Multivariate Cox Regression Model Research Articles

Effect of visceral fat area on prognosis of patients undergoing radical gastrectomy and construction of nomogram

BackgroundWe aim to investigate the impact of visceral fat area (VFA) on the prognosis of patients following radical gastric resection and develop a nomogram prediction model to forecast the prognosis of gastric cancer patients.MethodsWe retrospectively analyzed 156 patients who underwent laparoscopic radical gastrectomy for distal gastric cancer in the 900th hospital of the Joint Logistics Support Force from April 2018 to April 2020. We collected the CT image data and clinicopathological data one week prior to the operation and then used software to calculate the VFA, dividing it into two groups: a low VFA group (n = 71) and a high VFA group (n = 85). We compared the clinicopathological characteristics and early postoperative complications of the two groups. The Pearson χ2 test was used to analyze the correlation between body mass index (BMI) and VFA. We used the Kaplan-Meier method to draw the survival curve, analyzed the independent risk factors affecting the prognosis of gastric cancer patients using univariate and multivariate Cox regression models, and established a nomogram model for patient prognosis prediction.ResultsThe results of CT showed that VFA value was (95.89 ± 41.40) cm², and body mass index (BMI) was positively correlated with VFA value (r = 0.291, P < 0.001). The ROC curve shows that VFA can predict the prognosis of patients with gastric cancer significantly better than BMI (AUC = 0.826 vs. AUC = 0.707, P = 0.016). The incidence of incision fat liquefaction, pancreatic fistula, and abdominal infection in the high VFA group was higher than that in the low VFA group (P < 0.05). We followed up with all patients for 0.5–48.5 months, with a median follow-up time of 30 months. We used the Kaplan-Meier method to draw the survival curve. The results showed that the overall survival rate of patients in the high VFA group was significantly higher than that in the low VFA group (χ2 = 38.208, P < 0.001), and the high BMI group was significantly higher than that in the low BMI group (χ2 = 29.767, P < 0.001). Age, the degree of differentiation, complications after surgery, VFA, ASA grading, and TNM staging were all found to have independent effects on the prognosis of gastric cancer patients (Multivariate Cox regression analysis). Multivariate Cox regression analysis led to the construction of a nomogram prediction model for the total survival of gastric cancer patients. Its internal verification C-index was 0.881 (95% CI: 0.852–0.910), and the calibration chart showed good consistency.ConclusionsAge, differentiation degree, postoperative complications, VFA, ASA grading, and TNM staging are independent influencing factors for the prognosis of patients with gastric cancer. The constructed nomogram has excellent prediction accuracy and is helpful to evaluate the prognosis of patients.

Impact of long-term chemotherapy (CTx) on outcomes in pancreatic ductal adenocarcinoma (PDAC): A real-world UK multi-centre study.

687 Background: PDAC is associated with poor outcomes with limited treatment options. Here, we present a multi-institutional review evaluating outcomes following short and long-term CTx with or without treatment breaks in PDAC patients (pts). Methods: All consecutive PDAC pts receiving &gt; 3 CTx cycles between 2019 – 2023 at University College London Hospitals and Oxford University Hospitals were included. Treatment response, survival outcomes and predictors of clinical benefit were evaluated. Wilcoxon test, Kaplan-Meier and multivariate Cox regression models were performed. Results: Of the 213 screened pts, 127 eligible subjects met the study criteria. 1 st , 2 nd and 3 rd line CTx were received by 127, 40 and 2 pts, respectively. 21 pts had resectable disease (9 remained relapse-free after adjuvant CTx and 8 pts alive at post 2 years follow-up surveillance). 106 pts had unresectable or metastatic disease and were selected for final analyses (12% borderline resectable (BR), 19% locally advanced (LA), 9% localised disease who developed metastases and 60% de novo metastatic pts). 7 pts (7%) pts underwent genetic profiling on pt request or previous clinical trial screening; KRAS aberrations (N = 4), actionable PLAB2 / BRCA2 mutations (N = 2). BR and LA pts (N = 33) achieved a median PFS1 (Progression Free Survival while on 1 st line CTx) of 8.28 (95% Confidence Interval (CI), 5.49 – 15.11) and Overall Survival (OS) of 15.15 (95% CI, 9.46 – 26.41) months (mos). De novo metastatic pts (N = 64) attained a PFS1 of 6.64 (95% CI, 5.98 – 8.18) and OS of 9.30 (95% CI, 8.05 – 12.81) mos. Patient-specific factors in both cohorts comprising of age, gender, performance status, smoking history, co-morbidities were not associated with PFS1 and OS. Improved PFS was associated with ≥ 6 cycles of 1 st line CTx (P = &lt; 0.001), median duration of 1 st CTx of ≥ 3.58 mos (P = &lt; 0.001) and best response to 1 st CTx (P = 0.007). A favourable OS was associated with &gt; 1 line of CTx (P = &lt; 0.001), ≥ 6 cycles of 1 st line CTx (P = 0.009), median duration of 1 st CTx of ≥ 3.58 mos (P = &lt; 0.001) and best response to 1 st CTx (P = 0.002). Subjects receiving ≥ 6 cycles of 1 st CTx were younger than pts tolerating fewer cycles (median age 62.41 vs 72.25 years) (P = 0.04). In the localised disease group, improved PFS was associated with ≥ 6 cycles of 1 st line CTx (P = 0.003), median duration of 1 st CTx of ≥ 2.99 mos (P = 0.008) and local treatment after commencing 1 st line CTx (P = &lt; 0.001). These three factors were also associated with OS; P = 0.02, P = 0.02 and P = &lt; 0.001, respectively. Median number and duration of 1 st line CTx interruptions were not associated with PFS1 or OS in both cohorts. Conclusions: Despite challenges associated with long-term CTx, survival outcomes may be better in pts receiving CTx for longer periods and multiple treatment lines. Genetic profiling currently offers limited value but in carefully selected pts, localised treatment options may be associated with improved survival outcomes.

Treatment failure patterns in early versus late introduction of CAR T-cell therapy in large B-cell lymphoma.

CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL). This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration). We analyzed 354 patients treated with Axicabtagene ciloleucel (71%) and Lisocabtagene maraleucel (29%); 80 (23%) received early administration, and 274 (77%) late administration. One-year overall survival was higher in the early group (82% [95% CI 72-93] vs. 71% [95% CI 66-77], p = 0.048). However, the survival benefit was not sustained in multivariable Cox regression modeling and propensity score matching. One-year cumulative incidences of relapse were similar (37% [95% CI 24-50] vs. 43% [95% CI 37-49], p = 0.2), as were 1-year progression-free survival probabilities (62% [95% CI 50-76] vs. 50% [95% CI 44-57], p = 0.14). The early group exhibited a favorable toxicity profile, with lower rate of grade ≥2 cytokine release syndrome (26% vs. 39%, p = 0.031) and reduced cumulative incidence of severe neutropenia (41% [95% CI 30-52] vs. 55% [95% CI 49-60], p = 0.027). Our results indicate favorable outcomes with CAR-T irrespective of treatment line. The equivalence in disease control suggests that CAR-T resistance mechanisms persist in LBCL failing first-line therapy.

Clonal Hematopoiesis Is Associated With Adverse Clinical Outcomes and Left Ventricular Remodeling in Aortic Stenosis.

Clonal hematopoiesis of indeterminate potential (CHIP) has been linked to intensified systemic inflammation and represents a novel risk factor for atherosclerotic cardiovascular diseases, including aortic stenosis (AS). This study aimed to assess the clinical impact of CHIP in a cohort of severe AS patients undergoing transcatheter aortic valve implantation (TAVI). We enrolled 110 severe AS patients in this retrospective study. Targeted next-generation sequencing was employed to detect somatic mutations with a variant allele frequency >2% in 16 genes most frequently associated with CHIP. Correlative analyses on clinical, laboratory, and echocardiographic parameters were also performed. The primary endpoint was post-TAVI heart failure hospitalization. Multivariate Cox regression model was used to account for confounding effects of relevant clinical factors. CHIP was detected in 40 (36.4%) patients in our cohort. The most commonly mutated genes were DNMT3A, TET2, and ASXL1. With a median follow-up of 55.2months, patients carrying CHIP had a significantly higher heart failure hospitalization rate (adjusted HR: 3.060; 95% CI: 1.090-8.589; P=0.034) than those without CHIP. Additionally, patients harboring CHIP had higher serum ferritin levels, as well as echocardiographic evidence of left ventricular hypertrophy and diastolic dysfunction. Our study supports the adverse clinical impact of CHIP in AS patients undergoing TAVI, which could be attributed to systemic inflammation and maladaptive LV remodeling. Prospective trials are anticipated to validate our findings and provide further evidence that CHIP holds the potential of being an actionable therapeutic target in AS.

Selective internal radiation therapy with yttrium-90 resin microspheres followed by lenvatinib plus PD-1 inhibitor for large or huge advanced-stage hepatocellular carcinoma: A retrospective cohort study from China.

581 Background: Yttrium-90 resin microspheres have been introduced into China in recent years, but the efficacy or safety on Chinese patients are rarely reported. This study aimed to evaluate the efficacy and safety of selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres followed by lenvatinib and PD-1 inhibitor in Chinese patients with large (5.1–10.0 cm in diameter) or huge (&gt;10.0 cm) advanced-stage hepatocellular carcinoma (HCC). Methods: Data of large or huge Barcelona Clinic Liver Cancer stage C HCC patients treated with SIRT followed by lenvatinib plus PD-1 inhibitor from November 2022 to October 2023 were prospectively collected and retrospectively analyzed. Key endpoints included overall survival (OS), progression-free survival (PFS), complete response rate (CRR), objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, and adverse events (AEs) graded based on Common Terminology Criteria for Adverse Events v5.0. Risk factors affecting PFS were analyzed using univariate and multivariate Cox regression models. Results: A total of 30 patients (27 males, 3 females; mean age 54 ± 11 years) were included. The mean longest diameter of the tumor was 9.6 ± 4.2 cm (range: 5.2–17.6 cm). Nineteen (63.3%) patients had more than three intrahepatic lesions, 15 (50.0%) had vascular invasion, and 13 (43.3%) had extrahepatic metastasis. Sixteen (53.3%) patients had undergone prior anticancer therapies. Two patients received two SIRT procedures, and the rest had one. Lenvatinib and PD-1 inhibitor treatment was initiated 3–7 days after the initial SIRT procedure. CRR was 20.0%, ORR was 73.3%, and DCR was 90.0%. Median PFS was 8.0 months (95% CI, 5.6–10.4), and median OS was not reached. OS rates at 6, 12, and 18 months were 93%, 74%, and 74%, respectively. Univariate and multivariate analysis indicated that baseline alpha-fetoprotein levels, baseline eosinophil count, and neutrophil-to-lymphocyte ratio at 1 month after SIRT were independent risk factors for PFS. AEs of any grade occurred in 86.7% of patients, with grade 3 AEs in 23.3%, and no grade 4/5 AEs were recorded. Conclusions: SIRT followed by lenvatinib and PD-1 inhibitor demonstrates promising efficacy and a favorable safety profile in Chinese patients with large or huge advanced-stage HCC.

Abstract TMP98: Low-dose Rivaroxaban plus Antiplatelet Treatment in Patients With Symptomatic Intracranial Atherosclerotic Stenosis：A Prospective Observational Study

Background: The secondary prevention of symptomatic intracranial atherosclerotic stenosis (sICAS) remains a significant challenge. In the recent COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial, the combination of low-dose rivaroxaban with antiplatelet therapy demonstrated better efficacy in preventing vascular events in patients with coronary atherosclerosis compared to antiplatelet therapy alone. This study aimed to evaluate the efficiency of dual pathway inhibition on recurrent stroke and vascular events in patients with sICAS. Methods: Patients with sICAS admitted within 7 days of symptom onset were identified from the hospital-based database from January 2019 to June 2023. We compared the clinical outcomes of low-dose rivaroxaban combined with antiplatelet therapy (Rivaroxaban 2.5mg bid plus asprin or clopidogrel) and antiplatelet therapy alone (dual antiplatelet therapy or antiplatelet monotherapy) among patients with sICAS. The primary outcome was a composite of all-cause death, ischemic stroke or transient ischemic attack, and acute coronary syndrome within one year post-stroke. Propensity score matching was performed in a 1:3 ratio for the two groups of patients to mitigate confounders, adjusted hazard ratios (HR) were estimated using multivariate Cox regression model. The win-ratio method was employed to assess the composite outcome. Results: Among 1,308 patients, 123 (9.4%) were prescribed rivaroxaban and antiplatelet therapy. In the matched population, the primary endpoint event rate in this group was lower (11/123 [8.9%] vs. 63/369 [17.1%], P=0.029). Multivariate Cox regression analysis revealed a significant benefit from low-dose rivaroxaban (adjusted HR=0.459, 95% CI: 0.234-0.897, P=0.023). In addition, coronary heart disease (adjusted HR=1.674, 95% CI: 1.013-2.766, P=0.044) was identified as a risk factor associated with composite outcome during the 1-year follow-up. In the analysis of the hierarchical composite end point, the results for the primary end point favored rivaroxaban plus antiplatelet therapy (win ratio=1.948, 95% CI: 1.134-3.346, P=0.016). Conclusions: Low-dose rivaroxaban combined with antiplatelet therapy was superior to antiplatelet therapy alone for the prevention of all-cause death, recurrent stroke and acute coronary syndrome among patients with sICAS. These findings are preliminary and warrant further investigation through randomized controlled trials.

Abstract TMP70: Intracortical type of lobar cerebral microbleed predicts risk of recurrent intracerebral hemorrhage in spontaneous intracerebral hemorrhage survivors

Introduction and Objective: Lobar cerebral microbleed (CMB) is frequently found in patients with spontaneous intracerebral hemorrhage (ICH) and is closely linked to cerebral amyloid angiopathy (CAA) and risk of recurrent ICH. Lobar CMB could be further topographically categorized into intracortical type or subcortical white matter (WM) type, and our previous study showed that CAA is more related to the intracortical lobar CMB. The current study aimed to determine if the types of lobar CMB can predict risks ofrecurrent ICH and long-term vascular outcomes in patients with spontaneous ICH. Methods: A total of 587 patients with spontaneous ICH were included. Clinical data, neuroimaging markers, and 2-year follow-up outcomes (recurrent ICH, incident ischemic stroke, vascular mortality and composite outcome) were collected. We categorized patients into 4 different groups based on their lobar CMB types: Type 1 (strictly intracortical type, n=52), Type 2 (strictly subcortical WM type, n=127), Type 3 (mixed intracortical and subcortical WM type, n=86), and Type 4 (no lobar CMB, n=277). The associations between lobar CMB type and follow-up outcomes were assessed using multivariable Cox regression models with adjustment of age, sex, hypertension, diabetes mellitus and hyperlipidemia. We also examined the dose-relationship between intracortical lobar CMB number and ICH recurrence risk. Results: Compared to patients without lobar CMB (Type 4), patients with strictly intracortical lobar CMB type (Type 1) had higher ICH recurrence rate (HR 3.90[1.30-11.75], p=0.015) and composite outcomes (HR 2.55[1.26-5.17], p=0.009], p&lt;0.001), while patients with strictly subcortical WM lobar CMB type (Type 2) was associated with high risk of composite outcomes (HR 2.22[1.31-3.79], p=0.003) and a trend toward risk of incident ischemic stroke (HR 2.12 (0.89-5.05), p=0.091) but not ICH (HR 1.66 [0.66-4.19], p=0.282). Mixed type (Type 3) was not associated with follow-up vascular events. For patients with at least one lobar CMB, three or more intracortical CMBs significantly elevated ICH recurrence risk (HR 2.85 [1.18-6.88], p=0.020). Conclusions: Topographical type of lobar CMB may have clinical significance in predicting ICH recurrence risks and vascular outcomes in ICH survivors. Patients with lobar CMBs restricted in the intracortical region, or with multiple number of intracortical lobar CMBs, are predisposed to higher ICH recurrence rate.

Plant-based diets and the risk of lung cancer: a large prospective cohort study.

Plant-based diets are increasingly recognized for cancer prevention, yet their specific impact on lung cancer (LC) risk remains insufficiently examined. This study aims to assess the relationship between plant-based diets adherence and the incidence of LC. Data from the Prostate, Lung, Colorectal, and Ovarian cancer screening trial were analyzed. The plant-based diet index (PDI) was developed to assess adherence to plant-based diets. Multivariable Cox regression model was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) model was performed to examine risk across the PDI spectrum. Prespecified subgroup analyses identified potential modifiers, and sensitivity analyses tested the association's robustness. Of the 98,459 participants included, 1,642 developed LC over an average follow-up of 8.83 years. Higher PDI scores were associated with a lower LC risk (HR quartile 4 vs. 1: 0.75, 95% CI: 0.65-0.87, P trend < 0.001), evident in both non-small cell lung cancer (HR quartile 4 vs. 1: 0.76, 95% CI: 0.65-0.88, P trend < 0.001) and small cell lung cancer (HR quartile 4 vs. 1: 0.73, 95% CI: 0.49-1.09, P trend = 0.046). RCS analyses further confirmed these relationships. The association was stronger among participants with lower BMI, smokers, those without a history of emphysema or diabetes, those without a family history of LC, and those with lower physical activity (all P trend < 0.001). Sensitivity analyses consistently supported these findings. Our findings reveal an inverse correlation between PDI and LC risk, supporting the potential benefits of plant-based diets in LC prevention. ClinicalTrials.gov ID: NCT00339495 (URL: https://www. gov/study/NCT00339495 ).

Prognostic Value of Nevus-Associated Melanoma in Patients with Melanoma.

Although most melanomas develop de novo, about 30% are nevus-associated melanomas, where the prognostic value is unclear. Our study aimed to determine whether nevus-associated melanoma is associated with sentinel lymph node (SLN) status and prognosis in patients with melanoma. The Sentinel Lymph Node Working Group database, which includes comprehensive clinicopathological and outcome data, was utilized to investigate the association of nevus-associated melanoma with SLN status as well as relapse-free (RFS), melanoma-specific (MSS), and overall survival (OS) using multivariable logistic regression and Cox regression modeling. A total of 3447 adult patients with a median follow-up of 2.6 years (interquartile range 0.9-6.9) were evaluable. Compared with de novo melanomas, nevus-associated melanomas showed a significant correlation with younger age as well as favorable histological features. The presence of a nevus-associated melanoma was not identified as an independent factor for SLN status (odds ratio 1.06, 95% confidence interval [CI] 0.80-1.41; p=0.68). Compared with de novo melanomas, nevus-associated melanomas provided independent prognostic information for a favorable RFS (hazard ratio [HR] 0.67, 95% CI 0.53-0.84; p<0.001), MSS (HR 0.54, 95% CI 0.34-0.85; p=0.008), and OS (HR 0.42, 95% CI 0.30-0.57; p<0.001). Melanomas associated with pre-existing nevi appear to be an independent favorable prognostic factor for recurrence and survival and may potentially be used as a clinical parameter for identifying patients with lower risk of recurrence.

Serum mucin 5AC (MUC5AC) as a predictor of outcomes and microscopic distant metastasis in pancreatic ductal adenocarcinoma (PDA).

767 Background: Our prior studies demonstrated that tissue extracellular MUC5AC (EM) detection (EM-D) is associated with early recurrence, and serum MUC5AC (sM) levels have prognostic value in resected PDA following neoadjuvant therapy. This study evaluates the predictive value of post-operative sM before adjuvant therapy (AT). Methods: Serum samples, collected from January 2010 to June 2021 and sourced from the Ohio State University biorepository, were analyzed using enzyme-linked immunoassays with a human MUC5AC kit (NBP2-76703). Multivariate (MV) Cox regression models quantified progression-free survival (PFS) and overall survival (OS), while Wilcoxon tests compared group differences. Results: Nineteen patients had serum samples available post-operative and pre-AT. The cohort's median age was 65 years (range: 48-83), predominantly Caucasian (n=18), and 58% female. Serum was collected a median of 2 weeks (range: 1-16) after surgery, with a mean sM level of 1.1 ng/mL (range: 0.42 to 3.3). Most patients (17/19) received Gemcitabine-based therapy, one received chemoradiation, and another FOLFIRINOX. Among patients, 3 had no recurrence (Nr), 10 experienced distant metastases only (mets), 3 had local recurrence only (Lr-o), and 3 had both Lr and liver recurrence (Liv/Lr). In the MV model, incorporating sM, EM-D, and AT, higher sM levels (HR=2.83, p=0.04) and negative EM-D (HR=6.85, p=0.02) were associated with increased recurrence risk, whereas AT type did not influence recurrence. Regarding OS, sM was significant (HR=2.95, p=0.04) while other factors were not. Elevated sM levels correlated with metastasis risk (mets vs. Liv/Lr vs. Lr-o vs. Nr = 1.54 vs. 0.61 vs. 0.62 vs. 0.92, p=0.01). Patients with locoregional recurrence had significantly lower sM than those with distant metastasis and no recurrence (mets vs. Liv/Lr+Lr-o vs. Nr = 1.54 vs. 0.62 vs. 0.92, p=0.005). In a separate cohort of 10 metastatic patients (mean sM of 1.8 ng/mL, range: 0.43 to 11.2), liver metastases were linked to significantly lower sM than non-liver metastases (0.54 vs. 3, p=0.02), while peritoneal metastases were associated with higher sM levels (3 vs. 0.6, p=0.04). Conclusions: This small study suggests that sM can serve as a biomarker for assessing outcomes and recurrence sites post resection before the initial dose of AT. Elevated sM should prompt suspicion of microscopic metastases, particularly non-liver metastases.

Association of triglyceride-glucose related indices with mortality among individuals with MASLD combined with prediabetes or diabetes

BackgroundThe prognostic significance of triglyceride-glucose (TyG)-related indices in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) combined with prediabetes or diabetes is not yet fully understood. In this study, we explored their predictive value for mortality in this specific population.MethodsPatients with MASLD were identified from the National Health and Nutrition Examination Survey (NHANES III) database. TyG and its related parameters [TyG-waist circumference (TyG-WC), TyG-waist-to-height ratio (TyG-WHtR), TyG-weight-adjusted waist index (TyG-WWI), and TyG-body mass index (TyG-BMI), ] were calculated. To examine the association between TyG-related indices and mortality risk, Cox regression models were utilized. Furthermore, we employed restricted cubic spline (RCS) analysis to investigate potential dose-response relationships. The predictive ability of the TyG indices for mortality was assessed by analyzing the time-dependent area under the curve (AUC).ResultsIn the cohort of patients with prediabetes or diabetes, 46.5% were diagnosed with MASLD. Over a median follow-up of 25.4 years, 1,163 individuals (53.9%) died, with 329 (15.3%) deaths attributed to cardiovascular causes and 78 (3.6%) to diabetes. Multivariate Cox regression models showed that TyG, TyG-BMI, TyG-WHtR, TyG-WWI, and TyG-WC were associated with all-cause and cardiovascular/diabetes-specific mortality. Furthermore, RCS analysis revealed a positive linear relationship between the TyG and TyG-WWI indices and all-cause mortality (p for nonlinear = 0.920; p = 0.525, respectively). In contrast, the TyG-WC, TyG-BMI, and TyG-WHtR indices exhibited a positive nonlinear association with all-cause mortality (p for nonlinear = 0.001; = 0.003; = 0.007, respectively). Time-dependent AUC curves demonstrated that the TyG-WWI index was the most robust predictor of both all-cause and cardiovascular mortality.ConclusionsElevated levels of TyG, TyG-BMI, TyG-WHtR, TyG-WWI, and TyG-WC indices were associated with a poorer prognosis in MASLD patients with prediabetes or diabetes, with TyG-WWI being the strongest predictor.

Whole exome sequencing-based homologous recombination deficiency test for epithelial ovarian cancer.

The homologous recombination deficiency (HRD) test is an important tool for identifying patients with epithelial ovarian cancer (EOC) benefit from the treatment with poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi). Using whole exome sequencing (WES)-based platform can provide information of gene mutations and HRD score; however, the clinical value of WES-based HRD test was less validated in EOC. We enrolled 40 patients with EOC in the training cohort and 23 in the validation cohort. The WES-based HRD score was calculated using the scarHRD software. We first evaluated the concordance of the HRD status defined by the Myriad MyChoice CDx and then assessed the value of HRD on clinical prognosis in patients with EOC. The HRD score defined by the WES-based test was positively correlated with that of the Myriad MyChoice® CDx test (r = 0.82, p < 0.01) in the training cohort. In compared to HRD status of Myriad test, the sensitivity, specificity, positive predictive value, and negative predictive value of the WES-based HRD test were 93.5% (29/31), 77.8% (7/9), 93.5% (29/31), and 77.8% (7/9), respectively. Patients with positive HRD status defined by WES-based scarHRD test and Myriad MyChoice® CDx test were both highly associated with platinum sensitive response (both Fisher's exact test, p = 0.002) as well as the superior progression-free survival (both log-rank p = 0.002). The multi-variate Cox regression model incorporated with optimal debulking surgery showed that the recurrence risk was decreased in the patients with positive HRD status, either defined by Myriad MyChoice® CDx test (Hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.14-0.79, p = 0.013) or WES-based test Myriad MyChoice® CDx test (HR 0.34, 95% CI 0.14-0.80, p = 0.014). Nine patients had mutations in the genes involved in HR DNA repair, and all of them were positive for HRD. In the validation group, 23 patients were defined as positive HRD by WES-based testing. Six positive HRD patients and 5 negative HRD patients received maintenance PARPi. The median responsive interval of PARPi was 17 months in positive HRD patients and 3 months in negative HRD patients. The WES-based test is a potential option for determining the HRD status in EOC patients, and desires for further validation in large-scale cohorts.

P-2275. Impact of Epstein-Barr Virus (EBV) Donor Serostatus on Post-transplant Mortality and Post-Transplant Lymphoproliferative Disorder in Thoracic Organ Transplant EBV-Seropositive Recipients: Data from the Organ Procurement and Transplantation Network

Abstract Background Epstein Barr Virus (EBV) donor positive (D+) serostatus is a risk factor for Post-Transplant Lymphoproliferative Disorder (PTLD) in EBV-seronegative recipients. The impact of donor EBV serostatus on mortality and PTLD in EBV-seropositive recipients (R+) in thoracic organ transplant (TOT) is unknown.Table 1.Baseline demographic and clinical characteristics of EBV D-/R+ and EBV D+/R+ TOT recipients Methods Using the Organ Procurement and Transplantation Network database, we identified 47,201 EBV R+ TOT recipients between 01/2004 – 12/2021. The primary exposure was EBV D+ and the primary outcomes were death and PTLD. Multivariable Cox regression models were used to assess the relationship between donor EBV serostatus and the outcome of death and PTLD.Figure 1.Kaplan-Meier survival plots for EBV D-/R+ (solid line) versus EBV D+/R+ (dashed line) post heart (red line) and lung (blue line) transplantation Results Of 47,201 EBV R+ TOT recipients, 48.5% were lung and 51% were heart transplant recipients. The majority (93.4%) were EBV D+/R+, with median age of 59 years and 66.8% males. EBV D-/R+ and D+/R+ TOT recipients differed in CMV donor and recipient status, donor median age, sex, and graft failure (Table 1). The incidence rate of death was 7.2 per 100 person-years in EBV D+/R+ compared to 6.9 per 100 person-years in EBV D-/R+, p=0.156. Survival did not differ by EBV donor status, but it was lower in lung transplant (Figure 1). The incidence rate of PTLD was 0.26 per 100-person years in EBV D+/R+ compared to 0.33 per 100-person years in EBV D-/R+, p= 0.073. EBV D+ status was not associated with increased hazard of death in both univariable (crude hazard ratio [HR] of 1.05; confidence interval [CI], 0.98-1.11; p=0.15) and multivariable analyses (adjusted HR of 0.96; 95% CI, 0.90-1.02; p=0.14), after controlling for donor age, CMV D+ status, and the following recipient factors: age, sex, race, insurance, pre-transplant life support, pre-transplant malignancy, rejection, and graft failure. EBV D+ status was associated with decreased hazard of PTLD when adjusting for recipient age and graft failure (adjusted HR of 0.74; 95% CI, 0.56-0.98; p=0.03). In subgroup analyses by organ, EBV D+ status was associated with decreased hazard of PTLD in lung (adjusted HR of 0.56; 95% CI, 0.40-0.78; p=0.001) but not in heart transplant recipients (adjusted HR of 1.18; 95% CI, 0.71-1.96; p =0.50) (Figure 2).Figure 2.Kaplan-Meier PTLD-free survival plots for EBV D-/R+ (solid line) versus EBV D+/R+ (dashed line) post heart (red line) and lung (blue line) transplantation Conclusion Among EBV-seropositive TOT recipients, EBV D- status may be associated with increased risk of PTLD, particularly in lung transplant recipients. Disclosures Alissa J. Inc, MD, MSc, Takeda: Honoraria Sara Belga, MD, MPH, Takeda, Moderna, AstraZeneca, GSK: Advisor/Consultant|Takeda, Moderna, AstraZeneca, GSK: Grant/Research Support|Takeda, Moderna, AstraZeneca, GSK: Honoraria

P-2293. Does Granulocyte-Macrophage Colony-Stimulating Factor as Adjunctive Therapy Affect Mortality in Patients with Hematologic Malignancies?

Abstract Background Invasive pulmonary aspergillosis (IPA) remains a major cause of illness and death in neutropenic patients (pts) with hematologic malignancies (HM). Because outcomes of IPA are mostly host-driven, adjunct host-targeted immunotherapies such as granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used in cases of refractory or high-risk IPA, though the impact of GM-CSF on outcome remains unclear. Methods We reviewed records of all consecutive pts with HM and microbiologically documented IPA from sputum or bronchoalveolar lavage culture at MD Anderson Cancer Center (January 2016 - October 2021). Independent risk factors of 42-day (d) mortality and the impact of GM-CSF on outcomes were analyzed using multivariate Cox regression analysis. Results Of the 106 included IPA pts, 52 (49%) had leukemia/myelodysplastic syndrome and 54 (51%) had lymphoma/myeloma; 85 (80%) had active malignancy at IPA diagnosis (Figure 1). Thirty-two pts (30%) had a history of hematopoietic stem cell transplant and 37 (35%) had neutropenia &amp;lt; 100/µL at IPA diagnosis. Thirty-five pts (33%) received adjunct GM-CSF (Figure 1), started at a median of 3 d after initiating antifungal therapy (interquartile range [IQR] 1 – 18). The median duration of adjunct GM-CSF was 7 d (IQR 2 – 15). Forty-two-day all-cause mortality after IPA diagnosis was high (47%) and comparable in pts receiving GM-CSF and those who did not (51% vs. 45%, p = 0.54). Independent predictors of 42-d mortality were active HM (adjusted hazard ratio [aHR] 3.83, p = 0.026), neutropenia &amp;lt; 500/µL (aHR 1.83, p = 0.045), and albumin &amp;lt; 3 g/dL (aHR 2.45, p = 0.004) at IPA diagnosis (Table 1). Considering these co-variables and the timing of GM-CSF, the impact of adjunct GM-CSF on 42-d mortality remained insignificant (p = 0.19) in the multivariate Cox regression model (Table 1). Conclusion In a setting of significant IPA burden (i.e., culture-proven disease, neutropenic malnourished pts with active HM) and high overall mortality, adjunct GM-CSF therapy did not affect IPA outcomes. Early culture-independent biomarker-driven IPA diagnosis and immune markers for assessment of the host’s net state of immunosuppression will be pivotal to evaluate whether early preemptive deployment of host-targeted immunomodulators improves IPA outcomes in pts with HM. Disclosures Sebastian Wurster, MD, MSc, Astellas Pharma: Grant/Research Support|Gilead Sciences: Grant/Research Support Dimitrios P. Kontoyiannis, MD, AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Knight: Advisor/Consultant|Merck: Advisor/Consultant|Scynexis: Advisor/Consultant

Three-dimensional right ventricular ejection fraction: a strong predictor of outcomes in patients undergoing cardiac surgery, a multicenter study.

Abstract Background Cardiac surgery is the cornerstone of treatment of several heart conditions.1 Risk stratification before surgery is crucial to patient’ prognostic, but commonly used scores do not include right ventricular (RV) function.2 Purpose To evaluate if 3D RV ejection fraction (RVEF) is independently associated with in-hospital outcomes in patients undergoing cardiac surgery after adjusting for the EuroSCORE. Methods Prospective multicenter (3 centers in 2 countries) cohort study of adult patients undergoing cardiac surgery. A comprehensive transesophageal echocardiogram was performed in the operating room before the surgery to capture dedicated acquisitions of the RV. The images were analyzed offline in TOMTEC imaging system. The primary outcome was a composite of in-hospital mortality or need of temporary ventricular assistance device after surgery. Exploratory endpoints were time on mechanical ventilation and time on inotropes after the surgery. Univariate and multivariable Cox regression model was used to analyze the association of RVEF with the primary outcome after adjusting for the EuroSCORE. Results We included 248 patients. The median age was 60 y/o and 43% were female. Aortic valve repair or replacement and CABG were the most common procedures. Sixty nine percent had normal RVEF (RVEF ≥45%) and 31% low RVEF (RVEF &amp;lt;45%). Baseline demographic characteristics were similar between groups except for atrial fibrillation, which was more common in the low RVEF group. Left ventricular ejection fraction was lower in patients with low RVEF (50 ± 14 vs. 54 ± 12, p=0.041). The volume of the atria and the RV size were higher in patients with low RVEF (p&amp;lt;0.04 for all). RV function parameters (TAPSE, FAC and RVFWLS) were lower in the group of low RVEF (p&amp;lt;0.001 for all). The group with low RVEF showed higher PASP (42 ± 19 vs. 53 ± 27 mmHg, p=0.003) and lower RV–pulmonary artery coupling [0.54 (IQR 0.33 – 0.78 mm/mmHg) vs. 0.34 (IQR 0.24 – 0.53 mm/mmHg), p&amp;lt;0.001]. The primary outcome occurred in 28 patients (11%). Table 1 illustrates the univariate and multivariable association of RVEF as a continuous variable as well as other parameters with the primary outcome. When analyzing groups of low vs high RVEF (binary variable), patients with low RVEF showed higher risk of the primary outcome [HR 2.46 (95% CI 1.10, 5.50), p=0.028]. At 30 days, the survival free of the primary endpoint was 72±8% vs. 93±3% (p&amp;lt;0.001) in low vs normal RVEF, respectively (Figure 2, panel A). Further, RVEF was associated with shorter time on mechanical ventilation (r= -0.27, p&amp;lt;0.001) and shorter time on inotropes (r= -0.20, p=0.01); (Figure 2, panel B and C). Conclusion Three-dimensional RVEF is a strong predictor of outcomes in patients undergoing cardiac surgery. This multicenter study suggests that including RV function in the evaluation of patients undergoing surgery might improve stratification. Table 1. Figure 1.

Myocardial work and extravalvular cardiac damage stages: hand-in-hand predictors of all-cause mortality in patients undergoing transcatheter aortic valve replacement

Abstract In patients with aortic stenosis (AS) evaluating left ventricular (LV) systolic function is challenging due to the influence of increased afterload on traditional measures. Myocardial work (MW) analysis, a novel echocardiographic method, adjusts myocardial deformation to instantaneous LV pressure, providing a more accurate reflection of LV contractile state. Notably, prolonged LV pressure overload induces significant backward effects beyond the LV; the classification of this extravalvular cardiac damage effectively represents the cardiopulmonary system's involvement in AS. Both MW analysis and cardiac damage staging may possess significant prognostic value in the clinically complex cohort of transcatheter aortic valve replacement (TAVR) candidates. Thus, our objective was to evaluate the prognostic value of MW analysis and cardiac damage staging in TAVR patients. We enrolled 314 patients (79±6 years, 40% female) prior to TAVR. Echocardiographic assessments were conducted one day before the procedure. LV ejection fraction (EF) was calculated, global longitudinal strain (GLS) was measured using speckle-tracking echocardiography. LV pressure was estimated from systolic blood pressure and transaortic mean gradient, and global constructive work (GCW) was quantified using dedicated software. Based on echocardiographic data, we determined the extent of cardiac damage associated with AS, categorizing patients into Stage 0 (no cardiac damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (pulmonary artery vasculature or tricuspid valve damage), or Stage 4 (right ventricular damage). The primary endpoint was all-cause mortality, reached by 69 patients during a median follow-up period of 25 months. Preprocedural EF was 47±13 %, GLS was -12.3±4.2 %, GCW was 2043±769 mmHg%. 14 (5%) patients were classified as Stage 0, 61 (20%) as Stage 1, 133 (43%) as Stage 2, 22 (7%) as Stage 3, and 74 (24%) as Stage 4. GCW showed a decline through AS Stages (from Stage 0-4: 2963±652 vs. 2154±621 vs. 2174±706 vs. 2044±827 vs. 1553±757 mmHg%; p&amp;lt;0.001). Using univariate Cox analysis GCW (HR 0.968 [95% CI 0.938-0.998] per 100 unit change; p=0.034) and AS Staging (HR 1.236 [95% CI 1.016-1.505]; p=0.034) were associated with all-cause mortality, while EF (HR 0.982 [95% CI 0.964-1.001]; p=NS) and GLS (HR 1.047 [95% CI 0.989-1.108]; p=NS) were not. In multivariate Cox regression models, both GCW (HR 0.958 [95% CI 0.923-0.994] per 100 unit change; p=0.022) and AS cardiac damage staging (HR 1.281 [95% CI 1.040-1.577]; p=0.020) were significant independent predictors of all-cause mortality. In TAVR patients, preoperative GCW values continuously decreased across all AS Stages. GCW and AS Staging showed strong association with all-cause mortality in our cohort, while EF and GLS did not. Furthermore, GCW and AS Staging had higher prognostic value than any other echocardiographic measure, highlighing their role in preprocedural assessment before TAVR.

Mechanical dispersion predicts long-term survival of dialysis-dependent patients with preserved ejection fraction

Abstract Background Since cardiovascular disease is a major cause of death in patients with chronic kidney disease (CKD), echocardiographic risk stratification of CKD patients may be clinically important, especially if left ventricular (LV) systolic function is still preserved. Purpose To investigate the prognostic implications of conventional (LV mass) and advanced echocardiographic parameters [global longitudinal strain (GLS) and mechanical dispersion] in dialysis-dependent patients with preserved left ventricular ejection fraction (LVEF). Methods A total of 78 patients with LVEF≥50% were prospectively enrolled and followed for 60 months for all-cause death. LV mass was calculated using the ASE/EACVI recommended formula for estimating LV mass from LV linear dimensions and indexed to body surface area (LVMI). Longitudinal myocardial strain was measured by speckle-tracking echocardiography. The duration of mechanical contraction was determined as the time from the ECG R-wave to peak longitudinal strain in each of 18 LV segments. Mechanical dispersion was defined as the difference between the longest and shortest time intervals. Results In univariable analysis, age [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.07, p=0.014], diabetes mellitus (HR 2.16, 95%CI 1.03-4.52, p=0.042), LVMI (HR 1.02, 95%CI 1.01-1.03, p=0.001), GLS (HR 0.77, 95%CI 0.66-0.88) and mechanical dispersion (HR 1.01, 95%CI 1.01-1.02, p&amp;lt;0.001) were all predictive of all-cause mortality. The results of the multivariable Cox regression model are shown in the Figure: in addition to age, mechanical dispersion, LVM and GLS were found to be independent predictors of death from any cause. Patients with mechanical dispersion ≥260 ms had worse survival (HR 3.74, 95% 1.51-9.27) than those with a lesser degree of dispersion (p=0.004). Conclusions In dialysis-dependent patients with preserved LVEF, higher extent of mechanical dispersion is associated with worse long-term survival. Higher LV mass and reduced GLS were also identified as independent predictors of survival. Echocardiography-derived parameters may be useful for risk stratification in this vulnerable patient population.

P-312. Elimination of barrier contact precautions for Vancomycin-Resistant Enterococcus (VRE)-colonized patients was not associated with the acquisition of VRE in a tertiary care center

Abstract Background In April 2020, the University of Michigan discontinued barrier contact precautions for Vancomycin-Resistant Enterococcus (VRE) colonized patients while maintaining VRE surveillance. We conducted a retrospective cohort study to assess the impact of this policy change on the risk of VRE acquisition Inclusion and Exclusion Criteria of the Cohort Methods We analyzed patients admitted between 1/2018 and 3/2021 who underwent weekly surveillance. The primary outcome was VRE-free survival; the main exposure was admission before or after the contact precaution policy. Demographics, Elixhauser comorbidity index, antibiotic and PPI exposure, and colonization pressure were incorporated as covariates in an extended Cox proportional hazard model of VRE-free survival. Time-varying covariates were accounted for and modeled using log-transformed time. Patients were censored at discharge or death. VRE-free survival before and after change in contact precautions policy Change in contact precaution policy was not associated with an increased hazard of VRE-acquisition in single variable analysis Results We identified 2,221 patients admitted before the policy change and 1,830 after, with 225 cases of VRE acquisition before and 196 cases after. No significant differences in age, demographics, antibiotic use, or PPI exposure were observed among VRE patients admitted before and after the policy change. However, VRE patients admitted before the policy change had more medical comorbidities (mean Elixhauser: 23.64 before, 20.77 after; p=0.008) and lower exposure to colonization pressure (mean VRE patient days: 13.4 before, 29.9 after; p=0.019). In a multivariable extended Cox proportional hazard model, admission before or after the change in contact precaution policy showed no significant association with VRE-free survival (HR 0.81-1.1), or infection with VRE (HR 1.01, 95% CI 0.92-1.21). The most significant risk factors for VRE acquisition were vancomycin treatment (HR 1.60, 95% CI 1.25-2.03, p&amp;lt; 0.001) and PPI treatment (HR 1.43, 95% CI 1.15-1.77, p=0.001). Multivariable cox-regression model of risk factors for VRE acquisition There was no association between the change in contact precautions policy and risk of VRE acquisition Conclusion The policy change to eliminate isolation and barrier precaution requirements for VRE patients was associated with no detectible increase in the hazard of VRE acquisition. The most significant risk factors for VRE acquisition were vancomycin and PPI treatment. Our results suggest that appropriate use of PPI and antimicrobial stewardship may have a greater impact on preventing the spread and acquisition of VRE than barrier precautions. Disclosures Laraine Washer, MD, Ferring Pharmaceuticals: Advisor/Consultant

Risk of second primary malignancies among survivors of cutaneous melanoma: A nationwide population-based study in the Republic of Korea

There is limited data on the risk of second primary malignancies (SPMs) in Asian melanoma survivors. This study aimed to identify the risk of SPMs in Asian melanoma survivors. Standardized incidence ratios (SIRs) were calculated for overall and specific SPMs. The risk factor for overall SPM development was analyzed using a multivariable Cox regression model. A total of 10,070 patients with melanoma were included in the study. Melanoma survivors exhibited an increased risk of overall SPM (SIR, 1.51; 95% confidence interval [CI], 1.34–1.70). Additionally, specific SPMs were more common among melanoma survivors, including nonmelanoma skin cancer, oral cavity and pharyngeal cancer, renal cancer, female breast cancer, lung cancer, pancreatic cancer, and liver cancer. Independent risk factors for overall SPM development included a Charlson Comorbidity Index ≥ 1 (adjusted hazard ratio [aHR], 1.41; 95% CI, 1.07–1.87), and a body mass index ≥ 25 kg/m2 (aHR, 1.47; 95% CI, 1.04–2.08). Inherent uncertainty related to diagnostic codes may exist. The risk of overall and specific SPMs was significantly elevated in Asian melanoma survivors, particularly among those with invasive melanoma. Among modifiable factors, a high body mass index (BMI) was associated with an increased risk of SPM.

Association of oxidative balance score with all-cause and cardiovascular mortality in overweight and obese

BackgroundThe oxidative balance score (OBS) combines diverse dietary components with lifestyle factors to comprehensively evaluate oxidative stress. The investigation focuses on the link between the OBS and mortality outcomes, including cardiovascular and all-cause deaths, in overweight and obese individuals.MethodsThe analysis utilized data from the National Health and Nutrition Examination Survey (NHANES), covering the period from 1999 to 2018. Mortality information, categorized into all-cause and cardiovascular deaths, was gathered from the National Death Index (NDI). Kaplan–Meier survival analysis, along with multivariate Cox regression and restricted cubic spline (RCS) modeling, were utilized to explore the link between OBS and mortality risks. Subgroup analysis and sensitivity analysis were used to assess the robustness of the results and possible effect modifiers. Mediation analysis identifies pathways through which the independent variable affects the dependent variable.ResultsIn this study, 26,219 participants with overweight or obesity were enrolled, with an average age of 49.8 ± 17.4 years. During a median follow-up duration of 115 months, 2,239 participants (8.5%) died, including 837 (3.2%) from cardiovascular disease. According to Kaplan–Meier analysis, mortality was highest among participants in the lowest OBS quartile (Q1) and lowest among those in the highest quartile (Q4). Participants in the fourth OBS quartile experienced a 21.7% decrease in the risk of mortality from all causes and a 29.5% decrease in cardiovascular mortality risk, according to fully adjusted results, compared to those in the first quartile. These results were validated through subgroup analyses. The analysis of RCS revealed a notable inverse association between OBS and mortality outcomes. Mediation analysis indicates that white blood cell count (WBC) and gamma-glutamyl transferase (GGT) serve as significant mediators in the association between OBS and mortality risk.ConclusionElevated levels of OBS were strongly linked to reduced potential for both cardiovascular and all-cause mortality among individuals who are overweight or obese.