Estrada-Mendizábal, Ricardo J.

BACKGROUND: Catheter ablation for atrial fibrillation is a widely used rhythm-control strategy, yet its role in reducing thromboembolic risk and enabling oral anticoagulation (OAC) discontinuation remains uncertain. This meta-analysis aims to comprehensively synthesize and evaluate randomized controlled trial evidence supporting long-term antithrombotic strategies in patients with atrial fibrillation undergoing catheter ablation. METHODS: A systematic literature search was performed in MEDLINE/PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials evaluating antithrombotic strategies after catheter ablation for atrial fibrillation. The primary outcome was ischemic stroke. A frequentist network meta-analysis comparing reported treatment arms, along with a pooled incidence meta-analysis for outcomes of interest, was conducted. RESULTS: Four randomized controlled trials, including 3924 patients, met the inclusion criteria. Three trials compared long-term OAC continuation versus OAC discontinuation, and 1 compared OAC continuation with left atrial appendage occlusion after catheter ablation. No significant differences in stroke incidence were observed when comparing OAC or left atrial appendage occlusion with no antithrombotic therapy (incidence rate ratio, 0.90 [95% CI, 0.02–33.85]; P =0.95; incidence rate ratio, 0.79 [95% CI, 0.00–241.01]; P =0.94, respectively). Among patients who discontinued antithrombotic therapy without undergoing left atrial appendage occlusion (n=1161), with 2864 cumulative person-years of follow-up, the pooled incidence of stroke was 0.23 events per 100 person-years (95% CI, 0.02–2.43; I 2 =0%). CONCLUSIONS: This analysis reinforces that, across randomized data, the incidence of thromboembolic events in patients who discontinued OAC after successful ablation remained low. However, the evaluation of net clinical benefit is limited by the low number of events across all treatment arms, underscoring the need for larger studies with prolonged follow-up to further validate the safety of this strategy, particularly in higher-risk populations.

Background: One in five Americans turn to TikTok before calling their own physician. Objective: With social media on the rise as a source of health-related information, we aimed to investigate and evaluate popular content about mast cell activation syndrome (MCAS) on TikTok. Methods: Between June 14 and 16, 2024, four different MCAS-relevant phrases were searched on TikTok, and the top 50 most watched videos were analyzed independently by three subinvestigators. The global quality score (GQS) (range from 1 to 5) was applied to assess the value of the educational videos. The profession of the content creator, use of MCAS Vienna diagnostic criteria, association with postural orthostatic syndrome (POTS)/Ehlers Danlos syndrome (EDS), and information trends were also analyzed. Results: The 50 most watched MCAS-related videos collectively had > 6.5 million views, and the average number of views per video was 131,500. Most videos were created by health-care professionals (58%), including physicians (26%) and other health-care professionals (32%), whereas the minority were created by non‐health-care professionals (42%). Only one video included the MCAS Vienna criteria (2%), and 12 videos associated MCAS with POTS and/or EDS (24%). The average GQS was 1.94 (SD 0.34). Common MCAS misinformation trends included the following: inaccuracy of symptoms, diagnostic criteria, triggers, and treatment options. Conclusion: Most MCAS videos on TikTok contained misinformation, did not include key diagnostic criteria, and had poor GQS. The most viewed videos were primarily created by health-care professionals. Patients and health-care providers need to be aware of the quality of health-care information on social media.

Abstract Background: Hispanic American (HA) men with prostate cancer (PC) are more likely to have more aggressive and advanced diseases and greater mortality rates compared to non-Hispanic white (NHW) men. Resistance to the current anticancer therapy is the major hurdle that leads to poor clinical outcomes. Hedgehog, Notch, and Wnt signaling pathways play a crucial role in development, progression, and resistance to the various anticancer therapies. Here, we characterized the enrichment of Hedgehog, Notch, and Wnt signaling pathways and molecular tumors differences between HA and NHW patients. Methods: Our data consist of 88 PC tumors samples (HA=34, NHW=54) obtained from treatment-naive metastatic hormone-sensitive prostate cancer (mHSPC) that were analyzed by next-generation sequencing (592, NextSeq; Whole Exome Sequencing, NovaSeq) and Whole Transcriptome Sequencing (WTS; NovaSeq) (Caris Life Sciences, Phoenix, AZ). Pathway enrichment was determined by Gene Set Enrichment Analysis (GSEA, Broad Institute) by measurable TPM (transcripts per kilobase million). The medical records were reviewed in a deidentified fashion for clinical features. Statistical significance was determined using chi-square and Mann-Whitney U (p<0.05). Results: HA PC had enrichment of Hedgehog signaling (NES: 1.45, FDR=0.04), Notch signaling (NES: 1.41, FDR=0.07), and Wnt/β-catenin signaling (NES: 1.38, FDR=0.11) pathways compared to NHW tumors. HA tumors had higher expression of genes (HES1, Notch1, WNT1, WNT2; FC:1.1-2.5) associated with crosstalk between Hedgehog, Notch, and Wnt/β- catenin signaling pathways (all p<0.05). Moreover, HA tumors had higher expression of stemness (ALDH1A2, ALDH1A1, PROM1; FC: 1.7-3.0), drug efflux (ABCC1, ABCB1; FC: 1.1- 1.5), epithelial to mesenchymal transition (EMT) (TWIST1, MMP2; FC: 1.1-1.5), cell cycle (CCND2; FC: 1.2), inhibition of apoptosis (BIRC2, XIAP; FC: 1.1) and epigenetic (EP300, TET1, TET2; FC: 1.3-1.4) related genes compared to NHW tumors (all p<0.05). HA PC had higher frequency of Hedgehog and Wnt/β-catenin associated SPOP (16% vs 6.6%, p=0.2) and CTNNB1 (12% vs 2.2%, p=0.1) mutation compared to NHW PC. Conclusion: These results demonstrate that tumors from HA patients had enrichment of oncogenic Hedgehog, Notch, and Wnt/β-catenin signaling pathways, higher expression of stemness, drug efflux, EMT, cell cycle, inhibition of apoptosis and epigenetic-related genes, and mutations directly involved in activating the Hedgehog and Wnt/β-catenin signaling pathways. Together, these findings suggest that tumors from HA patients are enriched for gene signatures that promote cancer progression and therapy resistance. Additional research on collaboration and crosstalk between Hedgehog, Notch, and Wnt/β-catenin signaling pathways may help in designing better therapeutic strategies for HA men with mHSPC. Citation Format: Alejandro Recio-Boiles, Sachin Kumar Deshmukh, Ricardo J. Estrada-Mendizabal, Kenneth Barker, Sharon Wu, Joanne Xiu, Milan Radovich, Elisabeth I. Heath, Rana McKay, Juan Chipollini, Cynthia K. Miranti. Defining the role of Hedgehog, Notch, and Wnt signaling pathways in aggressive lethal prostate cancer of Hispanic men [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C100.

Abstract Pegfilgrastim is a sustained-duration form of the granulocyte colony-stimulating factor filgrastim to which a polyethylene glycol molecule is covalently bound to the N-terminal methionine residue. Although rare, anaphylaxis to pegfilgrastim has been reported. Desensitization is a safe management option for drug hypersensitivity. To date, no desensitization protocols to pegfilgrastim have been reported. We present the case of a 36-year-old female diagnosed with breast cancer who was treated with paclitaxel and carboplatin every two weeks plus pegfilgrastim, to which she developed anaphylaxis. The lack of alternative treatment options led to the decision to proceed with desensitization, which was carried out successfully with a novel 12-step, 1-bag protocol, allowing the safe resumption of the medication. Although the mechanisms underlying hypersensitivity to pegfilgrastim remain unknown, clinicians must be aware of the possibility of anaphylaxis to this medication and of the available treatment options, such as desensitization. To our knowledge, this is the first report of a desensitization protocol to pegfilgrastim.