Prognostic Outcome Research Articles

Identification and interaction analysis of molecular markers in myocardial infarction by bioinformatics and next-generation sequencing data analysis

BackgroundCardiovascular diseases are prevalent worldwide with any age, and it is characterized by sudden blockage of blood flow to heart and permanent damage to the heart muscle, whose cause and underlying molecular mechanisms are not fully understood. This investigation aimed to explore and identify essential genes and signaling pathways that contribute to the progression of MI.MethodsThe aim of this investigation was to use bioinformatics and next-generation sequencing (NGS) data analysis to identify differentially expressed genes (DEGs) with diagnostic and therapeutic potential in MI. NGS dataset (GSE132143) was downloaded from the Gene Expression Omnibus (GEO) database. DEGs between MI and normal control samples were identified using the DESeq2 R bioconductor tool. The gene ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed using g:Profiler. Next, four kinds of algorithms in the protein–protein interaction (PPI) were performed to identify potential novel biomarkers. Next, miRNA-hub gene regulatory network analysis and TF-hub gene regulatory network were constructed by miRNet and NetworkAnalyst database, and Cytoscape software. Finally, the diagnostic effectiveness of hub genes was predicted by receiver operator characteristic curve (ROC) analysis and AUC more than 0.800 was considered as having the capability to diagnose MI with excellent specificity and sensitivity.ResultsA total of 958 DEGs were identified, consisting of 480 up-regulated genes and 478 down-regulated genes. The enriched GO terms and pathways of the DEGs include immune system, neuronal system, response to stimulus and multicellular organismal process. Ten hub genes (namely cftr, cdk1, rps13, rps15a, rps27, notch1, mrpl12, nos2, ccdc85b and atn1) were obtained via protein–protein interaction analysis results. MiRNA-hub gene regulatory network and TF-hub gene regulatory network showed that hsa-mir-409-3p, hsa-mir-3200-3p, creb1 and tp63 might play an important role in the MI.ConclusionsAnalysis of next-generation sequencing dataset combined with global network information and validation presents a successful approach to uncover the risk hub genes and prognostic markers of MI. Our investigation identified four risk- and prognostic-related gene signatures, including cftr, cdk1, rps13, rps15a, rps27, notch1, mrpl12, nos2, ccdc85b and atn1. This gene sets contribute a new perspective to improve the diagnostic, prognostic, and therapeutic outcomes of MI.

Targeting the LMP1-ALIX axis in EBV+ nasopharyngeal carcinoma inhibits immunosuppressive small extracellular vesicle secretion and boosts anti-tumor immunity.

Immunotherapy has revolutionized the therapeutical regimen for nasopharyngeal carcinoma (NPC), yet its response rate remains insufficient. Programmed death-ligand 1 (PD-L1) on small extracellular vesicles (sEVs) mediates local and peripheral immunosuppression in tumors, and the mechanism of PD-L1 loading into these vesicles is garnering increasing attention. Latent membrane protein 1 (LMP1), a key viral oncoprotein expressed in Epstein-Barr virus (EBV)-positive NPC, contributes to remodeling the tumor microenvironment. However, the precise mechanisms by which LMP1 modulates tumor immunity in NPC remain unclear. Here, we aimed to investigate the roles and regulatory mechanisms of LMP1 and sEV PD-L1 in NPC immune evasion. We analyzed the impact of LMP1 on tumor-infiltrating lymphocyte abundance in NPC tissues and humanized tumor-bearing mouse models using multiplex immunofluorescence (mIF) and flow cytometry, respectively. Transmission electron microscopy and nanoparticle tracking analysis were employed to characterize sEVs. Immunoprecipitation-mass spectrometry was utilized to identify proteins interacting with LMP1. The regulatory effects of sEVs on tumor microenvironment were assessed by monitoring CD8+ T cell proliferation and interferon-γ (IFN-γ) expression via flow cytometry. Furthermore, the expression patterns of LMP1 and downstream regulators in NPC were analyzed using mIF and survival analysis. High LMP1 expression in NPC patient specimens and mouse models was associated with restricted infiltration of CD8+ T cells. Additionally, LMP1 promoted sEV PD-L1 secretion, leading to inhibition of CD8+ T cell viability and IFN-γ expression in vitro. Mechanistically, LMP1 recruited apoptosis-linked gene 2-interacting protein X (ALIX) through its intracellular domain and bound PD-L1 through its transmembrane domain, thereby facilitating the loading of PD-L1 into ALIX-dependent sEVs. Disruption of ALIX diminished LMP1-induced sEV PD-L1 secretion and enhanced the anti-tumor immunity of CD8+ T cells both in vitro and in vivo. Moreover, increased expression levels of LMP1 and ALIX were positively correlated with enhanced immunosuppressive features and worse prognostic outcomes in NPC patients. Our findings uncovered the mechanism by which LMP1 interacts with ALIX and PD-L1 to form a trimolecular complex, facilitating PD-L1 loading into ALIX-dependent sEV secretion pathway, ultimately inhibiting the anti-tumor immune response in NPC. This highlights a novel target and prognostic marker for NPC immunotherapy.

Expression Profiles of Integrin-Linked Kinase, Vascular Endothelial Growth Factor A, and Ephrin Type-A Receptor 2 in Colorectal Cancer Lymph Nodes.

Background Colorectal cancer (CRC) is the third most frequently diagnosed cancer globally, with a high incidence of morbidity and mortality. Early diagnosis of CRC is crucial for determining appropriate treatment regimens, thereby prolonging overall survival rates and improving prognostic outcomes. Objectives This study aimed to investigate the expression profiles of specific proteins in the lymph nodes (LNs) of CRC patients, including integrin-linked kinase (ILK), vascular endothelial growth factor A (VEGFA), and ephrin type-A receptor 2 (EphA2), through immunohistochemical studies. Methods The study involved a sample of 76 patients clinically diagnosed with CRC who were referred by their specialist oncologist. Tumor staging was determined based on the TNM classification. Immunohistochemical studies were conducted to measure the expression patterns of the candidate markers (ILK, EphA2, and VEGFA). Expression levels were scored as negative, low, or high. Results The highest percentage of CRC patients were diagnosed with conventional adenocarcinoma, predominantly in stages II and III. Of the 76 CRC tissue specimens, the majority (46, 60.52%) tested negative for lymphatic invasion, while the remaining 30 (39.47%) tested positive. According to the TNM classification, 14 samples had N1 (one invaded LN), and 16 had N2 (two or more invaded LNs). Furthermore, the percentage of patients with low and high EphA2 expression was significantly higher (p<0.0001) compared to the negative expression controls. Regarding ILK, 15 cases (50.0%) showed negative expression, while an equal number displayed positive expression. Additionally, the group with low VEGFA expression was statistically significantly higher (p=0.01) compared to the negative control. Conclusion The expression levels of EphA2, ILK, and VEGFA were found to be higher in LNs with lymphatic invasion compared to those with negative expression, highlighting the role of these proteins in CRC progression.

H3K27me3 Loss in Central Nervous System Tumors: Diagnostic, Prognostic, and Therapeutic Implications.

Central nervous system (CNS) tumors represent a formidable clinical challenge due to their molecular complexity and varied prognostic outcomes. This review delves into the pivotal role of the epigenetic marker H3K27me3 in the development and treatment of CNS tumors. H3K27me3, specifically the trimethylation of lysine 27 on the histone H3 protein, plays a crucial role in regulating gene expression and maintaining chromatin architecture (e.g., in X-chromosome inactivation). Notably, a reduction in H3K27me3 levels, frequently tied to mutations in the H3 gene family such as H3F3A and HIST1H3B, is evident in diverse brain tumor variants, including the diffuse midline glioma characterized by the H3K27M mutation and certain pediatric high-grade gliomas. The loss of H3K27me3 has been linked to more aggressive behavior in meningiomas, with the trimethylation loss associated with significantly shorter recurrence-free survival (RFS) among grade 2 meningiomas, albeit not within grade 1 tumors. Pediatric posterior fossa ependymomas characterized by a lowered H3K27me3 and DNA hypomethylation exhibit poor prognosis, underscoring the prognostic significance of these epigenetic alterations in CNS tumors. Comprehending the role of H3K27me3 in CNS tumors is vital for advancing diagnostic tools and therapeutic interventions, with the goal of enhancing patient outcomes and quality of life. This review underscores the importance of ongoing investigations into H3K27me to refine and optimize management strategies for CNS tumors, paving the way for improved personalized medicine practices in oncology.

Insight into Predictors of Cytoreduction Score Following Cytoreductive Surgery-Hyperthermic Intraperitoneal Chemotherapy for Gastric Peritoneal Carcinomatosis Improves Patient Selection and Prognostic Outcomes.

Peritoneal metastases due to gastric adenocarcinoma (GCPM) carry a dismal prognosis. A promising treatment strategy is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), but clear eligibility criteria for GCPM are lacking. We sought to identify factors associated with overall survival (OS) following CRS-HIPEC for GCPM to help optimize patient selection and clinical outcomes. In this single-center retrospective cohort study, we examined CRS-HIPEC outcomes for patients with GCPM between 2001 and 2021. After analyzing patient demographic, clinicopathologic, and perioperative variables, we applied multivariable Cox hazard models to assess factors associated with OS. We then assessed associations between baseline predictors and prognostically important variables using multivariable logistic regression. We analyzed 55 patients with GCPM who underwent CRS-HIPEC. Median age was 54 years and 42% were female. Median peritoneal carcinomatosis index (PCI) was 8, and 75% of patients achieved a cytoreduction completeness score (CC score) of 0. Median progression-free survival (PFS) was 6.9 months, and median OS was 14.1 months. On adjusted analysis, a CC score > 0 (HR 2.3, p = 0.02) was significantly associated with worse OS. A peritoneal carcinomatosis index greater than 13 (OR 52.6, p = 0.001) and fewer lymph nodes (especially < 18) resected with the primary tumor (OR 0.86, p = 0.042) in the metachronous setting were significantly associated with incomplete macroscopic cytoreduction (CC score > 0). We demonstrated that PCI > 13 and primary lymph nodes harvested < 18 in metachronous tumors are associated with CC score > 0, which in turn portends a worse OS. Although these results warrant prospective validation, they provide insight into improved selection of patients with GCPM for CRS-HIPEC.

New definition of borderline resectable colorectal liver metastasis based on prognostic outcomes.

Although surgical resection is the curative treatment for colorectal liver metastases (CRLM), the efficacy of neoadjuvant chemotherapy (NAC) has been discussed due to recent remarkable advances in chemotherapy. The definition of borderline resectable (BR) is most important, where neoadjuvant chemotherapy should be administered. This study aimed to examine a new definition of BR CRLM based on the results of the treatment outcomes. This study included 127 patients who underwent liver resection for CRLM after exclusion of conversion cases between April 2010 and December 2023. Upfront resection was performed for synchronous and single liver metastasis or metachronous liver metastases. NAC was administered for multiple synchronous liver metastases. In order to find a new definition of BR, we examined the prognostic factors obtained from the treatment outcomes. CA19-9 level > 37.0 was the only prognostic factor in the upfront group [hazard ratio (HR) 2.386, 95% CI, 1.583-4.769; p = 0.049]. in the NAC group, a maximum tumor diameter ˃3 cm (HR 2.248, 95% CI 1.038-4,867, p = 0.040), CA19-9 level > 37.0 (HR 2.239, 95% CI 1.044-4.800, p = 0.038), and a right-sided primary tumor in the colon (HR 2.770, 95% CI 1.284-5.988, p = 0.009) were identified as significant prognostic factors. In cases of CRLM, patients with CA19-9 levels > 37.0, or CA19-9 level with < 37.0 but with a primary tumor in the right colon or a maximum tumor diameter of > 3cm can be defined as BR CRLM and should be treated with NAC.

Prognostic Outcomes and Predictive Factors in Non-Metastatic Castration-Resistant Prostate Cancer Patients Not Treated with Second-Generation Antiandrogens.

Background/Objectives: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and high-risk features frequently have progression to life-threatening metastasis without second-generation antiandrogens. This study investigated nmCRPC patients for the survival and prognostic factors from a cohort before the approved use of second-generation antiandrogens. Methods: From March 2016 to January 2021, 326 patients treated with second-generation antiandrogens for metastatic castration-resistant prostate cancer (mCRPC) or metastatic castration-sensitive prostate cancer were retrieved. Forty-four patients experiencing nmCRPC with no use of second-generation antiandrogens were reviewed. The prognostic factors, at initial diagnosis or at nmCRPC, associated with metastasis-free survival (MFS) and overall survival (OS) were analyzed. Results: The median follow-up time after nmCRPC was 46 months. The median PSA level at nmCRPC was 2.7 ng/mL. Thirty-eight of forty-four patients with nmCRPC had a PSA doubling time (PSADT) of 10 months or shorter, and the median PSADT was 4 months. The median OS from nmCRPC was 53 months, and the median interval for nmCRPC patients progressing to mCRPC was 20 months. Upon univariate analysis, PSADT < 10 months (p = 0.049) and the very-high-risk group at the initial diagnosis (p = 0.043) were associated with significantly shorter post-nmCRPC MFS. The very-high-risk group (p = 0.031) was associated with significantly worse post-nmCRPC OS. In terms of survivals from the initial diagnosis of prostate cancer, Gleason grade ≥ 8 was the only independent factor with MFS and OS. Conclusions: Without second-generation antiandrogens, nmCRPC patients with PSADT <10 months and in the initial very-high-risk group developed subsequent mCRPC in a significantly faster fashion. Patients of the very-high-risk group had shorter survival rates after nmCRPC.

Primary Diffuse Large B-Cell Lymphoma of the Adrenal Glands: a Rare Cause of Paraneoplastic Neuropathy

The article presents a detailed analysis of clinical observation of primary diffuse large B-cell lymphoma of the adrenal glands, a rare disease affecting less than 1% of patients with non-Hodgkin’s lymphomas. It describes the case of a 46-year-old man hospitalized with progressive limb paralysis, later diagnosed as paraneoplastic polyradiculoneuropathy associated with bilateral adrenal lymphoma. The diagnostic challenges of this pathology, including ambiguous imaging results and the need for histological verification to confirm the diagnosis are discussed. Special attention is paid to the uniqueness of clinical manifestations and the importance of early symptom recognition to improve prognostic outcomes in highly aggressive forms of the disease. The necessity of multidisciplinary approach in managing such patients with the participation of oncologists, endocrinologists, and neurologists to optimize diagnostic and therapeutic processes is also emphasized.

The predictive value of PCT, SP-D and 8-iso-PGF2 α for the development of severe pneumonia in children

Background: To investigate the predictive value of predictive value of procalcitonin (PCT), 8-iso-prostaglandin F2α (8-iso-PG-F2α) and pulmonary surfactant-associated protein D (SP-D) for the development of severe pneumonia in children. Methodology: Children with severe pneumonia were selected as the pneumonia group, and children with non-pulmonary respiratory diseases were selected as the control group. PCT, 8-iso-PGF2α, and SP-D were compared between the pneumonia group and the control group at admission; PCT, 8-iso-PGF2α, SP-D, and Acute Physiology and Chronic Health Evaluation (APACHE-II), Pediatric Critical Illness Score (PCIS) and Clinical Pulmonary Infection Score (CPIS) scores were compared between children with severe pneumonia with different pathogen infection types and different prognostic outcomes; and the correlation between APACHE-II, CPIS, and PCIS scores and PCT, 8-iso-PGF2α, and SP-D levels was analysed in children with severe pneumonia. Results: PCT, 8-iso-PGF2α and SP-D in pneumonia group were higher than those in control group. PCT, 8-iso-PGF2α, SP-D, APACHE-II, CPIS, and PCIS were lower in good prognosis children than in poor prognosis children. APACHE-II, CPIS, and PCIS scores were positively correlated with PCT, 8-iso-PGF2α, and SP-D levels in children with severe pneumonia (P &lt; 0.05). Conclusion: PCT, SP-D and 8-iso-PGF2α levels relate to pathogen type, illness severity and prognosis in children with severe pneumonia. They can aiding early evaluation. Keywords: severe pneumonia in children; procalcitonin; 8-isoprostane F2α; pulmonary surfactant-associated protein D; disease assessment.

Genetic Variants ε2 and ε4 of APOE Predict Mortality and Poor Outcome Independently in Spontaneous Intracerebral Hemorrhage Within the Chinese Han Population.

The heightened mortality and disability rates, coupled with restricted neurological recovery post intracerebral hemorrhage (ICH), have sparked considerable attention toward its treatment and results. Simultaneously, the influence of the APOE gene on ICH prognosis has been well-documented. This research aimed to explore the relationship between specific APOE alleles in the present cohort and the incidences of mortality, recurrence, and adverse prognosis, as determined by neurological function assessments in ICH patients. Data on patients diagnosed with ICH and hospitalized in the Department of Neurology at our institution from October 2021 to March 2022 were collected, including determining their APOE genotypes. A 1-year follow-up was conducted to evaluate mortality, ICH recurrence, and modified Rankin Scale (mRS) scores at 3 and 12 months. Poor prognosis was defined as an mRS score of ≥ 3. Initially, we analyzed the relationships between different APOE alleles and mortality, recurrence, and poor prognosis. Subsequently, we explored additional factors influencing each prognostic outcome and conducted multivariate analysis to identify independent risk factors. An analysis was conducted on 289 patients diagnosed with ICH. The presence of the ε2 allele was found to be a significant independent predictor for unfavorable outcomes at both 3 months (p = 0.022, OR = 2.138, 95% CI [2.041, 3.470]) and 1 year (p = 0.020, OR = 5.116, 95% CI [5.044, 5.307]). Moreover, the ε4 allele was established as an independent risk factor for ICH recurrence within 1 year (p = 0.025, OR = 2.326, 95% CI [1.163, 2.652]), as well as for mortality at 3 months (p = 0.037, OR = 4.250, 95% CI [4.068, 4.920]) and 1 year (p = 0.023, OR = 4.109, 95% CI [4.016, 4.739]). In conclusions, Both APOE ε2 and ε4 variants independently heighten mortality risk, recurrence, and poor prognosis after ICH. The substantial influence underscores the need for additional investigation into the impact of APOE genotype on ICH prognosis.

Atypical Multifocal Granular Cell Tumor with FLT3 Y842C Somatic Mutation: A case report and a review of the literature.

Granular cell tumors (GCT) are predominantly benign neoplasms composed by cells with abundant eosinophilic granular cytoplasm. Although the majority of GCTs exhibit a benign clinical course, a minority display cytological atypia and may exhibit aggressive, cancer-like behavior. Definitive evidence of malignancy in GCTs is reliably established only through the presence of metastasis. Addi- tionally, a subset of GCTs demonstrates a high rate of recurrence, underscoring the need for better prog- nostic markers. Therefore, it is crucial to identify molecular markers associated with aggressive behavior in GCTs. Molecular analysis may be particularly beneficial in cases exhibiting cytological atypia to in- form clinical outcome prognostication and guide therapeutic strategies. In this case report, a 45-year-old female with multiple gastrointestinal GCTs is pre- sented. The patient did not have any genetic syndromes commonly associated with GCT, such as neu- rofibromatosis type 1, Noonan syndrome or LEOPARD syndrome. The tumors not only demonstrated nuclear atypia, but also harbored a unique FLT3 Y842C somatic alteration identified by next-genera- tion sequencing. The patient remains asymptomatic and under endoscopic surveillance two years after diagnosis and complete resection of the neoplasms. We presented an exceedingly rare case of multifocal atypical GCT in an adult without any previously known genetic syndrome. A tumoral FLT3 Y842C point mutation not previously reported in GCT was discovered. Although the precise significance of this finding is uncertain, FLT3 Y842C has been cataloged as likely pathogenic in ClinVar. This report underscores the potential predictive utility of next-generation sequencing in the characterization and management of rare neoplasms.

Bi-level Graph Learning Unveils Prognosis-Relevant Tumor Microenvironment Patterns in Breast Multiplexed Digital Pathology.

The tumor microenvironment is widely recognized for its central role in driving cancer progression and influencing prognostic outcomes. There have been increasing efforts dedicated to characterizing this complex and heterogeneous environment, including developing potential prognostic tools by leveraging modern deep learning methods. However, the identification of generalizable data-driven biomarkers has been limited, in part due to the inability to interpret the complex, black-box predictions made by these models. In this study, we introduce a data-driven yet interpretable approach for identifying patterns of cell organizations in the tumor microenvironment that are associated with patient prognoses. Our methodology relies on the construction of a bi-level graph model: (i) a cellular graph, which models the intricate tumor microenvironment, and (ii) a population graph that captures inter-patient similarities, given their respective cellular graphs, by means of a soft Weisfeiler-Lehman subtree kernel. This systematic integration of information across different scales enables us to identify patient subgroups exhibiting unique prognoses while unveiling tumor microenvironment patterns that characterize them. We demonstrate our approach in a cohort of breast cancer patients and show that the identified tumor microenvironment patterns result in a risk stratification system that provides new complementary information with respect to standard stratification systems. Our results, which are validated in two independent cohorts, allow for new insights into the prognostic implications of the breast tumor microenvironment. This methodology could be applied to other cancer types more generally, providing insights into the cellular patterns of organization associated with different outcomes.

Weight loss as a predictor of reduced survival in patients with lung cancer: a systematic review with meta-analysis.

The impact of weight loss on survival outcomes remains challenging in patients with lung cancer. The objective of this systematic review with meta-analysis was to assess the association of weight loss with survival outcomes in these patients. Two authors conducted a comprehensive literature search of PubMed, Web of Science, and Embase databases up to January 15, 2024. Observational studies that assessed the weight loss as a prognostic factor of overall survival and progression-free survival in patients with lung cancer were included this analysis. Weight loss defined by at least 5% loss of total body weight over 2 months. Fifteen studies involving 14,540 patients with lung cancer were included. Pooled adjusted hazard ratios (HR) indicated that weight loss was associated with reduced overall survival (HR 1.65; 95% confidence intervals [CI] 1.43-1.91) and progression-free survival (HR 1.40; 95% CI 1.15-1.71). Subgroup analysis showed that weight loss significantly predicted overall survival, regardless of study design, lung cancer subtypes, clinical stage of cancer, weight loss definition, or length of follow-up. Weight loss is a significant predictor of overall survival and progression-free survival in patients with lung cancer. Weight monitoring has potential to improve prognostication of survival outcomes for these patients.

Comprehensive analysis reveals that P4HA3 is a prognostic and diagnostic gastric cancer biomarker that can predict immunotherapy efficacy

Gastric cancer (GC) is one of the most challenging malignant tumors worldwide, primarily because of its high incidence and mortality rates. Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) has been established as a pivotal factor for facilitating cell proliferation, invasion, and metastasis across multiple human tumors. Nevertheless, the precise role of P4HA3in GC has not been fully elucidated. In this study, we used data from The Cancer Genome Atlas (TCGA) to examine the role of P4HA3 as a potential biomarker for predicting immunotherapy response in patients with GC. Our comprehensive analysis of data from the TCGA, TIMER, and other databases revealed a significant association between elevated P4HA3 expression in GC and adverse prognostic outcomes. Furthermore, we confirmed that P4HA3 expression was strongly correlated with immune infiltrating cells, immune infiltration markers, the tumor mutational burden (TMB), microsatellite instability (MSI), the immune score, the stromal score, and immune checkpoints, thus highlighting P4HA3 as a crucial and dependable therapeutic target within the context of immune-based antitumor strategies. Our findings suggest that P4HA3 may function as an immune-related biomarker in the pathogenesis and treatment of GC, indicating that P4HA3 is a promising prognostic and therapeutic target for this malignancy.

The onset characteristics and prognosis of patients with radiation-associated second primary malignancy: a pancancer study in the US SEER cancer registries.

Cancer survivors have an elevated risk of developing a second primary malignancy (SPM) after radiation therapy (RT). Data on the association between RT and SPM are limited. Our aim was thus to investigate the impact of RT on the risk of developing SPMs and to evaluate the specific characteristics and prognostic outcomes. We enrolled a pancancer cohort using data from the Surveillance, Epidemiology, and End Results registries spanning from January 1973 to December 2015. Multivariable Cox and the Fine-Gray competing risk regression were employed to assess the hazard ratio (HR) and 95% confidence interval (CI) of SPMs in patients who received RT in comparison to those with no RT (NRT). Poisson regression was used to evaluate the RT-associated risks (RR) and the standardized incidence ratio (SIR) for SPMs. The analysis identified 24 types of risk-increased SPMs (RI-SPMs), including malignancies of the oropharynx, hypopharynx, larynx, esophagus, lung, breast, liver, pancreas, stomach, colon, rectum, ovary, corpus uteri, ureter, vagina, urinary bladder, penis, testis, and kidney, among others. The cumulative incidence of those with RI-SPMs was higher than that of the NRT patients (19.8% vs. 15.3%; P<0.001). The RR for RI-SPMs decreased with increasing age at FPM diagnosis (aged 20-49 years: RR 1.52; age 50-69 years: RR 1.31; age 70 years: RR 1.21), and the RR increased with longer latency period following FPM diagnosis (60-119 months: RR 1.28; 120-239 months: RR 1.24; 240-360 months: RR 1.46). The 10-year overall survival of those with RI-SPMs was significantly lower than that of the matched NRT patients (28.5% vs. 31.7%; P<0.001). Patients with RI-SPMs warrant greater attention given their time-cumulative onset risk and poor prognosis. Long-term surveillance is necessary for cancer survivors treated with RT.

High expression of CD3+T-lymphocytes in cerebrospinal fluid increases the risk of critical cerebral hemorrhage with systemic inflammatory response syndrome (SIRS) after surgery

ObjectiveTo assess the frequency of lymphocyte subsets and other laboratory indicators in paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from critically ill patients with intracerebral hemorrhage (ICH) who developed systemic inflammatory response syndrome (SIRS) following surgery. IntroductionNeuroinflammation and systemic inflammatory responses significantly contribute to secondary brain injury following ICH. Post-surgery SIRS is known to worsen clinical outcomes in ICH patients; however, the immune response in the CSF and PB has not been fully characterized. Understanding immunological changes in ICH patients with SIRS could lead to improved clinical management and prognostic outcomes. MethodsThis study involved a retrospective analysis of data from patients with ICH who underwent surgery in the Neurological Intensive Care Unit (NICU) of Baoding No. 1 Hospital, Hebei Province, China, between January and July 2022. Patients were divided into SIRS and non-SIRS groups based on the clinical criteria. Demographic, clinical, and laboratory data, including lymphocyte subsets in CSF and PB, were collected and analyzed. This study compared lymphocyte subsets and other inflammatory markers between the SIRS and non-SIRS groups. ResultsPatients with SIRS demonstrated higher systolic blood pressure (SBP) at admission, worse 90-day prognoses, elevated inflammatory markers, increased levels of complement proteins C3 and C4, and lower levels of immunoglobulin G (IgG) compared to patients without SIRS. Between 3–6 days post-surgery, SIRS patients showed higher percentages of CD3+T cells, CD4+T cells, and CD4+/CD8+ ratios in the CSF than non-SIRS patients. CD3+T cell percentages in the CSF were consistently higher than those in the PB and were independent of PB levels. In contrast, CD3-CD16+CD56+ natural killer (NK) cell percentages were lower in patients with SIRS. No significant differences in PB lymphocyte subsets were found between the two groups. A high CSF CD3+T cell percentage (≥85.68 %) was identified as the strongest predictor of critical ICH with SIRS after surgery, with an appropriate use criterion (AUC) of 0.7742, sensitivity of 77.42 %, specificity of 76.19 %, and 95 % CI of 0.6655–0.8829 (P < 0.0001). ConclusionElevated levels of CD3+T lymphocytes in CSF are strongly associated with an increased risk of severe cerebral hemorrhage and SIRS following surgery. These findings suggest that monitoring CSF immune markers, particularly CD3+T lymphocytes, could serve as valuable predictors for the development of SIRS in critically ill ICH patients and inform post-surgical treatment strategies.

Establishment and verification of a prognostic immune cell signature-based model for breast cancer overall survival.

Breast cancer (BRCA) is a prevalent and aggressive disease. Despite various treatments being applied, a significant number of patients continue to experience unfavorable prognoses. Accurate prognosis prediction in BRCA is crucial for tailoring individualized treatment plans and improving patient outcomes. Recent studies have highlighted the significance of immune cell infiltration in the tumor microenvironment (TME), but predicting survival remains challenging due to the heterogeneity of BRCA. The aim of this study was thus to produce an immune cell signature-based framework capable of predicting the prognosis of patients with BRCA. The GSE169246 dataset was from the Gene Expression Omnibus (GEO) database, comprising single-cell RNA sequencing (scRNA-seq) data from 95 individuals with BRCA. Seurat, principal component analysis (PCA), the unified matrix polynomial approach (UMAP) algorithm, and linear dimensionality reduction were used to determine the heterogeneity of T cells. Overlapping analysis of differentially expressed genes (DEGs), genes associated with prognosis, and T-cell pharmacodynamics-related genes were used to obtain the T-cell core pharmacodynamics-related genes. The dimensionality of the T-cell core pharmacodynamics-related genes was reduced employing the least absolute shrinkage and selection operator (LASSO) Cox regression model and the LASSO model. The prognostic model was built via a Cox analysis of the overall survival (OS) information. The clinical sample included 95 patients with BRCA who underwent surgical treatment from October 2018 to October 2021 at the Second Affiliated Hospital of Qiqihar Medical University. Patients were divided into a good prognosis group and a poor prognosis group based on their prognostic outcomes. The predictive value of tumor characteristics and immune responses was validated through correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) analysis. A group of 95 genes was used to establish a prognostic model. In the GEO clinical sample, with a high-risk group demonstrating shorter median survival times (2,447 vs. 6,498 days, P=4.733e-12). Area under the curve (AUC) values of 0.75, 0.75, and 0.72 were obtained for 2-, 4-, and 6-year OS predictions, respectively. Clinical validation found that the 6-year OS of the favorable prognosis group was significantly higher than that of the unfavorable prognosis group (92.06% vs. 65.62%; P=0.005). Poor prognosis was positively correlated with age, tumor size, B-cell level, and CTLA4 level and negatively correlated with tumor stage (T1/T2), lymph node metastasis stage (N0), clinical stage I-II, CD3+T-cell, CD4+T-cell, CD8+T-cell, neutrophil, lymphocyte, natural kill cell, TIGIT expression and OS. The combined model of clinical parameters had an AUC value of 0.898. This study established a prognostic model that demonstrated excellent predictive value for OS of BRCA. The predictive model developed offers valuable insights into prognosis and treatment planning, emphasizing the importance of tumor characteristics and immune cell infiltration.

Oncologic outcomes based on lymphovascular space invasion in node-negative FIGO 2009 stage I endometrioid endometrial adenocarcinoma: a multicenter retrospective cohort study

BackgroundThe 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system includes lymphovascular invasion quantification as a staging criterion for endometrioid endometrial carcinomas; no lymphovascular invasion and focal invasion (≤4...

Assessment of the Right Ventricle Function in Patients With Significant Tricuspid Regurgitation: A Review.

Tricuspid regurgitation (TR) is an increasingly prevalent condition, especially in older populations, and presents significant challenges due to its association with right heart failure, hospital admissions, and high mortality rates. The management of TR has evolved, with new percutaneous valve repair and replacement techniques emerging alongside traditional surgical approaches. However, accurately assessing right ventricular (RV) function-a key prognostic factor in TR-remains difficult due to the RV's unique anatomy and sensitivity to loading conditions. Current echocardiographic methods, such as Tricuspid Annular Plane Systolic Excursion (TAPSE), S' wave analysis, and RV fractional area change (FAC), offer valuable insights but have limitations, particularly regarding load dependence and incomplete assessment of RV function. Advances in 3D echocardiography and myocardial strain imaging provide more comprehensive evaluations, yet challenges persist in integrating these measures in routine clinical practice. The review highlights the importance of a multimodal approach to RV assessment in TR patients, considering both the right atrium and pulmonary artery interactions, and explores potential future tools such as myocardial work and dynamic testing to improve prognostic accuracy and patient outcomes.

Impactful Cardiac CT and MRI Articles from 2023.

Cardiac imaging is important in diagnosing, treating, and predicting prognosis in patients with cardiovascular disease. Imaging protocols and analysis are consistently evolving, and the implementation of artificial intelligence-based applications is of increasing interest. This review presents recent advancements in noninvasive cardiac imaging, specifically focusing on cardiac CT and MRI, from notable publications across multidisciplinary journals in 2023 of interest to both radiologists and referring clinicians in the field. The discussion encompasses the latest trials of CT fractional flow reserve and the performance of the newest generation of photon-counting detector CT, particularly in coronary stenosis quantification. Additionally, it addresses coronary plaque quantification using artificial intelligence applications and their implications from large patient cohorts, alongside prognostic outcomes, and the value of coronary artery calcification scores. Various aspects of CT trials, such as anatomic planning before revascularization, high-risk plaque features, outcomes, and pericoronary fat index, are evaluated. New insights from cardiac MRI trials for cardiomyopathies, including cardiac amyloidosis, dilated cardiomyopathy, hypertrophic cardiomyopathy, myocarditis, and valvular disease, are also outlined. The review concludes by highlighting impactful societal statements and guidelines. Keywords: CT Angiography, MR Imaging, Transcatheter Aortic Valve Implantation/Replacement (TAVI/TAVR), Cardiac, Coronary Arteries, Heart, Left Ventricle © RSNA, 2024.