Forrest General Hospital

TPS4202 Background: The MET proto-oncogene and its receptor tyrosine kinase gene product (c-Met protein) are involved in normal cellular functions such as cell proliferation and differentiation but can be abnormally activated and upregulated in cancer to promote tumor growth. MET gene amplification and increased c-Met protein expression are associated with poor survival outcomes in gastric cancer. The antibody-drug conjugate Temab-A (ABBV-400) is composed of the c-Met–directed antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor. A phase 1 study (NCT05029882) investigating Temab-A monotherapy demonstrated manageable safety and encouraging efficacy in patients with previously treated, advanced GEA, with an objective response rate of 29% (12/42) and clinical benefit rate of 71% (30/42) (Strickler et al. Ann Oncol . 2024;35:1439P). This study evaluates Temab-A in combination with fluorouracil (5-FU), leucovorin/folinic acid (LV), and budigalimab (budi; a PD-1–blocking antibody). Methods: This multicenter,phase 2, open-label, randomized study (NCT06628310) will enroll ~180 adult patients with HER2-negative a/m GEA who have not received prior systemic therapy in the a/m setting, have not received a prior PD-(L)1 inhibitor, have Eastern Cooperative Oncology Group performance status 0–1, and have measurable disease per RECIST v1.1. Primary objectives of the study are to evaluate safety and tolerability, evaluate efficacy as measured by progression-free survival and objective response, and select the recommended phase 3 dose of Temab-A in combination with 5-FU, LV, and budi. Secondary objectives include assessment of dose-limiting toxicities (DLTs) in the dose-escalation stage, evaluation of pharmacokinetics, and further evaluation of efficacy measures (duration of response, disease control, and overall survival). The study consists of 2 stages: dose escalation and dose optimization. During BOIN-directed dose escalation, ~18 patients receive escalating doses of Temab-A administered once every 4 weeks (Q4W) in combination with fixed doses of 5-FU (2400 mg/m 2 Q2W), LV (400 mg/m 2 Q2W), and budi (500 mg Q4W). DLTs are assessed during the first 28-day cycle. During dose optimization, ~162 patients are randomized 1:1:1 to 1 of 2 selected doses of Temab-A in combination with 5-FU, LV, and budi or a control arm of FOLFOX + budi. Randomization is stratified by PD-L1 expression and primary tumor location. Treatment is administered until disease progression, intolerable toxicity, or other discontinuation criteria are met. Either archived formalin-fixed paraffin-embedded tissue or a fresh biopsy is required for biomarker research that will include evaluation of c-Met protein expression and MET genomic alterations. Clinical trial information: NCT06628310 .

SUMMARY Delirium frequently occurs among hospital in-patients, with significant attributable healthcare costs. It is associated with long-term adverse outcomes, including an eightfold increased risk of subsequent dementia. The purpose of this article is to inform clinicians of the best practices for spotting, stopping and treating delirium and provide guidance on common challenging clinical dilemmas. For spotting delirium, suggested screening tools are the 4 ‘A's Test (in general medical settings) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Prevention is best achieved with multicomponent interventions and targeted strategies focusing on: (a) avoiding iatrogenic causes; (b) brain optimisation by ensuring smooth bodily functioning; (c) maintaining social interactions and normality. Non-pharmacological approaches are the first line for treatment; they largely mirror prevention strategies, but the focus of empirical evidence is on prevention. Although sufficient evidence is lacking for most pharmacological approaches, an antipsychotic at low doses for short durations may be of utility for highly distressing or high-risk situations, particularly in hyperactive delirium, but only as a last resort.

Introduction: High sensitivity C-reactive protein (hsCRP), a biomarker of inflammation, can risk stratify patients for cardiovascular disease including heart failure (HF). It is not well established if inflammation increases the risk of HF in patients with chronic kidney disease (CKD) and if hsCRP can be utilized to risk stratify patients with CKD for their risk of incident HF. Aims: We assessed the role of hsCRP in risk stratifying patients with CKD for incident HF. Methods: We studied participants of 3 major epidemiologic cohorts: Atherosclerosis Risk in Communities Study, Multi-Ethnic Study of Atherosclerosis, and Jackson Heart Study. High inflammation was classified as hsCRP >3 mg/L and CKD was classified as estimated glomerular filtration rate <60 mL/min/1.73m2. Participants were stratified into 3 groups: neither CKD nor high inflammation, CKD without high inflammation, or CKD with high inflammation. Cox hazards models adjusted for age, sex, race, body mass index, smoking, alcohol use, diabetes, hypertension, and coronary disease were utilized for analysis. Results: 8,692 participants with 460 incident HF events followed over a median 8.32 years were included in our analysis. Participants with CKD without high inflammation (HR = 1.45; 95% CI 1.14 to 1.85) and CKD with high inflammation (2.05; 1.61 to 2.61) were associated with an increased risk of incident HF compared with participants without CKD or high inflammation (referent, Figure). Furthermore, participants with CKD and a hsCRP >3 mg/L had an increased risk of incident HF (1.41; 1.06 to 1.88) compared with participants with CKD but hsCRP ≤3 mg/L (referent). Conclusions: Patients with CKD and high levels of inflammation carry a 2-fold increased risk of incident HF. In patients with CKD, hsCRP levels >3mg/L may be useful to risk stratify patients with increased risk of developing HF.

Background: Socioeconomic status is an often-overlooked risk factor for cardiovascular disease (CVD). Low family income is a measure of socioeconomic status and may portend worse CVD burden. Therefore, we assessed the association of family income with cardiovascular risk factor and disease burden in American adults. Methods: This retrospective analysis included data from participants aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Family income to poverty ratio (PIR) was calculated by dividing family (or individual) income by the poverty guidelines specific to the survey year and used as a measure of socioeconomic status. The association of PIR with the presence of cardiovascular risk factors and CVD as well as cardiac mortality and all-cause mortality was examined. Results: We included 35,932 unweighted participants corresponding to 207,073,472 weighted, nationally representative participants. Participants with lower PIR were often female and more likely to belong to race/ethnic minorities (non-Hispanic Black, Mexican American, other Hispanic). In addition, they were less likely to be married/living with a partner, to attain college graduation or higher, or to have health insurance. In the adjusted analysis, the prevalence odds of diabetes mellitus, hypertension, coronary artery disease (CAD), congestive heart failure (CHF), and stroke largely decreased in a step-wise manner from highest (≥5) to lowest PIR (<1) (Table 1). In the adjusted analysis, we also noted a mostly dose-dependent association of PIR with the risk of all-cause and cardiac mortality during a mean 5.7 and 5.8 years of follow up, respectively. Conclusions: Public policy efforts should be directed to alleviate these disparities to help improve cardiovascular outcomes in this vulnerable subgroup.

ObjectivesWe sought to determine utilization and outcomes of perioperative temporary mechanical circulatory support (tMCS) in the current practice of cardiac surgery.BackgroundtMCS is an evolving adjunct to cardiac surgery not fully characterized in contemporary practice.MethodsUsing the nationwide inpatient sample we retrospectively analyzed hospital discharge data between January 1, 2016 and December 31, 2019. ICD‐10‐CM procedure codes were used to identify and divide patient hospitalizations into those who had preoperative tMCS (pre‐tMCS) versus tMCS instituted the day of surgery or afterwards (sd/post‐tMCS).ResultsIn all, 1,383,520 hospitalizations met inclusion criteria. 86,445 (6.25%) had tMCS. tMCS was utilized in 8.74% of coronary artery bypass grafting (CABG), 2.58% of isolated valve, and 9.71% of valve/CABG; operations. 29,325 (33.9%) had pre‐tMCS while 57,120 (66.1%) had sd/post‐tMCS. The use of tMCS was associated with greater inpatient mortality (15.66% vs. 1.53%, p < .001), longer length of stay (LOS) (14.4 vs. 8.5 days, p < .001), and higher mean inflation‐adjusted costs ($93,040 ± 1038 vs. $51,358 ± 296, p < .001) compared to no use. Inpatient mortality (5.98% vs. 20.63%, p < .001), LOS (13.87 vs. 14.68, p < .001), and cost ($82,621 ± 1152 SEM vs. $98,381 ± 1242) were all significantly lower with pre‐tMCS compared to sd/post tMCS. When analyzed separately, mortality was higher with later utilization of tMCS (5.98% pre, 17.1% sd, and 49.05% postsurgical date insertion, p < .001).ConclusionsPerioperative tMCS is utilized in 6.25% of modern cardiac surgery, with two‐thirds of cases instituted on the day of surgery or afterwards. The use of tMCS is associated with significantly higher mortality, longer LOS, and higher costs. Among patients undergoing tMCS, earlier utilization is associated with better outcomes.