Multivariate Cox Proportional Hazards Model Research Articles

Survival and risk factors for metastatic colorectal cancer patients with a history of prior malignancy

Given concerns about treatment, there is uncertainty surrounding the effect of prior malignancy on the survival of individuals with metastatic colorectal cancer. This study sought to evaluate how prior malignancy impacts the survival of patients with metastatic colorectal cancer (mCRC). Patients diagnosed with stage IV mCRC (per the American Joint Committee on Cancer [AJCC] 6th edition) between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Those without a prior history of malignancy were assigned to the control group, whereas those with a prior history of malignancy were assigned to the research group. Propensity score matching (PSM) was utilized to ensure that the baseline characteristics were balanced. The Kaplan‒Meier method was used for survival analysis, as were the multivariate Cox proportional hazard model and multivariate competing risk model. The PSM analysis included 54365 eligible patients with mCRC. Among them, 4,845 (8.9%) had a history of prior malignancy. A history of prior malignancy was associated with a greater cancer-specific survival rate (adjusted hazard ratio (AHR) ) = 0.49; 95% CI [0.47–0.51]). Subgroup analyses revealed that a prior diagnosis of a skin tumour (AHR = 1.37; 95% CI [1.11–1.69]) and a history of prior malignancy of more than five years (AHR = 1.39; 95% CI [1.23–1.57]) had adverse effects on the clinical outcomes of patients with mCRC. Our findings suggest that patients with a prior malignancy diagnosis may experience prolonged survival. Subgroup analysis indicated that a malignancy diagnosed more than 5 years ago may adversely impact the clinical outcomes of patients with mCRC. Therefore, we advocate for active standardized treatment for these patients and propose expanding the range of prior malignancies included in clinical trials based on publication timelines, primary tumour locations, and genetic testing results. The objective is to facilitate timely and proactive treatment for patients following the disclosure of results, thereby instilling confidence in the management of mCRC.

Abstract 18: Relation of Migraine to Stroke Risk in Postmenopausal Women: Findings from the Women’s Health Initiative

Introduction: Migraines are a known risk factor for stroke among reproductive-aged women, though the relation of migraines to stroke risk among postmenopausal women remains unclear. We assessed the association between a history of diagnosed migraine and incident stroke among postmenopausal women and investigated age differences in the association. Methods: We included women enrolled in the Women’s Health Initiative (WHI), a large longitudinal cohort study of postmenopausal women in the U.S. We excluded women with a history of stroke or TIA at baseline or with missing data on history of migraine or key covariates. The primary exposure was a history at baseline of self-reported migraine diagnosed by a physician. The primary outcome was incident stroke (total, ischemic [IS], or hemorrhagic [ICH]). Multivariable Cox proportional hazards models were used to test the cause-specific hazard ratios (HRs) between migraine history and total stroke, IS (overall and by subtype), and ICH, sequentially adjusted for age and traditional and female-specific risk factors. Using multivariable Cox proportional hazard models, we then quantified the association between migraine history and total stroke by age in 5-year groups at baseline. Results: 130,277 participants were included. The median age at baseline was 61 years (IQR 56-67 years) for those with a migraine history compared to 63 years (IQR 57-69 years) for those without. Overall, 5,743 strokes occurred over a median follow-up period of 19.9 years (IQR 9.1-25). In multivariable-adjusted models (Table), there was a marginal association between migraine history and total stroke (HR=1.07; 95% CI, 0.99-1.17) and a significant association between migraine history and IS (HR=1.12; 95% CI, 1.02-1.23), most pronounced in the cardioembolic category. Migraine was not associated with risk of ICH (HR=0.85, 95%CI, 0.67-1.09). Risk appears to be of greatest magnitude in early (HR 1.26, 95% 0.93-1.72) and late (HR 1.16, 95%CI 0.89-1.50) postmenopausal years (Figure), though the differences by age group were not statistically significant. Conclusions: Over a 20-year follow-up period, postmenopausal women with self-reported histories of migraine had a higher risk of IS, but not total or ICH, suggesting that migraine history contributes to ischemic stroke risk during the postmenopausal years. Along with other known risk factors, migraine history should be considered in stroke risk factor screening and prevention efforts after menopause.

Changes in peri-operative chemotherapy and radiation use among patients with resected pancreatic ductal adenocarcinoma (PDAC) between 2004-2021 in the US SEER dataset.

697 Background: PDAC peri-operative management changed over 20 years. Randomized data supports adjuvant and multiagent chemotherapy (CT), while peri-operative chemoradiotherapy (RT) was used selectively in the US. We examined recent trends in treatment with outcomes in surgically resected PDAC patients. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) 17 dataset, we identified surgically resected primary M0/MX PDAC cases from 2004-2021 over 3-year periods (P1-P6). Neoadjuvant (NCT), adjuvant (ACT), or multiagent (MACT) CT scheduling was included. χ² analysis assessed cohort characteristics over time and multinomial logistic regression assessed odds of CT allocation adjusted by cohort characteristics. Multivariable Cox proportional hazards model assessed treatment-related overall survival (OS) adjusted for cohort characteristics. Results: Among 55,293 cases of M0/MX PDAC, 21,904 (40%) completed surgery. Median age was 66 years; stages were T1/T2/T3/T4 (8.0/25/59/6.0%) and N0/N+ (38/54%). RT use declined (P1:P6, 41%->18% p<0.001) while CT use increased (P2:P6, 63%->79%, p<0.001). NACT (P2:P6, 4.1%->23% p<0.001) and MACT (P2:P6, 1.6%->20%, p<0.001) use increased while ACT decreased (P2:P6, 58%->36%, p<0.001). CT is likely to be allocated to young patients (<65yo) with Stage II-III tumors located at the pancreatic head (OR>1.00, p<0.001). Median OS increased over time (P1:P6, 18mo->32mo, p<0.001). Multivariable analysis shows that Adjuvant RT (HR 0.84 [0.81-0.87], p<0.001) and all CT (NCT: HR 0.71 [0.66-0.77], p<0.001; ACT: HR 0.63 [0.60-0.66], p<0.001; MACT: HR 0.65 [0.60-0.71], p<0.001) improved OS. Conclusions: This study shows decreased RT and increased CT adoption from 2004-2021. Median OS improved over the years, potentially due to peri-operative advances during this study period. Trends in treatment use over 3-year periods. RTN (%) CTN (%) Neo CTN (%) MACTN(%) P1: 2004-2006N=2661 1087 (41) 0 (0) a 0 (0) a 0 (0) a P2: 2007-2009N=3185 1185 (37) 2021 (63) 129 (4.1) 50 (1.6) P3: 2010-2012N=3536 1226 (35) 2460 (70) 267 (7.6) 138 (3.9) P4: 2013-2015N=3947 1210 (31) 2880 (73) 434 (11) 244 (6.2) P5: 2016-2018N=4224 971 (23) 3256 (77) 676 (16) 491 (12) P6: 2019-2021N=4351 787 (18) 3430 (79) 1003 (23) 857 (20) a No cohorts reported chemotherapy use during period 1. RT: Radiation Therapy; CT: Chemotherapy; NCT: Neoadjuvant Chemotherapy; MACT: Multiagent Chemotherapy.

Clinical treatment score Post-5 Years (CTS5) predicts the benefit of postmastectomy radiotherapy in patients with T1-2N1 luminal breast cancer.

To investigate the clinical value of Clinical Treatment Score Post-5 Years (CTS5) to predict the survival benefits of postmastectomy radiotherapy (PMRT) of patients with T1-2N1 luminal breast cancer (BC). Patients who were diagnosed with T1-2N1 luminal BC between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results database. The chi-square test, binomial logistic regression, Kaplan-Meier analysis, and multivariable Cox proportional hazard model were used for statistical analyses. A total of 11190 patients were included with a median follow-up time of 76 months. Regarding the CTS5 classification, 1641 (14.7%), 3915 (35.0%), and 5633 (50.3%) patients had low-risk, intermediate-risk, and high-risk diseases, respectively. Patients with younger age, T2 stage, higher tumor grade, a higher number of positive lymph nodes, infiltrating lobular carcinoma subtype, and receipt of chemotherapy were associated with the receipt of PMRT (all P<0.05). The multivariate analysis showed that the receipt of PMRT was the independent prognostic factor associated with better BCSS (P=0.005) and OS (P<0.001). The sensitivity analysis showed that PMRT did not improve BCSS (low-risk, P=0.932; intermediate-risk, P=0.952) and OS (low-risk, P=0.637; intermediate-risk, P=0.825) compared to those without PMRT in the low-risk and intermediate-risk groups. However, PMRT improved BCSS (P=0.003) and OS (P<0.001) in those with high-risk groups compared to those without PMRT. CTS5 is an innovative model that could predict the survival benefit of PMRT for T1-2N1 luminal BC patients.

Kidney Biopsy-Proven Diabetic and Non-Diabetic Kidney Diseases and Outcomes in Patients With Type 2 Diabetes Receiving Dialysis: The REIN Registry.

Chronic kidney disease (CKD) in patients with diabetes does not always equate to diabetic kidney disease (DKD). This study aims to delineate and compare the clinical characteristics, survival rates, and access to kidney transplantation among patients with type 2 diabetes commencing dialysis, who were classified by kidney biopsy as having either DKD or non-diabetic kidney disease (non-DKD). We used the comprehensive French Renal Epidemiology and Information Network registry to analyze baseline clinical characteristics at dialysis inception and outcomes defined as death and access to kidney transplantation. We employed a multivariate Cox proportional hazards model and the Fine-Gray competing risk model to assess the probabilities of mortality and transplantation. Adults in the Renal Epidemiology and Information Network registry in France with a diagnosis of type 2 diabetes who initiated kidney replacement therapy from January 2009 to December 2015 and had a previous native kidney biopsy. We analyzed data from 2,869 patients with diabetes, 45% of whom had a biopsy-confirmed diagnosis of DKD. Among these patients, half presented additional histopathological findings indicative of nephroangiosclerosis and focal segmental glomerulosclerosis. The clinical profiles of patients with DKD and non-DKD were largely comparable. There were no significant differences in dialysis survival rates or kidney transplantation access between the groups, even after adjusting for confounding variables and considering competing risks. At the 6-year mark, the mortality rate was 60.3% (95% CI: 55.5-64.5) for the DKD group and 60.3% (95%CI: 55.9-64.3) for the non-DKD group. Multivariable Cox analysis revealed no significant difference in mortality risk between the DKD and non-DKD groups. The study limitations include potential residual confounders, lack of predialysis data, kidney biopsies possibly outdated, nonrandom biopsy indications, and survival bias because of analysis at dialysis inception. In patients with diabetes initiating dialysis, clinical characteristics and outcomes following dialysis initiation were similar in biopsy-proven DKD versus non-DKD. Our results suggest that the diabetic milieu has a more significant impact on outcomes in patients with diabetes treated with dialysis than the underlying pathological kidney diagnosis.

Association of malnutrition at diagnosis with survival among older adults with pancreatic cancer.

680 Background: Malnutrition is common among older adults newly diagnosed with pancreatic cancer. However, the implications of malnutrition among this vulnerable population are poorly understood. We sought to understand the association between malnourishment at diagnosis and overall survival (OS) among older adults with pancreatic cancer. Methods: We included adults aged ≥ 60 years with newly diagnosed pancreatic cancer, who were enrolled in the University of Alabama at Birmingham (UAB) Cancer and Aging Resilience Evaluation (CARE) registry between October 2017 and April 2024. To assess nutritional status, we administered an abridged version of the Patient-Generated Subjective Global Assessment (abPG-SGA) to patients at baseline prior to receiving chemotherapy. Using abPGSGA scores, we categorized patients as either normal (score ≤ 5) or malnourished (score ≥ 6). All participants were followed until death or until the cutoff date of July 10, 2024. We employed Kaplan-Meier survival analysis to estimate overall survival (OS) for both malnourished and non-malnourished groups and compared them using log-rank test. Additionally, we built multivariable Cox proportional hazards models to test the association between malnutrition and OS, while controlling for age at diagnosis, sex, race/ethnicity, and cancer stage. Results: A total of 274 patients were included; the median age at diagnosis was 70 (interquartile range, IQR: 65-75) years with 52% males, 75% non-Hispanic White and 52% with Stage IV disease at diagnosis. At baseline, 59% of patients were malnourished, and the median abPGSGA score was 8 (IQR 4-14). Patients who were malnourished had a similar demographic and clinical characteristics as compared to those without malnutrition. Over a median follow up of 36 months, a total of 202 patients (74 %) died. The median overall survival (OS) was significantly lower for malnourished patients at 13 months compared to 21 months for non-malnourished patients (log-rank test, p &lt; .001). After adjusting for potential age, sex, race/ethnicity and cancer stage, malnutrition at diagnosis remained independently associated with worse survival outcomes (adjusted HR: 1.762; 95% CI: 1.316–2.358; p &lt; .001). Conclusions: Our study reports that malnutrition at baseline is significantly associated with worse overall survival in older adults with pancreatic cancer. These findings underscore the importance of early nutritional assessment and intervention to enhance outcomes in this population.

An exploratory study of serum creatine kinase as a prognostic marker for patients with resectable pancreatic cancer: looking into the relationship with body composition

BackgroundAmong cancer patients, pancreatic cancer patients have the highest rate of sarcopenia, which is a critical prognostic factor. Serum creatine kinase (CK) is closely related to skeletal muscle mass and has been reported to decline with the progression of cancer. This study investigated whether preoperative serum CK is associated with the survival of patients with pancreatic cancer.MethodsData were obtained from patients with pathologically confirmed pancreatic cancer between June 2016 and March 2022. The prognostic significance of CK was analyzed based on sex-stratified groups. The Kaplan-Meier method was used to compare overall survival (OS) and disease-free survival (DFS). Multivariate Cox proportional hazards models were used to determine prognostic factors. Body composition was analyzed based on preoperative abdominal CT images to explore the sex-specific associations between skeletal muscle area (SMA) and serum CK levels.ResultsA total of 166 patients were included in this study. Sarcopenia was presented in 70 patients (42.2%). A low serum CK level showed a significant correlation with the diagnosis of sarcopenia in male patients (P = 0.026). The levels of CK did not predict the outcome in female patients, while a low preoperative CK was notably linked to shorter OS in male patients (median OS: 15 months vs. 33 months, P = 0.011; median DFS: 5 months vs. 14 months, P = 0.007). Multivariate analyses further confirmed the effect of CK in predicting OS (CK>44 IU/L, HR:0.226, 95% CI:0.107–0.478, P < 0.001) and DFS (CK>44 IU/L, HR:0.272, 95% CI:0.139–0.529, P < 0.001) of male patients. Correlation analysis revealed a significant association between SMA and CK levels in male patients (r = 0.225, P = 0.025), and such a correlation was not observed in female patients (r = 0.088, P = 0.478).ConclusionThe pretherapeutic CK may represent a simple marker for predicting poor survival in male patients with resectable pancreatic cancer, thereby aiding in the selection of therapeutic strategies.

Abdominal myosteatosis measured with computed tomography predicts poor outcomes in patients with glioblastoma.

Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM). We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and females using known predictors of GBM overall survival (OS) as covariates. A sex-specific composite score of predisposing and protective factors was constructed using the relative importance of each metric in GBM OS. Higher skeletal muscle volume and lower skeletal muscle fat fraction were associated with better OS in the entire dataset. A robust and independent effect on GBM OS was seen specifically for fraction of inter/intramuscular adipose tissue to total adipose tissue after correction for known survival predictors and comorbidities. Worse OS was observed with increased abdominal aortic calcification volume in both sexes. There was a significant difference in GBM OS among participants stratified into quartiles based on sex-specific composite predisposing and protective scores. The relationship between body composition and GBM OS provides an actionable advancement toward precision medicine in GBM management, as lifestyle and dietary regimens can alter body composition and metabolism and from there GBM survival.

ASA Class Is a Stronger Predictor of Early Revision Risk Following Primary Total Knee Arthroplasty than BMI.

Although there is a known correlation between obesity and revision risk following total knee arthroplasty (TKA), there is an ongoing debate regarding the appropriateness of denying TKA solely based on the body mass index (BMI) of a patient. Our aim was to determine whether a patient's American Society of Anesthesiologists (ASA) class predicts their risks of early all-cause revision and revision for periprosthetic joint infection (PJI) following primary TKA, independent of their BMI. Data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) were obtained regarding all patients who underwent primary TKA for osteoarthritis in Australia from January 1, 2015, to December 31, 2022. Estimated hazard ratios of all-cause revision and revision for PJI, as well as predicted risks of revision within 3 months, 1 year, and 2 years, as a function of patient ASA class and BMI, were calculated with use of multivariable Cox proportional hazards models. A total of 274,786 primary TKAs (54.5% female; mean age, 68.3 years) were included in the study, of which 5,401 were revised during the study period. Compared with BMI, ASA class was a stronger predictor of the risks of all-cause revision and revision for PJI following primary TKA. Patients with an ASA class of 3 to 4 had higher risks of all-cause revision and revision for PJI at multiple time points after TKA compared with patients with an ASA class of 1 to 2, regardless of BMI. Although ASA class and BMI are theoretically interrelated variables, we found that a patient's ASA class was more strongly associated with their risks of early all-cause revision and revision for PJI following primary TKA than their BMI. Employing a BMI threshold in isolation when assessing fitness for TKA may be inappropriate, and surgeons should give greater weight to the other medical comorbidities and general perioperative fitness of the patient. Patients with poorly controlled comorbidities should be referred for medical optimization prior to TKA. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Impact of expression of metabolic genes on patient (pts) outcomes in metastatic colorectal cancer (mCRC): Data from CALGB/SWOG 80405 (Alliance).

224 Background: Metabolic pathways are reprogrammed during CRC development, leading to increased glycolysis, glutaminolysis, and fatty acid synthesis. Understanding the impact of metabolic reprogramming on treatment outcomes is paramount. Hence, we investigated whether the tumor gene expression of 4 selected major metabolic genes ( PKM, SLC2A1 , SLC16A1 , and CAV1 ) could affect treatment response in pts enrolled in the CALGB/SWOG 80405 trial. Methods: 433 mCRC pts treated with either bevacizumab (bev, n = 226) or cetuximab (cet, n = 207) in combination with first-line chemotherapy were analyzed. RNA was isolated from FFPE tumor samples and sequenced on the HiSeq 2500 (Illumina). Overall survival (OS) and progression-free survival (PFS) were compared between groups of pts categorized by tertiles of gene expression (high [H], medium [M] and low [L]). Logrank P -values provide a non-parametric unadjusted assessment of differences. Likelihood ratio tests (LRT) were computed from multivariate Cox proportional hazards models, adjusting for age, sex, ECOG, tumor side, number of metastatic sites, KRAS , CMS, and treatment. Results: PKM gene expression was associated with cet treatment outcomes with PKM- low tumors showing significantly longer PFS and OS (median PFS: 14.3 vs 9.8 vs 8.1 months, L vs M vs H, P &lt; 0.0001, LRT P = 0.011; median OS: 45.9 vs 31.2 vs 20.9 months, P &lt; 0.0001, LRT P = 0.12). Low SLC2A1 was also associated with longer OS in cet-treated pts (32.4 vs 35.8 vs 25.2 months, P = 0.02, LRT P &lt; 0.0001). Similar results were observed in bev-treated pts where low SLC2A1 expressing tumors had longer OS (37.4 vs 26.1 vs 29 months, P = 0.037, LRT P = 0.069) and a non-significant trend for longer PFS (13.1 vs 11 vs 9.5 months, P = 0.076). CAV1 low gene expression was associated with longer OS in cet-treated pts (37.4 vs 34 vs 21.5 months, P = 0.0048, LRT P = 0.013), while no significant associations were found in bev-treated (interaction LRT P = 0.0009). No significant results were observed for SLC16A1 . Conclusions: The intratumoral expression of metabolic genes was prognostic and predictive in mCRC pts treated with first-line therapy. GLUT1 (encoded by SLC2A1 ) and PKM2 (encoded by PKM ) promote aerobic glycolysis of cancer cells, known as Warburg effect, supporting rapid cell proliferation and survival. CAV1 has been shown to be involved in mitochondrial bioenergetics and fatty acid metabolism and to play either a tumor suppressor or oncogenic role depending on the cancer type and stage. Lower expression of SLC2A1 and PKM was associated with improved survival and increased benefit from cet treatment in our cohort. Low CAV1 expression was also associated with increase survival suggesting a cancer-promoting role in mCRC. Our results suggest that targeting cancer cell metabolism through novel inhibitors of the aforementioned pathways may be a promising therapeutic strategy.

A comprehensive study of clinical and molecular features in patients with metastatic colorectal cancer with and without liver mets.

242 Background: Colorectal cancer (CRC) most frequently metastasizes to the liver, and patients (pts) with liver metastasis (mets) at the time of metastatic diagnosis tend to have poorer outcomes compared to pts with non-liver mets. However, the reason for this discrepancy is not well-defined. We thus aimed to identify any distinct molecular or clinical characteristics that could contribute to the poor outcomes associated with liver mets of CRC. Methods: Pts diagnosed with metastatic CRC from 2014-2022 were identified using the institutional molecular database of CRC. Demographic, clinical, and molecular data were collected by reviewing electronic medical records. Time to next treatment was defined as the time between 1st and 2nd line treatment. We utilized Fisher’s exact tests for categorical variables and both Kaplan-Meier analysis and multivariate Cox proportional hazards models to analyze survival data, with a p-value threshold of &lt;0.05 for statistical significance. Results: We identified a total of 217 pts, including pts with liver mets (N=146) and non-liver mets (N=71) at time of diagnosis. Pts with non-liver mets were more likely to have rectal primary than those pts with liver mets (40% vs. 15%, p=0.0001), indicating a distinct pattern of recurrence. Common driver mutations such as KRAS, BRAF, and TP53 were observed at equal frequencies in the liver and non-liver cohorts. In pts without liver mets, age had a significant effect on OS (p &lt; 0.05, HR 1.1). Pts without liver mets with colon primary had worse OS compared to rectum primary (HR= 0.48, 95% CI: 0.24–0.96, p = 0.038). For pts without liver mets, KRAS was not a predictor of outcomes, while BRAF was associated with poorer OS (p&lt;0.001, HR 7.09, 95%CI: 2.31-21.8). Contrarily, for pts with liver mets, KRAS mutation was significantly associated with worse survival (mOS 40.4 vs 61.7 mos, HR 2.04, 95% CI: 1.26-3.30, p=0.004). BRAF mutations were also associated with worse OS for this cohort (p=0.039 and HR 2.86, 95%CI: 1.06-7.77). Median time to the next treatment was significantly shorter in pts with liver mets (13.6 mos) than in pts with non-liver mets (22.6 mos) (HR 1.82, 95% CI 1.28-2.59; p&lt;0.001). OS was longer for pts with non-liver mets compared to those with liver mets (mOS 52.9 mos vs 46.7 mos) though it did not reach statistical significance, likely due to the small sample size. Conclusions: Liver metastasis of CRC is associated with systemic therapy resistance with a shorter time on treatment, indicating treatment resistance associated with liver mets is not limited to immunotherapy. Given similar molecular characteristics in pts with and without liver mets, treatment resistance may be related to the inherent tumor microenvironment of the liver. In this study, pts with distinct molecular features had poorer outcomes, highlighting the importance of developing targeted therapeutics in this population.

Pediatric Age-Prioritized Waitlisting Policy Potentially Disadvantages Adolescents on Dialysis Not Listed for Transplant Until Adulthood.

Current kidney transplant (KT) policies offer advantages in waiting time and organ allocation priority to pediatric patients waitlisted before 18 years old. This study evaluates the effects of this policy for patients who are on dialysis before, but not waitlisted until after, age 18. Patients aged 11-25 years and waitlisted between 2001 and 2022 for KT were identified in the OPTN STAR data file for analysis. Cohorts were defined by age and dialysis status at time of listing: Peds if < 18 yo, young adult (YA) if ≥ 18 yo; NYOD-not yet on dialysis or OD-on dialysis at time of listing, with YA groups further segregated by age at dialysis initiation. Cumulative incidence of transplant was calculated for waitlisted patients. Graft survival was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. p values < 0.01 were significant. Amongst 35 764 KT registrations, candidates who initiated dialysis as pediatric patients but were not waitlisted until after turning 18 years old (YA + OD < 18) have the highest rate of nontransplantation (33.5%) and longest time on dialysis (median: 2103 days) before deceased donor (DD) KT. YA + OD < 18 patients were sixfold less likely than Peds + OD patients to undergo DDKT at 5 years after listing. YA + OD < 18 recipients had the worst post-KT graft survival of all groups at 5 years with adjusted hazard ratio of 1.477 (95% confidence interval: 1.218-1.792) compared to Peds-NYOD (p < 0.001). Current allocation policies significantly disadvantage candidates who initiate dialysis before, but are not listed until after age 18, and should be re-examined to address these inequities.

The gut microbiome is associated with disease-free survival in stage I-III colorectal cancer patients.

Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker. Accordingly, we leveraged baseline fecal samples from N = 166 stage I-III CRC patients in the ColoCare Study, a prospective cohort of newly diagnosed CRC patients. We sequenced the V3 and V4 regions of the 16S rRNA gene to characterize fecal bacteria. We calculated estimates of alpha diversity, beta diversity, and a priori- and exploratory-selected bacterial presence/absence and relative abundance. Associations of microbial metrics with DFS were estimated using multivariable Cox proportional hazards models. We found that alpha diversity was strongly associated with improved DFS, most strongly among rectal cancer patients (Shannon HRrectum = 0.40 95% CI = 0.19, 0.87; p = .02). Overall microbiome composition differences (beta diversity), as characterized by principal coordinate axes, were statistically significantly associated with DFS. Peptostreptococcus was statistically significantly associated with worse DFS (HR = 1.62, 95% CI = 1.13, 2.31; p = .01 per 1-SD) and Order Clostridiales was associated with improved DFS (HR = 0.62, 95% CI = 0.43-0.88; p = .01 per 1-SD). In exploratory analyses, Coprococcus and Roseburia were strongly associated with improved DFS. Overall, higher bacterial diversity and multiple bacteria were strongly associated with DFS. Metagenomic sequencing to elucidate species, gene, and functional level details among larger, diverse patient populations are critically needed to support the microbiome as a biomarker of CRC outcomes.

Factors predicting asymptomatic splenic artery aneurysm expansion in patients managed conservatively: A single-center, retrospective, observational study.

Although splenic artery aneurysms (SAAs) are relatively rare in the general population, they represent the most prevalent type among visceral artery aneurysms. This study aimed to identify predictors of SAA expansion during follow-up and to contribute to a more comprehensive understanding of the natural history of SAAs. This single-center, retrospective, observational study included 137 patients with SAAs who were managed conservatively with computed tomography follow-up for a minimum of 1 year. The primary outcome was sac expansion, defined as any increase in the maximum sac diameter (≥1 mm) observed on follow-up computed tomography. The relationships between clinical variables and SAA expansion were examined. The incidence of SAA expansion was 35.0% (48/137). Eligible patients were categorized into 2 groups: the no-change (n = 89, 65.0%) and expansion (n = 48, 35.0%) groups. The 2 groups did not exhibit significant differences in demographic characteristics or risk factors, except for a higher likelihood of current smoking and portal hypertension in the expansion group. The prevalence of SAA wall calcification was notably higher in the no-change group (41/89 [46.1%] vs 8/48 [16.7%]; P < .01). Multivariable Cox proportional hazards modeling revealed that SAA expansion was more likely to occur in current smokers (hazard ratio [HR], 4.34 [95% confidence interval [CI], 1.41-13.34]; P = .01) and in those with an initial maximum SAA diameter >14 mm (HR, 3.13 [95% CI, 1.61-6.08]; P < .01), but expansion was less likely to occur in patients with SAA wall calcification (HR, 0.27 [95% CI, 0.12-0.61]; P < .01). SAA expansion was associated with wall calcification and initial maximum SAA diameters >14 mm. Further larger-scale studies are required to ascertain risk factors for rapid expansion, which could ultimately identify which categories of patients benefit most from early prophylactic intervention.

Associations between physical activities and self-harm behaviour in depression across the genotype: findings from the UK biobank.

Physical activities are widely implemented for non-pharmacological intervention to alleviate depressive symptoms. However, there is little evidence supporting their genotype-specific effectiveness in reducing the risk of self-harm in patients with depression. To assess the associations between physical activity and self-harm behaviour and determine the recommended level of physical activity across the genotypes. We developed the bidirectional analytical model to investigate the genotype-specific effectiveness on UK Biobank. After the genetic stratification of the depression phenotype cohort using hierarchical clustering, multivariable logistic regression models and Cox proportional hazards models were built to investigate the associations between physical activity and the risk of self-harm behaviour. A total of 28 923 subjects with depression phenotypes were included in the study. In retrospective cohort analysis, the moderate and highly active groups were at lower risk of self-harm behaviour. In the followed prospective cohort analysis, light-intensity physical activity was associated with a lower risk of hospitalisations due to self-harm behaviour in one genetic cluster (adjusted hazard ratio, 0.28 [95% CI, 0.08-0.96]), which was distinguished by three genetic variants: rs1432639, rs4543289 and rs11209948. Compliance with the guideline-level moderate-to-vigorous physical activities was not significantly related to the risk of self-harm behaviour. A genotype-specific dose of light-intensity physical activity reduces the risk of self-harm by around a fourth in depressive patients.

Longer recreational screen time contributes to the risk of age-related macular degeneration: a UK Biobank cohort study and two-sample Mendelian randomisation.

Recreational screen time (RST) has been found to be associated with cognitive decline and neurodegenerative diseases. However, the association between RST and age-related macular degeneration (AMD), an ocular neurodegenerative disease, is still unclear. We aimed to elucidate the association between RST and AMD. This study consisted of three parts: 1) a prospective cohort study with 482 939 UK Biobank participants and a 12.8-year median follow-up to explore the association between RST and incident AMD; 2) a two-sample Mendelian randomisation (MR) analysis using summary-level genome-wide association analysis data for RST based on 526 725 European individuals to assess causality between RST and AMD; and 3) a cross-sectional study involving 38 478 UK Biobank individuals with optical coherence tomography data to investigate the link between RST and retinal thickness. Multivariable Cox proportional-hazards models showed that an increase in total daily RST was associated with a greater risk of developing AMD (hazard ratio (HR) per standard deviation (SD) increase = 1.05; 95% confidence interval (CI) = 1.03, 1.07, P < 0.001). With further analysis, we revealed that daily high RST (>4 h/d) significantly increased the risk of AMD compared with low RST (0-3 h/d) (HR = 1.09; 95% CI = 1.04, 1.15, P = 0.001), while moderate RST (3.5-4 h/d) had no significant effect on AMD. Restricted cubic spline plots revealed a linear dose-response association between RST and AMD. With MR analysis we confirmed the potential causal association between RST and AMD (odds ratio per SD = 1.26; 95% CI = 1.01, 1.59, P = 0.042). Multivariable linear models suggested that an increase in RST was associated with thinning of the outer and inner retinal layers and total macular thickness. Longer RST may be a potential causal risk factor for AMD and may lead to pathological retinal thinning. Reducing RST could be beneficial for preventing AMD, and future research should identify the most effective time points for intervening on RST.

Critical Time Intervals in Door-to-Balloon Time Linked to One-Year Mortality in ST-Elevation Myocardial Infarction

Background: Timely activation of primary percutaneous coronary intervention (PCI) is crucial for patients with ST-segment elevation myocardial infarction (STEMI). Door-to-balloon (DTB) time, representing the duration from patient arrival to balloon inflation, is critical for prognosis. However, the specific time segment within the DTB that is most associated with long-term mortality remains unclear. In this study we aimed to identify the target time segment within the DTB that is most associated with one-year mortality in STEMI patients. Methods: We conducted a retrospective cohort study at a tertiary teaching hospital. All patients diagnosed with STEMI and activated for primary PCI from the emergency department were identified between January 2013–December 2021. Patient demographics, medical history, triage information, electrocardiogram, troponin-I levels, and coronary angiography reports were obtained. We divided the DTB time into door-to-electrocardiogram (ECG), ECG-to-cardiac catheterization laboratory (cath lab) activation, activation-to-cath lab arrival, and cath lab arrival-to-balloon time. We used Kaplan-Meier survival analysis and multivariable Cox proportional hazards models to determine the independent effects of these time intervals on the risk of one-year mortality. Results: A total of 732 STEMI patients were included. Kaplan-Meier analysis revealed that delayed door-to-ECG time (&amp;gt;10 min) and cath lab arrival-to-balloon time (&amp;gt;30 min) were associated with a higher risk of one-year mortality (log-rank test, P &amp;lt; .001 and P = 0.01, respectively). In the multivariable Cox models, door-to-ECG time was a significant predictor for one-year mortality, whether it was analyzed as a dichotomized (&amp;gt;10 min vs ≤10 min) or a continuous variable. The corresponding adjusted hazard ratios (aHR) were 2.81 (95% confidence interval [CI] 1.42–5.55) for the dichotomized analysis, and 1.03 (95%CI 1.00–1.06) per minute increase, respectively. Cath lab arrival-to-balloon time also showed an independent effect on one-year mortality when analyzed as a continuous variable, with an aHR of 1.02 (95% CI 1.00–1.04) per minute increase. However, ECG-to-cath lab activation and activation-to-cath lab arrival times did not show a significant association with the risk of one-year mortality. Conclusion: Within the door-to-balloon interval, the time from door-to-ECG completion is particularly crucial for one-year survival after STEMI, while cath lab arrival-to-balloon inflation may also be relevant.

Association of pre- and post-diagnosis dietary total antioxidant capacity (TAC) and composite dietary antioxidant index (CDAI) with overall survival in patients with ovarian cancer: a prospective cohort study

BackgroundThe evidence on the relationship of dietary antioxidant nutrients with the survival of ovarian cancer (OC) remains scarce.ObjectiveThis study aimed to investigate these associations in a prospective cohort of Chinese patients with OC.MethodsIn this prospective cohort study, patients with epithelial OC completed a food frequency questionnaire at diagnosis and 12 months post-diagnosis, and were followed from 2015 to 2023. Dietary total antioxidant capacity (TAC) and composite dietary antioxidant index (CDAI) were calculated based on specific antioxidant nutrients. We examined the associations of pre-diagnosis, post-diagnosis, and changes from pre-diagnosis to post-diagnosis in TAC, CDAI, and representative antioxidant nutrients with overall survival (OS) among patients with OC. Multivariable Cox proportional-hazards models were applied to calculate the hazard ratios (HR) and 95% confidence intervals (CI). Dose–response relationships were evaluated by restricted cubic splines.ResultsAmong the total 560 patients with OC, there were 211 (37.68%) deaths during a median follow-up of 44.40 (interquartile range: 26.97–61.37) months. High pre-diagnosis TAC (HR = 0.58; 95% CI 0.38–0.8) and vitamin C intake (HRT3 vs. T1 = 0.36; 95% CI 0.21–0.61), and post-diagnosis TAC (HR = 0.57; 95% CI 0.37–0.8), CDAI (HR = 0.57; 95% CI 0.33–0.9), and β-carotene intake (HRT3 vs. T1 = 0.55; 95% CI 0.32–0.97) were significantly associated with improved OS. Compared to patients with constantly low pre- and post-diagnosis TAC and CDAI, those with consistently higher TAC (HRMedium-Medium vs. Low-Low = 0.53; 95% CI 0.29–0.97; HRHigh-High vs. Low-Low = 0.40; 95% CI 0.16–0.94) and CDAI (HRHigh-High vs. Low-Low = 0.33; 95% CI 0.12–0.88) experienced better OS.ConclusionHigh pre- and post-diagnosis TAC, and post-diagnosis CDAI were associated with improved OC survival, suggesting that consistent high-intake of antioxidant-rich food may be beneficial for the prognosis of OC.

P-566. Long-term virologic outcomes of oral two-drug vs three-drug antiretroviral regimens in children, adolescents and adults living with HIV

Abstract Background Despite the availability and efficacy of two-drug regimens (2DR) for HIV treatment, three-drug regimens (3DR) are mostly used by people with HIV (PWH). We evaluated virologic outcomes of initiating or switching to a 2DR vs 3DR among PWH in Washington, DC. Adjusted Cox Proportional Hazard Regression Model for Virologic Non-Suppression (viral load &amp;gt; 200 copies/mL) among PWH by Two- and Three-Drug Regimens in the DC Cohort, 2019-2023 Methods We included DC Cohort treatment-experienced participants initiating or switching to a 2DR or 3DR on or after July 2019 with ≥2 years of follow-up. Descriptive statistics for demographic and clinical factors at regimen initiation, including HIV viral load (VL) and CD4 count (cells/µL), were stratified by 2DR or 3DR. Multivariable Cox proportional hazard modeling was performed among participants virally suppressed (VS; VL&amp;lt; 200 copies/mL) at regimen initiation to assess the time to non-virologic suppression (non-VS) using adjusted hazard ratios (aHR) and 95% CI adjusting for demographics, HIV risk, and regimen. Among participants who were not VS at the time of regimen initiation, we conducted a sub-analysis of the time to VS. Results We analyzed 1782 participants (72.8% 3DR, 28.2% 2DR (161 switched from a 3DR); age 54.3 years (IQR 43.8-61.3), 68.8% male; 78.1% Black) with a median CD4 621 (IQR 409-868) at regimen initiation. Participants on 2DR were older (56.4 vs 53.6 years; p&amp;lt; 0.001) and had higher VS rates (93.8% vs 88.2%; p&amp;lt; 0.001) at regimen initiation and shorter regimen times (3.2 vs 3.8 years; p&amp;lt; 0.001) compared to 3DR. 2DR participants were more likely to have public vs private insurance and receive hospital vs community-based care. The risk of non-VS was higher among those with CD4 &amp;lt; 200 and 200-500 (aHR 1.5(1.0-2.1) and aHR 2.0(1.1-3.6), respectively) compared to those with CD4 &amp;gt;500. Those with public insurance were also more likely to experience non-VS (aHR 1.5; p&amp;lt; 0.05). While regimen type was not a significant predictor of non-VS, there was an elevated risk among those on 3DR (aHR 1.2) compared to 2DR [Figure]. Among those non-VS at regimen initiation (n=146), the median time to VS was similar among PWH on 2DR (14.1 months) and 3DR (13.8 months; p=0.76). Conclusion Non-VS PWH have similar time to VS regardless of whether they receive 2DR or 3DR, suggesting similar efficacy of 2DR and 3DR in these populations. Patients with CD4 &amp;lt; 500 had higher risk of non-VS on 2DR, supporting the usefulness of the CD4 criteria factor when selecting 2DR vs 3DR. Disclosures All Authors: No reported disclosures

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