Simple Score of Albumin and CRP Predicts High-Grade Toxicity in Patients with Multiple Myeloma Receiving CAR-T Therapy.

Administration of chimeric-antigen receptor T-cell (CAR-T) therapy is complex and associated with unique toxicities. Identifying patients at risk for inferior outcomes is important for individualized management. The Glasgow-prognostic score (GPS) is a simple score shown to be highly prognostic of outcomes in the setting of traditional chemotherapy or checkpoint inhibitor administration. We sought to evaluate the value of the GPS to predict outcomes of patients with relapse refractory multiple myeloma (RRMM) receiving anti-BCMA CAR-T therapy. We included all patients treated with commercial CAR-T therapy for RRMM between 5/1/2021 and 2/1/2023 at the Moffitt Cancer Center. The GPS (CRP >1 mg/dL, 1 point; albumin <3.5, 1 point) was calculated for all patients at lymphodepletion (day -6) and patients were grouped as high-risk GPS (score = 2) or low-risk GPS (0 or 1). The primary endpoint was overall survival (OS) at day 100. A total of 139 pts were included, with a median follow-up of 6.7 months (95% CI, 6.2 to 8.9 months). Pts were treated with either idecabtagene vicleucel (83%) or ciltacabtagene autoleucel (17%). In total, 14% were classified with high-risk GPS, with significantly increased risk for grade 3 cytokine release syndrome (P = .003) and ICANS of any grade (P < .001). Patients in the high-risk GPS group had significantly lower day-100 OS (68.4% versus 97.3%, P < .001), OS at 6 months (56% versus 91.8% P = .0019) and PFS at 6 months (38.3% versus 72.3%, P = .03). The association of GPS with day-100 OS remained significant in a multivariable model. In conclusion, the GPS identifies a group of high-risk patients with RRMM receiving CAR-T therapy who experience increased rates of immune-mediated toxicity and are at higher risk for early mortality.

In-hospital Outcomes of Aspiration Pneumonia Hospitalizations With Acute Heart Failure: A Nationwide Analysis.

Background and Objectives: There is a paucity of data regarding the impact of acute heart failure (AHF) on the outcomes of aspiration pneumonia (AP). Methods: Using National Inpatient Sample datasets (2016 to 2019), we identified admissions for AP with AHF vs. without AHF using relevant International Classification of Diseases, Tenth Revision codes. We compared the demographics, comorbidities, and outcomes between the two groups. Results: Out of the 121,097,410 weighted adult hospitalizations, 488,260 had AP, of which 13.25% (n=64,675) had AHF. The AHF cohort consisted predominantly of the elderly (mean age 80.4 vs. 71.1 years), females (47.8% vs. 42.2%), and whites (81.6% vs. 78.5%) than non-AHF cohort (all p<0.001). Complicated diabetes and hypertension, dyslipidemia, obesity, chronic pulmonary disease, and prior myocardial infarction were more frequent in AHF than in the non-AHF cohort. AP-AHF cohort had similar adjusted odds of all-cause mortality (adjusted odds ratio [AOR], 0.9; 95% confidence interval [CI], 0.78-1.03; p=0.122), acute respiratory failure (AOR, 1.0; 95% CI, 0.96-1.13; p=0.379), but higher adjusted odds of cardiogenic shock (AOR, 2.2; 95% CI, 1.30-3.64; p=0.003), and use of mechanical ventilation (MV) (AOR, 1.3; 95% CI, 1.17-1.56; p<0.001) compared to AP only cohort. AP-AHF cohort more frequently required longer durations of MV and hospital stays with a higher mean cost of the stay. Conclusions: Our study from a nationally representative database demonstrates an increased morbidity burden, worsened complications, and higher hospital resource utilization, although a similar risk of all-cause mortality in AP patients with AHF vs. no AHF.

Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion.

Prolonged cytopenias after chimeric antigen receptor (CAR) T cell therapy are a significant clinical problem and the underlying pathophysiology remains poorly understood. Here, we investigated how (CAR) T cell expansion dynamics and serum proteomics affect neutrophil recovery phenotypes after CD19-directed CAR T cell therapy. Survival favored patients with "intermittent" neutrophil recovery (e.g., recurrent neutrophil dips) compared to either "quick" or "aplastic" recovery. While intermittent patients displayed increased CAR T cell expansion, aplastic patients exhibited an unfavorable relationship between expansion and tumor burden. Proteomics of patient serum collected at baseline and in the first month after CAR-T therapy revealed higher markers of endothelial dysfunction, inflammatory cytokines, macrophage activation, and T cell suppression in the aplastic phenotype group. Prolonged neutrophil aplasia thus occurs in patients with systemic immune dysregulation at baseline with subsequently impaired CAR-T expansion and myeloid-related inflammatory changes. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion.

Etiologies and Predictors of 30-Day Readmission in Heart Failure: An Updated Analysis.

Background and Objectives: Readmissions in heart failure (HF), historically reported as 20%, contribute to significant patient morbidity and high financial cost to the healthcare system. The changing population landscape and risk factor dynamics mandate periodic epidemiologic reassessment of HF readmissions. Methods: National Readmission Database (NRD, 2019) was used to identify HF-related hospitalizations and evaluated for demographic, admission characteristics, and comorbidity differences between patients readmitted vs. those not readmitted at 30-days. Causes of readmission and predictors of all-cause, HF-specific, and non-HF-related readmissions were analyzed. Results: Of 48,971 HF patients, the readmitted cohort was younger (mean 67.4 vs. 68.9 years, p≤0.001), had higher proportion of males (56.3% vs. 53.7%), lowest income quartiles (33.3% vs. 28.9%), Charlson comorbidity index (CCI) ≥3 (61.7% vs. 52.8%), resource utilization including large bed-size hospitalizations, Medicaid enrollees, mean length of stay (6.2 vs. 5.4 days), and disposition to other facilities (23.9% vs. 20%) than non-readmitted. Readmission (30-day) rate was 21.2% (10,370) with cardiovascular causes in 50.3% (HF being the most common: 39%), and non-cardiac in 49.7%. Independent predictors for readmission were male sex, lower socioeconomic status, nonelective admissions, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, anemia, and CCI ≥3. HF-specific readmissions were significantly associated with prior coronary artery disease and Medicaid enrollment. Conclusions: Our analysis revealed cardiac and noncardiac causes of readmission were equally common for 30-day readmissions in HF patients with HF itself being the most common etiology highlighting the importance of addressing the comorbidities, both cardiac and non-cardiac, to mitigate the risk of readmission.

Utilization of Left Ventricular Assist Device for Congestive Heart Failure: Inputs on Demographic and Hospital Characterization From Nationwide Inpatient Sample.

Objectives The first goal of the study is to provide a descriptive overview of the utilization of left ventricular assist device (LVAD) for the treatment of congestive heart failure (CHF) and determine the rates of LVAD use stratified by patients' demographic and hospitals' characteristics in the United States. Next, is to measure the hospitalization outcomes of length of stay (LOS) and cost in inpatients managed with LVAD. Methods We conducted a cross-sectional study using the nationwide inpatient sample and included 184,115 patients (age ≥65 years) with a primary discharge diagnosis of hypertensive and non-hypertensive CHF and was further classified by inpatients who were managed with LVAD. We compared the distributions of demographic and hospital characteristics in CHF inpatients with versus without LVAD by performing Pearson's chi-square test for categorical variables, and independent sample t-test for continuous variables. Results The inpatient utilization of LVAD was 0.93% (1690 out of 184,115) in CHF patients. The LVAD cohort were younger compared to non-LVAD group (mean age, 69.9 years vs. 79.4 years). The utilization rate of LVAD was also almost four times higher in males (1.50%) compared to females (0.36%). Although whites (78.5%) accounted for majority of LVAD recipients, the rate of LVAD utilization was highest in blacks (1.04%) and lowest in Hispanics (0.58%) with whites having utilization rate of 0.89%. Medicare was the dominant primary payer to cover the LVAD inpatients (91.1%), though the rate of LVAD utilization is highest in private (2.22%) and lowest in those covered by public insurance (medicaid/medicare). CHF patients in public hospitals (1.79%) were more than twice more likely to receive LVAD than in private hospitals (0.83%) due to higher utilization rate. LVAD utilization rate was approximately 55 times higher in teaching hospitals (1.67%) compared to non-teaching hospitals (0.03%), and 20 times higher in large bed hospitals (1.41%) compared to small bed-size hospitals (0.07%). CHF patients that received LVAD had a significantly longer LOS (34.6 days vs 9.8 days) and higher inpatient treatment costs ($802,118 vs. $86,302) compared to non-LVAD group. Conclusion The inpatient utilization of LVAD was in CHF patients is higher in males, blacks and private health insurance beneficiaries. In terms of hospital characteristics, the utilization of LVAD for CHF management was higher in large bed sized, and public type and teaching hospitals compared to their counterparts. This data will allow us to devise strategies to improve LVAD utilization and increase its outreach for heart failure patients, especially those on the transplant waiting list. Despite its effectiveness, aggressive usage of LVAD is restricted due to cost-effectiveness and lack of technical confidence among medical professional due to complications.

Persistent Cannabis Abuse and Risk for Hospitalization for Acute Pancreatitis: A Cross-Sectional Study in United States Hospitals.

Objectives To explore the independent association between cannabis abuse and subsequent hospitalizations for acute pancreatitis (AP) and delineate the demographic differences among AP in patients with and without persistent cannabis abuse. Methods We conducted a retrospective cross-sectional study using the nationwide inpatient sample and included 50,444,133 patients (age 18-50 years) with a primary discharge diagnosis for medical illnesses and further grouped by presence of AP (N = 666,248). We used the logistic regression model to measure the odds ratio (OR) of the association between cannabis abuse and hospitalization for AP and adjusted it for demographic confounders and comorbid risk factors. Results Cannabis abuse significantly increases the odds for AP-related hospitalization (OR 2.12, P <0.001). When the regression model was controlled for potential risk factors (gall stones, cystic fibrosis, hypertriglyceridemia, hypercalcemia, hyperparathyroidism, abdominal surgeries, tobacco abuse, and alcohol abuse), cannabis abuse did not increase the odds for AP-related hospitalization (OR 0.72, P <0.001) due to the significant effect caused by gallstones (OR 30.98, P <0.001) and alcohol abuse (OR 12.69, P <0.001). AP inpatients with cannabis abuse were younger compared to non-cannabis abusers (mean age, 35.7 vs. 37.9 years), and majorly male (70.9% vs. 53.8%). AP was considerably more prevalent in whites (60.6%), followed by blacks (18.3%) and Hispanics (15.2%). Conclusion Cannabis abuse increased the unadjusted odds for AP-related hospitalization by two times, but after controlling for potential risk factors the adjusted odds of association significantly reduced. Cannabis-induced AP can be treated if a problematic recreational cannabis use pattern is discontinued at an earlier stage. Therefore, awareness campaigns and early supportive therapy among cannabis abusers might help diagnose and treat the comorbidity and improve the quality of life.