Reporting System Research Articles

Pharmacovigilance insights into drug-induced cystitis: analysis of FDA data from 2004 to 2024.

Drug-induced cystitis (DIC) significantly impacts patient quality of life and treatment outcomes. This study investigates the incidence and characteristics of DIC using data from the FDA Adverse Event Reporting System (FAERS). We reviewed FAERS reports related to cystitis from Q1 2004 to Q1 2024, compiling a list of potential causative drugs. The top 50 drugs with the highest number of cystitis reports were ranked. Statistical disproportionality analyses, including Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), were used to detect unusually high reporting frequencies of cystitis associated with specific drugs. From 17,703,515 FAERS reports spanning 2004-2024, 36399 involved cystitis. The majority of implicated drugs were antineoplastics. Busulfan, BCG, and mitomycin had the highest ROR and PRR values. Additionally, drugs such as defibrotide sodium, milrinone, and dyazide, which do not have cystitis listed on their labels, were identified, highlighting the need for increased clinical vigilance and awareness. The findings underscore the importance of ongoing pharmacovigilance in identifying and characterizing DIC. Further clinical studies are warranted to validate these associations and to develop strategies for mitigating the risk of DIC, thereby improving patient safety and treatment outcomes.

Diagnostic performance of adult-based thyroid imaging reporting and data systems in pediatric thyroid carcinoma: a retrospective study.

Thyroid nodules diagnosed in children pose a greater risk of malignancy compared to those in adults. However, there is no ultrasound thyroid nodule evaluation system aimed at children. The objective of this research is to assess the diagnostic performance of the adult-based American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) and Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) in pediatric thyroid carcinoma. The preoperative ultrasound images of 177 thyroid lesions in 136 pediatric patients aged 18 or younger who underwent thyroid surgery or fine needle aspiration (FNA) at our center from July 2017 to July 2022 were reviewed. The sonographic characteristics of pediatric thyroid carcinoma were compared and analyzed in contrast to benign nodules. All the nodules were evaluated by the ACR-TIRADS and the C-TIRADS respectively. Ultrasound features such as solid composition (94.8%), hypoechogenicity or marked hypoechogenicity (94.8-95.7%) and microcalcification (78.3-84.3%) were more common in pediatric malignant nodules (P-values < 0.05). The areas under receiver operating characteristic curves (AUC) of the ACR-TIRADS and the C-TIRADS in diagnosing pediatric thyroid carcinoma were 0.903-0.906,0.907-0.909 (P-value > 0.05). The interobserver agreement of both the ACR-TIRADS and the C-TIRADS was strong (weighted Kappa > 0.90). Both the C-TIRADS and the ACR-TIRADS owned great diagnostic performance and strong interobserver agreement in diagnosing pediatric thyroid carcinoma. However, a more complete and specific ultrasound evaluation system for pediatric thyroid nodules is still needed.

Systematic Review of AI-Assisted MRI in Prostate Cancer Diagnosis: Enhancing Accuracy Through Second Opinion Tools

Background: Prostate cancer is a leading cause of cancer-related deaths in men worldwide, making accurate diagnosis critical for effective treatment. Recent advancements in artificial intelligence (AI) and machine learning (ML) have shown promise in improving the diagnostic accuracy of prostate cancer. Objectives: This systematic review aims to evaluate the effectiveness of AI-based tools in diagnosing prostate cancer using MRI, with a focus on accuracy, specificity, sensitivity, and clinical utility compared to conventional diagnostic methods. Methods: A comprehensive search was conducted across PubMed, Embase, Ovid MEDLINE, Web of Science, Cochrane Library, and Institute of Electrical and Electronics Engineers (IEEE) Xplore for studies published between 2019 and 2024. Inclusion criteria focused on full-text, English-language studies involving AI for Magnetic Resonance Imaging (MRI) -based prostate cancer diagnosis. Diagnostic performance metrics such as area under curve (AUC), sensitivity, and specificity were analyzed, with risk of bias assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Results: Seven studies met the inclusion criteria, employing various AI techniques, including deep learning and machine learning. These studies reported improved diagnostic accuracy (with AUC scores of up to 97%) and moderate sensitivity, with performance varying based on training data quality and lesion characteristics like Prostate Imaging Reporting and Data System (PI-RADS) scores. Conclusions: AI has significant potential to enhance prostate cancer diagnosis, particularly when used for second opinions in MRI interpretations. While these results are promising, further validation in diverse populations and clinical settings is necessary to fully integrate AI into standard practice.

Do 5-Alpha Reductase Inhibitors Influence the Features of Suspicious Lesions on Magnetic Resonance Imaging and Targeted Biopsy Results for Prostate Cancer Diagnosis?

Introduction: 5-alpha reductase inhibitors (5-ARIs) change hormonal pathways and reduce prostate size. We evaluated the effects of 5-ARIs on prostatic multiparametric magnetic resonance imaging (mpMRI) suspicious findings and in the identification of prostate cancer using targeted biopsies. Methods: We conducted a retrospective study including 600 consecutive patients who, between 2017 and 2021, underwent combined transperineal fusion biopsies. Primary outcomes were Prostate Imaging Reporting and Data System version 2 (PIRADS v2) scores and the identification of clinically significant prostate cancer from suspicious lesions (targeted CSPC). Outcomes were compared between patients treated with 5-ARIs for a minimum of 6 months and the other patients. Results: Patients treated with 5-ARIs were older (p &lt; 0.001) with higher rates of previous prostate biopsies (p = 0.004). PIRADS scores were 3, 4, and 5 in 15 (29%), 28 (54%), and 9 (17%) patients among the 5-ARI group and 130 (24%), 308 (56%), and 110 (20%) patients among the others, and the scores were not different between the groups (p = 0.69). The targeted CSPC identification rate among 5-ARI patients was 31%, not different compared to the non-5-ARI group (p = 1). Rates of targeted CSPC for each PIRADS score were not affected by 5-ARI treatment. The 5-ARI was not associated with neither PIRADS ≥ 4 score nor targeted CSPC on logistic regression analyses (OR = 0.76, 95% CI 0.4–1.4 and OR = 1.02, 95% CI 0.5–1.9, respectively). Conclusions: 5-ARI treatment is not associated with PIRADS score alterations or targeted biopsy results. Patients treated by 5-ARIs with suspicious lesions should not be addressed differently during the mpMRI-related diagnostic process.

Development and Evaluation of Automated Artificial Intelligence-Based Brain Tumor Response Assessment in Patients with Glioblastoma.

To develop and evaluate an automated, AI-based, volumetric brain tumor MRI response assessment algorithm on a large cohort of patients treated at a high-volume brain tumor center. We retrospectively analyzed data from 634 patients treated for glioblastoma at a single brain tumor center over a 5-year period (2017-2021). The mean age was 56 +/-13 years. 372/634 (59%) patients were male, and 262/634 (41%) patients were female. Study data consisted of 3,403 brain MRI exams and corresponding standardized, radiologist-based brain tumor response assessments (BT-RADS). An artificial intelligence (AI)-based brain tumor response assessment algorithm was developed using automated, volumetric tumor segmentation. AI-based response assessments were evaluated for agreement with radiologist-based response assessments and ability to stratify patients by overall survival. Metrics were computed to assess the agreement using BTRADS as the ground-truth, fixed-time point survival analysis was conducted to evaluate the survival stratification, and associated P-values were calculated. For all BT-RADS categories, AI-based response assessments showed moderate agreement with radiologists' response assessments (F1 = 0.587-0.755). Kaplan-Meier survival analysis revealed statistically worse overall fixed time point survival for patients assessed as image worsening equivalent to RANO progression by human alone compared to by AI alone (log-rank P=0.007). Cox proportional hazard model analysis showed a disadvantage to AI-based assessments for overall survival prediction (P=0.012). AI-based volumetric glioblastoma MRI response assessment following BT-RADS criteria yielded moderate agreement for replicating human response assessments and slightly worse stratification by overall survival. GBM＝ Glioblastoma; RANO＝ Response Assessment in Neuro-Oncology; BTRADS＝ Brain Tumor Reporting and Data System; NLP = Natural Language Processing.

Assessing the Performance of Artificial Intelligence Assistance for Prostate MRI: A Two-Center Study Involving Radiologists With Different Experience Levels.

Artificial intelligence (AI) assistance may enhance radiologists' performance in detecting clinically significant prostate cancer (csPCa) on MRI. Further validation is needed for radiologists with different experiences. To assess the performance of experienced and less-experienced radiologists in detecting csPCa, with and without AI assistance. Retrospective. Nine hundred patients who underwent prostate MRI and biopsy (median age 67 years; 356 with csPCa and 544 with non-csPCa). 3-T and 1.5-T, diffusion-weighted imaging using a single-shot gradient echo-planar sequence, turbo spin echo T2-weighted image. CsPCa regions based on biopsy results served as the reference standard. Ten less-experienced (<500 prostate MRIs) and six experienced (>1000 prostate MRIs) radiologists reviewed each case twice using Prostate Imaging Reporting and Data System v2.1, with and without AI, separated by 4-week intervals. Cases were equally distributed among less-experienced radiologists, and 90 cases were randomly assigned to each experienced radiologist. Reading time and diagnostic confidence were assessed. Area under the curve (AUC), sensitivity, specificity, reading time, and diagnostic confidence were compared using the DeLong test, Chi-squared test, Fisher exact test, or Wilcoxon rank-sum test between the two sessions. A P-value <0.05 was considered significant. Adjusting threshold using Bonferroni correction was performed for multiple comparisons. For less-experienced radiologists, AI assistance significantly improved lesion-level sensitivity (0.78 vs. 0.88), sextant-level AUC (0.84 vs. 0.93), and patient-level AUC (0.84 vs. 0.89). For experienced radiologists, AI assistance only improved sextant-level AUC (0.82 vs. 0.91). AI assistance significantly reduced median reading time (250 s [interquartile range, IQR: 157, 402] vs. 130 s [IQR: 88, 209]) and increased diagnostic confidence (5 [IQR: 4, 5] vs. 5 [IQR: 4, 5]) irrespective of experience and enhanced consistency among experienced radiologists (Fleiss κ: 0.53 vs. 0.61). AI-assisted reading improves the performance of detecting csPCa on MRI, particularly for less-experienced radiologists. 3 TECHNICAL EFFICACY: Stage 2.

Mapping global public perspectives on mRNA vaccines and therapeutics.

The development and rollout of mRNA vaccines during COVID-19 marked a significant advancement in vaccinology, yet public hesitation to vaccination was prevalent, indicating the potential risk that future mRNA-based medical innovations will fail to be adopted. Utilizing a combined approach of large language models with manual validation and unsupervised machine learning, we conducted a social listening analysis to assess attitudes towards mRNA vaccines and therapeutics on Twitter from June 2022 to May 2023, contrasting online perspectives with data from the Vaccine Adverse Event Reporting System. Our findings reveal widespread negative sentiment and a global lack of confidence in the safety, effectiveness, and trustworthiness of mRNA vaccines and therapeutics, with frequent discussions of severe vaccine side effects, rumors, and misinformation. This underscores the need for targeted communication strategies to foster acceptance of medical treatments and strengthen public trust in order to enhance societal resilience to future health challenges.

Comparative Safety of Ultrasound Enhancing Agents: A Systematic Review and Bayesian Network Meta-Analysis: Comparative Safety Evaluation of Optison.

Ultrasound enhancing agents (UEAs), including Optison, Definity, and Lumason, enhance the diagnostic performance of echocardiography, particularly in patients with suboptimal acoustic windows. However, there remains a paucity of comparative safety assessments among the Food and Drug Administration (FDA)-approved UEAs. A PRISMA-guided systematic literature review performed in August 2023 searched Medline, Embase, Cochrane Library, and grey literature. Randomized and non-randomized comparative evidence on safety of contrast enhanced procedures were included. A feasibility assessment ensured homogeneity across studies by comparing patient characteristics and outcomes. Bayesian hierarchical network meta-regression was employed to indirectly compare published safety outcomes across different UEAs. In addition, adverse events (AEs) between 2019-2023 for each UEA were retrieved from the FDA Adverse Events Reporting System (FAERS), and comparative safety outcomes were derived using annual UEA administration in the US. Screening of 4146 records rendered 19 studies for inclusion in the indirect comparison analysis after feasibility assessment. Optison demonstrated favorable safety in direct comparisons with Definity and Lumason across the majority of investigated AEs. Network meta-regression results on serious adverse events (SAEs) within 30 minutes revealed odds ratios (ORs) of 0.59 (95% confidence interval: 0.27-1.23) and 0.63 (0.29-1.33) for Optison vs. Lumason and Definity, respectively, indicating a decreased risk of SAEs for Optison vs. Lumason and Definity, further supported by statistically significant ORs within FAERS: 0.01 (0-0.02), P<0.001 and 0.15 (0.05-0.48), P=0.001, for Optison vs. Lumason and Definity, respectively. In conclusion, our results restate the favorable comparative safety profile of Optison, providing new evidence to inform clinical decision-making.

A Descriptive Analysis of Siblicide: Examining Ten Years of Incidents Reported in the National Incident-Based Reporting System (NIBRS), 2013–2022

ABSTRACT Siblicide, the killing of one sibling at the hands of another, is an extreme act along the arc of sibling violence, situated within the family violence paradigm. Purpose: Siblicide in the human population remains poorly understood and under-examined in need of contemporary baseline descriptive profiles examining victim, offender, and incident-level characteristics to develop a new base of knowledge, without age or sex limitations, to facilitate future research and practice opportunities including intervention, prevention, and policy. Methods: The study draws on 10 years of officially reported siblicide in National Incident-Based Reporting System (NIBRS) data, 2013–2022, (N = 862). Results: Analyses suggest siblicide is more frequent among adult siblings than youth siblings. Fratricides are more prevalent than sororicides and more likely to include a firearm and result from an argument. Sororicides are more likely to include multiple offenders and/or victims. Conclusion: Assessing large-scale data to better understand the scope and scale of the problem, including the nexus of victims, offenders, and incident criteria, is an important step toward a framework of knowledge to facilitate micro-level study within the family dynamic leading to early intervention and prevention of siblicide.

Real-world research on beta-blocker usage trends in China and safety exploration based on the FDA Adverse Event Reporting System (FAERS).

Beta-blockers are widely used, with continuously updated clinical recommendations. However, their application faces challenges in personalized treatment and safety. The study aimed to investigate the frequency and patterns of prescribing beta-blockers in China and to explore potential adverse event risk signals associated with beta-blockers, providing reference for rational medication use in clinical settings. Prescription data for beta-blockers from January 2018 to June 2023 were extracted through the Hospital Prescription Analysis Collaborative Project in China to analyze clinical usage trends. While adverse drug reaction reports for beta-blockers were obtained from the FDA Adverse Event Reporting System (FAERS) database. The classification and standardization of adverse drug event (ADE) reports were based on the preferred terms (PT) and corresponding system organ classes (SOC) from the Medical Dictionary for Regulatory Activities (MedDRA). Signal detection utilized a proportion imbalance method. In clinical practice, metoprolol dominated beta-blocker prescriptions in China, accounting for 62.2%. Beta-blockers were primarily prescribed to the elderly (65.7%) and male patients (57.0%). However, off-label use of beta-blockers was relatively widespread. For instance, sotalol was prescribed for hypertension at 18.25%, while esmolol was used for angina and heart failure at rates of 12.94% and 14.98%, respectively. In addition, we identified newly discovered adverse reactions associated with beta-blockers, such as BRASH syndrome (metoprolol: n = 186, ROR = 391.285; carvedilol: n = 72, ROR = 256.459), acute kidney injury (bisoprolol: n = 247, ROR = 5.641), premature baby (labetalol: n = 110, ROR = 91.385), and sleep disorder (propranolol: n = 254, ROR = 10.98). Metoprolol led the beta-blocker market in China. Attention was warranted regarding the newly discovered adverse reactions, such as the risk of acute kidney injury with bisoprolol and the potential for BRASH syndrome with metoprolol and carvedilol.

Comparison of AI software tools for automated detection, quantification and categorization of pulmonary nodules in the HANSE LCS trial.

Participant management in a lung cancer screening (LCS) depends on the assigned Lung Imaging Reporting and Data System (Lung-RADS) category, which is based on reliable detection and measurement of pulmonary nodules. The aim of this study was to compare the agreement of two AI-based software tools for detection, quantification and categorization of pulmonary nodules in an LCS program in Northern Germany (HANSE-trial). 946 low-dose baseline CT-examinations were analyzed by two AI software tools regarding lung nodule detection, quantification and categorization and compared to the final radiologist read. The relationship between detected nodule volumes by both software tools was assessed by Pearson correlation (r) and tested for significance using Wilcoxon signed-rank test. The consistency of Lung-RADS classifications between Software tool 1 (S1, Aview v2.5, Coreline Soft, Seoul, Korea) and Software tool 2 (S2, Prototype ''ChestCTExplore'', software version ToDo, Siemens Healthineers, Forchheim, Germany) was evaluated by Cohen's kappa (κ) and percentual agreement (PA).The derived volumes of true positive nodules were strongly correlated (r > 0.95), the volume derived by S2 was significantly higher than by S1 (P < 0.0001, mean difference: 6mm3). Moderate PA (62%) between S1 and S2 was found in the assignment of Lung-RADS classification (κ = 0.45). The PA of Lung-RADS classification to final read was 75% and 55% for S1 and S2, but the incorporation of S1 into the initial nodule detection and segmentation must be considered here. Significant nodule volume differences between AI software tools lead to different Lung-RADS scores in 38% of cases, which may result in altered participant management. Therefore, high performance and agreement of accredited AI software tools are necessary for a future national LCS program.

Effectiveness of ultrasound-guided vacuum-assisted excision for treating benign breast lesions.

Ultrasound‑guided vacuum-assisted excision (UGVAE) and breast biopsy are widely used for the diagnosis and treatment of both benign and suspicious breast lesions. In this retrospective study, we aimed to determine the safety of UGVAE for benign breast lesions and provide guidance for clinical practice. We analyzed clinical and pathological data of female patients who had undergone UGVAE between January 2015 and December 2017 at our institution. All breast lesions were categorized according to the Breast Imaging Reporting and Data System (BI-RADS) before performing UGVAE. In our study cohort, UGVAE was used to resect 10,378 breast lesions from 5789 patients, and selected clinical and histopathological data were analyzed. The most common adverse events were postoperative bleeding (0.24%) and skin hypersensitivity (0.67%). The residual lesion rate was 2.27%. Fibroadenomas accounted for most of the benign lesions (7932 of 10,193; 77.82%). Breast cancer was diagnosed in 150 lesions from 128 patients. Multivariable binary logistic regression analyses showed that older age (odds ratio [OR] = 2.034, 95% confidence interval [CI]: 1.668-2.480, p < 0.001), higher BI-RADS category (OR = 9.514, 95% CI: 6.790-13.332, p < 0.001), and larger legion size (OR = 1.048, 95% CI: 1.019-1.077, p = 0.001) were associated with an increased likelihood of breast cancer. Ninety-six patients with breast cancer had undergone follow-up treatment, achieving a 3-year disease-free survival rate of 97.2% and a 3-year overall survival rate of 100%. UGVAE is a safe and effective means of removing benign breast lesions, causing minimal postoperative trauma and fewer complications compared with open surgery. Moreover, UGVAE had little impact on the follow-up treatment and survival of patients diagnosed with breast cancer.

Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes.

Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ??0 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ?? prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Quantitative Structure-Activity Relationship Models to Predict Cardiac Adverse Effects.

Drug-induced cardiotoxicity represents one of the most common causes of attrition of drug candidates in preclinical and clinical development. For this reason, the evaluation of cardiac toxicity is essential during drug development and regulatory review. In the present study, drug-induced postmarket adverse event combinations from the FDA Adverse Event Reporting System were extracted for 2002 drugs using 243 cardiac toxicity-related preferred terms (PTs). These PTs were combined into 12 groups based on their clinical relevance to serve as training sets. The optimal classification scheme was determined using a combination of data sources that included drug labeling information, published literature, clinical study data, and postmarket surveillance data. Two commercial QSAR platforms were used to construct 12 models, including general cardiac toxicity, cardiac ischemia, heart failure, cardiac valve disease, myocardial disease, pericardial disease, structural heart disease, cardiac arrhythmia, Torsades de Pointes, long QT syndrome, atrial fibrillation and ventricular arrhythmia, and cardiac arrest. The cross-validated performance for the new models reached a sensitivity of up to 80% and negative predictivity of up to 80%. These new models covering a wide range of cardiac endpoints will provide fast, reliable, and comprehensive predictions of potential cardiotoxic compounds in drug discovery and regulatory safety assessment.

Abstract 4137177: A pharmacovigilance investigation from the FAERS database on patients using pembrolizumab and its association with cardiac arrhythmias

Background: Arrhythmia is always a concern in oncological treatments. The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, enhancing the immune system's ability to combat malignancies. They are being more frequently used, revealing a range of immune-related adverse events (irAEs). This study aims to investigate the incidence of cardiac arrhythmias in patients receiving Pembrolizumab. Methods: We conducted a retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database, focusing on reports submitted between 2006 to 2024. Cases involving patients treated with ICs were identified, and information related to cardiac arrhythmias was extracted using the Medical Dictionary for Regulatory Activities (MedDRA). Patients ≥ 18 years of age treated with ICIs were included in this study. A disproportionality analysis was conducted to identify arrhythmia events associated with pembrolizumab by comparing it with other immune checkpoint inhibitors (nivolumab, ipilimumab, and atezolizumab) and the entire FAERS database using the reporting odds ratio (ROR) and information component (IC). Results: A comprehensive analysis of 61,236 reported cases of pembrolizumab use revealed a total of 3,901 cases with cardiac complications. Among these, 672 cases (17.22 %) of arrhythmias were reported, with 452 individuals (67.26%) requiring hospitalization and 172 cases (25.59%) resulting in fatalities. Atrial fibrillation emerged as the most prevalent arrhythmia (49.7%). The occurrence of ventricular tachycardia with an ROR of 1.67 (1.18–2.35) and an IC of 0.44 (0.01–1.46) and complete atrio-ventricular block with an ROR of 1.57 (1.19–2.08) and an IC of 0.40 (0.04–1.24) were statistically significant. The reported arrhythmias associated with pembrolizumab are tabulated in Table 1 . The majority of events were reported in males, as shown in Figure 1 . Conclusion: This research offers significant insights into the connection between ICIs and cardiac arrhythmias, utilizing real-world data from the FAERS database. Healthcare providers should monitor cardiac events in patients receiving ICIs and aim to achieve a balance between anticancer effectiveness and cardiovascular safety. Further investigation is necessary to better understand the underlying mechanisms of arrhythmia and enhance risk stratification strategies for this specific patient group.

Abstract 4147627: A Pharmacovigilance Study of Bempedoic Acid: Balancing Risks and Benefits

Introduction: Bempedoic acid has been approved by FDA since Feb 2020 as an adjunct to maximally tolerated statin therapy for the reduction of LDL-C, specifically in individuals afflicted by atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH). Bempedoic acid is also a viable alternative for patients intolerant to statins. Most recently, it has been approved to use for primary prevention of hyperlipidemia, alone or in combination with a statin. It is important to study its side effect profile as it is anticipated to be used more frequentlynin the future. Methods: We explored reported adverse events (AEs) of bempedoic acid using FDA Adverse Event Reporting System (FAERS). A total of 1202 adverse effects were reported until March 31, 2024. 69.97% AEs were reported by healthcare professionals (HCPs), which were further analyzed. AEs were analyzed in men (32.53%) vs women (53.24%) and in three age groups of 18-64, 65-85, and &gt;85 years. Results: A total of 586 (48.7%) events were serious adverse effects. Most common side effects were myalgia which included muscle pain, extremity pain and muscle spasm (25.04%), arthralgia including back pain and bone pain (18.47%), nausea (6.6%), headache(5.5%), gout (4.4%). Among the patients with adverse effects, 4.75% had cardiac side effects which included atrial fibrillation (12%), palpitation (29%), angina pectoris (18%), Myocardial Infarction (5%). Discussion: A thorough understanding of bempedoic acid's complex pharmacology empowers healthcare professionals to tailor treatment plans based on individual patient requirements. This enables informed decision-making in prescribing, optimizing dosage regimens, and mitigating potential adverse reactions. Most studies have been relatively short term in order to confirm the long term side effect profile. It would be beneficial to be cautious in using this medication for patients with above mentioned clinical conditions like myalgia, arthralgia, gout, rhabdomyolysis, atrial fibrillation, angina pectoris. Conclusion: Long term pharmacovigilance is needed to assess the safety profile of bempedoic acid over extended use. With the current increasing use of bempedoic acid, there is a need for more data on safety profiles. In future, further randomized trials are required to better assess the safety profile.

A real−world pharmacovigilance study of FDA Adverse Event Reporting System events for pralsetinib

BackgroundPralsetinib, a selective oral inhibitor of rearranged during transfection (RET) fusion proteins and oncogenic RET mutants, has shown significant efficacy in treating RET fusion-positive non-small cell lung cancer and thyroid cancer. However, since pralsetinib was approved in the United States in September 2020, there have been limited reports of post-marketing adverse events (AEs). In this study, we aimed to analyze the AE signals with pralsetinib on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice.MethodsAll AE reports were obtained from the FAERS database from the first quarter (Q3) of 2020 to the second quarter (Q2) of 2024. Various signal quantification techniques were used for analysis, including reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker (MGPS)-based empirical Bayesian geometric mean.ResultsOut of 8,341,673 case reports in the FAERS database, 1,064 reports of pralsetinib as the “primary suspected (PS)” AEs were recorded, covering 26 system organ classes and 256 preferred terms. Of the reports, 62.5% were from consumers rather than healthcare professionals. The most common systems were general disorders and administration site conditions (n = 704), investigations (n = 516), and gastrointestinal disorders (n = 405). A total of 95 significant disproportionality preferred terms (PTs) conformed to the four algorithms simultaneously. AEs that ranked the top three at the PT level were hypertension (n = 80), asthenia (n = 79), and anemia (n = 65). Of the 95 PTs with significant disproportionation, unexpected significant AEs such as increased blood calcitonin, increased myocardial necrosis marker, and bacterial cystitis were observed, which were not mentioned in the drug’s instructions. The median onset time of pralsetinib-associated AEs was 41 days [interquartile range (IQR) 14–86 days]. The majority of the AEs occurred in 30 days (42.86%).ConclusionOur pharmacovigilance analysis of real-world data from the FEARS database revealed the safety signals and potential risks of pralsetinib usage. These results can provide valuable evidence for further clinical application of pralsetinib and are important in enhancing clinical medication safety.

Abstract 4135303: Acute Pericarditis Secondary to Secukinumab Therapy

Background: Pericarditis is the most common pericardial disease worldwide and has a high recurrence rate of 15-30%. It is primarily idiopathic but can arise from infectious and non-infectious causes; drug related cases are rare. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody used for treating psoriasis, has been identified through the FDA Adverse Event Reporting System as potentially inducing pericarditis, though literature is scant. We report a case of acute pericarditis related to secukinumab use. Case presentation: A 28-year-old male with history of psoriasis on secukinumab therapy presented with sharp, central chest pain, and progressive shortness of breath for 3 weeks. He was evaluated for similar chest pain 3 weeks prior; CT chest showed small pericardial effusion and he was managed with analgesics without improvement. This admission, he had tachycardia, and ECG showed sinus rhythm with diffuse ST elevation and PR depression (Figure 1A). Troponin I levels were normal and inflammatory markers were elevated. Transthoracic echocardiogram (TTE) revealed a large pericardial effusion without tamponade physiology (Figure 1B). CT chest confirmed large pericardial effusion, increased in size compared to CT done 3 weeks prior (Figure 2). He was diagnosed with pericarditis and started on ibuprofen and colchicine which improved his symptoms. Search for viral etiology including testing for COVID, influenza A and B, RSV, hepatitis and HIV were negative. Immunological workup for ANA and rheumatoid factor was negative. Thus, secukinumab was thought to be the likely culprit. Follow-up TTE in 3 months showed resolution of pericardial effusion. Conclusion: This case underscores the importance of considering medication-induced pericarditis in patients presenting with typical symptoms, especially when on treatment with drugs like secukinumab. Given the growing evidence from pharmacovigilance databases and the severe potential outcomes of untreated pericarditis, clinicians should maintain vigilance for such adverse effects. Further research is warranted to clarify the mechanisms by which secukinumab may contribute to pericardial inflammation in order to optimize management strategies in affected patients.

NIMG-17. PREDICTIVE VALUE OF THE BRAIN TUMOR REPORTING AND DATA SYSTEM SCORE (BT-RADS) ON FUNCTIONAL OUTCOMES AND PROGRESSION-FREE SURVIVAL IN GLIOBLASTOMA PATIENTS

Abstract The Brain Tumor Reporting and Data System Score (BT-RADS) is a novel eight-point classification system that standardizes magnetic resonance imaging (MRI) reporting in glioblastoma (GB) patients. While previous studies have demonstrated BT-RADS predictive value in the prognosis and overall survival of high-grade glioma patients, its association with functional outcomes and progression-free survival (PFS) in GB patients is unclear. We aim to evaluate the BT-RADS predictive value on functional outcomes assessed through the Karnofsky Performance Scale (KPS) at one year post-diagnosis and on PFS. BT-RADS from MRI ~3 months post-diagnosis after chemo-radiation therapy (BT-RADS_1), and ~6 months post-diagnosis after the 6-month maintenance temozolomide (TMZ) cycle (BT-RADS_2) were analyzed. BT-RADS was classified as low (BT-RADS score 0-3a) and high (BT-RADS score 3b-4). In a univariate logistic regression analysis, BT-RADS_1 was a significant predictor (p=0.04) in discriminating an unfavorable KPS from a favorable one. In a multivariate logistic regression, in which the best model fit was the model containing BT-RADS_1 and MGMT tumor status (model p value=0.03), the ROC analyses indicate that BT-RADS_1 is not better than chance in differentiating an unfavorable KPS from a favorable one (model AUC=0.65; 95% CI=0.55, 0.76). The discriminatory ability of BT-RADS scores alone in predicting KPS outcomes was modest, as indicated by the AUC. This underscores the need for larger sample sizes. In a final model of BTRADS_1 and BT-RADS_2, accounting for MGMT tumor status, the risk of tumor progression was 50% lower (p value=0.003) with a low BT-RADS (0-3a) in the BT-RADS _1 group and 38% lower (p value=0.03) with a low BT-RADS (0-3a) in the BT-RADS_2 group. Considering the above-discussed findings, BT-RADS may represent a new tool in the clinical management of glioblastoma patients by informing on disease progression, prognosis, and quality of life.

Patient centered HCC surveillance - complementary roles of ultrasound and CT/MRI.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is the fastest growing cause of cancer death in the United States (U.S.) In the U.S., current national clinical practice guidelines from the 2023 American Association for the Study of Liver Diseases (AASLD) Practice Guidance and the recently updated Liver Imaging Reporting & Data Systems (LI-RADS) Ultrasound (US) Surveillance v2024 core recommend semi-annual serum α-fetoprotein and US screening of patients deemed to be high risk for developing HCC. In this article, we will explore the transition to a patient-centered approach to HCC surveillance, including the role of the new LI-RADS US Surveillance v2024 core and the use of visualization score for determining ultrasound quality, the known risk factors for poor US image quality, and the potential options for alternative surveillance strategies when US may not be a viable option for certain patients, including multiphasic computed tomography (CT), magnetic resonance imaging (MRI), and several abbreviated MRI protocols.