Low-risk Patients Research Articles

The Long-Term Functional and Oncologic Outcomes of Kidney-Sparing Surgery in Upper Tract Urothelial Carcinoma.

This study investigated the utilization of kidney-sparing surgery (KSS) as an alternative option to radical nephroureterectomy (RNU) in managing upper urinary tract urothelial carcinoma (UTUC) patients. Our study aimed to compare the functional outcomes and oncological outcomes between KSS and RNU. We retrospectively analyzed 252 patients with UTUC without clinical node positivity or metastasis who had been treated with either RNU or KSS. We collected information on each patient, including clinicopathological factors, renal function variations, and oncological outcomes. Hemodialysis-free survival (HDFS), stage 4 chronic kidney disease (CKD4) progression-free survival (PFS), recurrence-free survival (RFS), and overall survival (OS) were assessed using inverse probability of treatment weighting (IPTW)-weighted Kaplan-Meier analysis. The hazard ratio for oncological and functional outcomes of KSS was analyzed using the Cox proportional hazards model. The OS at 8 years was 77.06% (RNU) and 70.59% (KSS) and did not significantly differ between the two groups (p=0.691), although the KSS group experienced a higher recurrence rate. Functional outcomes indicated no significant difference in postoperative renal function at 1year; however, KSS was associated with better preservation of renal function (23.44% vs. 28.23%), albeit not statistically significant (p=0.055). Kaplan-Meier analysis revealed no significant disparities in CKD4 PFS between the KSS and RNU groups involved in the study (p=0.089), although the KSS group displayed poorer HDFS than the RNU group (p=0.001). KSS had no compromising survival outcomes when compared with RNU, not only in low-risk patients but also in high-risk patients with a normal contralateral kidney. The efficacy of renal function preservation was presented in this study, however the results were below our expectations.

Early prediction of acute-on-chronic liver failure development in patients with diverse chronic liver diseases.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days.Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT < 100, 109/L; 1 or 0] × 0.44 + [TBIL ≥ 35, µmol/L; 1 or 0] × 0.05 + [HDL-C < 0.5, mmol/L; 1 or 0] × 1.04 - Ln[Hb, g/L] × 0.89 + [BUN > 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P < 0.001). Additionally, the new score improved in predictive accuracy, time-dependent receiver operating characteristics, probability density function evaluations, and calibration curves, making it highly predictive for the onset of ACLF at all time points. The optimal cut-off value of 9.6 effectively distinguished between high- and low-risk patients for ACLF onset. These findings were further validated in a separate cohort of patients. A new progressive score, based on seven predictors, has been developed to accurately forecast the occurrence of ACLF within 7, 14, and 28 days in patients with various chronic liver diseases. This tool may be utilized to identify high-risk patients, tailor follow-up management, and guide the escalation of care, prognostication, and transplant evaluation.

Nomograms Predicting Survival, Recurrence and Beneficiary Identification of Adjuvant Chemotherapy in Treatment-naïve Patients with Rectal Cancer who Underwent Upfront Curative Resection: A multi-institutional study

Objective: To create and validate nomograms predicting overall survival and recurrence in treatment-naïve rectal cancer (RC) patients who underwent upfront surgery. Background: Although multidisciplinary treatment is standard for locally advanced RC, understanding surgical efficacy is important for determining indications for perioperative adjuvant therapy. Methods: RC patients who underwent upfront surgery at the Japanese Society for Cancer of the Colon and Rectum institutions were analyzed. A training cohort (n = 1925) of treatment-naïve patients who underwent surgery between 2007 and 2008 was analyzed to construct prognostic models predicting postoperative survival and recurrence. Discrimination and calibration were performed using an external validation cohort (n = 2957; Japanese colorectal cancer registry, procedures in 2005–2006). Effects of adjuvant chemotherapy on survival were evaluated based on nomogram prediction and Surveillance, Epidemiology, and End Results (SEER) data (n = 10,482; upfront surgery for RC in 2010–2015). Results: In the training cohort, age predicted survival, venous invasion predicted recurrence, and sex, tumor location, histological type, preoperative carcinoembryonic antigen, invasion depth, lymphatic invasion, positive radial margin, and numbers of metastatic nodes and examined nodes predicted both. Internal and external validated Harrell’s C-index values were respectively 0.77 and 0.75 for survival and 0.75 and 0.74 for recurrence. RC patients who underwent upfront surgery in the SEER database were stratified into 3 risk levels by nomogram score. Adjuvant chemotherapy did not improve 5-year survival in low-risk patients, but did so for middle-risk (62.4% vs 76.8%) and high-risk (39.4% vs 63.5%) patients. Conclusion: These nomograms could predict survival and recurrence after upfront curative resection of RC and identify cases expected to benefit more from adjuvant chemotherapy.

Analysis of immune status and prognostic model incorporating lactic acid metabolism-associated genes.

Cancer development is intricately linked with metabolic dysregulation, including lactic acid metabolism, which plays a pivotal role in tumor progression and immune evasion. However, its specific implications in gastric adenocarcinoma (STAD) remain unclear. This study introduces a novel methodology to evaluate lactic acid metabolism comprehensively in STAD, aiming to elucidate its prognostic significance and impact on immunotherapy efficacy. Targeted therapies directed at key lactic acid metabolism genes (LMGs) identified within the tumor microenvironment (TME) hold promise for personalized treatment strategies. Lactic acid metabolism patterns were assessed in 415 STAD patients using a panel of 21 LMGs. Cox regression and Lasso regression analyses were employed to develop a predictive risk model based on differentially expressed genes (DEGs). Validation of the model was conducted using independent cohorts from the GEO and TCGA databases, as well as additional datasets focused on immunotherapy responses. Further investigations into TME dynamics of lactic acid metabolism included functional assays targeting SLC16A3, a pivotal gene identified through our analyses. Patients were stratified into distinct risk groups based on their lactic acid metabolism profiles. Low-risk patients exhibited attenuated lactic acid metabolism, correlating with favorable clinical outcomes characterized by prolonged survival and enhanced responsiveness to immunotherapy. Notably, tumor cells within the TME demonstrated heightened levels of active lactic acid metabolism, particularly impacting tumor-infiltrating lymphocytes such as CD8 + T cells and regulatory T cells. Mechanistically, SLC16A3 emerged as a critical regulator promoting STAD cell proliferation, invasion, and migration while modulating the metabolic landscape. This study underscores the prognostic value of a lactic acid metabolism-based model in STAD, providing insights into its potential as a predictive biomarker for patient stratification and therapeutic targeting. The findings highlight SLC16A3 as a promising candidate for therapeutic intervention aimed at modulating lactic acid metabolism in the TME, thereby advancing personalized treatment strategies in gastric cancer management.

The IL-1β inhibitor canakinumab in previously treated lower-risk myelodysplastic syndromes: a phase 2 clinical trial.

In myelodysplastic syndromes (MDS), the IL-1β pathway is upregulated, and previous studies using mouse models of founder MDS mutations demonstrated that it enhances hematopoietic stem and progenitor cells' (HSPCs') aberrant differentiation towards the myeloid lineage at the expense of erythropoiesis. To evaluate whether targeting the IL-1β signaling pathway can rescue ineffective erythropoiesis in patients with MDS, we designed a phase 2 non-randomized single-arm clinical trial (NCT04239157) to assess the safety profile and efficacy of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS patients. We enrolled 25 patients with a median age of 74 years; 60% were male, 16% had lower-risk MDS, 84% had intermediate-1 risk MDS according to the International Prognostic Scoring System score, and 80% failed hypomethylating agent therapy. The study met the primary endpoint of defining the clinical activity of canakinumab, and the secondary objective of determining the safety profile, including the rate of transfusion independence, the duration of response, progression-free survival, leukemia-free survival, and overall survival. The overall response rate was 17.4%, with all responses including hematological improvement. Sequential post-hoc prospective single-cell RNA sequencing analyses of HSPCs and bone marrow mononuclear cells at different time points during therapy showed that canakinumab's on-target effects in hematopoietic populations expressing the IL-1β receptor decreased the TNF-mediated inflammatory signaling pathway but rescued ineffective erythropoiesis only in the context of lower genetic complexity. This study demonstrates that better stratification strategies could target lower-risk MDS patients more effectively.

A novel platelets-related gene signature for predicting prognosis, immune features and drug sensitivity in gastric cancer

BackgroundPlatelets can dynamically regulate tumor development and progression. Nevertheless, research on the predictive value and specific roles of platelets in gastric cancer (GC) is limited. This research aims to establish a predictive platelets-related gene signature in GC with prognostic and therapeutic implications.MethodsWe downloaded the transcriptome data and clinical materials of GC patients (n=378) from The Cancer Genome Atlas (TCGA) database. Prognostic platelets-related genes screened by univariate Cox regression were included in Least Absolute Shrinkage and Selection Operator (LASSO) analysis to construct a risk model. Kaplan-Meier curves and receiver operating characteristic curves (ROCs) were performed in the TCGA cohort and three independent validation cohorts. A nomogram integrating the risk score and clinicopathological features was constructed. Functional enrichment and tumor microenvironment (TME) analyses were performed. Drug sensitivity prediction was conducted through The Cancer Therapeutics Response Portal (CTRP) database. Finally, the expression of ten signature genes was validated by quantitative real-time PCR (qRT-PCR).ResultsA ten-gene (SERPINE1, ANXA5, DGKQ, PTPN6, F5, DGKB, PCDH7, GNG11, APOA1, and TF) predictive risk model was finally constructed. Patients were categorized as high- or low-risk using median risk score as the threshold. The area under the ROC curve (AUC) values for the 1-, 2-, and 3-year overall survival (OS) in the training cohort were 0.670, 0.695, and 0.707, respectively. Survival analysis showed a better OS in low-risk patients in the training and validation cohorts. The AUCs of the nomogram for predicting 1-, 2-, and 3-year OS were 0.708, 0.763, and 0.742, respectively. TME analyses revealed a higher M2 macrophage infiltration and an immunosuppressive TME in the high-risk group. Furthermore, High-risk patients tended to be more sensitive to thalidomide, MK-0752, and BRD-K17060750.ConclusionThe novel platelets-related genes signature we identified could be used for prognosis and treatment prediction in GC.

Identification of key programmed cell death genes for predicting prognosis and treatment sensitivity in colorectal cancer

Colorectal cancer (CRC) ranks third in global incidence and second in mortality. However, a comprehensive predictive model for CRC prognosis, immunotherapy response, and drug sensitivity is still lacking. Various types of programmed cell death (PCD) are crucial for cancer occurrence, progression, and treatment, indicating their potential as valuable predictors. Fourteen PCD genes were collected and subjected to dimensionality reduction using regression methods to identify key hub genes. Predictive models were constructed and validated based on bulk transcriptomes and single-cell transcriptomes. Furthermore, the tumor microenvironment, immunotherapy response, and drug sensitivity profiles among patients with CRC were explored and stratified by risk. A risk score incorporating the PCD genes FABP4, AQP8, and NAT1 was developed and validated across four independent datasets. Patients with CRC who had a high-risk score exhibited a poorer prognosis. Unsupervised clustering algorithms were used to identify two molecular subtypes of CRC with distinct features. The risk score was combined with the clinical features to create a nomogram model with superior predictive performance. Additionally, patients with high-risk scores exhibited decreased immune cell infiltration, higher stromal scores, and reduced responsiveness to immunotherapy and first-line clinical drugs compared with low-risk patients. Furthermore, the top ten non-clinical first-line drugs for treating CRC were selected based on their predicted IC50 values. Our results indicate the efficacy of the model and its potential value in predicting prognosis, response to immunotherapy, and sensitivity to different drugs in patients with CRC.

BN SO48 - Antibiotic prescribing for elective inguinal hernia repairs

Abstract Background Inguinal hernia repairs are a common procedure with over one million operations performed annually in Europe and the US. The European Hernia Society do not recommend the routine use of antibiotics in low-risk patients due to no significant benefit. They advise the consideration of prophylaxis for patients with risk factors including recurrence, age &amp;gt; 70 years or immunosuppression. Many surgeons are using antibiotic prophylaxis in all patients. However, inappropriate antibiotic use contributes to increased antibiotic resistance and increased healthcare cost. Our trust guidelines recommend a single dose of Cefuroxime in all patients undergoing an inguinal hernia repair with mesh. Method The aim of the project was to determine the compliance with current trust guidelines regarding antibiotic use in elective inguinal hernia repair with mesh. We also aimed to report on antibiotic prescribing patterns. Patients undergoing an elective inguinal hernia repair with mesh over a six-month period were identified. Data was collected retrospectively from electronic patient records and included patient’s age, if they were classed as high risk (age over 70, recurrence of hernia, diabetic, steroid therapy), if antibiotics were prescribed, and if so, which antibiotics were utilised. Results Eighty-five patients were included in the final data analysis. The median age of patients included was 67 years of age, and 93% were male. 41 patients were identified as high risk, and most patients were ASA II. Our results reported that 48% of patients were prescribed prophylactic antibiotics at induction. However, only two patients were prescribed the correct antibiotic, as per trust guidelines. Most patients were prescribed Co-Amoxiclav (78%), with a range of other antibiotics being used, including Flucloxacillin, Clarithromycin and Metronidazole. We identified 37% of high-risk patients were not prescribed antibiotics. Conclusion Our trust guidelines were not reflective of best practice and did not consider individual patient or procedure risk factors. We identified varied antibiotic prescribing patterns with low compliance to trust guidelines. Utilising our findings, we have created new guidelines, which recommend that in low-risk patients, routine antibiotic prophylaxis is not required. However, in the presence of patient-related risk factors as mentioned above, then a single dose of Cefuroxime is recommended. The updated guidelines will ensure good antimicrobial stewardship and reduce unnecessary antibiotic prescriptions. In addition, they accurately reflect the current evidence base surrounding antibiotic prophylaxis.

Abstract A009: Integrative multiomic analysis of extracellular vesicle transcriptomics profiling combined with cfDNA methylation reveals improved stratification of low-risk and high- risk prostate cancer patients in urine-based liquid biopsy

Abstract Introduction: Prostate cancer (PCa) ranks as the second most frequently diagnosed cancer and the sixth most prevalent cause of cancer-related mortality in men globally. In this study, we employ a multiomic approach that utilizes both urine cfDNA and extracellular vesicle (EV) RNA-derived analytes to improve the risk stratification of individuals with prostate cancer and compare this to multi-parametric MRI performance as well as risk calculators in the same cohort. Materials and Methods: Urine was collected from 95 individuals comprising 51 benign or low-risk (Grade Group (GG) &amp;lt;=1), 10 intermediate-risk (GG2) and 44 high-risk PCa patients (GG 3-5). EV-RNA and cfDNA were concurrently isolated from each urine specimen to exploit complementary information. We developed an EV-RNA sequencing platform targeting mRNAs and lncRNAs and targeted 50 million reads per sample; and cfDNA methylome profiling reached an equivalent sequencing depth. Expression of EV-RNA and splice variant Differential Transcript Usage (DTU) and cfDNA methylation patterns were analyzed using Bio-Techne’s multiomic platform. Machine learning-based feature selection algorithms identified biomarker signatures from each analyte. Receiver-operator characteristic curves (ROC) were generated utilizing leave-one-out cross-validation of naïve Bayes classifier models to compute the area under the curve (AUC). Individual signatures were integrated to create a multiomic classifier. Results: Differential gene expression (DEx) analysis identified 18 DEx genes between low and high-risk patients with both known and novel implications in PCa. Splice variant analysis unveiled 60 genes previously implicated in PCa with DTU. Over 18,000 differentially methylated bases were detected between high and low-risk PCa patients. Feature selection analysis identified the top ten features of EV-RNA expression, splice variants, and cfDNA methylation, resulting in an integrative multi-analyte signature. The multiomic signature demonstrated an AUC of 0.92, surpassing any individual analyte’s performance, as well as the performance achieved by PSA (AUC = 0.52) and MRI PI RADS(AUC=0.65). Conclusions: While biomarker signatures obtained from each analyte in this study resulted in effective stratification of PCa risk, the multiomic signature further improved the discriminatory power—underscoring the complementary nature of the signals. Thus, a multiomic biomarker discovery strategy leveraging cfDNA and EV cargo exhibits significant potential as a risk assessment tool for high-grade prostate cancer. This approach can facilitate more informed decision-making in the context of biopsy procedures. Citation Format: Sudipto K Chakrabortty, Dulaney Miller, Kyle Manning, Rikky Xing, Jeff Cole, Christopher Benway, Sinead Nguyen, Allan George, Yiyuan Yao, Elena M Cortizas, Christian Ray, Siva Gowrisankar, Seth Yu, Allan Pollack, Sandra M Gaston, Sanoj Punnen, Johan Skog. Integrative multiomic analysis of extracellular vesicle transcriptomics profiling combined with cfDNA methylation reveals improved stratification of low-risk and high- risk prostate cancer patients in urine-based liquid biopsy [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A009.

Abstract 4132875: Living Address Environmental Biotope Affects the Risk of Coronary Obstruction and Myocardial Ischemia Detected by Coronary Computed Tomography

Background: Several studies reported positive associations between air and noise pollution exposure and coronary artery calcification, but environmental effects on coronary obstruction and flow remain largely unknown. Hypothesis: Distance to road and airport, air pollution, and residential green space are linked to coronary artery obstruction and myocardial ischemia. Low CV-risk patients develop coronary obstruction due to environmental factors, while high-risk patients are more prone to develop myocardial ischemia. Methods: Consecutive patients screened by coronary CT angiography for stable chest pain between 01/01/2019 and 31/12/2020 were included in a registry. Distance to airport and major road, and exposure to PM2.5, NO 2 and normalized difference vegetation index (NDVI) were modelled at patients’ living address. Risk of obstructive coronary artery disease (OCAD, stenosis ≥50%) and abnormal fractional flow reserve (FFR CT &lt;80%) was assessed using propensity score (PS)-adjusted logistic regression. Subgroup analysis was performed according to gender and Framingham CV-risk categories. Results: We enrolled 2620 patients, including 420 (16%) FFR CT analyses. OCAD was reported in 518 (20%) patients and abnormal FFR CT in 276 (11%). People with OCAD lived closer to the airport (10.841 [7.869-19.022] km vs. 12.297 [8.691-22.843] km, p&lt;0.001). Distance to airport decreased OCAD risk (OR 0.983, 95%CI 0.974-0.992, per 1 km) in univariate analysis, with the association present in male, female, and low-risk patients. After PS-adjustment, a trend of association was present between airport distance and abnormal FFR CT risk (OR 0.986, 95%CI 0.969-1.003, per 1 km). Road distance tended to decrease OCAD risk in univariate and PS-adjusted analysis, in the general (OR 0.928, 95%CI 0.808-1.309; and OR 0.928, 95%CI 0.840-1.021, per 1 km) and high-risk population. NO 2 exposure tended to increase OCAD risk in univariate analysis (OR 1.012, 95%CI 0.997-1.027, per 1 µg/m 3 ), with the association only present in female patients, and disappearance after PS-adjustment. PM2.5 exposure showed no associations, while NDVI tended to increase OCAD risk in low-risk patients after PS-adjustment. Conclusion: Residential distance to airport is the major risk component compared to other urban exposome factors studied in this epidemiological observation. Green space tends to exert a cardioprotective effect in low-risk patients, whereas living close to major road worsens the risk in high-risk patients

Abstract 4135270: Clinical and Procedural Outcomes after Transcatheter Aortic Valve Replacement vs Surgical Aortic Valve Replacement in Severe Aortic Stenosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: A growing body of evidence from randomized controlled trials (RCTs) has demonstrated the superiority of transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR) irrespective of surgical risk in patients with severe aortic stenosis (SAS). Given the rise in TAVR procedures, analyzing trends in outcomes over time is critical to aid clinical decision-making. Hence, we pooled RCT data for a robust assessment of clinical and procedural outcomes in SAS patients undergoing TAVR and SAVR. Methods: PUBMED and SCOPUS were queried until April 2024. Trials were classified into high and low-risk groups based on surgical risk. The outcomes were analyzed at 30 days (short-term), 1 year (mid-term), and 5 years (long-term). Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI). Results: 10 RCTs with a total of 10,252 patients were included. There was no significant association between TAVR and SAVR in reducing all-cause mortality at 30 days (RR: 0.84 [0.64, 1.10]; Figure 1a). While TAVR was associated with a significantly lower all-cause mortality at 1 year (RR: 0.82 [0.68-0.97]; Figure 1b), it was linked with a significantly higher all-cause mortality at 5 years (RR: 1.14 [1.07-1.21]; Figure 1c). Myocardial infarction and stroke were similar in both groups up to 5 years. TAVR was associated with a lower risk of acute kidney injury for up to 1 year and atrial fibrillation for up to 5 years but a higher risk of new permanent pacemaker implantation and aortic valve re-intervention for up to 5 years. In low-risk patients, TAVR showed no significant differences from SAVR for all-cause mortality at 30 days and 5 years, but it was significant at 1 year. In high-surgical-risk patients, all-cause mortality was comparable between TAVR AND SAVR at 30 days and 1 year, with a higher rate observed with TAVR at 5 years. Conclusion: Compared with SAVR, TAVR was superior in reducing all-cause mortality at 1 year in low-risk patients and inferior in reducing all-cause mortality at 5 years in high-risk patients. A thorough evaluation of anatomical, clinical, and procedural factors is crucial to tailor the optimal intervention for each patient.

The 2-week wait pathway for suspected head and neck cancers in patients with throat and voice symptoms: referral patterns, common clinical practice and diagnostic efficacy of NICE guidelines.

The 2-week wait (2ww) referral pathway has been introduced into UK clinical practice to increase the early detection of cancer and improve survivals. The efficiency of this system for head and neck (H&N) cancers has been questioned over the years because of evidence of low pick-up rates. H&N cancers present with a wide variety of non-specific symptoms, particularly throat and voice symptoms. These symptoms need to be accurately interpreted together with risk factors if they are to be addressed adequately and overload of cancer facilities avoided. One of the most common outcomes of H&N 2ww referrals is laryngopharyngeal reflux (LPR), a common condition that could be diagnosed and managed in the primary care setting with a prescription of proton pump inhibitors (PPI) trials. We retrospectively analysed a cohort of consecutive patients referred on the 2ww pathway for throat and voice symptoms at University College London Hospital H&N cancer clinic during two months in 2019. A total of 101 patients (43.6% men, mean age 53.3 years) were included. Throat and voice symptoms were described as intermittent in 52.5% and non-lateralised in 88.1%. Diagnosis of LPR was made in 59.4% of the referrals. A PPI trial was prescribed by general practitioners (GPs) in only 7.9% of cases. The cancer pick-up rate in our cohort is 2.9%. An improved awareness of the symptoms of LPR could guide GPs to prescribe trials of PPIs in low-risk patients before rushing into a referral on a cancer pathway. This would improve the 2ww process on many levels, reduce the burden on the National Health Service and avoid patients' psychological distress.

Abstract 4134977: Utility of Coronary Artery Calcium Scoring in Low-Risk Patients: the Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Coronary artery calcium (CAC) scoring is a powerful tool for atherosclerotic cardiovascular disease (ASCVD) risk assessment. Guidelines recommend consideration of CAC scoring in intermediate risk patients, but it’s utility in low and borderline risk patients is less clear. Methods: We used data from 2,894 participants from MESA with low (&lt;5%) or borderline (5-&lt;7.5%) 10-year ASCVD risk defined by the pooled cohort equations (PCE). We evaluated the association between CAC score and coronary heart disease (CHD) and ASCVD risk using multivariable adjusted Cox proportional hazard models. We also evaluated if the addition of CAC to the pooled cohort equations (PCE) improved risk prediction using Harrell’s C-index and net reclassification improvement (NRI). Results/Data: Mean age was 54.1 ± 5.8 years with 66.9% women. Among low-risk individuals, the ASCVD event rate was 3.3% with CAC=0, and 7.8% with CAC&gt;0, and 4.7% vs. 11.4% among borderline-risk individuals. Natural-log transformed CAC score was associated with increased ASCVD risk in low-risk (HR 1.35, 95% CI 1.22-1.50) and borderline-risk (HR 1.29, 95% CI 1.15-1.45) individuals. Similar results were seen for CHD with higher HRs ( Table 1 ). The addition of CAC to the PCE improved the C-index (SE) among low/borderline risk individuals from 0.620 (0.023) to 0.671 (0.024). Continuous NRI was also significant with the addition of CAC to the PCE in low/borderline risk (0.422, 95% CI 0.248-0.611). Greater improvement was seen for CHD ( Table 2 ). Conclusions: The presence of CAC in low and borderline risk individuals is associated with increased ASCVD and CHD risk. The addition of CAC scoring to the PCE improved risk prediction in low and borderline risk individuals, suggesting potential clinical utility in this population.

Abstract 4134796: Safety of over 1000 consecutive, selected low risk patients with accelerated discharge from a chest pain unit with early generation cardiac troponin use, no cardiac functional or anatomic testing and no clinical risk scores

Introduction: Over 6 million patients (pts) present to US emergency departments annually with chest pain (CP), of which the majority are found to have no serious disease. Evaluation of these pts results in substantial costs for unnecessary hospitalization and extensive testing. We evaluated the utility of early discharge of selected low-risk (LR) CP pts from a chest pain unit (CPU) in which no predischarge testing or risk scores were used. Methods: This retrospective study analyzed 1,037 consecutive LR CP pts from a prospectively recorded database. LR was based on normal examination, stable hemodynamics, normal electrocardiograms (ECG), and negative cardiac troponin I, without pre-discharge functional or anatomic cardiac testing or risk scores. We assessed demographics, comorbidities, medications, and major cardiac events at 30 d and 6 mos post-discharge. Results: The study group of 1037 pts comprised 26% of the 4010 pts admitted to the CPU during the study interval from May 2005 to March 2015. Mean patient age was 55 yrs, 56% (n=575) were women, and comorbid conditions were frequent: hypertension (64.1%), dyslipidemia (46.1%), diabetes (25.7%), documented coronary artery disease (19.3%), previous revascularization (20.6%), previous myocardial infarction (10.1%). Length of stay (LOS) in the CPU to discharge was 10.4 hrs. Women received more discharge cardiac medications than men: antiplatelet agents, statins, beta blockers, ACE inhibitors, angiotensin II blockers, calcium channel blockers, and nitrates (p=0.0002 - 0.04). Follow-up (F/U) at 30 d was 91% (n=948) complete and revealed 0.3% (n=3) cardiac deaths, 0.6% (n=6) acute coronary syndromes (ACS), and 6.2% (n= 64) receiving revascularization. F/U at 6 mos was 90% (n=936) complete and total cumulative cardiac deaths were 0.9% (n=9), 0.7% (n=7) ACS and 6.3% (n=65) revascularization. Discussion: Cardiac events at both 30 d and 6 mos were very low and did not differ in men and women (P=0.8). LOS in CPU was minimized and patient safety was maintained. These selected LR pts remained at reduced risk for cardiac events despite a high rate of comorbidities. Early discharge of selected LR CP pts based on history, examination, ECG, and biomarker evaluation was safe and effective. Conclusion: This approach in selected LR pts has the potential to reduce unnecessary diagnostic testing and CPU LOS. This strategy could lead to substantial savings in healthcare costs without compromising patient safety.

Abstract 4115231: Higher Global Registry of Acute Coronary Events Score is Associated with Lower Invasive Coronary Angiograpy Use

Background: Use of invasive coronary angiography (ICA) and the selection of other interventions in patients who present with NSTEMI should be guided by clinical risk stratification. National guidelines recommend ICA use in patients with intermediate and high risk scores. The Global Registry of Acute Coronary Events (GRACE) score is a commonly used risk score that is based on clinical characteristics available at the time of admission. Aim: Examine if patients with NSTEMI with higher risk stratification scores are more likely to have ICA. Methods: This cross-sectional study included all patients who presented with NSTEMI to an academic medical center that serves a rural population over a 12-month period. Data were derived from the American College of Cardiology Chest Pain – MI Registry data collected by trained abstractors at the facility and were verifed by the study team. Additional data needed to calculate the GRACE Score were abstracted by the study team. GRACE Scores were categorized into low (1-88), moderate (89-118), and high (119-263) risk. Multivariable logistic regression was used to test if higher GRACE scores are more associated with ICA use controlling for patient factors not included in the GRACE Score and further examined by GRACE score category. Results: The total sample size was 434 patients (Mean age 65±13.8, 36% female and 36% Black). Patients transferred from outlying facilities accounted for 40% of the sample. ICA was performed for 94% of the patients. Increasing GRACE score was associated with lower ICA use (aOR 0.98, 95% CI 0.97-0.99). Odds of ICA use between the low-risk group and the intermediate risk group (aOR 0.60, 95% CI 0.19-1.91) did not significantly differ. Patients in the high-risk category were less likely to undergo ICA compated to low-risk patients (aOR 0.22, 95% CI 0.07-0.62). Conclusions: Use of ICA decreased as GRACE score increased in this patient sample, suggesting that additional factors beyond GRACE score likely influence ICA use in patients who presented with NSTEMI during this time period. Influence of patient factors as well as provider and patient risk aversion on ICA selection must be explored to better understand incongruence with guideline recommendations.

Influence of an Alternative Diagnosis on the Diagnosis of Pulmonary Thromboembolism

Background: The diagnosis of pulmonary embolism (PE) is based on the application of a priori probability scales such as the Wells scale or PERC. However, the clinical heterogeneity of this pathology results in the absence of a target population to apply these algorithms. The Wells score does consider the possibility of an alternative diagnosis, awarding an additional point if no other diagnosis is likely, yet the presence of objective alternative diagnoses can still complicate clinical assessment and lead to unnecessary testing or missed diagnoses. Objective: The aim of this study is to evaluate the discrimination capacity of clinical objective factors with a high negative predictive value for PE, compared to PERC in terms of reducing unnecessary testing across different risk strata of the Wells scale. Materials and Methods: This was a single-center retrospective cohort study, including patients who underwent chest CT angiography to rule out PE at a university hospital between 2008 and 2017, considering the presence of PE as the study outcome. The study collected demographic data, comorbidities, and clinical presentation data. The presence of objective criteria for pneumonia, heart failure, exacerbation of COPD, or the use of anticoagulation in non-oncological patients were considered a priori criteria with a high negative predictive value. Results: The analyses were performed on a cohort of 399 patients with an average age of 65 years and 53% females. A total of 139 patients were diagnosed with PE by CT angiography. The presence of factors with a high NPV showed a sensitivity of 100% in low-risk patients according to Wells, with sensitivity dropping below 50% in other populations. The association of these factors in the PERC plus criteria would allow a reduction of up to 34% in CT angiographies in patients with low risk according to the Wells scale. Conclusions: The combination of risk stratification of the Wells scale and PERC plus criteria allows an absolute reduction of 34.3% in the performance of CT angiographies in patients classified as low risk with a sensitivity and a negative predictive value of 100%. The preexistence of an alternative diagnosis does not allow ruling out PE in patients with intermediate or high risk according to the Wells scale.

Screening high-risk individuals for primary gastric adenocarcinoma: evaluating progression-free survival probability score in the presence and absence of Rictor expression after gastrectomy

ObjectiveDeveloping nomogram-based risk stratification model to determine 3-year and 5-year progression-free survival (PFS) and to identify high-risk patients with gastric adenocarcinoma based on different Rictor statuses.Methods1366 individuals who underwent radical gastric surgery to treat gastric adenocarcinoma at Shanxi Cancer Hospital from May 2002 to December 2020 were analyzed. Cox regression analysis was employed to create the nomograms. The nomograms’ performance was assessed using C-index, time receiver operating characteristic (t-ROC) curves, calibration curves, and decision curve analysis (DCA) curves in training and validation cohorts. Subsequently, patients were categorized into high-risk and low-risk groups based on the nomogram’s risk scores.ResultsThe Rictor (-) nomogram for predicting PFS included variables such as age, number of positive lymph nodes, vascular invasion, maximum diameter of the tumor, omentum metastasis, and expression of MSH2. In the internal validation, the C-index of the Rictor (-) nomogram was 0.760 (95%CI: 0.720-0.799), which was superior to the C-index of the American Joint Committee on Cancer (AJCC) 8th edition TNM staging (0.683, 95%CI: 0.646-0.721). Similarly, the Rictor (+) nomogram for predicting PFS included variables such as gender, age, pT stage, number of positive lymph nodes, neural invasion, maximum diameter of the tumor, omentum metastasis, Clavien-Dindo classification for complications, and CGA expression. The C-index of the Rictor (+) nomogram was 0.795 (95%CI: 0.764-0.825), which outperformed the C-index of the AJCC 8th edition TNM staging (0.693, 95%CI: 0.662-0.723). The calibration curves, t-ROC curves, and decision curve analysis for both nomogram models demonstrated their excellent prediction ability.ConclusionThis study presents the first risk stratification for Rictor status in gastric adenocarcinoma. Our model identifies low-risk patients who may not require additional postoperative treatment, while high-risk patients should consider targeted therapies that specifically target Rictor-positive indicators.

CTNI-57. REAL-WORLD EVIDENCE OF THE FREQUENCY OF POST-SURGICAL INITIAL OBSERVATION IN PATIENTS WITH IDH-MUTANT GLIOMA

Abstract BACKGROUND After initial resection of IDH-mutant gliomas, initial observation is an option for low-risk patients, to postpone potential therapy-related toxicities without impacting survival. Since NCCN guidelines for risk stratification are considered controversial, we aimed to assess the frequency of initial observation in IDH-mutant gliomas using real-world evidence in the US. METHODS We evaluated Optum claims from 2016-2021 of patients age ≥12 with ICD-10 codes for incident glioma. Since ICD-10 does not distinguish IDH-mutant from IDH-wild type (GBM) gliomas, we excluded patients with factors indicative of GBM (age&amp;gt;60/ hypofractionated RT/ carmustine wafer/ tumor-treating fields) to create a baseline cohort. We then evaluated the subgroup age &amp;lt;40 (&amp;lt;40 cohort), who have higher IDH-mutant incidence. To distinguish initial observation from surgical recovery, we assessed time from index surgery to first intervention. When 90% of first interventions had occurred those still without intervention were considered to undergo initial observation. RESULTS The baseline and &amp;lt;40 cohorts comprised 5404 and 646 patients, respectively. In the baseline cohort, 56% had intervention by day 90 (most commonly concurrent chemoradiation); peak intervention rate was 60%. Initial observation rate was 44%. In the &amp;lt;40 cohort, 47% had an intervention by day 90; peak intervention rate was 52%. Initial observation rate was 53%. CONCLUSIONS In both cohorts ≥90% of patients with likely IDH-mutant gliomas not initiating treatment within 3 months post-surgery continued in active observation. Initial observation rates were 44-53%, well above the levels we had expected based on NCCN guidelines. The cohorts likely include some GBM patients, for whom observation is unaccepted, and therefore these rates may understate actual initial observation rates for IDH-mutant glioma patients. These findings suggest that clinicians and patients have chosen initial observation over existing treatments, evincing a need for additional treatment options for this younger group of patients with considerably long life expectancy.

Phase 3 validation of PAaM for hepatocellular carcinoma risk stratification in cirrhosis

Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis. Molecular (Prognostic Liver Secretome signature with alpha-fetoprotein) and clinical (aMAP score) variable-based scores were integrated to develop PAaM, which was subsequently validated in two phase 3 biomarker validation studies: the statewide Texas HCC Consortium (THCCC) and nationwide HCC Early Detection Strategy (HEDS) prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation (PRoBE) design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events. Of 2,156 cirrhosis patients in THCCC, PAaM identified 404 (19%) high-risk, 903 (42%) intermediate-risk, and 849 (39%) low-risk patients with annual HCC incidence rates of 5.3%, 2.7%, and 0.6%, respectively. Compared to low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios (sHRs) for incident HCC of 7.51 (95% confidence interval [CI], 4.42-12.8) and 4.20 (95%CI, 2.52-7.01), respectively. Of 1,328 cirrhosis patients in HEDS, PAaM identified 201 (15%) high-risk, 540 (41%) intermediate-risk, and 587 (44%) low-risk patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate risk groups were associated with sHRs for incident HCC of 6.54 (95%CI, 3.85-11.1) and 1.77 (95%CI, 1.02-3.08), respectively. Subgroup analysis showed robust risk stratification across HCC etiologies, including metabolic dysfunction-associated steatotic liver disease (MASLD) and cured hepatitis C infection. PAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies.

Individualised prediction of chemotherapy benefit in early-onset colorectal cancer

PurposesWhether patients with early-onset colorectal cancer (EOCRC) receive chemotherapy has been controversial, so our study aimed to screen patients with EOCRC who benefit from chemotherapy.MethodsA total of 2166 EOCRC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into chemotherapy and non-chemotherapy groups, propensity score matching (PSM) was performed to balance the differences between the groups, and the Kaplan–Meier method was used to calculate the cancer-specific survival (CSS) of EOCRC patients. Multifactorial COX regression analysis was used to identify independent prognostic factors for CSS and to construct a nomogram for predicting CSS in EOCRC patients. The overall risk score was calculated based on Nomogram, and EOCRC patients were classified into high-risk and low-risk groups to assess further chemotherapy's therapeutic effect on patients with different risk stratification.ResultsBefore PSM, patients in the chemotherapy group had poorer CSS (p < 0.001). After PSM, there was no significant difference in patient CSS between the two groups (p = 0.057). Independent prognostic factors (Race, Grade, Pathology, AJCC.N, AJCC.M, CEA, Marital. Status) were screened according to multifactorial COX regression analyses and included in the Nomogram predicting CSS in EOCRC patients. A risk stratification system for EOCRC patients was further developed, and the results showed that chemotherapy had no significant effect on CSS in the low-risk group of patients, but in the high-risk group, chemotherapy significantly improved CSS in EOCRC patients.ConclusionsWe developed a clinical risk model by combining different risk factors, which can accurately screen those with high-risk EOCRC for benefit from chemotherapy. For low-risk EOCRC patients, our results did not observe a better survival benefit from chemotherapy, and more prospective studies are needed in the future to prove our conclusions.