Prognostic Marker In Patients Research Articles

Emerging Prognostic Markers in Patients Undergoing Liver Resection for Hepatocellular Carcinoma: A Narrative Review.

In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular invasion) and an increase in alpha-fetoprotein level. During the past decade, many new markers have been reported to correlate with prognosis after resection of HCC: liquid biopsy markers, gene signatures, inflammation markers, and other biomarkers, including PIVKA-II, immune checkpoint molecules, and proteins in urinary exosomes. However, not all of these new markers are readily available in clinical practice, and their reproducibility is unclear. Liquid biopsy is a powerful and established tool for predicting long-term outcomes after resection of HCC; the main limitation of liquid biopsy is represented by the cost related to its technical implementation. Numerous patterns of genetic expression capable of predicting survival after curative-intent hepatectomy for HCC have been identified, but published findings regarding these markers are heterogenous. Inflammation markers in the form of prognostic nutritional index and different blood cell ratios seem more easily reproducible and more affordable on a large scale than other emerging markers. To select the most effective treatment for patients with HCC, it is crucial that the scientific community validate new predictive markers for recurrence and survival after resection that are reliable and widely reproducible. More reports from Western countries are necessary to corroborate the evidence.

Value of zonulin as a diagnostic and prognostic marker in different degrees of nonalcoholic fatty liver disease

BackgroundNonalcoholic fatty liver disease (NAFLD) is a group of hepatic disorders ranging between simple form of accumulation of fat in hepatocytes (hepatic steatosis) and inflammation of liver internal tissues and injury of hepatocytes that is known as nonalcoholic steatohepatitis (NASH) with increasing levels of fibrosis and cirrhosis and hepatocellular carcinoma (HCC). The composition of one’s gut microbiota has a role in both the onset and progression of chronic liver disorders. One indicator of intestinal permeability is zonulin. In this study, we aimed to detect the value of zonulin as a diagnostic and prognostic marker in patients with different degrees of nonalcoholic fatty liver disease (steatosis, steatohepatitis, cirrhosis).This case–control study was conducted on 60 subjects in Gastroenterology and Bariatric Surgery Departments at Ain Shams University Hospitals who were divided into 3 groups: Group A: 20 patients underwent bariatric surgery and have mild NASH, Group B: 20 patients underwent bariatric surgery and have moderate-to-severe NASH, and Group C: 20 healthy controls, during a period 1 of year.ResultsThere was high statistically significant difference between the studied groups; as regard zonulin concentration, zonulin showed high diagnostic accuracy in diagnosis of NASH among hepatic patients with total accuracy of 81.7%, sensitivity of 72.5%, and specificity of 100.ConclusionSerum zonulin levels increase with steatosis severity in patients with NAFLD. This explains the high diagnostic accuracy of zonulin in diagnosis and prognosis of NASH among patients.

Role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte-ratio (PLR) in unresectable hepatocellular carcinoma (uHCC): Subgroup analysis of patients treated with camrelizumab (cam) + rivoceranib (rivo) in the CARES-310 trial.

e16197 Background: CARES-310 (NCT03764293) evaluated the combination of the PD-1 inhibitor, cam, and the VEGFR-2 tyrosine kinase inhibitor, rivo, compared to sorafenib (sor) for the treatment of 543 patients (pts) with uHCC. Cam + rivo significantly improved mOS (22.1 months [mo] [95% CI 19.1-27.2] vs 15.2 mo [13.0-18.5] HR 0.62 [95% CI 0.49-0.80]; one-sided p < 0.0001) and mPFS (5.6 mo [95% CI 5.5-6.3] vs 3.7 mo [2.8-3.7]; HR 0.54 [95% CI 0.44-0.67]; one-sided p < 0.0001) compared to sor. The most common (≥20%) grade ≥3 treatment-related adverse events (TRAEs) for cam + rivo were hypertension (37.5%) and increased AST (16.5%) vs palmar-plantar erythrodysesthesia syndrome (15.2%) for sor. An elevated level of inflammation, including NLR and PLR, have been associated with poor survival outcomes in pts with HCC (Lin S, et al. Trans Cancer Res. 2021). Here, we present a subgroup analysis of the CARES-310 trial evaluating the impact of baseline (BL) NLR and PLR status on pt outcomes. Methods: The subgroup of pts treated with cam+rivo and BL NLR < 5 or ≥5 and PLR < 300 or ≥300 were evaluated for mOS, mPFS, overall response rate (ORR), disease control rate (DCR), and safety. Results: Of 272 pts treated with cam+rivo, 64.3% of pts had extrahepatic spread, median AFP was 84.1 ng/mL, 86.8% were Child-Pugh (CP) class A5, 13.2% were CP class A6, 73.5% were ALBI grade 1, 26.5% were ALBI grade 2. Additionally, 249 pts had NLR < 5, 10 pts had NLR ≥5, 252 pts had PLR < 300, and 7 pts had PLR ≥300. Pts with BL NLR < 5 and PLR < 300 demonstrated improved outcomes in mOS, mPFS, ORR, and DCR vs pts with BL NLR ≥5 and PLR ≥300 (Table). Rates of any grade TRAEs and grade ≥ 3 TRAEs were comparable between pts with BL NLR < 5 and ≥5 and PLR < 300 and ≥300 (Table). Conclusions: These results suggest that NLR and PLR may serve as a prognostic marker in patients with uHCC, but larger studies are needed to validate these findings. Clinical trial information: NCT03764293 . [Table: see text]

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio as an Early Prognostic Marker in Patients with Ovarian Cancer: A Systematic Review and Meta-Analysis.

Presently, ovarian cancer remains the leading cause of death in gynecological malignancies. The survival rate of these patients is low, which might be caused by early metastases and delayed diagnosis. Therefore, it is crucial to investigate novel practical markers that provide early prognostic value which helps construct individualized treatment. A thorough investigation of the neutrophil-lymphocyte ratio (NLR) and lymphocyte ratio (PLR) in ovarian cancer patients was conducted using article selection from PubMed, Cochrane, Science Direct, and Google Scholar databases. The outcomes and hazard ratio (HR) were obtained using Review Manager 5.4, and the 95% Confidence Interval (CI) result was calculated. The chief endpoints of interest in this study include overall survival (OS) and progression-free survival (PFS). Sixteen studies with 3,862 patients were included with a mean age of 50.6 years and a mean follow-up of 45.84 months. Multivariate studies demonstrated that a higher NLR is associated with worse PFS and OS, HR 1.35;95% CI [1.05-1.74] and HR 1.46; 95% CI [1.16-1.83] respectively. Similar results are observed with PLR and poorer PFS and OS, HR 1.62; 95% CI [1.09-2.43] and HR 1.66; 95% CI [1.12-2.46]. Pre-treatment PLR and NLR were found to be prognostic factors in determining PFS and OS in ovarian cancer. High values in pre-treatment PLR and NLR may indicate worse clinical outcomes.

SLC7A11 and the glutathione pathway as novel prognostic markers in resectable pancreatic ductal adenocarcinoma: A metabolomics study of clinical specimens

Background/objectivesDespite the poor prognosis associated with pancreatic ductal adenocarcinoma (PDAC), there remains a lack of clarity regarding the metabolic pathways and their significant impact on its phenotype. Therefore, we aimed to utilize metabolomics to capture changes in clinical PDAC tissues and elucidate the significant metabolic pathways close to its phenotypes. MethodsThis basic research was retrospectively validated using database research, immunohistochemistry, and protein analysis based on the findings obtained from metabolomics using clinical tissues collected from prospectively registered patients with PDAC. mRNA expression analysis using a database and protein analysis using archived clinical specimens was performed to validate the candidate pathways identified using metabolomics. Between-group comparisons were analyzed using paired t-tests and log-rank test, and Kaplan–Meier curves illustrated survival times. ResultsPatients subjected to metabolomics revealed a significant increase in glutathione disulfide levels in PDAC tissues when compared to normal pancreatic tissues. The Cancer Genome Atlas database analysis revealed significant changes in glutathione pathway-related mRNAs in PDAC compared to that in the normal pancreas. Protein analysis of previously resected specimens demonstrated a significant increase in SLC7A11 expression in PDAC tissues. The abundance ratio of SLC7A11 isoforms was associated with the post-operative prognosis in resectable PDAC. ConclusionGlutathione disulfide levels were significantly increased in clinical PDAC metabolomics. Additionally, increased mRNA and protein expression in SLC7A11 was observed in PDAC. Furthermore, the SLC7A11 isoform abundance ratio may be a valuable prognostic marker in patients with resectable PDAC.

Preoperative and postoperative platelet-lymphocyte ratio as a prognostic marker for patients with soft tissue sarcoma treated with curative resection.

e23568 Background: In cancer development and progression, systemic inflammation has been implicated. Inflammatory markers have been identified as prognostic indicators in numerous malignancies. In this study, we explored the prognostic relevance of initial and postoperative systemic inflammatory markers (neutrophil -lymphocyte ratio, platelet -lymphocyte ratio) on relapse-free survival (RFS) and overall survival (OS) in patients with soft -tissue sarcoma (STS) who underwent curative resection. Methods: We included a total of 89 patients with STS who underwent extensive and radical resection at the Kyungpook National University Chilgok Hospital (Daegu, Korea,) between 2004 and 2018. Kaplan-Meier curves and RFS and OS were calculated using multivariate Cox proportional models. Results: The median age of the patients was 55 years (range 27 - 86) and the ratio of male-to-female ratio was approximately 1:1. A total of 67 (75.3%) patients demonstrated a high initial neutrophil-lymphocyte ratio(NLR) (≥4.1) and 65 (75.3%) showed a high initial platelet-lymphocyte ratio(PLR) (≥231). After curative resection, the number of patients with high NLR and PLR was 16(18.0%) and 17 (29.3%). In both the NLR and PLR groups, including the postoperative NLR and postoperative PLR subgroups, no significant differences were observed in terms of age, sex, histologic type, tumor site, tumor size, tumor depth, or American Joint Committee on Cancer staging when stratified into high and low subgroups. In the univariate and multivariate analyses, an elevated initial PLR ratio was significantly associated with a decreased RFS (hazard ratio[HR]: 2.120; 95% confidence interval[CI]: 1.021 - 4.883, p = 0.017) and OS (HR: 5.073; 95% CI: 1.731 - 14.87, p = 0.003). Patients with a high PLR (PLR > 231) had a median RFS of 24 months, whereas those with a low PLR (PLR ≤231) had a median RFS of 96 months. The median OS was 50 and 298 months for the high PLR and low PLR groups, respectively. Furthermore, a high postoperative PLR ratio was significantly associated with a decreased RFS (HR: 3.921; 95% CI: 1.738 - 8.845, p = 0.001) and OS (HR: 5.702; 95% CI: 1.099 -29.576, p = 0.038). Conclusions: The present results suggest that the preoperative and postoperative PLR ratio can be used as a cost- effective prognostic marker for oncologic outcomes in patients with STS who underwent surgery.

Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma.

We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival (p = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.

Prognostic significance of preoperative to postoperative serum carcinoembryonic antigen ratio after lobectomy for lung adenocarcinoma.

Lung adenocarcinoma with a preoperatively elevated serum carcinoembryonic antigen (CEA) value has a relatively poor postoperative prognosis. Although surgical resection generally results in a reduction in the CEA value, the significance of the change in the CEA value on the prognostic outcome remains unclear. Our study included 133 patients who underwent lobectomy with curative intent for lung adenocarcinoma representing a preoperative CEA value > 5.0. Statistical analysis was performed using a receiver operating characteristic analysis and a stepwise Cox proportional hazards analysis. Both the postoperative CEA value and postoperative-to-preoperative CEA ratio (CEA ratio) significantly affected the survival. Although the CEA ratio was not predictive of the survival in patients with postoperative CEA ≤ 6.2ng/ml (n = 105), it was predictive in the remaining patients with postoperative CEA > 6.2ng/ml (n = 28). Patients with postoperative CEA > 6.2ng/ml and a CEA ratio ≥ 0.39 (n = 7) showed the worst survival outcome. According to the multivariate analysis, the CEA ratio and postoperative nodal status were significant predictors of the survival in overall patients. The CEA ratio may be a useful prognostic marker in patients who undergo lobectomy for lung adenocarcinoma and show postoperative CEA > 6.2ng/ml. A high CEA ratio may indicate the presence of a subclinical residual tumor, which may lead to the development of subsequent recurrence.

Altered serum concentrations of IL-8, IL-32 and IL-10 in patients with lung impairment 6 months after COVID-19

Post-COVID symptoms are reported in 10–35 % of patients not requiring hospitalization, and in up to 80 % of hospitalized patients and patients with severe disease. The pathogenesis of post-COVID syndrome remains largely unknown. Some evidence suggests that prolonged inflammation has a key role in the pathogenesis of most post-COVID manifestations. We evaluated a panel of inflammatory and immune-mediated cytokines in individuals with altered HRCT features and in patients without any long-term COVID symptoms. Blood samples of 89 adult patients previously hospitalized with COVID-19 were collected and stratified as patients with and without HRCT evidence of fibrotic lung alterations. Serum analyte concentrations of IL-4, IL-2, CXCL10 (IP-10), IL-1β, TNF-α, CCL2 (MCP-1), IL-17A, IL-6, IL-10, IFN-γ, IL-12p70 and TGF-β1 (free active form) were quantified by bead-based multiplex assay. Clinical and functional data were recorded in a database.With the use of machine learning approach, IL-32, IL-8, and IL-10 proved to be associated with the development of HRCT evidence of lung sequelae at follow-up. Direct comparison of cytokine levels in the two groups showed increased levels of IL-32 and decreased levels of IL-8 in patients with lung impairment. After further stratification of patients by severity (severe versus mild/moderate) during hospitalization, IL-10 emerged as the only cytokine showing decreased levels in severe patients. These findings contribute to a better understanding of the immune response and potential prognostic markers in patients with lung sequelae after COVID-19.

An overview of prognostic markers in patients with CLL.

Chronic lymphocytic leukemia (CLL) is a low-grade B-cell lymphoproliferative disorder. It is the most prevalent type of leukemia in the western countries, with a median age at diagnosis of 70 years. In 2023, it is estimated that there will be 18,740 new cases of CLL, and an estimated 4,490 people will die of this disease. It represents 1.0% of all new cancer cases in the U.S. The rate of new cases was 4.6 per 100,000 men and women per year based on 2016-2020 cases, age-adjusted. Death rates from CLL are higher among older adults, or those 75 and older. The death rate was 1.1 per 100,000 men and women per year based on 2016-2020 deaths, age-adjusted. A common question that patients with CLL ask during their first clinic visit is: "How long will it be before I would need treatment?" Although this might seem like a simple question, the answer is not straight forward. CLL is a heterogenous disease, with a variable clinical course. Some patients may present with an aggressive disease requiring early initiation of treatment, while others have an indolent course and some, having so called smoldering CLL, may never need treatment. The variability in disease course can make predicting disease prognosis a complicated process. This brings forth the importance of establishing prognostic models that can predict disease course, time to treatment, and survival outcomes in such a heterogenous disease. The Rai and Binet staging systems were developed in the late 1970s to early 1980s. They separated patients into different stages based on clinical characteristics and laboratory findings. These simple staging systems are still in use; however, several prognostic markers need to be added for an individualized assessment and, with the recent development of genomic techniques leading to better understanding of CLL at the molecular level, newer prognostic markers have emerged.

Prognostic value and drug sensitivity of F‑box and leucine‑rich repeat protein 6 in glioma.

Gliomas are highly malignant and invasive tumors lacking clear boundaries. Previous bioinformatics and experimental analyses have indicated that F-box and leucine-rich repeat protein 6 (FBXL6), a protein crucial for the cell cycle and tumorigenesis, is highly expressed in certain types of tumors. The high expression level of FBXL6 is reported to promote tumor growth and adversely affect patient survival. However, the molecular mechanism, prognostic value and drug sensitivity of FBXL6 in glioma remain unclear. To address this, the present study analyzed FBXL6 expression in gliomas, utilizing data from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Analysis of FBXL6 mRNA expression levels, combined with patient factors such as age, sex and tumor grade using Kaplan-Meier plots and nomograms, demonstrated a strong correlation between FBXL6 expression and glioma progression. Co-expression networks provided further insights into the biological function of FBXL6. Additionally, using CIBERSORT and TISDB tools, the correlation between FBXL6 expression correlation tumor-infiltrating immune cells and immune genes was demonstrated to be statistically significant. These findings were validated by examining FBXL6 mRNA and protein levels in glioma tissues using various techniques, including western blot, reverse transcription-quantitative PCR and immunohistochemistry. These assays demonstrated the role of FBXL6 in glioma progression. Furthermore, drug sensitivity analysis demonstrated a strong correlation between FBXL6 expression and various drugs, which indicated that FBXL6 may potentially act as a future promising therapeutic target in glioma treatment. Therefore, the present study identified FBXL6 as a diagnostic and prognostic marker in patients with gliomas and highlighted its potential role in glioma progression.

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

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.

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. 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. 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 < 0.006), the model for end-stage liver disease (MELD) score was 11.29 ± 2.43 ( P < 0.001*), and the MELD-sarcopenia score was 21.29 ± 2.43 ( P < 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 < 0.001*), with a notable association with higher mortality ( P < 0.001). Multivariate analysis identified sarcopenia and ALBI scores as independent predictors of mortality in HCC ( P < 0.001*). In the development set, the ALBI-sarcopenia score successfully predicted mortality at a cutoff >-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 >-11.55 with an area under a curve of 0.842 (95% CI, 0.753-0.930). 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.