Vegivinti, Charan Thej Reddy

Abstract Background: Luspatercept, an erythroid maturation agent, has shown efficacy in improving anemia in both β-thalassemia and lower-risk myelodysplastic syndromes (MDS). In the BELIEVE trial, which led to its approval in transfusion-dependent β-thalassemia, thromboembolic events were notably higher in patients with risk factors such as splenectomy. More recently, the COMMANDS trial demonstrated superior transfusion independence with luspatercept over erythropoiesis-stimulating agents (ESAs) in ESA-naive, lower-risk MDS patients. However, limited data exist regarding comparative thrombotic risk in real-world MDS populations. We conducted a multicenter, real-world study to evaluate thrombotic event rates associated with luspatercept versus ESAs in MDS patients without prior venous thromboembolism (VTE). Methods: We queried the TriNetX Research Network, a federated real-time electronic health record (EHR) database covering over 100 million patients across major healthcare organizations. Adults (≥18 years) with a diagnosis of MDS (ICD-10-CM code D46) and no prior history of deep vein thrombosis (DVT) or pulmonary embolism (PE) were included. Patients were stratified based on treatment with luspatercept or ESAs (epoetin alfa or darbepoetin alfa). Propensity score matching (PSM) using a 1:1 nearest-neighbor algorithm without replacement was performed to balance demographics and clinical covariates. Primary outcomes included the incidence of DVT, PE, and composite VTE events within 12 months of therapy initiation. Results: A total of 6,448 patients with MDS and no prior VTE were identified: 5,698 received ESAs and 750 received luspatercept. The overall mean age was 72.5 ± 13.5 years, with 48.1% male. After PSM, 741 patients were included in each treatment arm. The matched cohort had a mean age of 76.7 ± 10.7 years, and 41.3% were female. In the ESA group, 58/741 (7.8%) developed DVT compared to 27/741 (3.6%) in the luspatercept group (Hazard Ratio [HR] 1.4; 95% CI, 0.9–2.3). PE occurred in 27 ESA-treated patients (3.6%) versus 13 luspatercept-treated patients (1.8%) (HR 1.3; 95% CI, 0.6–2.7; p=0.941). The overall composite VTE rate was 10.0% (74/741) in the ESA group and 4.9% (36/741) in the luspatercept group (HR 1.3; 95% CI, 0.9–2.0; p=0.732). Conclusion: In this large, multicenter real-world analysis, we observed a numerically lower incidence of thrombotic events with luspatercept compared to erythropoietin-based agents in patients with MDS, though differences did not reach statistical significance. These findings support the thrombotic safety profile of luspatercept observed in clinical trials and warrant further prospective validation.

Background: The use of cannabis in cancer patients has gained significant attention due to its analgesic properties, which help alleviate cancer-related pain. Studies have also shown the interference of cannabis with the coagulation system. We aimed to study the impact of cannabis use disorder (CUD) and Pulmonary embolism (PE) on outcomes in female breast cancer survivors, considering reports suggesting significant overlap between recreational and medicinal use. Our objective was to compare outcomes in CUD+ (with cannabis use disorder) and CUD- (without cannabis use disorder) cohorts to gain critical insights into this group and understand the impact of CUD on PE-related hospitalization and outcomes. Methods: National Inpatient Sample (NIS) data from 2020 was utilized in order to analyze inpatient cohorts of PE hospitalizations. The International Classification of Diseases 10 (ICD 10) codes for pulmonary embolism, cannabis use disorder, and female breast cancer were utilized to classify cohorts. All cases of female breast cancer and pulmonary embolism with an age >18 years were included in the final analysis. The primary outcome was the impact of CUD on PE-related hospitalizations in female breast cancer survivors. We also compared demographic correlations and comorbidities affecting outcomes between cohorts. Results: This study included a total of 508065 admissions among breast cancer survivors, with a median age of 74 years for the entire cohort. The prevalence of PE admissions was lower in CUD+ cohort compared to CUD- cohort (1.3% vs. 2.1%). The CUD+ cohort was relatively younger (median 66 vs 74 years, p<0.001). Overall, admission rates were higher among white patients (77%) and this trend was statistically significantly higher in the 76-100 th percentile household income group (p<0.002) compared to CUD+(50%) and CUD-(26.5%). Most admissions were non-elective (95.4%), with no statistical significance between CUD- and CUD+ patients (p=0.16). The majority of readmissions occurred in urban teaching hospitals (75.5%), with no significant difference observed between CUD- and CUD+ patients (p=0.111). Regionally, the South had a higher admission rate (37.2%) compared to other regions and this difference was statistically significant (p<0.001) between CUD- and CUD+ patients. Among the coexisting comorbidities, hypertension showed a significant difference between CUD- (70%) and CUD+(37.5%) patients (p<0.001). Alcohol use disorder (p<0.001) and cancer (p<0.001) had significant associations with CUD+, along with prior myocardial infarction (p=0.005) and drug use (p<0.001) were significantly associated with CUD+.Furthermore, there was difference in routine patient disposition between between CUD-(45.3%) and CUD+(37.5%),(p=0.033) and length of stay (4 VS 2 days), (p=0.033) and cost of stay (47033 vs 27668 $), (p=0.017). The multivariable logistic regression analysis showed that the odds of PE-related hospitalization in CUD+ vs CUD- cohorts among female breast cancer survivors were not statistically significant, with an OR of 0.79 (CI: 0.38-1.62, p=0.512). Subgroup analysis by age demonstrated no statistically significant differences in odds for PE-related hospitalization between CUD+ and CUD- cohorts. For the age group of 18-44 years, the OR was 1.37 (CI: 0.18-10.60, p=0.762). In the 45-64 years age group, the OR was 0.48 (CI: 0.15-1.53, p=0.215), and for those aged ≥65 years, the OR was 1.32 (CI: 0.48-3.67, p=0.590). Furthermore, the analysis by race indicated that the odds of PE-related hospitalization did not reach statistical significance in both white and black female breast cancer survivors with CUD. For white patients, the OR was 0.64 (CI: 0.23-1.73, p=0.375), while for black patients, the OR was 1.15 (CI: 0.38-3.46, p=0.804). Conclusion: Among female breast cancer survivors, the presence of CUD did not show a statistically significant impact on the odds of PE-related hospitalization. Subgroup analysis by age and race also revealed no significant differences in the odds of PE-related hospitalization between CUD+ and CUD- cohorts. These findings underscore the importance of considering CUD when managing pulmonary embolism in breast cancer survivor females and emphasize the need for further research to understand the complex interplay between these factors.

Abstract Background: Corticosteroid treatment is an effective and common therapeutic strategy for various inflammatory lung pathologies and may be an effective treatment for coronavirus disease 2019 (COVID-19). The purpose of this systematic review and meta-analysis of current literature was to investigate the clinical outcomes associated with corticosteroid treatment of COVID-19. Methods: We systematically searched PubMed, medRxiv, Web of Science, and Scopus databases through March 10, 2021 to identify randomized controlled trials (RCTs) that evaluated the effects of corticosteroid therapies for COVID-19 treatment. Outcomes of interest were mortality, need for mechanical ventilation, serious adverse events (SAEs), and superinfection. Results: A total of 7737 patients from 8 RCTs were included in the quantitative meta-analysis, of which 2795 (36.1%) patients received corticosteroids plus standard of care (SOC) while 4942 (63.9%) patients received placebo and/or SOC alone. The odds of mortality were significantly lower in patients that received corticosteroids as compared to SOC (odds ratio [OR] = 0.85 [95% CI: 0.76; 0.95], P = .003). Corticosteroid treatment reduced the odds of a need for mechanical ventilation as compared to SOC (OR = 0.76 [95% CI: 0.59; 0.97], P = .030). There was no significant difference between the corticosteroid and SOC groups with regards to SAEs and superinfections. Conclusion: Corticosteroid treatment can reduce the odds for mortality and the need for mechanical ventilation in severe COVID-19 patients.

AbstractThe purpose of this systematic review and meta‐analysis was to examine clinical outcomes associated with convalescent plasma therapy in COVID‐19 patients. We performed a literature search on PubMed, medRxiv, Web of Science, and Scopus to identify studies published up to December 10th, 2020 that examined the efficacy of convalescent plasma treatment for COVID‐19. The primary endpoints were mortality, clinical improvement, and hospital length of stay. We screened 859 studies that met the search criteria, performed full‐text reviews of 56 articles, and identified 15 articles that fulfilled inclusion criteria for meta‐analysis. The odds of mortality were significantly lower in the convalescent plasma group compared to the control group (OR = 0.59 [95% CI = 0.44; 0.78], P < .001), although results from two key randomized controlled trials did not support the mortality benefit. The odds of clinical improvement were significantly higher in the convalescent plasma group compared to the control group (OR = 2.02 [95% CI = 1.54; 2.65], P < .001). There was no difference in hospital length of stay between the convalescent plasma group and the control group (MD = −0.49 days [95% CI = −3.11; 2.12], P = .713). In all, these data indicate that a mortality benefit with convalescent plasma is unclear, although there remain benefits with convalescent plasma therapy for COVID‐19.