Thirumalareddy, Joseph

Introduction and importance: While vaping has increased significantly among young individuals, the effects of vape aerosol constituents on cardiac electrophysiological dynamics remain unknown. Case presentation: A 22-year-old female with a history of energy vaping presented with cardiac arrest. Found to have no pulse, CPR was started and an initial rhythm of ventricular tachycardia was obtained. Shock was administered with a follow-up rhythm of ventricular fibrillation. She was emergently defibrillated and entered atrial fibrillation with rapid ventricular response. Toxicology and troponins were all negative. Left heart catheterization and cardiac MRI were unremarkable. She was discharged with an external defibrillation vest and a tentative plan for outpatient electrophysiology study in the setting of negative work-up for cardiopulmonary arrest. Clinical discussion: Vaping-induced sudden cardiac arrest may be attributed to a reduction in cardiac repolarization reserve. Exposure to vegetable glycerin and propylene glycol, substances present in nearly all vape products, have been found to incite arrhythmias and disrupt cardiac conduction in animals. Acrolein, an aldehyde byproduct of glycerin, has also been found to induce arrhythmias due to autonomic dysfunction. Increased intracellular calcium concentration and free radical damage, which occur as a result of inhaling particulate matter generated from e-cigarettes, further propagates the risk of arrhythmia. Conclusion: The effects of inhaling vape aerosols remain not fully understood. While there is a perceived notion that nicotine-free aerosols may be harmless, that remains unclear. Further studies are needed to evaluate proarrhythmogenic effects and autonomic dysfunction from the various chemical substances present in vape aerosols.

Introduction and Importance: While the use of vaping has increased significantly among young individuals, the effects of the various vape aerosol chemical contents on cardiac electrophysiological dynamics remain unknown. Case Presentation: A 22-year-old female with a history of energy vaping but no significant past medical history presented with cardiac arrest. Found to have no pulse, CPR was started and initial rhythm of ventricular tachycardia was obtained. Shock was administered with follow-up rhythm of ventricular fibrillation. Patient was shocked again and entered atrial fibrillation with rapid ventricular response. She later cardioverted into sinus tachycardia and was intubated. Transthoracic echocardiogram showed normal ejection fraction but was otherwise unremarkable. Patient was extubated on day four of hospitalization. Left heart catheterization and cardiac MRI were completely unremarkable. Toxicology, urine analysis, and troponins were all negative. Patient was discharged with metoprolol tartrate, and a life-vest with outpatient follow-ups for possible implantable cardioverter-defibrillator placement in the setting of negative work up for sudden cardiac arrest. Clinical Discussion: Vaping-induced sudden cardiac arrest may be attributed to a reduction in cardiac repolarization reserve. Exposure to vegetable glycerin and propylene glycol, substances present in nearly all vape products, have been found to incite arrhythmias and disrupt cardiac conduction in animals. Acrolein,a byproduct of glycerin, has also been found to induce arrhythmias due to autonomic dysfunction. Increased prevalence of ventricular arrhythmias have also been noted with exposure to aerosols containing nicotine-free propylene glycol (PG).This likely stems from the impact of PG aerosols on the transient outward potassium current, which plays a significant role in early cardiac repolarization. Conclusion: The effects of inhaling vape aerosols remain not fully understood. While there is a perceived notion that nicotine-free aerosols may not be harmful, that remains unclear.Further studies should be conducted to evaluate for pro-arrhythmogenic effects and autonomic dysfunction from the various chemical substances present in vape aerosols.

Introduction The optimal maintenance regimen by prognostic categories remains unclear in newly diagnosed multiple myeloma (NDMM) patients undergoing autologous stem cell transplant (ASCT). Therefore, we conducted a systematic review and network meta-analysis (NMA) to assess the comparative effectiveness of novel agents by different prognostic groups. Methods A comprehensive systematically structured literature search was conducted to identify phase II/III randomized controlled trials (RCTs) evaluating maintenance therapies in post-transplant NDMM patients and reporting data by subgroups including but not limited to international staging system (ISS), and cytogenetic risk. High cytogenetic risk (HCR) and standard cytogenetic risk (SCR) were defined in accordance with the eligible trials. Main outcomes of interest were overall survival (OS) and progression-free survival (PFS). Precomputed hazard ratios (HR) with 95% CI were pooled using an inverse variance approach. A frequentist network meta-analysis was conducted. P-score (PS) were used to assess relative rankings of the treatments and were interpreted in congruency with pairwise estimates. Higher ranks indicated better efficacy. Results This NMA included six RCTs with 4119 participants and six unique treatment arms. In patients with SCR, the combination of carfilzomib, lenalidomide, and dexamethasone (KRd) improved PFS when compared to lenalidomide (Len; HR: 0.44; 95% CI: 0.24-0.81), daratumumab (Dara; 0.27; 0.13-0.55), ixazomib (Ixa; 0.26; 0.13-0.53), and no maintenance therapy (0.17; 0.09-0.32). Similarly, KR improved PFS compared to lenalidomide (Len; 0.56; 0.33-0.96), daratumumab (Dara; 0.34; 0.18-0.65), ixazomib (Ixa; 0.33; 0.17-0.63), and no maintenance therapy (0.21; 0.12-0.38). There was no statistically significant difference between KRd and KR. KRd was ranked as potentially the most efficacious treatment (rank 1) followed by KR (rank 2), Len (rank 3), Dara (rank 4), and Ixa (rank 5) for improving PFS in SCR. In patients with HCR, KRd (0.35; 0.14-0.92), KR (0.32; 0.15-0.67), Dara (0.43; 0.25-0.73), and Len (0.48; 0.35-0.64) improved PFS when compared to no maintenance therapy. No other significant differences were observed in HCR patients. KR was ranked as potentially the most efficacious treatment followed by KRd (rank 2), Dara (rank 3), Len (rank 5), and Ixa (rank 5) for PFS in HCR patients. In patients with ISS-I/II, KRd and KR improved PFS when compared to Dara (KRd vs. Dara - 0.32; 0.16-0.65, KR vs Dara - 0.50; 0.26-0.94), and Ixa (KRd vs. Ixa - 0.22; 0.11-0.45, KR vs Ixa - 0.35; 0.18-0.65). KRd, not KR, improved PFS when compared to Len (0.41; 0.22-0.76). Rankings were consistent with those observed in SCR patients. No significant differences were observed among mixed treatment comparisons for ISS-III patients. Limited number of trials reporting OS precluded formal assessment. Conclusions The current data suggest that KRd and KR may delay disease progression regardless of risk category. Overall survival data is still emerging and, if consistent, may influence clinical practice. We maintain a living meta-analysis to incorporate new evidence constantly.

6636 Background: Equitable regional enrollment in clinical trials is critical to addressing global inequities in health care outcomes. Therefore, we quantified disparities in regional recruitment in global cancer trials. Methods: Phase II/III clinical trials in prostate (PC), breast (BC), colorectal (CRC) and lung cancer (LC), and reporting regional recruitment were identified from Medline. Global regions were defined as North-(NA) and South- America (SA), Europe (EU), Africa (AF), Asia (AS), and Australia (AU). For multi-regional trials, enrollment incidence ratios (EIR) which compare region-wise trial enrollment against global estimates of region-wise specific cancer incidence obtained from Global Burden of Disease 2019 database. Trial-level EIRs were pooled using random-effects meta-analysis. A pooled EIR of < 1.0 indicates underrepresentation of a particular region in clinical trial enrollment compared to the actual burden of the specific cancer in that region. Statistical analyses were conducted in R v4.1.2. Results: Of the total 2125 trials identified, 1681 (79.1%) trials with 691,800 participants reported information regarding regional recruitment. Among those, only 1400 (65.9%) trials reported proportions of patients from pre-defined regions. A total of 1231 (57.9%) trials were single-regional recruiting patients from EU (589; 47.8%), NA (329; 26.7%), AS (295; 23.9%), AU (10; 0.8%), AF (4; 0.3%), and SA (4; 0.3%). There was significant underrepresentation of patients from AS (EIR: 0.47; 95% CI: 0.41-0.54) in cancer clinical trials. This was consistent across different cancers: PC (0.49; 0.35-0.71), BC (0.63; 0.43-0.94), CRC (0.63; 0.43-0.94), LC (0.39; 0.30-0.50). Similarly, there is a trend of under-representation of patients from AF (0.67; 0.43-1.04). Consistently, patients from were under-represented in PC (0.43; 0.24-0.77) and LC (0.26; 0.09-0.79) trials. Patients from NA (1.27; 1.08-1.51), EU (1.64; 1.57-1.72), and AU (5.41; 3.90-7.51) were significantly over-represented in multi-regional cancer clinical trials. The results are provided in table. Conclusions: There is suboptimal reporting of region-wise enrollment in cancer clinical trials. Representation of Africa and Asia in cancer clinical trials appears to be less than their expected share based on their burden of cancer incidence. [Table: see text]