Univariate Analysis Research Articles

Construction and Validation of a Prognostic Model Based on Pyroptosis-related Genes in Bladder Cancer.

Bladder cancer (BCa) is a highly prevalent disease with a poor prognosis. There is no better forecasting method for it yet. Current studies demonstrate that pyroptosis is involved in the development and progression of various cancers. This study employed bioinformatics techniques to analyze the data of BCa patients obtained from the TCGA and GEO databases in order to construct a prognostic risk model. The TCGA dataset was used for the training set, and the multiple external datasets (including GSE13507, GSE31684, GSE48075, IMvigor210, and GSE32894) were applied as the validation sets. Prognostic-associated pyroptosis genes screened by univariate Cox regression analysis were utilized to construct the lasso Cox regression model. GO and KEGG analysis results identified the selected genes that are primarily involved in the inflammation and cell death processes. The related patients were grouped into low- and high-risk groups. Kaplan-Meier survival analysis was performed to compare survival differences between the risk groups. The accuracy of this risk prediction model was assessed by ROC. We also applied the Human Protein Atlas (HPA) to detect the protein expression of these genes. Subsequently, qRT-PCR was performed to verify the expression of these model genes. There are 29 pyroptosis-related genes with significant expression differences between BCa and corresponding adjacent tissues, and 11 genes (SH2D2A, CHMP4C, MRFAP1L1, GBP2, EHBP1, RAD9A, ANXA1, TMEM109, HEYL, APOL2, ORMDL1) were picked by univariate and LASSO Cox regression analysis. Immunological cell infiltration and ssGSEA results further indicated that the low and high-risk groups were substantially correlated with the immune status of BCa patients. According to TCGA and multiple external datasets, Kaplan-Meier survival curves showed the overall survival rate of the high-risk group to be decreased. ROC curves showed the model established to be accurate and reliable. Moreover, the HPA database also demonstrated the verification of the modeled genes' expression in BCa and normal bladder tissue using the HPA database. qRT-PCR results also suggested the up-regulated EHBP1 and down-regulated RAD9A mRNA expression levels to be confirmed in 15 pairs of BCa and corresponding adjacent tissues. This study presents the development and validation of a novel gene signature associated with pyroptosis, which holds the potential for predicting patient outcomes in BCa and providing insights into the immune microenvironment of BCa.

Shape-sensing Robotic-assisted Bronchoscopy (SS-RAB) in Sampling Peripheral Pulmonary Nodules: A Prospective, Multicenter Clinical Feasibility Study in China.

The ION system is a shape-sensing robotic-assisted bronchoscopy (SS-RAB) platform developed to biopsy peripheral pulmonary nodules (PPNs). There is a lack of data describing the use of this system in the Chinese population. The study aimed to assess the feasibility and safety of using SS-RAB to diagnose PPNs across multiple centers within China. This prospective, multicenter study used SS-RAB in consecutive patients with solid or sub-solid PPNs 8 to 30mm in largest diameter. Primary endpoints were diagnostic yield and the rates of procedure- or device-related complications. Radial endobronchial ultrasound (rEBUS) was to confirm lesion localization, followed by sampling, using the Flexision biopsy needle, biopsy forceps, and cytology brush. Subjects with nonmalignant index biopsy results were followed up to 6 months. A total of 90 PPNs were biopsied from 90 subjects across 3 centers using SS-RAB. The median nodule size was 19.4mm (IQR: 19.3, 24.6) in the largest dimension. In all (100%) cases, the catheter successfully reached the target nodule with tissue samples obtained. The diagnostic yield was 87.8% with a sensitivity for malignancy of 87.7% (71/81). In a univariate analysis, nodule lobar location, presence of bronchus sign, and rEBUS view were associated with a diagnostic sample, but only rEBUS view showed an association in a multivariate analysis. The overall pneumothorax rate was 1.1% without pneumothorax requiring intervention, and there was no periprocedural bleeding. As an emerging technology in the Chinese population, SS-RAB can safely biopsy PPNs with strong diagnostic performance.

Association between preoperative appendiceal histology grade and Pseudomyxoma peritonei grade offer a solution to avoid right hemicolectomy during cytoreductive surgery and HIPEC

Introduction& objectives: Treatment of PMP consists of appendectomy, cytoreductive surgery (CRS) and HIPEC. Right-sided hemicolectomy is necessary only when PMP is high grade, given the lymphatic invasion risk. To date, no single preoperative factor was identified as predictive of PMP grade.Materials & methods: Preoperative factors of a prospective cohort study on PMP were retrospectively analysed, in order to identify situations linked with high or low grade appendiceal PMP. The main outcome was PMP grade on definitive histology after CRS. Resultsn=105. In univariate analysis, the grade of the appendiceal tumor, systematically reviewed in an expert center, showed an OR of 25.00 (95% CI: 3.30–189.27; p = 0.001) and an NPV of 93.75 [85.36, 100]. Peritoneal biopsy demonstrated an OR of 19.80 (95% CI: 2.30–170.71; p = 0.002) and a PPV of 90 [71.41, 100]. In multivariate analysis, these two factors remained significantly associated with PMP grade. ConclusionWhenever appendiceal tumor is low grade on preoperative histology, the colon has to be spared unless completeness of CRS is compromised, which is a high-grade feature in fact. In case of high grade appendiceal tumor and/or peritoneal biopsy, right-sided hemicolectomy is warranted. If no histology is available preoperatively, adapt to intraoperative lesions as no preoperative factors seem to be predictive.

Association of serum lipid profile with liver fibrosis in HCV‑coinfected HIV patients on suppressive anti‑retroviral therapy.

Hepatitis C virus (HCV) coinfection in individuals living with human immunodeficiency virus (HIV) (PLWH) may affect lipid metabolism and accelerate the progression of chronic hepatitis. Therefore, the identification of risk factors for progressive liver disease is needed. The present study aimed to examine the prevalence and clinical features associated with liver fibrosis in HCV-coinfected HIV patients, including metabolic markers. A total of 105 patients coinfected with HIV and HCV were recruited and liver fibrosis was assessed using the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI). Logistic regression analyses indicated that patients aged >50 years and with a CD4+ cell count <350 cells/µl had an 11.4-times higher (P=0.001) and a 5.7-times higher (P=0.017) risk of liver fibrosis, as determined by FIB-4 score, compared to patients aged ≤40 years and a CD4+ cell count of ≥350 cells/µl, respectively. In addition, patients naïve to HCV treatment or receiving treatment had 5.4- and 12.7-times higher risks for liver fibrosis, as determined by APRI, than those with sustained virologic response (SVR) (P=0.003 and P=0.033, respectively). Univariate analysis indicated lower risks of liver fibrosis, as determined by APRI, in the patients with abnormally high levels of cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) than those with normal levels [odds ratio (OR) 0.3, 95% confidence interval (CI) 0.1-0.9, P=0.037; OR 0.4, 95% CI 0.2-0.9, P=0.041; OR 0.2, 95% CI 0.1-0.5, P=0.001] and multivariate analysis suggested only patients with high levels of LDL had a lower risk for liver fibrosis determined by APRI (OR 0.1, 95% CI 0.3-0.8, P=0.029). Consistently, serum levels of cholesterol, HDL and LDL were significantly lower in the patient groups with more advanced fibrosis, evaluated by FIB-4 score and APRI, than those without liver fibrosis and the levels of cholesterol and LDL in the patients achieving SVR were higher than those with no response or not receiving treatment (all P<0.05). In conclusion, the present study identified serum lipid levels as associated factors of hepatic fibrosis, together with age, CD4+ cell count and HCV treatment status, in HCV-coinfected PLWH on long-term suppressive anti-retroviral therapy.

Association of Iron Therapy with Mortality in Patients with Acute Myocardial Infarction and Iron Deficiency.

Iron deficiency (ID) is common in patients with acute myocardial infarction (AMI). It is unknown whether patients with AMI combined with ID will benefit from iron supplementation therapy. This study aimed to assess the relationship between iron therapy and mortality in AMI patients. Retrospective analysis was performed in subjects screened from the Medical Information Mart in Intensive Care-IV database. The data were obtained from ICU patients admitted to Beth Israel Deaconess Medical Center between 2008 and 2019. The patients were divided into two groups according to iron treatment exposure. Propensityscorematching(PSM) was performed in the original cohort at a 1:1 ratio. Univariate and multivariate analyses were performed to adjust for confounding factors. The primary outcome was 28-day mortality. A total of 426 patients were included in this study. After 1:1 PSM, 208 patients were analyzed. Iron treatment was associated with a lower risk of 28-day mortality (9 deaths (8.65%) in the iron treatment group vs. 21 deaths (20.19%) in the non-iron treatment group; HR = 0.39; 95% CI = 0.17-0.89; p = 0.025) and in-hospital mortality (4 deaths (3.85%) in the iron treatment group vs. 12 deaths (11.54%) in the non-iron treatment group; OR, 0.15; 95% CI, 0.03-0.74; p = 0.029). Iron treatment was associated with reduced 28-day mortality in patients with AMI combined with ID. Iron treatment had no significant effect on the length of hospitalization or the length of ICU stay. Prospective studies are needed to verify this conclusion.

Online Education in Hungary and Armenia during the Pandemic and Its Aftermath

After the breakout of the COVID-19 pandemic our lives have been profoundly changed, including higher education, where a digital form has emerged as a result. This paper presents some of the results of nearly two and a half years of research conducted in two countries. The first objective was to analyse the experience of the transition to digital education, digital competencies and equipment of staff during the COVID-19 pandemic, and the second was to summarise the impact of the alternatives to digital education at universities after the pandemic. It was also aimed at describing how digital education at the universities of these two countries with very different cultures has been tackled and whether the experiences are different. The research was carried out by means of a questionnaire including 592 instructors from Hungary and 111 from Armenia. The researchers analysed the data using SPSS 28 statistical software. Univariate and multivariate analyses were conducted, including frequency, mean and standard deviation tests, cross-tabulation analysis, ANOVA, independent samples t-test, and correlation. analyse The current study suggests that the two culturally different countries did not have completely different practices, and also the smoothness of the transition to digital education has a major impact on how digital solutions are integrated into university education in the two countries in the future. To conclude, the pandemic induced the emergence of online education, which is here to stay with us in the future to supplement traditional, offline forms.

DPD Quantification Correlates With Extracellular Volume and Disease Severity in Wild-Type Transthyretin Cardiac Amyloidosis

BackgroundThe pathophysiological hallmark of wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is the deposition of amyloid within the myocardium. ObjectivesThis study aimed to investigate associations between quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake and myocardial amyloid burden, cardiac function, cardiac biomarkers, and clinical status in ATTRwt-CM. MethodsForty ATTRwt-CM patients underwent quantitative DPD single photon emission computed tomography/computed tomography to determine the standardized uptake value (SUV) retention index, cardiac magnetic resonance imaging to determine extracellular volume (ECV) and cardiac function (RV-LS), and assessment of cardiac biomarkers (N-terminal prohormone of brain natriuretic peptide [NT-proBNP], troponin T) and clinical status (6-minute walk distance [6MWD], National Amyloidosis Centre [NAC] stage). ATTRwt-CM patients were divided into 2 cohorts based on median SUV retention index (low uptake: <5.19 mg/dL, n = 20; high uptake: ≥5.19 mg/dL, n = 20). Linear regression models were used to assess associations of the SUV retention index with variables of interest and the Mann-Whitney U or chi-squared test to compare variables between groups. ResultsATTRwt-CM patients (n = 40) were elderly (78.0 years) and predominantly male (75.0%). Univariable linear regression analyses revealed associations of the SUV retention index with ECV (r = 0.669, β = 0.139, P < 0.001), native T1 time (r = 0.432, β = 0.020, P = 0.005), RV-LS (r = 0.445, β = 0.204, P = 0.004), NT-proBNP (log10) (r = 0.458, β = 2.842, P = 0.003), troponin T (r = 0.422, β = 0.048, P = 0.007), 6MWD (r = 0.385, β = −0.007, P = 0.017), and NAC stage (r = 0.490, β = 1.785, P = 0.001). Cohort comparison demonstrated differences in ECV (P = 0.001), native T1 time (P = 0.013), RV-LS (P = 0.003), NT-proBNP (P < 0.001), troponin T (P = 0.046), 6MWD (P = 0.002), and NAC stage (I: P < 0.001, II: P = 0.030, III: P = 0.021). ConclusionsIn ATTRwt-CM, quantitative cardiac DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage, providing a valuable tool to quantify and monitor cardiac disease burden.

Association of Collagen Changes in Distal Anastomotic Margin and Anastomotic Stenosis after Neoadjuvant Chemoradiotherapy for Rectal Cancer.

Neoadjuvant chemoradiotherapy (nCRT) for rectal cancer can lead to structural changes in collagen in the tumor microenvironment and increase the risk of postoperative anastomotic stenosis (AS). However, the quantitative relationship between AS and collagen has not been defined. This study is to quantitatively analyze the collagen features in rectal cancer and explore the relationship between the changes of collagen and postoperative anastomotic stenosis after nCRT. This is a retrospective study. A total of 371 patients with rectal cancer were included. Collagen features in the resection margin of rectal cancer anastomosis was extracted by multiphoton imaging. The least absolute shrinkage operator logistic regression was performed to select features related to AS and the collagen score (CS) was constructed. Area under the receiver operating curve (AUROC) and decision curve analysis were performed to evaluate the discrimination and clinical benefit of the nomogram. The probability of AS was 23% in the training cohort and 15.9% in the validation cohort. In the training cohort, the distance between tumor and resection margin, anastomotic leakage and CS were independent risk factors for postoperative AS in univariate and multivariate analyses. A nomogram was constructed based on these results. The prediction nomogram showed good discrimination (AUROC 0.864; 95% CI 0.776 to 0.952) and was validated in the validation cohort (AUROC 0.918; 95% CI 0.851 to 0.985). CS is an independent risk factor for AS in rectal cancer after nCRT. The predictive model based on CS can predict the occurrence of postoperative AS.

T-wave Peak-to-End Changes Quantified by Time-Warping Predicts Ventricular Fibrillation in a Porcine Myocardial Infarction Model.

The T-peak-to-T-end ( Tpe) interval has shown potential in predicting ventricular arrhythmic risk. It is an appealing index to be measured during ischemia since it is less influenced by ST-segment changes than the early part of the T wave. A time-warping-based index, derived from a spatially transformed PCA lead, [Formula: see text], quantifying changes in the Tpe morphology, has previously demonstrated utility in tracking repolarization changes induced by a 5-minute ischemia model in humans. The value of [Formula: see text] as a predictor of ventricular fibrillation (VF) episodes is assessed in a porcine model of myocardial ischemia with ischemia maintained for 40 minutes. From 32 pigs undergoing a coronary occlusion, pre-occlusion and occlusion ECG recordings from 10 pigs suffering a VF episode after 10 min of occlusion (Delayed VF) and 16 that did not had any episode during the recording were analyzed. The [Formula: see text] series was measured by comparing Tpe morphologies at different stages of the occlusion relative to the peak-to-end morphology of a baseline T-wave. During baseline, [Formula: see text] remained stationary with an intra-recording median [IQR] value of 1.60 [1.33] ms. During artery occlusion, [Formula: see text] followed a well-marked gradual increasing trend as ischemia progressed, reaching a median of 14.58 [17.72] ms. [Formula: see text] averages were significantly higher ( ) in the VF group than in the Non-VF group at time intervals 0-5, 5-10, 10-15, 15-20, 20-25 min after occlusion onset and at 10-15, 5-10 and 5-0 minutes prior to VF episode, with median values of 12.5, 18.8, 26.8, 24.0, 31.0, 18.6, 25.0 and 28.8 vs 6.3, 7.6, 8.0, 7.8, 7.8, 8.5, 7.2 and 6.0 ms, respectively. The [Formula: see text] interval was also significantly higher in the VF group at all analyzed time periods, but with a lower significance level. Pigs with maximum [Formula: see text] ≥ 20.0 ms and [Formula: see text] ≥ 85.4 ms had significantly higher risk for VF occurring in the early 5-10 minutes interval, with 90.0%/75.0% and 80.0%/69.0% sensitivity/specificity, respectively. Univariate Cox analysis yielded hazard ratios of 12.5 for [Formula: see text] vs 5.5 for [Formula: see text]. The time-warping-based index, [Formula: see text], is a stronger VF predictor than [Formula: see text] during ischemia in a porcine model, advising for further clinical exploration studies in humans.

Low serum creatine kinase level is associated with poor prognosis in patients with hepatocellular carcinoma: A retrospective single‑center study.

Previous studies have reported low serum creatine kinase (s-CK) levels as a poor prognostic factor in various cancers. However, there have been no reports on its significance in hepatocellular carcinoma. The present study aimed to evaluate the association of the preoperative s-CK levels with clinicopathologic features and their prognostic impact on survival in patients with hepatocellular carcinoma. This retrospective study included 163 patients with hepatocellular carcinoma (127 male and 36 female patients; median age, 69 years) who underwent radical liver resection between January 2004 and December 2021. A cutoff preoperative s-CK level of 91 U/l determined by receiver operating characteristic curve analysis was used to evaluate the significance of s-CK in predicting overall and recurrence-free survival. In addition, the prognostic impact of s-CK was evaluated using univariate and multivariate analysis. s-CK level was not associated with clinicopathologic factors. Overall survival and recurrence-free survival of the low s-CK group were significantly worse compared with the high s-CK group (P=0.043 and P=0.029, respectively). By multivariate analysis, low s-CK was an independent risk factor for poor overall survival and recurrence-free survival (P=0.019 and P=0.014, respectively). This trend was the same for male patients, but no significant difference was observed for female patients. Low preoperative s-CK level might be a poor prognostic biomarker in patients with hepatocellular carcinoma.

Postoperative Access and Compliance Following Medial Patellofemoral Ligament Reconstruction in Hispanic Adolescents Mirrors the Non-Hispanic Adolescent Population.

Disparity in surgical care of patellar instability patients has not been fully investigated in the adolescent Hispanic population. This demographic has been shown to have differences in their care, including a lower rate of surgical treatment for patellar instability. Socioeconomic factors have been cited as a factor that influences patient outcomes and its relationship with ethnicity in context of patellar instability has not been evaluated. Review performed of patients <19 years of age who underwent MPFL reconstruction between September 2008 and December 2015. Demographics, patient median household income data, and clinical variables were collected. Generalized linear mixed model (GLMM) with subject as random effects factor was utilized to evaluate differences between ethnicity groups due to nonindependence of data. It was then expanded to incorporate interactions between ethnicity and income. Ninety-five patellar dislocation events met criteria in 85 adolescents (mean age: 15.5y). Thirty-four (40%) adolescents identified as Hispanic. In univariate analysis no differences were found between Hispanic and non-Hispanic patients. The multivariate GLMM demonstrated a significant interaction between ethnicity and income. The Hispanic group in the >100% State median income category had the highest rate of postoperative clinic appointments attended ( P =0.019). The Hispanic group in the <100% State median income category had the lowest rate of physical therapy appointments attended ( P =0.044). No differences were observed for duration of follow-up ( P =0.57) or final Kujala score ( P =0.75). Hispanic ethnicity alone is not associated with inferior postoperative management after MPFL reconstruction in adolescents. However, when socioeconomic status is considered, Hispanic patients of lower-income backgrounds are found to have lower compliance with postoperative rehab recommendations. Level III.

Breast cancer promotes the expression of neurotransmitter receptor related gene groups and image simulation of prognosis model

Breast cancer (BC), a prevalent and severe malignancy, detrimentally affects women globally. Its prognostic implications are profoundly influenced by gene expression patterns. This study retrieved 509 BC-associated oncogenes and 1,012 neurotransmitter receptor-related genes from the GSEA and KEGG databases, intersecting to identify 98 relevant genes. Clinical and transcriptomic expression data related to BC were downloaded from the TCGA, and differential genes were identified based on an FDR value <0.05 & |log2FC| ≥ 0.585. Univariate analysis of these genes revealed that high expression of NSF and low expression of HRAS, KIF17, and RPS6KA1 are closely associated with BC survival prognosis. A prognostic model constructed for these four genes demonstrated significant prognostic relevance for BC-TCGA patients (P < 0.001). Subsequently, an immunofunctional analysis of the BC oncogene-neurotransmitter receptor-related gene cluster revealed the involvement of immune cells such as T cells CD8, T cells CD4 memory resting, and Macrophages M2. Further analysis indicated that immune functions were primarily concentrated in APC_co_inhibition, APC_co_stimulation, CCR, and Check-point, among others. Lastly, a prognostic nomogram model was established, and ROC curve analysis revealed that the nomogram is a vital indicator for assessing BC prognosis, with 1-year, 3-year, and 5-year survival rates of 0.981, 0.897, and 0.802, respectively. This model demonstrates high calibration, clinical utility, and predictive capability, promising to offer an effective preliminary tool for clinical diagnostics.

Efficacy of timing‑dependent infusion of nivolumab in patients with advanced gastric cancer.

Although an association exists between the timing of immune checkpoint inhibitor (ICI) administration and therapeutic efficacy in several types of cancer, to the best of our knowledge, no reports exist regarding this relationship in gastric cancer (GC). The present study aimed to evaluate the optimal timing of ICI (nivolumab) administration in patients with advanced GC. A total of 58 consecutive patients with advanced GC who received nivolumab monotherapy after ≥2 chemotherapy regimens were retrospectively evaluated. These patients were divided into two groups according to the median time of nivolumab administration: i) Early-timing and (ii) late-timing groups, and the efficacy was assessed in both groups. The early-timing group had significantly longer overall survival (OS) than the late-timing group [median OS 8.2 months; 95% confidence interval (CI), 4.2-12.9 vs. median OS 5.4 months; 95% CI, 3.6-6.1]. Moreover, patients in the early-timing group had significantly longer progression-free survival (PFS) than those in the late-timing group (median PFS 2.6 months; 95% CI, 1.3-3.9 months vs. median PFS 1.6 months; 95% CI, 0.9-2.1 months). Furthermore, univariate analysis showed that early timing, immune-related adverse events and nonsteroidal anti-inflammatory drug administration were associated with longer OS and PFS. Cutoff Finder analysis revealed that the optimal timing of nivolumab administration for achieving better outcomes was before 12:06 p.m. Nivolumab administration in the morning, especially before 12:06 p.m., had a better clinical impact on patients with advanced GC.

Evaluation and analysis of neurocognitive dysfunction in patients with colorectal cancer after radical resection: A retrospective study

BACKGROUND With the continuous progress of colorectal cancer treatment technology, the survival rate of patients has improved significantly, but the problem of postoperative neurocognitive dysfunction has gradually attracted attention. AIM To analyze the risk factors for delayed postoperative neurocognitive recovery (DNR) after laparoscopic colorectal cancer surgery and constructed a risk prediction model to provide an evidence-based reference for the prevention and treatment of DNR after laparoscopic colorectal cancer surgery. METHODS The clinical data of 227 patients with colorectal cancer who underwent laparoscopic surgery and regional cerebral saturation oxygenation (rScO2) monitoring at our hospital from March 2020 to July 2022 were retrospectively analyzed. Common factors and potential factors affecting postoperative DNR were used as analysis variables, and univariate analysis and multifactor analysis were carried out step by step to determine the predictors of the model and construct a risk prediction model. The predictive performance of the model was assessed by the receiver operating characteristic (ROC) curve, the calibration curve was used to assess the fit of the model to the data, and a nomogram was drawn. In addition, 30 patients who met the inclusion and exclusion criteria from January 2023 to July 2023 were selected for external verification of the prediction model. RESULTS The incidence of postoperative DNR in the modeling group was 15.4% (35/227). Multivariate analysis revealed that age, years of education, diabetes status, and the lowest rScO2 value were the independent influencing factors of postoperative DNR (all P &lt; 0.05). Accordingly, a DNR risk prediction model was constructed after laparoscopic colorectal cancer surgery. The area under the ROC curve of the model was 0.757 (95%CI: 0.676-0.839, P &lt; 0.001), and the Hosmer-Lemeshow test of the calibration curve suggested that the model was well fitted (P = 0.516). The C-index for external validation of the row was 0.617. CONCLUSION The DNR risk prediction model associated with rScO2 monitoring can be used for individualized assessment of patients undergoing laparoscopic colorectal cancer surgery and provides a clinical basis for the prevention of DNR after surgery.

Preoperative systemic inflammatory response index as a prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy

BACKGROUND The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged. AIM To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma (dCCA) who underwent pancreatoduodenectomy (PD). METHODS This single-center study included 216 patients with dCCA after PD between January 1, 2011, and December 31, 2022. The individuals were categorized into two sets based on their systemic inflammatory response index (SIRI) levels: A low SIRI group (SIRI &lt; 1.5, n = 123) and a high SIRI group (SIRI ≥ 1.5, n = 93). Inflammatory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves. Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival (OS) and recurrence-free survival (RFS). RESULTS The study included a total of 216 patients, with 58.3% being male and a mean age of 65.6 ± 9.6 years. 123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA. SIRI had an area under the curve value of 0.674 for diagnosing dCCA, showing better performance than other inflammatory biomarkers. Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD, leading to lower OS [hazard ratios (HR) = 1.868, P = 0.006] and RFS (HR = 0.949, P &lt; 0.001). Additionally, survival analysis indicated a significantly better prognosis for patients in the low SIRI group (P &lt; 0.001). CONCLUSION It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD.

Adverse Childhood Experiences in the Post-COVID Era

ABSTRACT This study explored Adverse Childhood Experiences (ACEs) in relation to the COVID-19 pandemic using YRBSS survey data on youth grades 9–12 and was analyzed using weighted sample prevalence, univariant weighted analysis, and multivariable weighted logistic regressions. Models adjusted for age, sex, ethnicity, race, sexual identity, smoking, alcohol, and illicit drug use. Inclusion criteria were those aged 14 years or older. Results showed decreased violence, substance use, and sexual health risk in 2021 compared to 2019, but increased mental health risk. Black individuals had higher odds of violence and victimization and sexual health risk. Gay, lesbian, and bisexual youths faced increased odds of various risks (p < .05). Understanding ACEs post-COVID-19 is crucial for mitigating their long-term effects on health.

Abstract B140: Further evaluation of social determinants of health including association of neighborhood disadvantage and population density with severity of activity- and mood- related interference in primary brain tumor patients

Abstract Purpose: Growing evidence links living in rural or socioeconomically disadvantaged areas with worse outcomes in cancer patients. Our previous work indicated that growing up in a rural area and experiencing food insecurity in childhood are associated with more severe activity and mood-related interference from symptoms in the primary brain tumor (PBT) population. This study investigates the association of current neighborhood deprivation and population density with activity- and mood-related interference in a cross-sectional cohort of 555 patients with a PBT enrolled in a natural history study (NCT03251989). Methods: National Area Deprivation Index (ADI) and population density were dichotomized into more (&amp;gt;40) and less (&amp;lt;40) disadvantaged and urbanized (&amp;gt;1,000 persons/sq mi) and non-urbanized (&amp;lt;1,000 persons/sq mi). Activity- and mood-related interference was stratified into none/mild (0-1) and moderate/severe (2-10). Logistic regression was used to test univariate and multivariate associations of moderate/severe activity- and mood-related interference with demographic and clinical variables. Bonferroni-Holm was implemented to adjust for multiple comparisons (p &amp;lt; 0.001) in univariate analyses. We used backwards elimination multivariate analyses to fit the final model. Variables were included modeling when univariate p &amp;lt;0.10. Results: The sample included more males (57%), median age 49 (range 18-85), living in more disadvantage neighborhoods (25%), and primarily in urbanized areas (61%). The majority (74%) had high grade tumors, most commonly glioblastoma (39%), with 49% with tumor recurrence, and 21% on active treatment. Univariate analysis showed neither ADI nor population density was significantly associated with activity-related interference (ADI OR=1.35, 95% CI [0.85, 2.13]; population density OR=1.20, 95% CI [0.80, 1.79]) or mood-related interference (ADI OR=0.85, 95% CI [0.52, 1.38]; population density OR=1.19, 95% CI [0.78, 1.81]). In the multivariate analyses tumor diagnosis (OR=0.92 CI [0.53, 1.58]) growing up in a non-urbanized area (OR=1.56 CI [1.02, 2.40]), not having enough to eat when growing up (OR=2.50 CI [1.13, 5.54], and number of surgeries (OR=1.50 CI [1.00, 2.23]) remained associated with moderate/severe activity-related interference with ADI, and similar results were found in the population density model. Tumor recurrence (OR=1.77 CI [1.17, 2.66]) and comorbidities (OR=0.53 CI [0.33, 0.85]) were associated with moderate/severe mood-related interference with ADI and similar results were found in the population density model. Conclusions: Although activity- and mood-related interference were not associated with current ADI or population density, activity-related interference was significantly related to early life social variables including growing up in a rural area and not having enough to eat growing up. This study may be foundational for future study directions exploring other social deprivation factors early life or current that contributes to more interference in the PBT population. Citation Format: Tara S. Davis, Bennett A. McIver, Kimberly Reinhart, Elizabeth Vera, Vivian A. Guedes, Macy L. Stockdill, Orieta Celiku, Terri S. Armstrong, Michelle L. Wright. Further evaluation of social determinants of health including association of neighborhood disadvantage and population density with severity of activity- and mood- related interference in primary brain tumor patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B140.

Abstract C098: CYR61 expression in prostate cancer patients at City of Hope

Abstract In the US, African-American (AA) and Hispanic/Latino (H/L) men have higher rates of advanced prostate cancer (PCa), increased PCa-specific mortality, and are more likely to undergo metastasis than non-Hispanic White (NHW) men attributed to a lack of access to early screening, and a higher prevalence of risk factors such as obesity, diet, and genetic differences. Consequently, effective treatment of advanced PCa and elimination of racial and ethnic disparities for this malignancy require the identification of mechanisms of disease progression. In PCa, the cysteine-rich angiogenic inducer 61 (CYR61) contributes to malignant cell growth through interactions with extracellular ligands, such as integrins avb3 and a6b4. In previous studies, we have found that CYR61 is upregulated in metastatic PCa cell lines and knockdown of this protein significantly reduced metastatic cell proliferation, viability, prostasphere formation, and activation of the PI3/AKT pathway, indicating a potential utilization of CYR61 inhibition in the therapy of metastatic PCa. Interestingly, we have observed that in metastatic PCa cell models, IGF1 induction increased CYR61 protein expression. However, the correlation between PCa aggressiveness and levels of CYR61 in tumor-derived tissues from patients is poorly studied. Our goal with this study is to identify possible correlations in CYR61 expression that may reflect health disparities in PCa outcomes. We used in silico analyses from whole exome paired tumor/normal DNA sequencing and tumor RNA sequencing data available on 542 PCa cases in the City of Hope POSEIDON database to determine whether gene expression of CYR61 and IGF1 was correlated with genetic ancestry, Gleason score, and tumor purity. In univariate analyses, we found that H/L PCa cases had significantly higher levels of expression of CYR61 than NHW PCa cases (p = 0.043) and that both H/L and AA PCa cases had higher IGF1 expression levels, although only significant in AA (p=0.031). We also found that PCa patients with Gleason scores of 8 and higher had significantly lower expression of IGF1 than those with Gleason scores of 7 or less (p=0.006). Both CYR61 and IGF1 expression levels were significantly lower in those with luminal B (p=0.00000000053, p=0.000009, respectively) and with basal subtypes (p=0.00035, p=0.000069, respectively compared to luminal A subtype. Tumor purity was estimated by RNA-seq based on 141 genes specific to stroma and 141 genes specific to immune cells. CYR61 expression was significantly correlated with stromal and immune infiltration. These results suggest that reduced CYR61 expression is associated with more aggressive PCa. Additional analyses are ongoing to understand the interplay of variables of race and ethnicity, age, Gleason score, and tumor purity and to investigate outcomes of biochemical recurrence and death from PCa. Citation Format: Greisha L. Ortiz-Hernandez, Yuan Chun Ding, Susan L. Neuhausen. CYR61 expression in prostate cancer patients at City of Hope [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C098.

Prediction of pathological response and lymph node metastasis after neoadjuvant therapy in rectal cancer through tumor and mesorectal MRI radiomic features

Establishing predictive models for the pathological response and lymph node metastasis in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) based on MRI radiomic features derived from the tumor and mesorectal compartment (MC). This study included 209 patients with LARC who underwent rectal MRI both before and after nCRT. The patients were divided into a training set (n = 146) and a test set (n = 63). Regions of interest (ROIs) for the tumor and MC were delineated on both pre- and post-nCRT MRI images. Radiomic features were extracted, and delta radiomic features were computed. The predictive endpoints were pathological complete response (pCR), pathological good response (pGR), and lymph node metastasis (LNM). Feature selection for various models involved sequentially removing features with a correlation coefficient > 0.9, and features with P-values ≥ 0.05 in univariate analysis, followed by LASSO regression on the remaining features. Logistic regression models were developed, and their performance was evaluated using the area under the receiver operating characteristic curve (AUC). Among the 209 LARC patients, the number of patients achieving pCR, pGR, and LNM were 44, 118, and 40, respectively. The optimal model for predicting each endpoint is the combined model that incorporates pre- and delta-radiomics features for both the tumor and MC. These models exhibited superior performance with AUC values of 0.874 (for pCR), 0.801 (for pGR), and 0.826 (for LNM), outperforming the MRI tumor regression grade (mrTRG) which yielded AUC values of 0.800, 0.715, and 0.603, respectively. The results demonstrate the potential utility of the tumor and MC radiomics features, in predicting treatment efficacy among LARC patients undergoing nCRT.

Identification and Validation of an Invasion-Related Disease-Free Survival Prognostic Model for Tongue Squamous Cell Carcinoma

Introduction: Tongue squamous cell carcinoma (TSCC) &lt;underline&gt;is&lt;/underline&gt; a common malignant tumour type with aggressive invasion and a poor prognosis. To date, invasion-related gene expression signatures for the prognostic stratification of TSCC patients are unavailable in clinical practice. This study aimed to assess the impact of invasion-related genes on the prognosis of TSCC patients. Methods: We obtained mRNA profiles and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (TCGA-TSCC and GSE41116, respectively). The TSCC samples from the TCGA-TSCC cohort were randomly divided into TCGA training and TCGA test datasets at a 7:3 ratio. Next, a disease-free survival (DFS) prognostic risk model was established on the basis of univariate and stepwise multivariate Cox regression analyses of the TCGA training cohort. Moreover, prognostic genes were screened. The model was subsequently evaluated and validated using the TCGA test and GSE41116 datasets. In addition, the prognostic genes were validated in the human TSCC cell line UM1 and the human oral keratinocyte (HOK) cell line using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Results: A total of 70 candidate genes related to invasion were identified in the TCGA-TSCC cohort. DFS data were subsequently constructed, and 6 prognostic genes, HMGN2, MYL12B, ACTB, PPP1CA, PSMB9, and IFITM3, were identified. The TSCC samples were divided into high- and low-risk groups in the TCGA training, TCGA test, and GSE41116 cohorts, respectively. In particular, patients with TSCC in the low-risk group had longer DFS than those in the high-risk group. Furthermore, qRT-PCR analysis confirmed that the expression levels of the 6 prognostic genes were significantly greater in the TSCC cell line UM1 than in the HOK cell line. Conclusion: This study identified new invasion-related target genes related to poor prognosis in TSCC patients, providing new insights into the underlying mechanisms of TSCC invasion.