the sixth month, and 4.4 ± 1.9 at the 12th month (p < 0.01). In terms of the WOMAC score, the average value was 69.7 ± 6.4 before the treatment and 36.1 ± 11.8 at the final follow-up at the 12th month (p < 0.01). No complications were observed in any patient during the treatment or the follow-up period. Non-surgical thermal GNRFA therapy of knee osteoarthritis provides significant outcomes in terms of pain and functionality, with no significant systemic or local side effects. Therefore, the technique can be considered as an alternative to other methods when treating advanced osteoarthritis.

Peptide-based delivery of therapeutics in cancer treatment.

Current delivery strategies for cancer therapeutics commonly cause significant systemic side effects due to required high doses of therapeutic, inefficient cellular uptake of drug, and poor cell selectivity. Peptide-based delivery systems have shown the ability to alleviate these issues and can significantly enhance therapeutic loading, delivery, and cancer targetability. Peptide systems can be tailor-made for specific cancer applications. This review describes three peptide classes, targeting, cell penetrating, and fusogenic peptides, as stand-alone nanoparticle systems, conjugations to nanoparticle systems, or as the therapeutic modality. Peptide nanoparticle design, characteristics, and applications are discussed as well as peptide applications in the clinical space.

Medical cannabis oil for benign essential blepharospasm: a prospective, randomized controlled pilot study.

To examine the efficacy and safety of medical cannabis in benign essential blepharospasm (BEB). This is a prospective, double-blind, placebo-controlled study. All consecutive adult BEB patients who had been treated with BTX-A injectionswithout success between 3/2019 and 2/2020 were recruited. The study patients were randomly allocated into a treatment and a control (placebo) group in a 1:1 ratio. The treatment group used cannabis drops and the control group used cannabis oil drops during the first 6weeks of the study, and both groups were treated with the medical cannabis drops during the second 6weeks. The cannabis dose was gradually increased for each patient depending upon effect and tolerability. Three patients were included in each group(treatment andcontrol groups). The mean duration of spasm attack during the first 6weeks was 4.29min in the treatment group and 73.9min in the placebo group (P < 0.01). During the last 6weeks, the treatment group used an average of 6.27 drops and the placebo group used an average of 5.36 drops (P = 0.478). There were 61 spasm events in the treatment group and 94 spasm events in the placebo group (P = 0.05). The mean duration of spasm attack was 1.77 and 8.96min, respectively (P < 0.01). The side effects were mild, and they included general fatigue, dry mouth, and insomnia. Medical cannabis can be an effective and safe treatment for BEB as a second line after BTX-A injections when used for 3months. No significant ocular or systemic side effects was associated with the treatment.

Use of Systemic Mycophenolate Mofetil Therapy in Ocular Surface Inflammatory Pathologies at the Initiative and Responsibility of the Ophthalmologist.

The purpose of the study was to evaluate the efficacy and safety of systemic mycophenolate mofetil (MMF) treatment in ocular surface inflammatory diseases. For this retrospective study, patients who were treated with systemic MMF for ocular surface inflammatory diseases between March 2020 and March 2022 were evaluated. Apart from demographic data, examination notes including MMF treatment indication and systemic side effect interrogation and routine laboratory examinations during drug treatment were extracted from the patient records. Detailed staging scores were performed according to the diagnosis including Foster and Mondino for ocular mucous membrane pemphigoid (MMP) and limbal stem cell deficiency scoring for limbal transplantation. For thorough evaluation, anterior segment pictures were used. Fourteen patients were enrolled to the study, with a mean age of 58 ± 12. MMP (6, 42.8%) and limbal allograft transplantation (6, 42.8%) constituted the main indications for the MMF treatment, followed by keratitis-ichthyosis-deafness (KID) syndrome (1, 7.2%) and Mooren's ulcer (1, 7.2%). Five of six patients with MMP regressed according to both staging systems. Only one remained stable which was evaluated as Stage 3. Furthermore, while all limbal transplant groups (6) stabilized and showed regression according to the individualized limbal stem cell deficiency staging system with no rejection during follow-up. Furthermore, patients with Mooren's ulcer and KID syndrome showed control of the inflammation and stabilization after MMF treatment. No significant systemic side effects apart from constipation and nausea (3) were observed in patients whose routine laboratory tests were stable throughout the follow-up. MMF has the potential to be a valuable and safe systemic agent of first choice in the control of ocular surface inflammatory disorders, especially when topical treatment is not effective. With such studies, it is predicted that MMF may reach wider usage areas with the increase in its effectiveness and safety in its use for ocular surface inflammatory pathologies.

Preclinical Dose-Escalation Study of ZSJ-0228, a Polymeric Dexamethasone Prodrug, in the Treatment of Murine Lupus Nephritis.

Glucocorticoids (GCs) are widely used in the clinical management of lupus nephritis (LN). Their long-term use, however, is associated with the risk of significant systemic side effects. We have developed a poly(ethylene glycol) (PEG)-based dexamethasone (Dex) prodrug (i.e., ZSJ-0228) and in a previous study, demonstrated its potential therapeutic efficacy in mice with established LN, while avoiding systemic GC-associated toxicity. In the present study, we have employed a dose-escalation design to establish the optimal dose-response relationships for ZSJ-0228 in treating LN and further investigated the safety of ZSJ-0228 in lupus-prone NZB/W F1 mice with established nephritis. ZSJ-0228 was intravenously (i.v.) administered monthly at four levels: 0.5 (L1), 1.0 (L2), 3.0 (L3), and 8.0 (L4) mg/kg/day Dex equivalent. For controls, mice were treated with i.v. saline every 4 weeks. In addition, a group of mice received intraperitoneal injections (i.p.) of Dex every day or i.v. injections of Dex every four weeks. Treatment of mice with LN with ZSJ-0228 dosed at L1 resulted in the resolution of proteinuria in 14% of the mice. Mice treated with ZSJ-0228 dosed at L2 and L3 levels resulted in the resolution of proteinuria in ∼60% of the mice in both groups. Treatment with ZSJ-0228 dosed at L4 resulted in the resolution of proteinuria in 30% of the mice. The reduction and/or resolution of the proteinuria, improvement in renal histological scores, and survival data indicate that the most effective dose range for ZSJ-0228 in treating LN in NZB/W F1 mice is between 1.0 and 3.0 mg/kg/day Dex equivalent. Typical GC-associated side effects (e.g., osteopenia, adrenal glands atrophy, etc.) were not observed in any of the ZSJ-0228 treatment groups, confirming its excellent safety profile.

Efficacy of topical dorzolamide 2% in diabetic cystoid macular edema.

To study the effect of topical dorzolamide 2% on macular thickness reduction in diabetic cystoid macular edema (CME). This was a prospective, non-randomized, open study including eyes with diabetic macular edema (DME). All eyes received topical dorzolamide 2% three times daily for one month. Changes in best-corrected visual acuity (BCVA), and central macular thickness (CMT) by optical coherence tomography) were evaluated at 1wk, 1, and 3mo post-treatment. Ninety-three eyes (84 patients) were included. Mean±SD (logMAR) BCVA improved significantly from 1.08±0.26 pretreatment to 0.66±0.24 at 1mo and 0.87±0.26 at 3mo post-treatment (P<0.001 both). The mean±SD CMT was significantly reduced from 535.27±97.4 µm at baseline to 357.43±125.8 µm at 1mo and 376.23±114.5 µm at 3mo post-treatment (P<0.001 both). No significant ocular or systemic side effects were recorded. Topical dorzolamide 2% results in significant improvement of mean BCVA and reduction of mean CMT at 3mo post-treatment. It can be used as an effective, affordable, and safe therapy for treatment of non-refractory diabetic CME.

The Efficacy, Safety, and Side Effects of Intrapericardial Triamcinolone Treatment in Children with Post-surgical Pericardial Effusion: A Case Series

Intrapericardial triamcinolone can be used to treat chronic pericardial effusion (PE) in adults; however, pediatric data are lacking. In this case series we aim to evaluate the efficacy, safety, and side effects of intrapericardial triamcinolone in children with PE. The incidence and treatment of post-surgical PE from 2009 to 2019 were determined using the institutional surgical database and electronic patient records. Furthermore, a retrospective analysis of efficacy, safety, and side effects of intrapericardial triamcinolone treatment for chronic post-surgical PE was performed. The incidence of postoperative PE requiring treatment was highest after atrial septal defect (ASD) closure when compared to other types of cardiac surgery (9.7% vs 4.3%). Intrapericardial treatment with triamcinolone resolved pericardial effusion in 3 out of 4 patients. All patients developed significant systemic side effects. Surgical ASD closure is associated with an increased risk of development of PE requiring treatment. Intrapericardial triamcinolone is an effective treatment for chronic postoperative PE in children, but is always associated with significant systemic side effects. Close monitoring and treatment of adrenal insufficiency are mandatory in these cases.

Electrophysiological effects and clinical utility of propafenone in children.

This retrospective case series study sought to describe the safety and clinical effectiveness of propafenone for the control of arrhythmias in children with and without CHD or cardiomyopathy. We reviewed baseline characteristics and subsequent outcomes in a group of 63 children treated with propafenone at 2 sites over a 15-year period Therapy was considered effective if no clinically apparent breakthrough episodes of arrhythmias were noted on the medication. Sixty-three patients (29 males) were initiated on propafenone at a median age of 2.3 years. CHD or cardiomyopathy was noted in 21/63 (33%). There were no significant differences between demographics, clinical backgrounds, antiarrhythmic details, side effect profiles, and outcomes between children with normal hearts and children with CHD or cardiomyopathy. Cardiac depression at the initiation of propafenone was more common amongst children with CHD or cardiomyopathy compared to children with normal hearts. Systemic ventricular function was diminished in 15/63 patients (24%) prior to starting propafenone and improved in 8/15 (53%) of patients once better rhythm control was achieved. Other than one child in whom medication was stopped due to gastroesophageal reflux, no other child experienced significant systemic or cardiac side effects during treatment with propafenone. Propafenone achieved nearly equal success in controlling arrhythmias in both children with normal hearts and children with congenital heart disease or cardiomyopathy (90% versus 86%, p = 0.88). Propafenone is a safe and effective antiarrhythmic medication in children.