Background/Objectives: The purpose of this study was to investigate the association between cardiovascular adverse drug events (ADEs) and the use of COVID-19 medicines. Methods: The analyses were conducted by leveraging pharmacovigilance data from the Food and Drug Authority (FDA) Adverse Event Reporting System (FAERS) and TriNetX electronic health records (EHRs). Transcriptomic data from human embryonic stem cell-derived cardiomyocytes (hESC-CMs) exposed to remdesivir were analyzed to provide supportive biological context for the observed cardiovascular safety signals. Results: Comparative analysis of three approved COVID-19 therapies revealed that COVID-19 patients treated with remdesivir had a higher risk of cardiovascular events than those treated with Paxlovid or REGEN-COV. FAERS analysis further indicated that bradycardia, hypotension, and cardiac arrest were the most frequently reported cardiovascular events associated with remdesivir, which was validated by propensity score-matched EHR data. These findings suggest an association between remdesivir exposure and increased cardiovascular ADEs relative to other COVID-19 therapies. Sex-stratified analysis using FAERS and EHR did not show strong sex-dependent patterns for remdesivir-associated cardiovascular ADEs. Age-stratified analyses of EHR data showed age-associated variation across the three cardiovascular ADEs. Bradycardia displayed a non-uniform pattern with higher prevalence in the youngest and oldest age groups, hypotension showed an overall age-associated increase, and cardiac arrest showed only a weak age-associated effect. Pathway enrichment analysis on transcriptomic data revealed that the "cGMP-PKG signaling pathway", "dilated cardiomyopathy", and "calcium signaling pathway" were enriched among genes up-regulated by remdesivir exposure. Conclusions: In summary, our integrated analysis of pharmacovigilance, EHR, and transcriptomic data provides convergent evidence for associations between remdesivir and cardiovascular ADEs and offers biological context into these associations.

Brain-heart interactions have garnered considerable interest in the landscape of traumatic brain injury (TBI). This scoping review focused on bradycardia caused by high intracranial pressure (ICP), brainstem injury, autonomic imbalance, hypothalamic-pituitary-adrenal axis disruption, or massive bleeding. The latter condition is attributed to a physiological phenomenon called relative bradycardia (RB). True bradycardia results from underlying physiological or pathological cardiac disorders, whereas RB has different definitions and implications in medical and surgical settings. The former reflects pulse-temperature dissociation, while the latter reflects pulse-pressure dissociation. However, it can reflect an abnormal neurological response called the Cushing reflex. Therefore, bradycardia may indicate imminent shock after TBI associated with torso injuries or high ICP following severe isolated TBI. RB is underrecognized and underappreciated in emergency settings. This review investigated whether RB affects patient survival and neurological function. Physicians should approach patients presenting with RB with a high index of suspicion and timely management.

SUMMARYSalmonella enterica serovars Typhi and Paratyphi A cause enteric (typhoid/paratyphoid) fever, a systemic disease that remains a major source of morbidity and mortality worldwide. The most distinctive clinical manifestations, such as sustained fever with relative bradycardia, leukopenia, neuropsychiatric symptoms/encephalopathy, and ileal perforation, have long lacked a unifying mechanistic explanation. Over the past two decades, studies of typhoid toxin have reframed how we understand this disease. Typhoid toxin is a human-adapted, chimeric A2B5 exotoxin assembled exclusively inside infected cells. It couples an ADP-ribosyltransferase (PltA) and a DNase I-like nuclease (CdtB) on a pentameric delivery ring (PltB or the alternate, PltC), that recognizes N-acetylneuraminic acid (Neu5Ac)-terminated human sialoglycans. The toxin is produced by bacteria residing within the Salmonella-containing vacuole (SCV), secreted across the bacterial envelope into the SCV lumen by a phage-derived pathway now classified as type 10 secretion system, sorted for export by the host CI-M6PR/COPII trafficking machinery, and then re-enters distant target cells via retrograde transport to the endoplasmic reticulum (ER). Recent work has linked typhoid toxin to leukopenia, blood-brain barrier disruption causing encephalopathy, gut-vascular and immune dysfunction leading to intestinal perforation, and hepatobiliary injury. The discovery of an alternate B-subunit (PltC) established a paradigm of modular B-subunit exchange that diversifies receptor usage, tissue tropism, and biology. Collectively, these insights redefine typhoid fever as a toxin-driven immunovascular disease and identify actionable targets for neutralizing antibodies and barrier-protective therapies.

We report a rare case of diffuse large B-cell lymphoma (DLBCL) presenting with both nasal and cardiac tumors. The patient was a 77-year-old man who initially visited a local clinic with a two-month history of right-sided nasal discharge and nasal obstruction. A tumor lesion was identified in the nasal cavity, and he was subsequently referred to our hospital. Blood tests revealed leukocytosis, and computed tomography demonstrated a right nasal tumor, multiple lymphadenopathies, and an irregular mass in the right atrium. A biopsy of the nasal lesion confirmed the diagnosis of DLBCL. Transthoracic echocardiography revealed a relatively immobile cardiac mass, approximately 50 mm in diameter, located in the right atrium, which was suspected to represent cardiac infiltration of lymphoma. Chemotherapy with polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone was initiated. During the clinical course, the patient exhibited tachycardic atrial fibrillation and sinus pauses lasting up to approximately six seconds, suggesting tachycardia-bradycardia syndrome. With ongoing chemotherapy, the cardiac tumor showed a marked reduction in size over time. To date, the patient has been successfully managed without pacemaker implantation. This case suggests that careful management, including close monitoring, is crucial for arrhythmias associated with cardiac involvement of malignant lymphoma.

Desert rose (Adenium obesum) is a plant from the family Apocynaceace that can cause cardiac glycoside toxicosis if ingested. A 33-year-old male blue and gold macaw (Ara ararauna) ate a desert rose flower from an indoor houseplant. After ingestion, the patient fell onto the floor, regained its balance, and then ran to its owners who witnessed the patient "foaming at the mouth" with its "cheeks turning blue." The macaw proceeded to collapse, continued to foam at the mouth, and had what appeared to be a seizure. Upon presentation 2 hours postexposure, the macaw was moribund, in shock, and recumbent with rigid limbs and had dark blue cheeks and severe bradycardia (40 beats per minute). The bird was placed in flow-by oxygen in a warm incubator and, shortly thereafter, began regurgitating frank blood and passing melena. The patient's treatment protocol included atropine, parenteral fluids, dextrose, calcium-gluconate, vitamins, anti-inflammatory therapy, antibiotics, and activated charcoal gavage. The initial plasma biochemistry panel revealed a severe hyperkalemia (>10 mmol/L) that was treated with furosemide. Diagnostic testing and supportive treatment continued for 12 days, including hyperbaric oxygen therapy. Continuous incubator flow-by oxygen coupled with multiple hyperbaric oxygen treatments significantly improved perfusion, facilitating recovery. Three years following exposure to the desert rose flower, the owners consider the bird to have normal behavior and no clinical signs associated with the toxicosis.