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Effectiveness and safety of direct oral anticoagulation vs. warfarin for primary prevention of stroke and bleeding risk among patients with atrial fibrillation.
No full textBackground: Atrial fibrillation (AF) patients carry a high risk of stroke, and treatment related bleeding complications. Evidence for the safety and efficacy of anticoagulation remains sparse with conflicting results. Objective: We sought to investigate the effectiveness and safety of direct oral anticoagulant (DOAC) versus warfarin in atrial fibrillation patients. Methods: We performed a systematic literature search on PubMed, EMBASE, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) from inspection until July 30th, 2024, without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model, and a p-value of \u3c0.05 was considered statistically significant. Results: A total of 7 RCTs with 79,001 patients were included (46069 in DOAC and 32932 in the warfarin group) in the analysis. The mean age of the patients in DOAC and the warfarin groups was 72.8 and 72.9 years, respectively. Pooled analysis of primary and secondary endpoints showed that DOAC significantly reduced the risk of stroke or systemic embolism by 18% (OR, 0.82(95%CI: 0.75-0.91), P\u3c0.01), stroke by 19% (OR, 0.81(95%CI: 0.68-0.97), P=0.02), and hemorrhagic stroke by 57% (OR, 0.43(95%CI: 0.33-0.56), P\u3c0.01) when compared with warfarin. However, the risk of ischemic stroke (OR, 0.96(95%CI: 0.78-1.18), P=0.69), major bleeding (OR, 0.84(95%CI: 0.67-1.06), P=0.14) and myocardial infarction (OR, 1.07(95%CI: 0.89-1.28), P=0.45) was comparable between DOAC and the warfarin group of patients. The use of DOACs was associated with lower odds of all-cause mortality (OR, 0.91(95%CI: 0.85-0.97), P\u3c0.01) when compared with the warfarin group of patients. Conclusion: In this comprehensive analysis of randomized controlled trials data, the use of DOACs was associated with reduction in stroke or systemic embolism, hemorrhagic stroke, and all cause mortality, compared with warfarin therapy. Major bleeding risk was comparable between both groups of patients
Comparative effectiveness of CAR-T cell therapy and BiTE therapy in relapsed/refractory diffuse large B-cell lymphoma: A propensity score matching analysis using real-world data from the US collaborative network database
No full textBackground: Diffuse Large B-cell lymphoma is the most common form of non-Hodgkin lymphoma. Relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) presents significant treatment challenges. CAR-T cell therapy and BiTE therapies have emerged as promising options. This study aims to compare their effectiveness using propensity score matching, leveraging real-world data from the TriNetX network to assess clinical outcomes and guide treatment decisions for DLBCL. Methods: This retrospective cohort study utilized the TriNetX database, a global health research network, to identify adult patients with relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) who received CAR-T cell therapy or BiTE therapy. The CAR-T cell therapy included axicabtagene, lisocabtagene, tisagenlecleucel) or BiTE therapy included Epcoritamab and Glofitamab. A propensity score matching (PSM) approach was used to balance baseline characteristics between the two treatment groups, minimizing confounding biases. Key covariates such as age, sex, comorbidities, model. 1:1 matching was performed using nearest-neighbour matching without replacement, ensuring comparability between the CAR-T and BiTE groups. Results: Before PSM, there were 1,533 patients in the CAR-T cohort and 142 patients in the BITE therapy cohort; however, after PSM, there were 133 patients in both cohorts. Mean age (59.4 vs 57.9 years), male (60.53% vs 57.04%), white (76.69% vs 72.18%). Compared to BITE therapy, CAR-T therapy demonstrated improved overall survival (OS) (hazard ratio [HR] 0.45 (95% CI 0.32-0.61, p , 0.95). BITE therapy also had a higher risk for pancytopenia (odds ratio [OR] 4.663 [2.35-9.26], p , 0.01). The risk of diarrhoea and fatigue was, however, not statistically significant. Conclusions: This study provides valuable realworld insights into the comparative effectiveness of CAR-T cell therapy and BiTE therapy for relapsed/refractory DLBCL. The results, derived from propensity score-matched cohorts, offer far-reaching help to guide the holistic management of this patient population
AML-617: Longitudinal Trends (1999–2023) and Forecasted Mortality (2024–2050) in AML-Associated Sepsis Among US Older Adults
No full textSepsis remains a major complication in acute myeloid leukemia (AML), conferring a 4-fold increased risk in adult patients with AML compared with adult patients without AML. Objective: This study analyzes sepsis-related mortality trends in US adults aged ≥65 years with AML (1999–2023), highlights socioeconomic disparities, and projects mean age-adjusted mortality rates (AAMR) through 2050 to guide targeted public health efforts. Methods: We conducted a retrospective analysis of CDC WONDER mortality data (1999–2023) using ICD-10 codes A41 (sepsis) and C92.0 (AML) from the Multiple Cause of Mortality dataset. We standardized AAMR to the 2000 U.S. population and calculated per million. We assessed trends using Joinpoint regression to estimate annual percentage change (APC) with a 95% confidence interval (CI). Future AAMR projections through 2050 were estimated using Holt\u27s linear exponential smoothing model in R. Results: From 1999 to 2023, AML-associated sepsis resulted in 16,060 deaths in the US. The AAMR increased from 11.8 per million (95% CI, 10.7–12.9) in 1999 to 17.1 per million (95% CI, 16.0–18.2) in 2019, with an APC of 1.19% (P \u3c 0.000001). Men exhibited higher mortality rates than did women, with AAMR of 20.52 per million (95% CI, 19.9–20.5) compared with 10.06 per million (95% CI, 9.7–10.1). Non-Hispanic White patients exhibited the highest change in APC of 1.2778% (95% CI, 0.9302–1.6778; P \u3c 0.00001) from 1999 to 2023. The Northeast region had the highest AAMR at 20.3 per million (95% CI, 17.4–23.2) in 2018. Moreover, rural areas showed a rise in mortality rates, from 6.5 per million (95% CI, 4–10) to 16.1 per million (95% CI, 12.8–19). Arkansas had the highest AAMR among all states. Forecasting data indicate AAMR will increase to 20.53 per million (95% CI, 18.84–22.22) by 2050. Conclusion: This study highlights the growing burden of AML-associated sepsis mortality among older adults in the US. The disproportionate effect on men, non-Hispanic White patients, and residents of the Northeast and Arkansas—along with projections of continued overall increases in mortality—underscores the need for prevention strategies, improved access to care, and tailored public health interventions. Grant/Funding Acknowledgements: None
Sex-stratified mortality and disability-adjusted life years (DALYs) due to gastric cancer among older adults (70+) from 1990 to 2021: A global burden of disease study
No full textBackground: Gastric cancer is a malignant disease characterized by the uncontrolled growth of cells in the stomach lining and is a global health concern. It is a significant health burden in older adults, with long-term complications affecting quality of life and survival. We aim to explore sex-stratified trends in mortality and disability-adjusted life years (DALYs) due to Gastric Cancer from 1990 to 2021. Methods: We obtained sex-stratified data for older adults aged 70 years and above with Gastric Cancer from the Global Burden of Disease (GBD) from 1990 to 2021. The mortality rates were age-standardized and expressed per 100,000 deaths. Trends were analyzed as annual percentage change (APC) and average APC (AAPC) using Joinpoint Regression. Results: From 1990 to 2021, deaths due to Gastric Cancer in older adult males increased globally from 187,690 to 305,807 per annum, with age-standardized mortality rates (ASMRs) decreasing from 227 to 140 and standardized DALYs decreasing from 3734 to 2189. In females, deaths rose from 147,867 to 188,861, with ASMRs declining from 124 to 68 and DALYs declining from 1908 to 979. Despite the apparent rise in deaths, ASMRs exhibited a significant decline in both sexes, with an AAPC of -1.53% (95% CI: -1.56 to -1.49) in males and -1.91% (-1.94 to -1.88) in females. The DALYs showed a significant decline in females with an AAPC of -2.13% (-2.16 to -2.1) but a significant increase in males with an AAPC of -1.72% (-1.75 to -1.69). Males experienced the greatest APC decline in deaths of -3.33% from 2004 to 2007, while females showed their steepest decline of -3.50% during the same period. Prior to this, males exhibited a decline of -1.59% from 1990 to 1998, followed by a non-significant increase of 0.06% from 1998 to 2004. For females, the decline was more pronounced from 1990 to 1998 at -2.13%. After 2007, males experienced declines of -1.24% from 2007 to 2010 and -1.24% from 2018 to 2021. In contrast, females saw declines of -2.29% from 2007 to 2014, followed by a smaller decline of -1.36% till 2021. DALYs in females showed the greatest decline of -4.01% from 2004 to 2007, after decreases of -2.19% (1990-1998) and -1.21% (1998-2004). This was followed by declines of -2.73% till 2015 and -1.22% till 2021. Males saw the steepest decline of -3.74% from 2004 to 2007, with earlier reductions of -1.56% (1990-1998) and -0.07% (1998-2004), followed by -2.85% till 2015 and -1.68% till 2021. Conclusions: Although ASMRs declined, the recent decline in ASMRs in females is becoming less pronounced highlighting the importance of ongoing monitoring and improvement strategies. The disparity in DALYs between males and females also demands the need for targeted interventions addressing malespecific challenges to reduce the burden of Gastric Cancer
Efficacy of subsequent treatment after combination therapy in non-clear cell renal cell carcinoma (nccRCC)
No full textBackground: The treatment landscape of front-line nccRCC has evolved with recent trials demonstrating the efficacy of combination systemic therapy. However, the efficacy of treatment after combination therapy is unknown. This study evaluates the efficacy of VEGF-based regimens in nccRCC patients (pts) previously treated with combination regimens. Methods: ORACLE is a real-world, multi-center, retrospective database that includes nccRCC patients that received combination systemic therapies (IO+IO, IO+VEGF and VEGF+ mTOR) in any line. Subsequent treatments were categorized as VEGF only regimens (cabozantinib vs other VEGF), IO+ VEGF and VEGF+ mTOR. The primary endpoint was objective response rate (ORR) assessed by investigator review using RECIST 1.1. Secondary endpoints included disease control rate (DCR), defined as the proportion of patients achieving complete or partial responses or stable disease, time to treatment progression (TTP), calculated from the date of VEGF-based initiation to progression or last follow-up using the Kaplan-Meier method. Differences between groups were estimated with the log-rank test, and categorical outcomes were compared with the chi-square test. Results: 105 pts who received VEGF – based regimens after combination therapy were included in the analysis. Baseline characteristics: median age: 59 years, 71 % male, 58% white, 25% black, 87% ECOG 0-2. IMDC-risk categories included:21% favorable, 59% intermediate and 20% poor risk. Histology included papillary (40%), unclassified (32%), chromophobe (16%) and other rare subtypes (12%). Prior combination therapies included IO+IO: 62%, IO+ VEGF: 34% and VEGF+ mTORi:4%. 70% pts received combination therapy in the first line setting while the remainder received combination therapy in a second or later line. Outcomes with subsequent treatments are described in Table1. IMDC risk score correlated with TTP. Conclusions: Modest antitumor activity was observed with VEGF- based approaches in combination therapy refractory nccRCC. Optimal management of nccRCC remains an unmet need
Fusing quality improvement and education frameworks to reduce delays in tumor genotyping at community cancer centers
No full textBackground: Delays in obtaining tumor genotyping results hinder the ability of communitybased oncologists to develop timely and effective treatment plans for patients with metastatic colorectal cancers (mCRC).Based on these identified challenges, a quality improvement educational intervention was developed to improve genotyping workflows and enhance clinicians\u27 ability to incorporate timely biomarker testing results into treatment planning for patients with mCRC. Methods: Educational workshops were conducted at five US community cancer centers to address delays in tumor genotyping and their impact on treatment planning. These workshops aimed to enhance clinician knowledge and practice strategies for molecular testing protocols and treatment planning. Physician champions at each center facilitated learner engagement, encouraged multidisciplinary collaboration, and promoted institutional change by driving discussions tailored to their centers\u27 specific challenges and baseline performance metrics. To date, pre- and post-intervention data have been collected from a mix of tumor board captured-metrics and case data compiled in spreadsheets. Baseline and follow-up analyses of patient cases (pre N = 96, post N = 62) evaluated changes in molecular testing rates enabling insights into the effectiveness of the intervention. Results: 90 clinicians participated in the educational workshops, collection of case data is ongoing. Results collected thus far show an overall average reduction of 20.6 days for tumor genotyping results being ready (51.7 days pre vs 31.1 days post). Physician champions report increased consistency in ordering molecular profiling earlier after the education. However, unresolved challenges remain, including insufficient tissue sampling that delay genotyping results as well as the initiation of chemotherapy while awaiting results, which may limit the immediate use of targeted therapies. Conclusions: Cases collected to date suggest that targeted educational workshops addressing genotyping delays formCRCat community cancer centers can drive measurable improvements in molecular testing workflows and reduce time to results. These changes highlight the potential of such interventions to enhance treatment planning timelines in order to optimize therapeutic decision-making. However, persistent barriers limiting further reductions in treatment initiation time underscore the need for continued efforts to address systemic challenges
Emiltatug ledadotin (Emi-Le): A B7-H4-directed dolasynthen antibody-drug conjugate (ADC) being investigated in phase 1 dose expansion in patients with triple negative breast cancer who received at least one prior topoisomarase-1 inhibitor ADC
No full textBreast cancer is the leading cause of cancer death for women worldwide, with triple-negative breast cancer (TNBC) considered one of the more aggressive breast cancers, accounting for ∼15% of all cases. Unfortunately, there remains an unmet medical need for effective and well-tolerated treatments for advanced/metastatic TNBC; in heavily pretreated patients, standard-of-care single-agent chemotherapy has limited efficacy, with response rates of ∼5%, PFS ∼7 weeks. Emiltatug ledadotin (Emi-Le; XMT-1660) is a B7-H4-directed Dolasynthen ADC designed with a precise, target-optimized drug-to-antibody ratio (DAR 6) and a proprietary auristatin F-HPA microtubule inhibitor payload with controlled bystander effect. The FDA has granted Emi-Le two Fast Track designations for the treatment of adult patients with breast cancer, including patients with TNBC who have previously been treated with topoisomerase-1 inhibitor (topo-1) ADCs. Initial dose escalation clinical data from the ongoing Phase 1 trial at doses ranging from 38.1-67.4 mg/m2 per cycle demonstrated a 23% confirmed response rate in patients with B7-H4 high TNBC who were heavily pretreated all of whom received at least one prior topo-1 ADC. Methods: Based on encouraging clinical activity and tolerability data in the initial dose escalation data, the expansion portion (EXP) of the Phase 1 trial has been initiated and is actively enrolling patients. EXP has a Simon 2-stage design and will evaluate two doses in patients with advanced/metastatic TNBC who have received 1-4 prior lines of systemic therapy, including at least one topo-1 ADC. Patients will be evaluated for B7- H4 expression prospectively by IHC and will be stratified into B7-H4 TPS high and B7-H4 TPS low cohorts. The first EXP dose is 67.4 mg/m2 Q4W. Dose exploration is ongoing to identify a potential second higher EXP dose. The protocol includes the option for multiple additional indications, including HR+/HER2- breast cancer, endometrial cancer, ovarian cancer, and ACC-1
Organ Care System Heart Perfusion (OHP) Registry Annual Report 2024 - Donation After Brain Death (DBD) Donors
No full textPurpose: We report one-year outcomes of donor after brain dead (DBD) hearts procured with the organ care system (OCS) compared to static cold storage (SCS) with data from Organ Procurement and Transplantation Network (OPTN) and Organ Care System Heath Perfusion (OHP) registry. Methods: OHP Registry was created to collect donor and recipient’s characteristics, and post-transplant outcomes for all OCS heart transplant cases in the real-world setting in the US. The DBD donor cohort perfused with the OCS and those transported using SCS were identified using OPTN database during the same time period. Donor, recipient data as well as transplant outcomes were compared. Additionally, utilization rate after OCS perfusion and primary graft dysfunction (PGD) rate was collected for the OCS arm, using the OHP registry. Cohorts were propensity matched on the UNOS status, ventricular assist device (VAD), ventilator support, and recipient diagnosis to evaluate the survival. Results: A total of 549 OCS and 3559 SCS patients were included. Utilization rate on OCS was 97.7% (549/562) after OCS perfusion. The number of donors over the age 40 and 55 were significantly higher in the OCS arm (33.9% vs 25.9% and 4.2% vs 1.7% respectively). The donor to recipient center distance was over twice as long (median 698 miles vs 286; p\u3c0.05) in the OCS arm, with longer total cross-clamp time (mean 414.9 min vs 221.4 min; p\u3c0.05). Donors in the OCS cohort arm were more than twice more likely to be refused prior to acceptance than the SCS arm (median refusal 11 vs 5; p\u3c0.05). The OCS recipients were significantly older (51.8 years old vs 49.4 years old), less dialysis dependent (4.2% vs 7.5%), less status 1 (13.7% vs 20.9%), more status 4 (17.3% vs 13.2%) and more status 1-3 with durable VAD (13.1% vs 8.7%), (p\u3c0.05, respectively). Severe PGD rate was 10.4% in the OCS arm, which captured 80.3% of the whole OCS recipients. When matched 1:1 (549 patients in each), OCS cohort had similar 6-month (90.4% vs 91.3%) and 12-month (89.1% vs 90.7%) survival compared to the SCS cohort (p=0.147). Conclusion: Despite OCS was being utilized for higher risk donors and recipients, the outcomes were similar to SCS. This suggests that the OCS approach can lead to expansion of the donor pool and expansion of recipient access to donors without compromising early outcome
Comparative analysis of the DanGer shock trial to randomized cardiogenic shock trials and real-world registries
No full textBACKGROUND: The Danish-German Cardiogenic (DanGer) Shock Trial reported lower mortality with a percutaneous micro-axial flow pump compared to standard care in patients with STEMI-related cardiogenic shock. It remains unclear how the DanGer Shock trial population compares to randomized controlled trials (RCTs) and real-world registries studying temporary mechanical circulatory support (tMCS) for acute myocardial infarction with cardiogenic shock (AMICS).
METHODS: A systematic review and meta-analysis of RCTs and registries involving tMCS for AMICS was performed. Patient characteristics and outcomes were compared to those in the DanGer Shock Trial.
RESULTS: From 2005 to 2023, seven RCTs (1201 patients) and ten registries (2100 patients) were analyzed. DanGer Shock patients had fewer comorbidities, lower blood pressure, lower Left ventricular ejection fraction (LVEF), higher heart rates, and shorter times to tMCS initiation (5.5 ± 2.7 vs. 19.1 ± 38.3 h, p \u3c 0.0001) than RCT patients. They required shorter tMCS durations, less mechanical ventilation, and inotropic support. DanGer patients experienced fewer bleeding events, infections, and limb ischemia, with similar 30-day mortality but higher stroke rates. Compared to registry patients, DanGer Shock patients had fewer comorbidities but required longer tMCS, more mechanical ventilation, and inotropic support, with fewer complications and lower 30-day mortality.
CONCLUSION: DanGer Shock patients had better survival despite worse initial hemodynamics, possibly due to fewer comorbidities, earlier tMCS initiation, and an algorithmic treatment approach