Adoptive cell therapies have transformed the treatment landscape for hematologic malignancies. Yet, translation to solid tumors remains constrained by antigen heterogeneity, an immunosuppressive tumor microenvironment (TME), and poor persistence of conventional CAR-T cells. In response, innate immune cell platforms, particularly chimeric antigen receptor–engineered natural killer (CAR-NK) cells and chimeric antigen receptor–macrophages (CAR-MΦ), have emerged as promising alternatives. This review summarizes recent advances in the design and application of CAR-NK and CAR-MΦ therapies for solid tumors. We highlight key innovations, including the use of lineage-specific intracellular signaling domains (e.g., DAP12, 2B4, FcRγ), novel effector constructs (e.g., NKG7-overexpressing CARs, TME-responsive CARs), and scalable induced pluripotent stem cell (iPSC)-derived platforms. Preclinical data support enhanced antitumor activity through mechanisms such as major histocompatibility complex (MHC)-unrestricted cytotoxicity, phagocytosis, trogocytosis, cytokine secretion, and cross-talk with adaptive immunity. Early-phase clinical studies (e.g., CT-0508) demonstrate feasibility and TME remodeling with CAR-MΦ. However, persistent challenges remain, including transient in vivo survival, manufacturing complexity, and risks of off-target inflammation. Emerging combinatorial strategies, such as dual-effector regimens (CAR-NK⁺ CAR-MΦ), cytokine-modulated cross-support, and bispecific or logic-gated CARs, may overcome these barriers and provide more durable, tumor-selective responses. Taken together, CAR-NK and CAR-MΦ platforms are poised to expand the reach of engineered cell therapy into the solid tumor domain.

Background: Appendiceal neuroendocrine tumors (NETs) rank as the third most frequent neoplasm affecting the appendix, originating from enterochromaffin cells. This study aims to evaluate the influence of various prognostic factors on the mortality rates of patients diagnosed with NETs of the appendix. Methods: Conducted retrospectively, the study involved 3346 patients, utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Our analysis centered on investigating demographic characteristics, clinical features, overall mortality (OM), and cancer-specific mortality (CSM) among the cohort. Variables showing a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox regression analysis. A Hazard Ratio (HR) > 1 indicated an unfavorable prognosis. Results: In the multivariate analysis, higher OM and CSM were observed in males, older age groups, tumors with distant metastasis, poorly differentiated tumors, and those who underwent chemotherapy. Non-Hispanic Black individuals showed elevated mortality rates. Conclusion: Delayed diagnosis may contribute to the increased mortality in this community. Improved access to healthcare and treatment is crucial for addressing these disparities. Larger prospective studies are needed to pinpoint the underlying causes of elevated mortality in non-Hispanic Black populations, and randomized controlled trials (RCTs) are warranted to evaluate therapies for advanced-stage appendix NETs.

Background: Transcatheter aortic valve replacement (TAVR) has become the preferred treatment for severe aortic stenosis in high- and intermediate-risk patients, with expanding indications for lower-risk populations. However, post-procedural complications, such as stroke, conduction disturbances, and heart failure readmissions, remain concerns. The aim of our study is to analyze the national trends in TAVR procedures, in-hospital outcomes, major readmission causes, and the association of risk factors for readmissions following TAVR. Methods: We analyzed NIS data (2018–2022) to assess TAVR utilization trends, patient demographics, and in-hospital outcomes. The NRD (2021–2022) was used to evaluate 60-day readmission rates for stroke, complete heart block, and heart failure. Multivariate regression models were employed to identify risk factors having significant association with major readmission causes. Results: TAVR utilization increased from 10,788 cases in 2018 to 17,784 in 2022, with a concurrent decrease in in-hospital mortality (1.33% to 0.90%) and length of stay (3.88 to 2.97 days). Of 123,376 TAVR index admissions in 2021, 28,654 patients had 66,100 readmission events (53.57%) in the 60 days following discharge. Heart failure (17,566 cases, 26.57% of readmissions) was the most common readmission cause, followed by complete heart block (1760 cases, 2.66% of readmissions) and stroke (284 cases, 0.42% of readmissions). Predictors of post-TAVR stroke included uncontrolled hypertension (OR 2.29, p < 0.001) and chronic heart failure (OR 2.73, p < 0.001). Left bundle branch block (LBBB) was strongly associated with complete heart block (OR 12.89, p < 0.001) and heart failure readmissions (OR 7.65, p < 0.001). Conclusions: TAVR utilization has increased with improving perioperative outcomes, but post-TAVR readmissions remain significant, particularly for heart failure, stroke, and conduction disturbances. Pre-procedural uncontrolled hypertension, hyperlipidemia, congestive heart failure, and atrial fibrillation were risk factors with significant association with stroke in the 60 days following TAVR. The presence of documented pre-procedural LBB, RBB, as well as BFB were risk factors with significant association with complete heart block following TAVR placements. Pre-procedural LBB, RBB, BFB, and atrial fibrillation were risk factors having significant association with heart failure readmissions in the 60 days following TAVR.

Background: Heart transplantation (Htx) remains the definitive therapy for patients with end-stage heart failure. Despite advancements in mechanical circulatory support (MCS), immunosuppressive strategies, and organ allocation policies, donor availability remains a major limitation. This study analyzes the trends in Htx in the United States between 2016 and 2022, focusing on demographic shifts, mortality trends, and 30-day readmission patterns. Methods: We utilized the National Inpatient Sample (NIS) from 2016 to 2022 and the National Readmissions Database (NRD) for 2021 to identify Htx admissions using ICD-10 PCS code O2YA0Z0. Patient characteristics, mortality rates, and readmission patterns were analyzed using ANOVA and multivariate logistic regression, with statistical significance defined as p < 0.05. Results: The total number of Htx procedures increased from 641 in 2016 to 773 in 2022. The mean age of transplant recipients remained between 45 and 50 years, with no significant differences across years. Racial and socioeconomic disparities persisted, with approximately 60% of transplants occurring in White patients and 21–26% of recipients belonging to the lowest income quartile. All-cause in-hospital mortality remained stable at 4–7%. The 30-day readmission rate in 2021 was 57.7%, with heart failure, transplant rejection, and infections being the leading causes. Peripheral vascular disease (PVD) was the only comorbidity significantly associated with higher 30-day readmission risk (OR: 1.815, 95% CI: 1.477–2.230). Conclusions: Htx utilization has increased over time, driven by improvements in donor allocation and perioperative management. However, racial and socioeconomic disparities remain, and readmission rates continue to be high. Future efforts should focus on optimizing post-transplant care and addressing disparities to improve long-term outcomes.

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only mild to moderate liver fibrosis. However, there is limited understanding of how fibrosis severity interacts with other clinical variables, such as patient age, to affect mortality. This study aims to explore how fibrosis scores relate to both overall and cancer-specific mortality in US HCC patients, with an emphasis on how this relationship may shift across different age groups. Methods: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database to identify 15,796 adult patients diagnosed with HCC between 2010 and 2021. Baseline demographics, disease characteristics, and treatment variables were examined. Mortality outcomes were evaluated using Cox proportional hazard regression. Variables significant at p < 0.1 in univariate analysis were included in multivariate models to identify independent predictors of mortality (with hazard ratios [HRs] > 1 signifying increased risk). A secondary analysis assessed how age modifies the association between fibrosis score and mortality. Results: The study population was predominantly male (77.2%), with most patients aged 60–79 (59.6%) and presenting with localized disease (61%). A majority had advanced liver fibrosis or cirrhosis (81.7%) and lived in large urban areas (62.9%). Crude comparisons indicated that male sex, older age, single status, advanced tumor stage, lower income, and cirrhosis were linked to worse outcomes. In adjusted models, independent predictors of increased mortality included male sex, older age, unmarried status, and more advanced disease stage. Receipt of surgery or chemotherapy was associated with a lower risk of death. Notably, the influence of fibrosis on mortality was found to be greater in older patients than in their younger counterparts. Conclusions: This analysis identifies key prognostic indicators in HCC and suggests that the relationship between fibrosis and survival is not uniform across age groups. These findings support the need for age-specific clinical management strategies and highlight the potential benefit of early detection and appropriate interventions, even in non-cirrhotic patients.

Background: Aim of the study is to analyze the trends and outcomes in Left Ventricular Assist Device (LVAD) placements between the years 2016 and 2022 using the National Inpatient Sample (NIS). Methods: Using the NIS for the years 2016–2022, we identified the total number of LVAD placements using the PCS 10 code 02HA0QZ. In-hospital outcomes and healthcare resource utilization burden were assessed. Stratification of outcomes with Extracorporeal Membrane Oxygenation (ECMO) support were performed for the years 2018–2022. Outcome analysis variance in admissions requiring ECMO support was performed using multivariate regression analysis. A two tailed p-value < 0.05 was used to determine statistical significance. Results: A general decreasing trend was observed in the total number of LVAD placements, with 852 total admissions requiring LVAD placements identified in 2016 compared to 665 in 2022. The admissions for LVAD placements requiring ECMO support had an increasing trend, with 2.21% of admissions needing ECMO support in 2018 compared to 12.18% in 2018. After multivariate regression analysis, the association between all-cause mortality during the hospital stay for LVAD placements and requirement of ECMO was found to be significant, with an odds ratio of 2.34 (1.83–4.42, p-value: 0.001). Conclusions: A general decreasing trend in LVAD placements was observed between 2016 and 2022. All-cause mortality and hospital charges during the admission had a stable trend over the years. The requirement of ECMO support had an increasing trend from 2018 to 2022. Requirement of ECMO support during the admissions for LVAD placements had a statistically significant association with all-cause mortality during the admission. A 11.50% readmission rate was observed in the 30 days following discharge, with heart failure being the major cause of readmission.