Onasemnogene Abeparvovec (Zolgensma) is a gene therapy for the treatment of Spinal Muscular Atrophy (SMA) with improved motor neuron function and the potential for a singular treatment. Information on its adverse drug reactions is mainly from clinical trials and real-world studies with extensive sample sizes are lacking. In this study, we analyzed the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) database to assess the drug safety profile of Zolgensma. A total of 1951 adverse event reports associated with onasemnogene abeparvovec (Zolgensma), containing 778 import important medical event (IME) signals, were identified from the FAERS database, and multiple disproportionate analysis algorithms were used to determine the significance of these adverse events. This study identified 281 onasemnogene abeparvovec-related adverse events (AEs), including some significant adverse events not mentioned in the product labelling. Elevated liver enzymes, fever, vomiting, and thrombocytopenia were the most common adverse reactions. Most adverse events manifested within the initial month of onasemnogene abeparvovec use, especially the first 8 days, but some may still occur after 1 year of treatment. Sex-specific scrutiny revealed differing risk levels for adverse events among women and men. Thrombocytopenia and thrombotic microangiopathy are more common in patients weighing ≥8.5 kg, and changes in renal function need to be closely monitored if thrombotic microangiopathy occurs. The above findings provide valuable insights into optimizing the utilization of onasemnogene abeparvovec, improving its effectiveness, and minimizing potential side effects, thereby greatly facilitating its practical application in clinical settings.

Various studies have reported the association between cardiac markers and hepatic disorders. The main objective of this review article was to elucidate the significance of important cardiac indicators such as ischemia-modified albumin, cardiac troponin, cardiac natriuretic peptides, creatine kinase, creatine kinase-MB, lactate dehydrogenase, heart-type fatty acid-binding protein, osteopontin, soluble suppression of tumorigenicity 2, C-reactive protein, and lipoprotein(a) in the development of hepatic disorders. In addition, it highlighted recent notable discoveries and accomplishments in this field and identified areas requiring further investigation, ongoing discussions, and potential avenues for future research. Early identification and control of these cardiac markers might be helpful to control the prevalence of hepatic disorders associated with cardiovascular diseases.

Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities, such as major hepatic resections and liver transplantation. In addition to the organ's post reperfusion injury, this syndrome appears to play a central role in the dysfunction of distant tissues and systems. Thus, continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates. Treprostinil is a synthetic analog of prostaglandin I2, and its experimental administration has shown encouraging results. It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation, where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min. Treprostinil improves renal and hepatic function, diminishes hepatic oxidative stress and lipid peroxidation, reduces hepatictoll-like receptor 9 and inflammation, inhibits hepatic apoptosis and restores hepatic adenosine triphosphate (ATP) levels and ATP synthases, which is necessary for functional maintenance of mitochondria. Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflammatory cytokines; therefore, it can potentially minimize ischemia-reperfusion injury. Additionally, it may have beneficial effects on cardiovascular parameters, and much current research interest is concentrated on this compound.

Human gene replacement therapies such as onasemnogene abeparvovec (OA) use recombinant adeno-associated virus (rAAV) vectors to treat monogenic disorders. The heart and liver are known target organs of toxicity in animals; with cardiac and hepatic monitoring recommended in humans after OA dosing. This manuscript provides a comprehensive description of cardiac data from preclinical studies and clinical sources including clinical trials, managed access programs and the post-marketing setting following intravenous OA administration through 23 May 2022. Single dose mouse GLP-Toxicology studies revealed dose-dependent cardiac findings including thrombi, myocardial inflammation and degeneration/regeneration, which were associated with early mortality (4-7 weeks) in the high dose groups. No such findings were documented in non-human primates (NHP) after 6 weeks or 6 months post-dose. No electrocardiogram or echocardiogram abnormalities were noted in NHP or humans. After OA dosing, some patients developed isolated elevations in troponin without associated signs/symptoms; the reported cardiac adverse events in patients were considered of secondary etiology (e.g. respiratory dysfunction or sepsis leading to cardiac events). Clinical data indicate cardiac toxicity observed in mice does not translate to humans. Cardiac abnormalities have been associated with SMA. Healthcare professionals should use medical judgment when evaluating the etiology and assessment of cardiac events post OA dosing so as to consider all possibilities and manage the patient accordingly.

This study sought to investigate risk factors for 6-week mortality of patients with decompensated liver cirrhosis associated esophagogastric variceal bleeding (EGVB) and clinical characteristics of myocardial injury in cirrhotic patients with EGVB. This retrospective cohort study included 249 patients with decompensated liver cirrhosis associated EGVB in the Department of Emergency. Patients were divided into two groups including liver cirrhosis associated EGVB without myocardial injury and liver cirrhosis associated EGVB with myocardial injury. Myocardial injury, recurrent bleeding, total bilirubin (TBIL) level and dyslipidemia are independent risk factors for 6-week mortality in liver cirrhosis associated EGVB. Among all patients with liver cirrhosis associated EGVB, 90 (36.2%) had myocardial injury and 159 individuals (63.8%) not. The 6-week mortality in the group with myocardial injury was 21%, which was significantly higher than that of 7% in the group without myocardial injury. More patients in the myocardial injury group smoked, had moderate to severe esophageal varices, liver failure, and Child-Pugh C liver function compared to the non-myocardial injury group. Myocardial injury, recurrent bleeding, TBIL level and dyslipidemia are independent risk factors for death within 6 weeks in liver cirrhosis associated EGVB. The 6-week mortality is considerably higher in patients with myocardial injury in liver cirrhosis associated EGVB than those without myocardial injury.

Hepatocellular cancer (HCC) is a leading cause of cancer-related mortality worldwide, and chronic hepatitis B virus infection (CHB) has been a major risk factor for HCC development. The pathogenesis of HBV-related HCC has been a major focus revealing the interplay of a multitude of intracellular signaling pathways, yet the precise mechanisms and their implementations to clinical practice remain to be elucidated. This study utilizes publicly available transcriptomic data from the livers of CHB patients in order to identify a population with a higher risk of malignant transformation. We report the identification of a novel list of genes (PCM1) which can generate clear transcriptomic sub-groups among HBV-infected livers. PCM1 includes genes related to cell cycle activity and liver cancer development. In addition, markers of inflammation, M1 macrophages and gamma delta T cell infiltration are present within the signature. Genes within PCM1 are also able to differentiate HCC from normal liver, and some genes within the signature are associated with poor prognosis of HCC at the mRNA level. The analysis of the immunohistochemical stainings validated that proteins coded by a group of PCM1 genes were overexpressed in liver cancer, while minimal or no expression was detected in normal liver. Altogether, our findings suggest that PCM1 can be developed into a clinically applicable method to identify CHB patients with a higher risk of HCC development.

The development of sensitive myocardial-specific cardiac biomarkers allows for detection of very small amounts of myocardial injury or necrosis. Myocardial injury (MI) as a prelude of the serious perioperative complication myocardial infarction, should be paid more attention, especially in elderly susceptible patients. Myocardial injury after abdominal surgery in elderly patients has not been described yet. The objectives of this study were to identify the incidence, predictors, characteristics and the impact of MI on outcome in elderly patients underwent abdominal surgery.

Patients aged  ≥ 65 who underwent abdominal surgery longer than 2 h between January 2016 and March 2017 were reviewed. Patients with peak troponin I level of 0.04 ng/ml or greater (abnormal laboratory threshold) within once-administration-period and without non-ischemia troponin elevation proof (e.g., sepsis) were assessed for characteristics and prognosis. Risk factors of MI were determined by multivariable regression.

Among 285 patients with whole information, 36 patients (12.6%) suffered MI, only 2 patients (0.7%) fulfilled definition of myocardial infarction. With most of them occurred within first 7 days after surgery. Multivariable analysis showed that coronary artery disease (CAD) history [odds ratio (OR) 2.817, P = 0.015], non-laparoscopic surgery (OR 5.181, P = 0.030), blood loss ≥ 800 ml (OR 3.430, P = 0.008), non-venous maintain (OR 2.105, P = 0.047), and infection (OR 4.887, P = 0.008) as risk factors for MI. MI was associated with longer hospital stay (P = 0.006), more cardiac consultation (P = 0.011), higher infection(P = 0.016) and reoperation(P = 0.026) rate.

MI is common in elderly patients who underwent abdominal surgery, while myocardial infarction is infrequent. They are both associated with risk factors and worse prognosis. MI deserves more attention especially in elderly patients. Troponin I measurement is a useful test after massive surgery, which can help risk-stratifying patients, effective preventing, prompt managing and predicting outcomes. Routine monitoring of cardiac biomarkers especially within 7 days after abdominal surgery in elderly patients is recommended.