Prognostic Marker In Patients Research Articles

Prognostic significance of Klotho expression in patients with renal cell carcinoma.

Various molecular markers have been investigated in renal cell carcinoma (RCC) without significant reliability. We analyzed Klotho (tumor suppressive protein) expression in RCC to investigate its association with tumor-stage, grade, disease-free-survival (DFS) and overall-survival (OS). Data of histologically confirmed patients of RCC with complete clinical follow-up were retrieved from Medical-Record-Library. Tissue sections of tumor and normal parenchyma were prepared from the blocks. Immunohistochemical studies for Klotho were done with commercially available kit (EPR6856, Ab181373; Abcam, Cambridge MA, USA). Klotho expression was scored between 0-3 and grouped into weak/absent (0, 1) and moderate/strong (2, 3). Tumors stages and grades were grouped into low stage (I and II) and high stage (III and IV) and into low grade (grade 1 and 2) and high grade (grade 3 and 4) according to WHO/ISUP grading. The histopathologists were blinded as to the clinical and follow-up data. Various prognostic factors were analyzed with respect to Klotho expression. Kaplan-Meier curves were created for DFS and OS. Fifty-four patients of mean age 55.15 ± 13.34 years and M:F ratio of 1.8:1 were included. Normal renal tissue had strong expression of Klotho in all. In tumor tissue 20 (37%) had negative, 7 (13%) had weak, 14 (25.9%) had moderate and 13 (24.1%) had strong Klotho expression. Significantly more patients had absent/weak Klotho expression with higher grade (16/24 (66.7%) vs 7/25 (28%); p = 0.007), higher stage (22/33 (66%) vs 5/21 (23.8%); p = 0.002), LVI (12/14 (85.7%) vs 2/14 (14.3%); p = 0.002), sinus-fat-invasion (16/21 (76.2%) vs 5/21 (23.8%); p = 0.002), renal-vein-involvement (14/18 (77.8%) vs 4/18 (22.2%); p = 0.004), necrosis (17/26 (65.3%) vs 9/26 (34.6%); p = 0.029) and metastasis (8/9 (88.9%) vs 1/9 (11.1%); p = 0.01). Median DFS and OS were significantly lower in patients with weak/absent Klotho expression (12 vs 23 months, p = 0.023 and 15 vs 33 months, p = 0.006 respectively). Kaplan-Meier curves showed lower estimated DFS and OS in patients with weak/absent expression. We conclude that Klotho expression in renal tumor could be a good prognostic marker in patients with RCC.

Lipocalin-2 as a prognostic marker in patients with acute exacerbation of idiopathic pulmonary fibrosis

BackgroundLipocalin-2 (LCN2) is a secretory glycoprotein upregulated by oxidative stress; moreover, patients with idiopathic pulmonary fibrosis (IPF) have shown increased LCN2 levels in bronchoalveolar lavage fluid (BALF). This study aimed to determine whether circulatory LCN2 could be a systemic biomarker in patients with IPF and to investigate the role of LCN2 in a bleomycin-induced lung injury mouse model.MethodsWe measured serum LCN2 levels in 99 patients with stable IPF, 27 patients with acute exacerbation (AE) of IPF, 51 patients with chronic hypersensitivity pneumonitis, and 67 healthy controls. Further, LCN2 expression in lung tissue was evaluated in a bleomycin-induced lung injury mouse model, and the role of LCN2 was investigated using LCN2-knockout (LCN2 -/-) mice.ResultsSerum levels of LCN2 were significantly higher in patients with AE-IPF than in the other groups. The multivariate Cox proportional hazards model showed that elevated serum LCN2 level was an independent predictor of poor survival in patients with AE-IPF. In the bleomycin-induced lung injury mouse model, a higher dose of bleomycin resulted in higher LCN2 levels and shorter survival. Bleomycin-treated LCN2 -/- mice exhibited increased BALF cell and protein levels as well as hydroxyproline content. Moreover, compared with wild-type mice, LCN2-/- mice showed higher levels of circulatory 8-isoprostane as well as lower Nrf-2, GCLC, and NQO1 expression levels in lung tissue following bleomycin administration.ConclusionsOur findings demonstrate that serum LCN2 might be a potential prognostic marker of AE-IPF. Moreover, LCN2 expression levels may reflect the severity of lung injury, and LCN2 may be a protective factor against bleomycin-induced acute lung injury and oxidative stress.

FT4-to-FT3 ratio is a novel prognostic marker in subacute combined spinal cord degeneration patients.

The FT4-to-FT3 ratio (FFR) variations in patients with subacute combined spinal cord degeneration (SCSD) as a potentially useful prognostic indicator are still unknown. This study aimed to investigate the changes of FFR as a potentially valuable prognostic predictor in patients with SCSD. This study included 144 consecutive SCSD patients who received standard diagnostic and therapeutic procedures between January 2015 and December 2021 and were admitted to the Department of Neurology at the First Affiliated Hospital of Bengbu Medical University. At the time of admission, we gathered data on all patients' demographics, daily routines, previous chronic conditions, medication histories, and other clinical details. For the purpose of measuring FFR, blood samples were specifically taken within 48 h of admission. The degree of neurological impairment of patients was assessed using the functional disability scale at the time of admission. At 6 months following discharge, the Modified Rankin Scale (mRS) was used to evaluate the clinical prognosis. To evaluate the relationship between the FFR and the risks of a poor outcome (mRS > 2), univariate and multivariate logistic regression analysis was utilized. The significance of the FT4/FT3 ratio in predicting the clinical outcomes in SCSD patients 6 months after discharge was assessed using the area under curve-receiver operating characteristic (AUC-ROC). About 90 patients (62.5%) of the 144 patients had poor outcomes, while 54 (37.5%) had favorable outcomes. Higher FFR at admission was independently linked to higher odds of a poor outcome, according to a logistic analysis. With an optimized cutoff value of >2.843, the FFR exhibited the maximum accuracy for predicting a poor outcome, according to the AUC‒ROC curve (AUC 0.731, P < 0.001; sensitivity, 77.8%; specificity, 83.3%). FFR was identified as an independent predictor of poor outcomes by multivariate logistic regression (OR, 2.244; 95% CI, 1.74-2.90; P < 0.001). We discovered that in patients who had a bad result 6 months after discharge, the FFR had dramatically increased at the time of admission, providing a unique prognostic marker in patients with SCSD.

Abstract PO5-05-11: The effect of eribulin treatment for patients with HER2-low breast cancer

Abstract Background: Eribulin, a nontaxane, synthetic microtuble dynamics inhibitor, induces longer overall survival (OS) in patients with advanced or metastatic breast cancer (MBC). Interestingly, it also improves the tumor immune microenvironment via vascular remodeling. DESTINY-Breast04 trial showed that trastuzumab deruxtecan resulted in significantly longer OS of human epithelial growth receptor 2 (HER2)-low breast cancer patients, and this mechanism may also be related to tumor microenvironment. In this study, we investigated the effect of eribulin for patients with HER2-low breast cancer. Materials and Methods: This retrospective study comprised 97 MBC treated with eribulin from August 2011 to April 2019 at our institute. HER2 levels were determined through tumor biopsy specimen at first medical examination. We evaluated the correlations between HER2 levels and clinicopathological features, including the prognosis and immune related markers in each breast cancer subtype. We also classified the progressive disease (PD) into progression due to pre-existing lesion (PPL) and progression due to new metastasis (PNM) based on systemic computed tomography findings, and investigated the relationships between HER2 expression and PD types. Results: HER2-high group had significantly better OS than other groups (p=0.021, log-rank). Hormone receptor (HR)-negative/HER2-low patients had significantly better progression-free survival (PFS) than HR-negative/HER2-negative (p=0.024, log-rank). Though we also examined HER2 levels of recurrent tumor specimen, it was not a significantly useful prognostic marker in patients with HR-negative breast cancer (p=0.085, log-rank). There was no significant correlation between HER2 expression and any tested clinicopathological parameter, including absolute lymphocyte count, neutrophil-to-lymphocyte ratio and tumor infiltrating lymphocytes. PD were observed in 64 patients (PPL: n=47, PNM: n=17). PD type of all HR-positive/HER2-high patients was PNM, whereas all HR-negative/HER2-high patients was PPL (p=0.035). HER2-low group tended to have a higher PPL rare than negative group (83.3% vs 69.2%). Conclusions: In HR-negative/HER2-low group, PFS was improved by eribulin treatment, which might be due to unique anticancer effect of eribulin, suppression of epithelial-mesenchymal transition. Further study of this mechanism through basic research is important. Also, assessment of HER2 from primary tumor may be more useful than recurrent specimen. Citation Format: Wataru Goto, Saeko Henmi, Mariko Nishikawa, Asuka Kouchi, Rika Kouhashi, Akimichi Yabumoto, Koji Takada, Yuka Asano, Yukie Tauchi, Kana Ogisawa, Tamami Morisaki, Shinichiro Kashiwagi. The effect of eribulin treatment for patients with HER2-low breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-11.

A-45 | Red blood cell distribution width as a long-term prognostic marker in patients with coronary artery disease undergoing percutaneous coronary intervention: An updated meta-analysis

A-45 | Red blood cell distribution width as a long-term prognostic marker in patients with coronary artery disease undergoing percutaneous coronary intervention: An updated meta-analysis

Prognostic value of exercise longitudinal right ventricular free wall strain in patients with sickle cell disease.

Longitudinal right ventricular free wall strain (RVFWS) has been identified as an independent prognostic marker in patients with pulmonary hypertension. Little is known however about the prognostic value of RVFWS in patients with sickle cell (SC) disease, particularly during exercise. We therefore examined the prognostic significance of RVFWS both at rest and with exercise in patients with SC disease and normal resting systolic pulmonary artery pressure (SPAP). Consecutive patients with SC disease referred for bicycle ergometer stress echocardiography (SE) were enrolled ftom July 2019 to January 2021. All patients had measurable tricuspid regurgitation velocity (TRV). Conventional echocardiography parameters, left ventricular global longitudinal strain (LVGLS), RVFWS, and ventriculoarterial coupling indices (TAPSE/SPAP and RVFWS/SPAP) were assessed at rest and peak exercise. Repeat SE was performed at a median follow-up of 2years. The cohort consisted of 87 patients (mean age was 31 ± 11years, 66% females). All patients had normal resting TRV < 2.8m/s, RVFWS and LVGLS at baseline. There were 23 (26%) patients who had peak stress RVFWS < 20%. They had higher resting and peak stressTRV andSPAP, but lower resting and peak stressTAPSE/SPAP, RVFWS/SPAP, and LVGLS as well as lower peak stresscardiac output when compared to patients with peak stressRVFWS ≥ 20% (p < 0.05). Patients with baseline peak stressRVFWS < 20% had a significant decrease in exercise performance at follow-up (7.5 ± 2.7min at baseline vs. 5.5 ± 2.8min at follow-up, p < 0.001). In the multivariate analysis, baseline peak stressRVFWS was the only independent predictor of poorer exercise performance at follow-up [odds ratio 8.2 (1.2, 56.0), p = 0.033]. Among patients with SC disease who underwent bicycle ergometer SE, a decreased baseline value of RVFWS at peak stress predicted poorer exercise time at follow-up.

Changes of Serum Midkine as a Dynamic Prognostic Factor in Detection for Thyroid Cancer and Comparison with Fine-Needle Aspiration

Background: Midkine plays a significant role in the pathophysiology of malignant and other diseases since it is involved in a number of physiological processes, including development, reproduction, and repair. Different types of cells express this protein. Thus, in healthy conditions, significant MDK expression is observed in lymphocytes, the epidermis, and the bronchial epithelium. The sample obtained during fine needle aspiration can help in the diagnosis of or rule out disorders like cancer. Blood is the most practical and least likely bodily fluid to pollute while diagnosing illnesses. Finding successful prognostic markers in patients with well-defined thyroid cancer was the goal of the current investigation.Methods: Midkine level was measured in serum samples by using Elisa technique for 80 patients (40 patient was diagnosed with papillary thyroid carcinoma and another 40 with benign thyroid goiter), Age (25-55) from Iraqis people.Results: The current study revealed highly significant difference the median serum level of medkine in the TC patients was much higher than that of BTT patients with a highly significant difference The sensitivity and specificity of the test at cut off value of medkine=129 pg/ml were 90% for both. While FNA result, the sensitivity and specificity of FNAC was 80.77% and 89.66% respectively.Conclusions: The thyroid cancer group's serum MDK result was noticeably higher than that of the healthy control groups. proposed that the midkine might serve as a biochemical marker for thyroid cancer early identification and diagnosis.Keywords: Thyroid cancer; Papillary thyroid carcinoma; Midkine; ELISA; FNA

Prognostic Utility of Left Atrial Strain From MRI Feature Tracking in Ischemic and Nonischemic Dilated Cardiomyopathy: A Multicenter Study.

BACKGROUND. MRI-based prognostic evaluation in patients with dilated cardiomyopathy (DCM) has historically used markers of late gadolinium enhancement (LGE) and feature tracking (FT)-derived left ventricular global longitudinal strain (LVGLS). Early data indicate that FT-derived left atrial strain (LAS) parameters, including reservoir, conduit, and booster, may also have prognostic roles in such patients. OBJECTIVE. The purpose of our study was to evaluate the prognostic utility of LAS parameters, derived from MRI FT, in patients with ischemic or nonischemic DCM, including in comparison with the traditional parameters of LGE and LVGLS. METHODS. This retrospective study included 811 patients with ischemic or nonischemic DCM (median age, 60 years; 640 men, 171 women) who underwent cardiac MRI at any of five centers. FT-derived LAS parameters and LVGLS were measured using two- and four-chamber cine images. LGE percentage was quantified. Patients were assessed for a composite outcome of all-cause mortality or heart failure hospitalization. Multivariable Cox regression analyses including demographic characteristics, cardiovascular risk factors, medications used, and a wide range of cardiac MRI parameters were performed. Kaplan-Meier analyses with log-rank tests were also performed. RESULTS. A total of 419 patients experienced the composite outcome. Patients who did, versus those who did not, experience the composite outcome had larger LVGLS (-6.7% vs -8.3%, respectively; p < .001) as well as a smaller LAS reservoir (13.3% vs 19.3%, p < .001), LAS conduit (4.7% vs 8.0%, p < .001), and LAS booster (8.1% vs 10.3%, p < .001) but no significant difference in LGE (10.1% vs 11.3%, p = .51). In multivariable Cox regression analyses, significant independent predictors of the composite outcome included LAS reservoir (HR = 0.96, p < .001) and LAS conduit (HR = 0.91, p < .001). LAS booster and LGE were not significant independent predictors in the models. LVGLS was a significant independent predictor only in a model that initially included LAS booster but not the other LAS parameters. In Kaplan-Meier analysis, all three LAS parameters were significantly associated with the composite outcome (p < .001). CONCLUSION. In this multicenter study, LAS reservoir and LAS conduit were significant independent prognostic markers in patients with ischemic or nonischemic DCM, showing greater prognostic utility than the currently applied markers of LVGLS and LGE. CLINICAL IMPACT. FT-derived LAS analysis provides incremental prognostic information in patients with DCM.

Appraisal of a newly developed ALBI-sarcopenia score as a prognostic marker in patients with hepatocellular carcinoma

Objective This study aimed to evaluate the impact of the combined Albumin–bilirubin (ALBI)/sarcopenia score as a newly developed prognostic model for hepatocellular carcinoma (HCC), with a focus on its utility in predicting mortality. Methods This prospective study was conducted on HCC patients who were followed for 1 year or until death. Sarcopenia was assessed radiologically by computed tomography at the level of L3. The study consisted of two sets: a development set in which the new ALBI-sarcopenia score was created, comprising 262 HCC patients, followed by an internal validation set with 100 patients. Results The development cohort primarily included males (69.5%), aged 59.6 ± 8.09 years. In patients with sarcopenia, the ALBI score was −2.03 ± 0.42 (P &lt; 0.006), the model for end-stage liver disease (MELD) score was 11.29 ± 2.43 (P &lt; 0.001*), and the MELD-sarcopenia score was 21.29 ± 2.43 (P &lt; 0.001*). The distribution of barcelona clinic liver cancer (BCLC) staging was as follows: BCLC A 18 (15.9%), BCLC B 63 (55.8%) and BCLC C 32 (28.3%) (P &lt; 0.001*), with a notable association with higher mortality (P &lt; 0.001). Multivariate analysis identified sarcopenia and ALBI scores as independent predictors of mortality in HCC (P &lt; 0.001*). In the development set, the ALBI-sarcopenia score successfully predicted mortality at a cutoff &gt;−11 with an area under a curve of 0.837 (95% CI, 0.784–0.889), while in the validation set, it predicted mortality at a cutoff &gt;−11.55 with an area under a curve of 0.842 (95% CI, 0.753–0.930). Conclusion The newly introduced ALBI-sarcopenia score has demonstrated superior effectiveness in comparison to MELD-sarcopenia score, overcoming the shortcomings associated MELD score in forecasting outcomes for patients with HCC.

Association of Increased Inter-arm Blood Pressure Difference with Long-term Clinical Outcomes in Patients with Acute Myocardial Infarction Who Underwent Percutaneous Coronary Intervention.

Objective Patients with acute myocardial infarction (AMI) often have peripheral artery disease (PAD). It is well known that the long-term clinical outcomes of AMI are worse in patients with a low ankle-brachial index (ABI) than in patients with a preserved ABI. Unlike ABI, the association between the inter-arm blood pressure difference (IABPD) and clinical outcomes in patients with AMI has not yet been established. This retrospective study examined whether or not the IABPD is associated with long-term clinical outcomes in patients with AMI. Methods We included 979 patients with AMI and divided them into a high-IABPD group (IABPD ≥10 mmHg, n=31) and a low-IABPD group (IABPD <10 mmHg, n=948) according to the IABPD measured during hospitalization for AMI. The primary endpoint was the all-cause mortality rate. Results During a median follow-up duration of 694 days (Q1, 296 days; Q3, 1,281 days), 82 all-cause deaths were observed. Kaplan-Meier curves showed that all-cause death was more frequently observed in the high-IABPD group than in the low-IABPD group (p<0.001). A multivariate Cox hazard analysis revealed that a high IABPD was significantly associated with all-cause death (hazard ratio 2.061, 95% confidence interval 1.012-4.197, p=0.046) after controlling for multiple confounding factors. Conclusion A high IABPD was significantly associated with long-term all-cause mortality in patients with AMI. Our results suggest the usefulness of the IABPD as a prognostic marker for patients with AMI.

Blood Cell Ratios Unveiled: Predictive Markers of Myocardial Infarction Prognosis.

Even if the management and treatment of patients with non-ST-elevation myocardial infarction (NSTEMI) have significantly evolved, it is still a burgeoning disease, an active volcano with very high rates of morbidity and mortality. Therefore, novel management and therapeutic strategies for this condition are urgently needed. Lately, theories related to the role of various blood cells in NSTEMI have emerged, with most of this research having so far been focused on correlating the ratios between various leukocyte types (neutrophil/lymphocyte ratio-NLR, neutrophil/monocyte ratio-NMR). But what about erythrocytes? Is there an interaction between these cells and leukocytes, and furthermore, can this relationship influence NSTEMI prognosis? Are they partners in crime? Through the present study, we sought, over a period of sixteen months, to evaluate the neutrophil/red blood cell ratio (NRR), monocyte/red blood cell ratio (MRR) and lymphocyte/red blood cell ratio (LRR), assessing their potential role as novel prognostic markers in patients with NSTEMI. There was a statistically significant correlation between the NRR, LRR, MRR and the prognosis of NSTEMI patients. These new predictive markers could represent the start of future innovative therapies that may influence crosstalk pathways and have greater benefits in terms of cardiac repair and the secondary prevention of NSTEMI.

Evaluation of models to predict prognosis in patients with advanced hepatocellular carcinoma treated with TACE combined with apatinib.

The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

Impact of Preoperative Serum Albumin Level on the Outcome of Colorectal Cancer Surgery.

Background Gastrointestinal malignancy surgeries are known to have a risk of postoperative complications. Preoperative nutritional status has been suggested as a potential predictor of postoperative outcomes, with low serum albumin levels utilized as a marker of malnutrition and increased risk of postoperative complications. This paper investigated the association between preoperative serum albumin levels and postoperative outcomes in patients undergoing colorectal cancer surgery. Methods This retrospective data-maintained study was based on all patients aged 18 years and above who underwent colorectal cancer surgery at King Abdulaziz Medical City, Riyadh, Saudi Arabia between 2015 and 2022. Results A total of 400 patients were included in the study. With an average age of 64.43 years. Males represented 254 (63%) of the patients, while females accounted for 146 (37%). Thirty percent of patients had hypoalbuminemia (i.e., albumin level below 35 g/L) before surgery. Among the sample, 112 (28%) experienced complications after surgery. The mean albumin level for patients who experienced postoperative complications was 30.46 g/L while patients without complications had a normal albumin level. As for the length of hospital stay, it was eight days for patients with a normal albumin level and 23 days for hypoalbuminemia patients. Conclusion In conclusion, preoperative hypoalbuminemia is associated with poor patient outcomes and can be utilized as a prognostic marker for patients in need of colorectal cancer surgery.

Valor pronóstico de la razón desplazamiento sistólico del plano del anillo tricuspídeo/presión arterial pulmonar sistólica en la amiloidosis cardiaca

Introduction and objectivesThe tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/SPAP) ratio is a noninvasive surrogate of right ventricular to pulmonary circulation that has prognostic implications in patients with heart failure (HF) or pulmonary hypertension. Our purpose was to evaluate the prognostic value of the TAPSE/SPAP ratio in patients with cardiac amyloidosis. MethodsWe used the database of the AMIGAL study, a prospective, observational registry of patients with cardiac amyloidosis recruited in 7 hospitals of the Autonomous Community of Galicia, Spain, from January 1, 2018 to October 31, 2022. We selected patients whose baseline TAPSE/SPAP ratio was calculated with transthoracic echocardiography. Long-term survival and survival free of HF hospitalization were assessed by means of 5 different multivariable Cox regression models. Median follow-up was 680 days. ResultsWe studied 233 patients with cardiac amyloidosis, among whom 209 (89.7%) had transthyretin type. The baseline TAPSE/SPAP ratio correlated significantly with clinical outcomes. Depending on the multivariable model considered, the adjusted hazard ratios estimated per 0.1mm/mmHg increase of baseline TAPSE/SPAP ratio ranged from 0.76 to 0.84 for all-cause mortality. Similarly, the ratios for all-cause mortality of HF hospitalization ranged from 0.79 to 0.84. The addition of the baseline TAPSE/SPAP ratio to the predictive model of the United Kingdom National Amyloidosis Centre resulted in an increase in Harrell's c-statistic from 0.662 to 0.705 for all-cause mortality and from 0.668 to 0.707 for all-cause mortality or HF hospitalization. ConclusionsReduced TAPSE/SPAP ratio is an independent adverse prognostic marker in patients with cardiac amyloidosis.

Time to positivity of Klebsiella pneumoniae in blood cultures as prognostic marker in patients with intra-abdominal infection: A retrospective study

ABSTRACT Klebsiella pneumoniae is a common causative pathogen of intra-abdominal infection with concomitant bacteraemia, leading to a significant mortality risk. The time to positivity (TTP) of blood culture is postulated to be a prognostic factor in bacteraemia caused by other species. Therefore, this study aimed to investigate the prognostic value of TTP in these patients. The single-centred, retrospective, observational cohort study was conducted between 1 July 2016 and 30 June 2021. All adult emergency department patients with diagnosis of intra-abdominal infection and underwent blood culture collection which yield K. pneumoniae during this period were enrolled. A total of 196 patients were included in the study. The overall 30-day mortality rate was 12.2% (24/196), and the median TTP of the studied cohort was 12.3 h (10.5–15.8 h). TTP revealed a moderate 30-day mortality discriminative ability (area under the curve 0.73, p < 0.001). Compared with the late TTP group (>12 h, N = 109), patients in the early TTP (≤12 h, N = 87) group had a significantly higher risk of 30-day morality (21.8% vs. 4.6%, p < 0.01) and other adverse outcomes. Furthermore, TTP (odds ratio [OR] = 0.79, p = 0.02), Pitt bacteraemia score (OR = 1.30, p = 0.03), and implementation of source control (OR = 0.06, p < 0.01) were identified as independent factors related to 30-day mortality risk in patients with intra-abdominal infection and K. pneumoniae bacteraemia. Therefore, physicians can use TTP for prognosis stratification in these patients.

PRDM1 rs2185379, unlike BRCA1, is not a prognostic marker in patients with advanced ovarian cancer.

Ovarian cancer (OC) is mostly diagnosed in advanced stages with high incidence-to-mortality rate. Nevertheless, some patients achieve long-term disease-free survival. However, the prognostic markers have not been well established. The primary objective of this study was to analyse the association of the suggested prognostic marker rs2185379 in PRDM1 with long-term survival in a large independent cohort of advanced OC patients. We genotyped 545 well-characterized advanced OC patients. All patients were tested for OC predisposition. The effect of PRDM1 rs2185379 and other monitored clinicopathological and genetic variables on survival were analysed. The univariate analysis revealed no significant effect of PRDM1 rs2185379 on survival whereas significantly worse prognosis was observed in postmenopausal patients (HR = 2.49; 95%CI 1.90-3.26; p= 4.14 × 10 - 11) with mortality linearly increasing with age (HR = 1.05 per year; 95%CI 1.04-1.07; p= 2 × 10 - 6), in patients diagnosed with non-high-grade serous OC (HR = 0.44; 95%CI 0.32-0.60; p= 1.95 × 10 - 7) and in patients carrying a gBRCA1 pathogenic variant (HR = 0.65; 95%CI 0.48-0.87; p= 4.53 × 10 - 3). The multivariate analysis interrogating the effect of PRDM1 rs2185379 with other significant prognostic factors revealed marginal association of PRDM1 rs2185379 with worse survival in postmenopausal women (HR = 1.54; 95%CI 1.01-2.38; p= 0.046). Unlike age at diagnosis, OC histology or gBRCA1 status, rs2185379 in PRDM1 is unlikely a marker of long-term survival in patients with advance OC.

Abstract 3466: Prognostic implications of lymph node micrometastasis in patients with gastric cancer

Abstract Purpose: The clinical significance of lymph node micrometastasis (LNMM) remains controversial in gastric cancer (GC). In this study, we investigated the prognostic impact of patients with LNMM GC.Methods: A total of 624 patients with pathologically lymph node metastasis negative (pN0) and N1 status (pN1) who underwent gastrectomy between 2004 and 2018 were enrolled in this retrospective study. The diameter of tumor cell clusters in metastatic lymph nodes was measured in 120 patients with pN1 GC. Results: Patients with lymph node tumors of diameter &amp;lt; 1500 μm (LNMM) had significantly better prognosis than those with tumors of diameter ≥ 1500 μm (p = 0.012; log-rank test). Cox’s proportional hazards model revealed that LNMM (p = 0.016), several dissected lymph nodes (p = 0.049), and the provision of adjuvant chemotherapy (p = 0.002) were independent prognostic factors for overall survival of patients with pN1 GC. There was no significant difference in overall survival between patients with LNMM who received chemotherapy and those who did not (p = 0.332). Conclusions: LNMM is associated with favorable prognosis and could be an independent prognostic marker in patients with pN1 GC. LNMM in GC may be considered as one of the factors preventing adjuvant chemotherapy. Citation Format: Atsushi Yamamoto, Hirotaka Okamoto. Prognostic implications of lymph node micrometastasis in patients with gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3466.

Abstract 3420: Androgen receptor (CAG)n polymorphism: A genomic marker for prostate cancer prognosis independent of histopathological parameters

Abstract The androgen receptor (AR) serves as a pivotal transcription factor in prostate cancer (PCa) development. Its transcriptional activity is linked to the number of glutamines in the N-terminal domain. While current screening for PCa and prognostic biomarkers include serum prostate-specific antigen (PSA) levels and histopathological characteristics (specifically, ISUP grade and margin involvement), the heterogeneity of these tumors underscores the need for additional markers to enhance clinical management. Thus, this study aimed at characterizing an Argentinian PCa patient cohort based on the CAG polymorphism (CAG)n in AR and establish associations between genotypes and clinical-pathological characteristics to refine disease prognosis. We designed a hospital-based case-case study for PCa patients to determine the association between AR polymorphisms and PCa biochemical relapse after radical prostatectomy (RP). We retrospectively recruited 112 patients histologically diagnosed with PCa at the Hospital de Clínicas José de San Martín, Buenos Aires, Argentina. All patients underwent RP as their primary therapeutic strategy. All patients were, by definition, Hispanics, predominantly of Caucasian ancestry and, at a lesser extent, Amerindian or African. Written informed consent and institutional review board approval were acquired. Blood samples were collected post-RP for genomic DNA extraction using the CTAB method. (CAG)n in AR was genotyped by fluorescent PCR followed by capillary electrophoresis, and correlations between genotypes and clinical-pathological variables were analyzed using R. Results categorized patients into three subgroups based on the length of the CAG tandem repeat in AR: long (&amp;gt;23 repeats, n=29), medium (20-23 repeats, n=44), and short (&amp;lt;20 repeats, n=38). No associations were found between the length of the polymorphism and age of diagnosis, pre-RP PSA serum values, ISUP grade, and margin involvement. However, patients with family cancer history had a higher frequency of the intermediate-length allele (p=0.02). Moreover, among patients with pre-RP PSA &amp;lt;10 ng/ml and intermediate-length allele had 2.72-fold risk of biochemical recurrence (BCR) (HR=2.72, 95%CI=1.05-7.03, p=0.039). Furthermore, multivariable BCR analysis including the ISUP grade and margin involvement as co-variates showed that the (CAG)n in AR was independent of these histopathological parameters (HRadj=3.37, 95%IC=1.24-9.10, padj=0.017). Altogether, the AR polymorphism is associated with family history of cancer. Consequently, determining the number of CAG repetitions in AR through a blood sample could serve as an independent prognostic marker in patients with PSA &amp;lt;10 ng/ml prior to PR, independent of the histopathological features. Citation Format: Gastón Mario Pascual, Agustina Sabater, Juan Bizzotto, Rocio Seniuk, Pablo Sanchis, Carlos M. Roggero, Carlos Scorticati, Osvaldo Mazza, Elba Vazquez, Ayelen Toro, Geraldine Gueron, Javier Cotignola. Androgen receptor (CAG)n polymorphism: A genomic marker for prostate cancer prognosis independent of histopathological parameters [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3420.

Apatinib beyond first progression is associated with prolonged overall survival in patients with advanced breast cancer: Results from an observational study.

In the present study, the efficacy and safety of a low dose of apatinib in the treatment of patients with advanced breast cancer (ABC) in a real-world setting were assessed, the impact of continuous anti-angiogenic therapy beyond progression was determined and the factors associated with efficacy were evaluated. A total of 63 patients with ABC who were treated with apatinib and for whom several lines of treatment had failed were retrospectively analyzed in Tangshan People's Hospital (Tangshan, China) between January 2016 and October 2022. Apatinib was administered orally combined with chemotherapy, endocrine therapy, targeted therapy or monotherapy at a dose of 250 mg per day. Apatinib administration was continued in certain patients beyond first progressive disease (PD), and these patients were defined as the continued anti-angiogenic treatment beyond first progression (CABF) group, while those who discontinued apatinib were defined as the non-CABF group. In the evaluation of the first efficacy, the objective response rate was 33.3%. A total of 26 patients continued to receive apatinib post-first PD and were allocated to the CABF group. The median overall survival (OS) time of the 63 patients was 16 months. Log-rank univariate analysis revealed that the OS time was significantly associated with molecular subtype (P=0.014), CABF (P=0.004), and the neutrophil-to-lymphocyte ratio (NLR) (P=0.011). Multivariate Cox regression analysis revealed that being in the non-CABF group and a high NLR were independent risk factors for lower OS time (P=0.017 and P=0.041, respectively). These results support the continued administration of low-dose apatinib beyond progression and the use of NLR as an easily accessible prognostic marker in patients with ABC treated with apatinib.

Diabetes mellitus does not alter mortality or hospitalisation risk in patients with newly diagnosed heart failure with preserved ejection fraction: Time to rethink pathophysiological models of disease progression.

Type 2 diabetes is a common and adverse prognostic co-morbidity for patients with heart failure with reduced ejection fraction (HFrEF). The effect of diabetes on long-term outcomes for heart failure with preserved ejection fraction (HFpEF) is less established. Prospective cohort study of patients referred to a regional HF clinic with newly diagnosed with HFrEF and HFpEF according to the 2016 European Society of Cardiology guidelines. The association between diabetes, all-cause mortality and hospitalisation was quantified using Kaplan-Meier or Cox regression analysis. Between 1st May 2012 and 1st May 2013, of 960 unselected consecutive patients referred with suspected HF, 464 and 314 patients met the criteria for HFpEF and HFrEF respectively. Within HFpEF and HFrEF groups, patients with diabetes were more frequently male and in both groups patients with diabetes were more likely to be treated with β-adrenoceptor antagonists and angiotensin converting enzyme inhibitors. After adjustment for age, sex, medical therapy and co-morbidities, diabetes was associated with increased mortality in individuals with HFrEF (HR 1.46 95% CI: 1.05-2.02; p = .023), but not in those with HFpEF (HR 1.26 95% CI 0.92-1.72; p = .146). In unselected patients with newly diagnosed HF, diabetes is not an adverse prognostic marker in patients with HFpEF, but is in HFrEF.