Prognostic Relevance Research Articles

Prognostic Relevance of Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Arterial Pressure Ratio and Its Association With Exercise Hemodynamics in Patients With Normal or Mildly Elevated Resting Pulmonary Arterial Pressure

BackgroundEchocardiographic TAPSE/sPAP ratio is a non-invasive surrogate for right ventricular-pulmonary arterial (RV-PA) coupling. It has been related to outcome in patients with moderate to severe pulmonary hypertension (PH). Research QuestionIs RV-PA coupling of prognostic relevance in patients with suspected PH but only normal or mildly elevated mean pulmonary arterial pressure (mPAP) and is it associated with impaired exercise capacity and exercise hemodynamics? Study Design and MethodsPatients with mPAP<25mmHg who underwent echocardiography and exercise right heart catheterization in our PH-clinic, were retrospectively analyzed. Mild PH was defined by mPAP 21-24mmHg and exercise PH (EPH) by a mPAP/cardiac-output (CO) slope >3mmHg/L/min. Multivariate analysis was performed to identify independent predictors for clinical worsening, defined by disease-related hospitalization, transplantation, or death. Results237 patients (female: N=155; median age: 64 (IQR 54-73) years, no PH N=147; mild PH N=90; EPH N=202) were included. During the observation time of 63 (IQR:29-104) months, 36 patients died and 126 events of clinical worsening occurred. TAPSE/sPAP ratio turned out as age- and sex independent predictor of mortality (HR 0.09 95% CI: (0.01 – 0.62) p=0.014) and clinical worsening (HR 0.05 95% CI: (0.35-0.78); p=0.002). TAPSE/sPAP was also significantly correlated to 6-minute walk distance (r= 0.33; p<0.001) and exercise hemodynamics (mPAP/CO slope: rρ=-0.56, p<0.001). The best multivariate predictive model for clinical worsening in this patient collective consisted of TAPSE/sPAP ratio (HR: 0.71 (0.53-0.95), p=0.021), NT-proBNP (HR 1.15 (0.99-1.34), p=0.065) and 6MWD (HR: 0.998 (0.995-1.00), p=0.042). InterpretationIn patients with suspected PH but normal or only mildly elevated resting mPAP, TAPSE/sPAP ratio is an independent predictor of outcome. In addition, it is significantly associated with exercise capacity and exercise hemodynamics and may be a helpful tool in the prediction of future clinical worsening of this patient population.

Soluble MIC-A, IPI, and response to treatment strongly predict survival in patients with germinal center diffuse large B cell lymphoma.

To analyze lymphocyte subsets and sMIC-A in germinal center DLBCL. sMICA, sMICB, and peripheral blood lymphocyte subsets (CD4+, CD8+, NK, NKT, γδ T cells, and dendritic cells) were analyzed in 59 patients and 60 healthy donors. Patients had decreased numbers of type 1 and type 2 dendritic cells, NK, iNKT, CD4 T, and CD8 T cells, and higher levels of sMIC-A. The 2-year PFS for high IPI scores and high sMIC-A was 24% and 28%, respectively. The 2-year OS for high IPI scores and high sMIC-A was 42% and 33%. The 2-year PFS and OS for patients not achieving response to treatment were 0% and 10%, respectively. The MICPI score (one point each for high IPI score and high sMIC-A) showed that those patients summing two points had worse PSF and OS. Patients with DLBCL have decreased numbers of peripheral lymphocyte subsets and high levels of sMIC-A. The addition of sMIC-A to IPI could improve its prognostic relevance.

Role of C-reactive Protein and Procalcitonin in Early Diagnostic Accuracy and Their Prognostic Significance in Sepsis.

Sepsis is a serious condition that often results in high fatality rates, particularly in intensive care units (ICUs). Its nonspecific clinical characteristics makes early diagnosis and therapy difficult, despite how critical they are. The use of biomarkers like procalcitonin (PCT) and C-reactive protein (CRP) in the diagnosis and prognosis of sepsis has demonstrated encouraging results. In contrast to PCT, which is highly selective for bacterial infections, CRP is an acute-phase protein that reflects systemic inflammation. This study aimed to assess the diagnostic accuracy and prognostic significance of CRP and PCT in early sepsis detection and outcome prediction. This study was a retrospective cohort study that involved 90 patients in the ICU who met the criteria for sepsis-3. CRP and PCT levels, clinical data, and outcomes were obtained from electronic medical records. The diagnostic accuracy was tested using receiver operating characteristic (ROC) curves, while the prognostic relevance was analyzed by Kaplan-Meier survival analysis and Cox proportional hazards regression. The mean CRP level was 102.3 mg/L and PCT level was 5.4 ng/mL. ROC analysis revealed an area under the curve (AUC) of 0.78 for CRP and 0.82 for PCT, indicating better diagnostic performance for PCT. High levels of CRP and PCT were associated with poorer survival, with median survival times of 18 and 15 days, respectively, for high-level groups. Cox regression identified CRP and PCT as significant predictors of mortality, with hazard ratios of 1.50 and 1.68, respectively. Both CRP and PCT are valuable biomarkers for diagnosing and prognosticating sepsis. PCT, with its higher specificity for bacterial infections, demonstrates superior diagnostic accuracy compared to CRP. Elevated levels of both biomarkers are associated with increased mortality risk, highlighting their potential role in early sepsis management and outcome prediction.

Covert Consciousness in the ICU.

For critically ill patients with acute severe brain injuries, consciousness may reemerge before behavioral responsiveness. The phenomenon of covert consciousness (i.e., cognitive motor dissociation) may be detected by advanced neurotechnologies such as task-based functional MRI (fMRI) and electroencephalography (EEG) in patients who appear unresponsive on the bedside behavioral examination. In this narrative review, we summarize the state-of-the-science in ICU detection of covert consciousness. Further, we consider the prognostic and therapeutic implications of diagnosing covert consciousness in the ICU, as well as its potential to inform discussions about continuation of life-sustaining therapy for patients with severe brain injuries. We reviewed salient medical literature regarding covert consciousness. We included clinical studies investigating the diagnostic performance characteristics and prognostic utility of advanced neurotechnologies such as task-based fMRI and EEG. We focus on clinical guidelines, professional society scientific statements, and neuroethical analyses pertaining to the implementation of advanced neurotechnologies in the ICU to detect covert consciousness. We extracted study results, guideline recommendations, and society scientific statement recommendations regarding the diagnostic, prognostic, and therapeutic relevance of covert consciousness to the clinical care of ICU patients with severe brain injuries. Emerging evidence indicates that covert consciousness is present in approximately 15-20% of ICU patients who appear unresponsive on behavioral examination. Covert consciousness may be detected in patients with traumatic and nontraumatic brain injuries, including patients whose behavioral examination suggests a comatose state. The presence of covert consciousness in the ICU may predict the pace and extent of long-term functional recovery. Professional society guidelines now recommend assessment of covert consciousness using task-based fMRI and EEG. However, the clinical criteria for patient selection for such investigations are uncertain and global access to advanced neurotechnologies is limited.

Study on the prediction model of liver cancer based on chronic liver disease and the related molecular mechanism

Introduction and objectiveDue to the high heterogeneity of HCC, which leads to poor prognostic outcomes for patients, there is a need to develop a novel predictive model for accurate classification of HCC in order to improve patient survival rates. Materials and methodsThe data of the HCV, cirrhosis, and HCC were obtained from TCGA and GEO databases. Multivariable Cox regression analysis and survival analysis was conducted to assess the prognostic relevance of these differentially expressed genes. Single-cell sequencing was used to explore the intercellular interaction patterns and identify relevant signaling pathways. Drug sensitivity analysis was conducted to determine personalized treatment strategies for patients. ResultsIn this study, we conducted integrated analysis of hepatitis, cirrhosis, and hepatocellular carcinoma datasets and identified 10 liver disease progression genes associated with prognosis. These genes exhibited significant downregulation in expression as the disease advanced, suggesting their crucial involvement in HCC development. By performing multivariable Cox analysis, we established a prognostic model for liver disease progression to predict the prognosis of HCC patients. The model was validated using ROC analysis, demonstrating good accuracy and stability in prognostic evaluation. Single-cell sequencing analysis revealed that these genes primarily exert their effects through the MIF signaling pathway during HCC progression. Furthermore, we observed that patients in the low-risk group exhibited higher sensitivity to TACE treatment, while patients in the high-risk group showed better response to sorafenib treatment. ConclusionsIn summary, we have elucidated the key genes involved in the progression of liver diseases and established a precise prognostic model for assessing the prognosis of HCC patients. Our study provides novel insights and strategies for the treatment of HCC.

The prognostic relevance of pleural effusion in patients with COVID-19 - A German multicenter study

PurposeThis study evaluates the prognostic significance of pleural effusion (PE) in COVID-19 patients across thirteen centers in Germany, aiming to clarify its role in predicting clinical outcomes. MethodsIn this retrospective analysis within the RACOON project (Radiological Cooperative Network of the COVID-19 pandemic), 1183 patients (29.3 % women, 70.7 % men) underwent chest CT to assess PE. We investigated PE's association with 30-day mortality, ICU admission, and the need for mechanical ventilation. ResultsPE was detected in 31.5 % of patients, showing a significant correlation with 30-day mortality (47.5 % in non-survivors vs. 27.3 % in survivors, p < 0.001), with a hazard ratio of 2.22 (95 % CI 1.65–2.99, p < 0.001). No significant association was found between PE volume or density and mortality. ICU admissions were noted in 46.8 % of patients, while mechanical ventilation was required for 26.7 %. ConclusionPleural effusion is present in a significant portion of COVID-19 patients and independently predicts increased 30-day mortality, underscoring its value as a prognostic marker. Its identification, irrespective of volume or density, should be a priority in radiological reports to guide clinical decision-making.

Prognostic relevance of preoperative CA 19-9 values in stage III rectal adenocarcinoma: retrospective analysis and clinical implications

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;To investigate prognostic significance of preoperative levels of the Carbohydrate anti-gen 19-9 (CA 19-9) in patients with stage III rectal adenocarcinoma who underwent a treatment at the Clinical Centre of the University of Sarajevo.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;A retrospective cohort study included 84 patients who underwent radical anterior rectal resection due to grade III rectal adenocarcinoma, followed by adjuvant chemotherapy according to the FOLFOX protocol (Oxaliplatin, Leucovorin, 5-Fluorouracil (5-FU)). The patients were divided into two groups according to CA 19-9 values (&amp;amp;ge;27 U/mL and &amp;amp;lt;27 U/mL, respectively).&amp;amp;nbsp;&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; &amp;lt;br /&amp;gt;High pre-operative CA 19-9 values predicted an increased probability of postoperative metastases, especially liver, lung and abdominopelvic metastases, as well as three-year disease-free survival (3Y-DFS) and three-year overall survival (3Y-OS). The 3Y-DFS rate for patients with high CA 19-9 was 64.5%, while for those with low CA 19-9 it was 87.2%. The 3Y-OS rate for patients with high CA 19-9 was 89.8%, while for those with low CA 19-9 it was 65.7%. Univariate and multivariate regression analysis confirmed that a high level of CA 19-9 is an independent predictor for DFS and OS shorter than three years.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; Pre-operatively elevated values of CA 19-9 in rectal adenocarcinoma have a significant role in predicting the outcome in patients with stage III rectal adenocarcinoma.&amp;lt;/p&amp;gt;

49P Prognostic relevance of baseline exosome-delivered PD-1, PD-L1, pan-BTN3As and BTN3A1 in advanced cholangiocarcinoma patients: Can immune checkpoints act as a sentinel for predicting survival?

49P Prognostic relevance of baseline exosome-delivered PD-1, PD-L1, pan-BTN3As and BTN3A1 in advanced cholangiocarcinoma patients: Can immune checkpoints act as a sentinel for predicting survival?

Pan-Cancer Screening and Validation of CALU's Role in EMT Regulation and Tumor Microenvironment in Triple-Negative Breast Cancer.

Cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression and the development of resistance to therapies across a range of malignancies, notably breast cancer. This study aims to elucidate the specific role and prognostic relevance of CALU across multiple cancer types. The association between CALU expression and prognosis, along with clinical characteristics in BRCA, HNSC, KIRP, LGG, and LIHC, was analyzed using data from the TCGA, GTEx, and GEO databases. Transcriptomic analysis of TCGA BRCA project data provided insights into the interaction between CALU and epithelial-mesenchymal transition (EMT) marker genes. Using TIMER and TISCH databases, the correlation between CALU expression and tumor microenvironment infiltration was assessed, alongside an evaluation of CALU expression across various cell types. Furthermore, CALU's influence on TNBC BRCA cell lines was explored, and its expression in tumor tissues was confirmed through immunohistochemical analysis of clinical samples. This study revealed a consistent upregulation of CALU across several tumor types, including BRCA, KIRP, LIHC, HNSC, and LGG, with elevated CALU expression being associated with unfavorable prognoses. CALU expression was particularly enhanced in clinical contexts linked to poor outcomes. Genomic analysis identified copy number alterations as the principal factor driving CALU overexpression. Additionally, a positive correlation between CALU expression and CAF infiltration was observed, along with its involvement in the EMT process in both CAFs and malignant cells. In vitro experiments demonstrated that CALU is highly expressed in TNBC-BRCA cell lines, and knockdown of CALU effectively reversed EMT progression and inhibited cellular migration. Immunohistochemical analysis of clinical samples corroborated the elevated expression of CALU in tumors, along with alterations in EMT markers. This comprehensive pan-cancer analysis underscores CALU's critical role in modulating the tumor microenvironment and facilitating cell migration via the EMT pathway, identifying it as a potential therapeutic target.

Redefining YAP1 in small cell lung cancer: shifting from a dominant subtype marker to a favorable prognostic indicator.

Molecular and transcription factor subtyping were recently introduced to identify patients with unique clinical features in small cell lung cancer (SCLC). However, its prognostic relevance is yet to be established. This study aims to investigate the clinical implications and prognostic significance of transcription factor subtyping in SCLC using immunohistochemistry. One hundred and ninety consecutive SCLC patients treated with platinum-based chemotherapy at a single institution were retrospectively reviewed. Expression of ASCL1, NeuroD1, POU2F3, and YAP1 was assessed by immunohistochemical staining and applied to determine the transcription factor subtype of each case. The association among transcription factors was not entirely mutually exclusive. YAP1 expression was the most significant prognostic indicator compared with other transcription factors or their related subtypes. Among patients with limited-stage disease (LD), complete response (CR) rates were 46.2% and 22.4% in the YAP1-positive and YAP1-negative groups, respectively. The median duration of response among patients who achieved CR was 64.8 and 36.4 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.06). Median overall survival (OS) in LD was 35.6 and 16.9 months in the YAP1-positive and YAP1-negative groups, respectively (P=0.03). In extensive-stage disease (ED), the median OS was 11.3 months for the YAP1-positive group and 11 months for the YAP1-negative group (P=0.03). Positive expression of YAP1 can be associated with durable CR and favorable survival outcomes in patients with SCLC, especially in LD.

Latent Class Analysis Reveals, in patient profiles, COVID-19–related better prognosis by calcifediol treatment than glucocorticoids

Calcifediol and glucocorticoids have been repositioned for the treatment of COVID-19 and may reduce severity, the need for intensive care unit admission and death. Objectiveto identify class or profiles of patients hospitalized and treated with COVID-19 pneumonia using latent class clustering methods to assess the clinical and prognostic relevance of the resulting patients’ profiles. Poor prognosis was defined as death or need for ICU admission, good prognosis, the opposite. With special interest in differential responses to calcifediol. SettingReina Sofia University Hospital, Córdoba Spain. PatientsRetrospective observational cohort study of patients admitted for COVID-19. ClinicalTrials.gov public database (NCT05819918). Inclusion criteria: (i) Age ≥ 18 and ≤ 90 years, (ii) Pneumonia characterized by the presence of infiltrates on chest X-ray or CT scan, (iii) SARS-CoV-2 infection, confirmed, and (iv) CURB Scale 65 >1. DesignLatent class analysis, for obtaining homogeneous clusters, without specifying a priori the belonging group, and selecting the optimal number of clusters by minimizing information criteria. Evaluating the differences between groups for each variable by means of chi-square, Fisher's exact test and Kruskal-Wallis test. Results707 patients hospitalized from 10 March 2020 until 4 March 2022 were included. For the treatment variable, differences were found between class 3 (60 % treated with calcifediol only) and classes 1 (less than 1 % calcifediol only vs. 82 % treated with both), 2 (less than 1 % calcifediol only vs. 82 % treated with both) and 4 (1 % calcifediol only vs. 84 % treated with both). Class 3, (60 % with calcifediol), had a significantly better prognosis compared to patients treated with glucocorticoids alone (OR: 15.2, 95 % CI: [3.73–142], p<0.001) or no treatment (OR: 7.38, 95 % CI: [2.63–30.2], p<0.001). Conclusionsour real-life study shows that calcifediol treatment significantly reduces the need for ICU admission and improved prognosis in patients hospitalized for COVID-19 pneumonia, especially in the profile of patients receiving it without glucocorticoids.

Integrated Analysis of Phagocytic and Immunomodulatory Markers in Cervical Cancer Reveals Constellations of Potential Prognostic Relevance.

Despite improvements in vaccination, screening, and treatment, cervical cancer (CC) remains a major healthcare problem on a global scale. The tumor microenvironment (TME) plays an important and controversial role in cancer development, and the mechanism of the tumor's escape from immunological surveillance is still not clearly defined. We aim to investigate the expression of CD68 and CD47 in patients with different histological variants of CC, tumor characteristics, and burden. This is a retrospective cohort study performed on paraffin-embedded tumor tissues from 191 patients diagnosed with CC between 2014 and 2021 at the Medical University Pleven, Bulgaria. Slides for immunohistochemical (IHC) evaluation were obtained, and the expression of CD68 was scored in intratumoral (IT) and stromal (ST) macrophages (CD68+cells) using a three-point scoring scale. The CD47 expression was reported as an H-score. All statistical analyses were performed using R v. 4.3.1 for Windows. Infiltration by CD68-IT cells in the tumor depended on histological type and the expression of CD47. Higher levels of the CD47 H-score were significantly more frequent among patients in the early stage. Higher levels of infiltration by CD68-ST cells were associated with worse prognosis, and the infiltration of CD68-IT cells was associated with reduced risk of death from neoplastic disease. TME is a complex ecosystem that has a major role in the growth and development of tumors. Macrophages are a major component of innate immunity and, when associated with a tumor process, are defined as TAM. Tumor cells try to escape immunological surveillance in three ways, and one of them is reducing immunogenicity by the overexpression of negative coreceptors by T-lymphocytes and their ligands on the surface of tumor cells. One such mechanism is the expression of CD47 in tumor cells, which sends a "don't eat me" signal to the macrophages and, thus, prevents phagocytosis. To our knowledge, this is the first study that has tried to establish the relationship between the CD47 and CD68 expression levels and some clinicopathologic features in CC. We found that the only clinicopathological feature implicating the level of CD68 infiltration was the histological variant of the tumor, and only for CD68-IT-high levels were these observed in SCC. High levels of CD47 expression were seen more frequently in pT1B than pT2A and pT2B in the FIGO I stage than in the FIGO II and III stages. Infiltration by large numbers of CD68-IT cells was much more common among patients with a high expression of CD47 in tumor cells. A high level of infiltration by CD68-ST cells was associated with a worse prognosis, and a high level of infiltration by CD68-ST cells was associated with a lower risk of death from cancer.

Targeting treatment resistance: unveiling the potential of RNA methylation regulators and TG-101,209 in pan-cancer neoadjuvant therapy

BackgroundTumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk of recurrence. However, drug resistance during neoadjuvant therapy is a significant hurdle. Recent studies suggest a correlation between RNA methylation regulators (RMRs) and response to neoadjuvant therapy.MethodsUsing a multi-center approach, we integrated advanced techniques such as single-cell transcriptomics, whole-genome sequencing, RNA sequencing, proteomics, machine learning, and in vivo/in vitro experiments. Analyzing pan-cancer cohorts, the association between neoadjuvant chemotherapy/immunotherapy effectiveness and RNA methylation using single-cell sequencing was investigated. Multi-omics analysis and machine learning algorithms identified genomic variations, transcriptional dysregulation, and prognostic relevance of RMRs, revealing distinct molecular subtypes guiding pan-cancer neoadjuvant therapy stratification.ResultsOur analysis unveiled a strong link between neoadjuvant therapy efficacy and RNA methylation dynamics, supported by pan-cancer single-cell sequencing data. Integration of omics data and machine learning algorithms identified RMR genomic variations, transcriptional dysregulation, and prognostic implications in pan-cancer. High-RMR-expressing tumors displayed increased genomic alterations, an immunosuppressive microenvironment, poorer prognosis, and resistance to neoadjuvant therapy. Molecular investigations and in vivo/in vitro experiments have substantiated that the JAK inhibitor TG-101,209 exerts notable effects on the immune microenvironment of tumors, rendering high-RMR-expressing pan-cancer tumors, particularly in pancreatic cancer, more susceptible to chemotherapy and immunotherapy.ConclusionsThis study emphasizes the pivotal role of RMRs in pan-cancer neoadjuvant therapy, serving as predictive biomarkers for monitoring the tumor microenvironment, patient prognosis, and therapeutic response. Distinct molecular subtypes of RMRs aid individualized stratification in neoadjuvant therapy. Combining TG-101,209 adjuvant therapy presents a promising strategy to enhance the sensitivity of high-RMR-expressing tumors to chemotherapy and immunotherapy. However, further validation studies are necessary to fully understand the clinical utility of RNA methylation regulators and their impact on patient outcomes.

Oncogenic pathway signatures predict the risk of progression and recurrence in well-differentiated pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (pNETs) are genomically diverse tumors. The management of newly diagnosed well-differentiated pNETs is limited by a lack of sensitivity of existing biomarkers for prognostication. Our goal was to investigate the potential utility of genetic markers as a predictor of progression-free survival (PFS) and recurrence-free survival (RFS). Whole-exome sequencing of resected well-differentiated, low and intermediate-grade (G1 and G2) pNETs and normal adjacent tissue from patients who underwent resection from 2005 to 2015 was performed. Genetic alterations were classified using pan-genomic and oncogenic pathway classifications. Additional samples with genetic and clinicopathologic data available were obtained from the publicly available International Cancer Genome Consortium (ICGC) database and included in the analysis. The prognostic relevance of these genomic signatures on PFS and RFS was analyzed. Thirty-one patients who underwent resection for pNET were identified. Genomic analysis of mutational, copy number, cytogenetic, and complex phenomena revealed similar patterns to prior studies of pNETs with relatively few somatic gene mutations but numerous instances of copy number changes. Analysis of genomic and clinicopathologic outcomes using the combined data from our study as well as the ICGC pNET cohort (n = 124 patients) revealed that the recurrent pattern of whole chromosome loss (RPCL) and metastatic disease were independently associated with disease progression. When evaluating patients with local disease at the time of resection, RPCL and alterations in the TGFβ oncogenic pathway were independently associated with the risk of recurrence. Well-differentiated pNETs are genomically diverse tumors. Pathway signatures may be prognostic for predicting disease progression and recurrence.

Tumor contour irregularity on preoperative CT predicts prognosis in renal cell carcinoma: a multi-institutional study

Radiology-based prognostic biomarkers play a crucial role in patient counseling, enhancing surveillance, and designing clinical trials effectively. This study aims to assess the predictive significance of preoperative CT-based tumor contour irregularity in determining clinical outcomes among patients with renal cell carcinoma (RCC). We conducted a retrospective multi-institutional review involving 2218 patients pathologically diagnosed with RCC. The training and internal validation sets included patients at Zhongshan Hospital between January 2009 and August 2019. The external test set comprised patients from the First Affiliated Hospital, Zhejiang University School of Medicine (January 2016 to January 2018), the Xiamen Branch of Zhongshan Hospital (November 2017 to June 2023), and the Cancer Imaging Archive. The contour irregularity degree (CID), quantified as the ratio of irregular cross-sections to the total tumor cross-sections, was analyzed for its prognostic relevance across different subgroups of RCC patients. A novel CID-based scoring system was developed, and its predictive efficacy was evaluated and compared with existing prognostic models. The CID exhibited significant discriminatory power in predicting overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS) among patients with RCC tumors measuring 3cm or larger (all p<0.001). Multivariate analyses confirmed the CID as an independent prognostic indicator. Notably, the CID augmented prognostic stratification among RCC patients within distinct risk subgroups delineated by SSIGN models and ISUP grades. The CID-based nomogram (C-Model) demonstrated robust predictive performance, with C-index values of 0.88 (95%CI: 0.84-0.92) in the training set, 0.92 (95%CI: 0.88-0.98) in the internal validation set, and 0.86 (95%CI: 0.81-0.90) in the external test set, surpassing existing prognostic models. Routine imaging-based assessment of the CID serves as an independent prognostic factor, offering incremental prognostic value to existing models in RCC patients with tumors measuring 3cm or larger. This study was funded by grants from National Natural Science Foundation of China; Shanghai Municipal Health Commission; China National Key R&D Program and Science and Technology Commission of Shanghai Municipality.

Role of androgen receptor expression in the metastatic potential of colorectal carcinoma

Background The prevalence of colorectal cancer (CRC) is widespread and associated with significant morbidity and deaths. In CRC, hormone receptors, such as androgen receptors (AR), are pathologically modified. Additional research is required to understand better its function and predictive and therapeutic value in CRC metastatic potential. Objective To assess the AR status in CRC primary tumors and metastatic lymph nodes. Methods Tissue microarray and immunohistochemical techniques were applied to 75 CRC cases with lymph node (LN) metastases. We correlate the results with all relevant clinicopathological indicators of prognostic relevance. Results and conclusion Out of the 75 cases that were analyzed, 16% of CRC primaries and 12% of LN metastases had nuclear AR that was focally positive. AR expression was significantly correlated with advanced age, conventional non-mucinous histology, lower grade, and arousal on top of adenoma. A deeper invasion was likewise linked to AR expression; however, this association was not statistically significant. AR expression has a positive prognostic influence since the median overall and disease-free survival of cases with positive AR expression in either primary carcinomas or LN metastases were significantly higher than that of cases with negative expression in both primary and LN metastases. We assume that AR expression in CRC has a positive prognostic influence.

Prevalence and prognostic relevance of electrocardiographic abnormalities among patients with ANCA-associated vasculitis.

Current guidelines provide limited evidence for cardiovascular screening in ANCA-associated vasculitis (AAV). This study aimed to investigate the prevalence of electrocardiogram (ECG) abnormalities and associations between no, minor or major ECG abnormalities with cardiovascular mortality in AAV patients compared with matched controls. Using a risk-set matched cohort design, patients diagnosed with granulomatosis with polyangiitis or microscopic polyangiitis with digital ECGs were identified from Danish registers from 2000-2021. Patients were matched 1:3 to controls without AAV on age, sex, and year of ECG measurement. Associated hazards of cardiovascular mortality according to ECG abnormalities were assessed in Cox regression models adjusted for age, sex, and comorbidities, with subsequent computation of 5-year risk of cardiovascular mortality standardized to the age- and sex-distribution of the sample. A total of 1431 AAV patients were included (median age: 69 years, 52.3% male). Median follow-up was 4.8 years. AAV was associated with higher prevalence of left ventricular hypertrophy (17.5% vs 12.5%), ST-T deviations (10.1% vs 7.1%), atrial fibrillation (9.6% vs 7.5%), and QTc prolongation (5.9% vs 3.6%). Only AAV patients with major ECG abnormalities demonstrated significantly elevated risk of cardiovascular mortality [HR 1.99 (1.49-2.65)] compared with controls. This corresponded to a 5-year risk of cardiovascular mortality of 19.14% (16-22%) vs 9.41% (8-11%). Patients with AAV demonstrated a higher prevalence of major ECG abnormalities than controls. Notably, major ECG abnormalities were associated with a significantly increased risk of cardiovascular mortality. These results advocate for the inclusion of ECG assessment into routine clinical care for AAV patients.

Association between blood urea nitrogen-to-potassium ratio and 30-day all-cause mortality in patients with non-traumatic subarachnoid hemorrhage

BackgroundThe mortality risk is exceptionally high in non-traumatic subarachnoid hemorrhage (SAH). Elevated blood urea nitrogen (BUN) levels and hypokalemia are prevalent issues in patients with non-traumatic SAH. To explore the correlation between the blood urea nitrogen-to-potassium ratio (BPR) and 30-day all-cause mortality in non-traumatic SAH patients. MethodsWe systematically extracted specific clinical data from the Medical Information Mart for Intensive IV (MIMIC-IV) database. To assess the prognostic relevance of the BPR, we categorized patients into those experiencing in-hospital mortality within 30 days and those surviving, subjecting them to both univariate and multivariate Cox regression analyses. The optimal BPR cut-off value was identified using Receiver Operating Characteristic (ROC) curve analysis, employing the maximum Youden index to predict survival status. Furthermore, we employed Kaplan–Meier (K–M) analysis to illustrate survival curves. ResultsA cohort comprising 608 patients with non-traumatic SAH was enrolled in the investigation. Multivariate Cox regression analysis identified the BPR as an independent predictor of all-cause mortality within 30 days of admission for patients with non-traumatic SAH (Hazard Ratio [HR], 1.13; 95 % Confidence Interval [CI], 1.04–––1.23; P<0.05). Further refinement resulted in the establishment of an optimized prediction model (AUC=83.61 %, 95 % CI: 79.73 % − 87.49 %) for forecasting all-cause mortality at 30 days post-hospital admission in patients with non-traumatic SAH. ConclusionThe BPR emerges as an independent prognostic indicator for all-cause mortality within the initial 30 days of admission among non-traumatic SAH patients.

Prognostic and immunological significance of tertiary lymphoid structures in nasopharyngeal carcinoma.

220 Background: Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues found in non-lymphoid organs, characterized by the presence of CD20+ B cell follicles adjacent to a T cell zone. Their presence has been associated with improved survival in various tumor types. However, the role of TLSs in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we investigated the prognostic and immunological significance of TLSs in NPC patients. Methods: The investigation involved a discovery cohort (n = 145) comprising NPC patients diagnosed at Sun Yat-sen University Cancer Center between July 2010 and December 2016, with pretreatment primary tumor samples collected. An independent validation cohort included 150 NPC patients with gene expression profiles, among whom Hematoxylin &amp; Eosin (H&amp;E)-stained slides were available for 95 patients. The primary endpoint of this study is overall survival, defined as the duration of time from diagnosis until death from any cause. The presence of TLSs was assessed on H&amp;E and CD20-stained slides. Analyses of tumor-infiltrating immune cell subsets, differentially expressed genes, and BCR/TCR clonotypes were performed to explore the association between TLSs and the anti-tumor immune response. A molecular definition of TLSs was proposed and assessed for its prognostic value across multiple cohorts. Results: The presence of TLSs was independently associated with a favorable overall survival (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank p = 0.04), surpassing the significance of B cell density in multivariate analysis (HR, 0.83; 95% CI, 0.38-1.79, log-rank p = 0.63). These findings were corroborated in the independent validation cohort. TLSs positively correlated with multiple immune-related pathways and a higher proportion of functionally mature immune cells. Notably, the counts of BCR and TCR clonotypes showed a significant positive correlation with the TLSs score. We proposed a TLSs gene signature and demonstrated its prognostic relevance across multiple cohorts, including patients treated with immune checkpoint blockade. Conclusions: TLSs exhibit heightened immune activity and indicate improved survival outcomes in NPC patients. A TLSs gene signature was proposed and demonstrated its prognostic relevance across multiple cohorts, indicating potential guidance for treatment decisions in cancer.

Major Adverse Cardiovascular Events: The Importance of Serum Levels and Haplotypes of the Anti-Inflammatory Cytokine Interleukin 10.

Cardiovascular diseases (CVDs) represent major medical and socio-economic challenges worldwide. There is substantial evidence that CVD is closely linked to inflammatory changes triggered by a complex cytokine network. In this context, interleukin 10 (IL-10) plays an important role as a pleiotropic cytokine with an anti-inflammatory capacity. In this study (a substudy of ClinTrials.gov, identifier: NCT01045070), the prognostic relevance of IL-10 levels and IL-10 haplotypes (rs1800896/rs1800871/rs1800872) was assessed regarding adverse cardiovascular outcomes (combined endpoint: myocardial infarction, stroke/transient ischemic attack, cardiac death and death according to stroke) within a 10-year follow-up. At baseline, 1002 in-patients with CVD were enrolled. Serum levels of IL-10 were evaluated utilizing flow cytometry (BD™ Cytometric Bead Array). Haplotype analyses were carried out by polymerase chain reactions with sequence-specific primers (PCR-SSP). In a survival analysis, IL-10 haplotypes were not proven to be cardiovascular prognostic factors in a 10-year follow-up (Breslow test: p = 0.423). However, a higher IL-10 level was associated with adverse cardiovascular outcomes (Breslow test: p = 0.047). A survival analysis considering adjusted hazard ratios (HRs) could not confirm this correlation (Cox regression: adjusted HR = 1.26, p = 0.168). In the present study, an elevated IL-10 level but not IL-10 haplotypes was linked to adverse cardiovascular outcomes (10-year follow-up) in a cohort of CVD patients.