Survival Of Patients Research Articles

Role of triggering receptor expressed on myeloid cells 1/2 in secondary injury after cerebral hemorrhage

Intracerebral hemorrhage (ICH) is a common severe emergency in neurosurgery, causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically, especially among patients with poor functional outcomes. ICH is often accompanied by decreased consciousness and limb dysfunction. This seriously affects patients’ ability to live independently. Although rapid advances in neurosurgery have greatly improved patient survival, there remains insufficient evidence that surgical treatment significantly improves long-term outcomes. With in-depth pathophysiological studies after ICH, increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH. In basic and clinical studies of various systemic inflammatory diseases, triggering receptor expressed on myeloid cells 1/2 (TREM-1/2), and the TREM receptor family is closely related to the inflammatory response. Various inflammatory diseases can be upregulated and downregulated through receptor intervention. How the TREM receptor functions after ICH, the types of results from intervention, and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown. An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response, significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage, and thus improve the ability of patients to live independently.

Comparative Performances of 4 Serum NfL Assays, pTau181, and GFAP in Patients With Amyotrophic Lateral Sclerosis.

Selecting the most appropriate blood tests is crucial for the management of patients with amyotrophic lateral sclerosis (ALS). This study evaluates the diagnostic and prognostic performance of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated tau 181 (pTau181) biomarkers in ALS to establish their clinical relevance and cutoff values. In a cohort of patients from the ALS center in Montpellier, we conducted a head-to-head comparison of 4 different technologies and 3 distinct serum analytes: NfL was tested using the ultrasensitive Simoa and the microfluidic Ella platforms, along with 2 assays recently set up on clinical-grade platforms: Lumipulse and Elecsys. We also used Elecsys to assess serum GFAP and pTau181. Our cohort included 139 patients with ALS and 70 non-ALS patients, with a mean age of 66.1 ± 11.4 years and 47.4% of women. The mean follow-up was 42 ± 26.3 months for patients with ALS and 141.6 ± 106.3 months for non-ALS patients, with a mortality rate of 85.5% vs 7.7%. There was a high correlation between all methods tested for serum NfL quantification (R2 = 0.939 to 0.963). The area under the curve (AUC) for ALS diagnosis was 0.889 (0.827-0.932) for NfL Simoa, 0.906 (0.847-0.944) for Ella, 0.912 (0.853-0.948) for Lumipulse, and 0.910 (0.851-0.946) for Elecsys. Serum pTau181 and GFAP showed poor diagnostic performance with AUCs of 0.565 (0.472-0.649) and 0.546 (0.461-0.636), respectively. Kaplan-Meier survival analysis revealed significant hazard ratios (4.4-5.4) for blood NfL. Patients with ALS had a 40%-50% chance of surviving 50 weeks below the prognostic cutoff values while survival rates dropped to near zero above. NfL and GFAP levels were associated with age and body mass index, considered confounding factors. pTau181 levels varied significantly in patients with ALS depending on the site of onset. This study demonstrates the consistent performance of 4 immunoassays for serum NfL quantification in ALS. NfL showed high diagnostic and prognostic accuracy, making it suitable for individual assessment, unlike GFAP or pTau181. We propose diagnostic and prognostic cutoff values for serum NfL, providing a basis for wider implementation, especially with the clinically accredited Lumipulse and Elecsys platforms, which are becoming standard practice. This study provides Class II evidence that serum NfL levels are useful in identifying over 80% of patients with ALS and predicting survival in patients with ALS compared with pTau181 and GFAP levels.

Long-term outcomes after pediatric cardiac surgery: A 20-year single-institution study.

PurposeThis study evaluated the long-term outcomes and factors associated with survival in patients undergoing cardiac surgery with cardiopulmonary bypass at a children's cardiac center.MethodsA retrospective cohort study was conducted between 2001 and 2020 Outcomes included early or late survival and associated risk factors for survival.ResultsSurvival had a mean of 16.78years (95% CI 16.50-17.06). The survival rates at 1, 5, 10, and 19years were 91, 88, and 88%, respectively. Cox regression analysis indicated that age HR = 0.39, 95% CI [0.26-0.59], the RACHS-1 scale HR = 9.92, 95% CI [3.67-26.79], open chest HR = 1, 90, 95% CI [1.20-3.00], cardiac arrest HR = 3.91, 95% CI [2.40-6.36] and peritoneal dialysis HR = 6.71, 95% CI [4, 33-10.38], were independently associated with worse survival.Conclusionslong-term survival of children who undergo cardiac surgery at our single center was satisfactory. Age, higher RACHS score, delayed sternal closure, cardiac arrest, and peritoneal dialysis were strong predictors of adverse outcomes affecting early and long-term survival of pediatric cardiac surgery.

Spectrum of presentation of intraocular metastases from cutaneous melanoma in the era of immunotherapy and targeted therapies.

Intraocular metastases from cutaneous melanoma are rare. Diagnosis can be challenging and there is currently no consensus on treatment. However, with the increasing incidence of this cancer and improved survival of patients treated with targeted BRAF-MEK inhibitors and checkpoint inhibitors, it is likely that more cases will be referred to ocular oncology clinics. Single-centre retrospective study. We included all the patients diagnosed with intraocular metastases from cutaneous melanoma seen between 2017 and 2022. The first patient had bilateral choroidal metastases and unilateral vitreous cells (treated with external beam radiotherapy and immunotherapy), the second had unilateral amelanotic vitreous metastasis (treated with vitrectomy and BRAF-MEK inhibitors) and the third had bilateral multifocal choroidal metastases (treated with BRAK-MEK inhibitors followed by immunotherapy). The fourth patient (previously reported) had unilateral anterior segment and vitreous metastases (treated with immunotherapy and enucleation). Interestingly, two patients had a history of uveitis in the affected eye, unrelated to the ocular metastases. All four patients had synchronous systemic metastases. The diagnosis of intraocular metastases from cutaneous melanoma is generally clinical but it is sometimes challenging because of possible masquerade syndromes. The presence of other extraocular metastatic sites is an indicator of the diagnosis. Cytopathologic proof combined with genetic analysis is sometimes necessary for diagnosis, especially with amelanotic vitreous debris or in rare cases where systemic screening is negative. New treatments with targeted BRAF-MEK inhibitors and checkpoint inhibition may avoid external beam radiotherapy and enucleation in some patients.

Efficacy of Age-Adjusted Dyspnea, Eosinopenia, Consolidation, Acidemia and Atrial Fibrillation Score in Predicting Long-Term Survival in COPD-Related Persistent Hypercapnic Respiratory Failure

Background and Objectives: Hypercapnic respiratory failure (HRF) is a critical clinical condition commonly encountered in acute exacerbations of chronic obstructive pulmonary disease (COPD), leading to high morbidity and mortality rates. The existing scoring systems have primarily been developed for short-term mortality prediction, and their impact on long-term survival has not been sufficiently investigated. This study aims to identify the prognostic factors affecting long-term survival in patients with persistent HRF due to COPD and to evaluate the effectiveness of the Age-Adjusted DECAF (A-DECAF) score, which was created by incorporating the age variable into the existing DECAF score, in predicting long-term survival. Materials and Methods: This retrospective study included patients admitted to an intensive care unit from an emergency department with HRF between April 2022 and November 2023. The demographic data, comorbidities, the laboratory results, and the treatment protocols were recorded. The A-DECAF scores were calculated and analyzed using Kaplan–Meier and ROC analyses. Survival assessment was conducted with Kaplan–Meier analysis, while univariate and multivariate Cox regression analyses were performed to identify the prognostic factors. Results: Among 357 patients, 24.4% died within one year after discharge. The deceased patients were significantly older (p < 0.001) and had higher APACHE-II, DECAF, and A-DECAF scores (p < 0.001 for all). ROC analysis showed that the A-DECAF score had the highest sensitivity (93.1%) and accuracy (AUC = 0.813) for survival prediction. Kaplan–Meier analysis indicated lower survival rates with increasing A-DECAF scores. Cox regression identified the A-DECAF score as the strongest independent predictor (p < 0.001), while lung cancer (p = 0.044) and invasive mechanical ventilation (p = 0.039) also negatively impacted survival. Conclusions: The A-DECAF score is an effective tool for predicting long-term survival in patients with COPD and persistent HRF, particularly aiding clinical decisions regarding elderly populations. Further research is needed to validate its use in diverse patient groups.

Prognostic and immunological implications of protein kinases in gastric cancer: a focus on hub gene ABL2 and its impact on the polarization of M2 macrophages

BackgroundProtein kinases are essential cellular signal modulators involved in tumorigenesis, metastasis, immune response, and drug resistance. However, the comprehensive features and clinical significance of protein kinases in gastric cancer (GC) remain inconclusive.MethodsWe analyzed the transcriptional profiles of protein kinases in GC patients from the GEO and TCGA databases. Based on differentially expressed kinase genes (DE-KGs), a novel cluster was identified to assess its association with patient survival and the tumor microenvironment (TME) in GC. Subsequently, an optimal DE-KGs-based model (DE-KGsM) was determined using 101 machine-learning algorithm combinations. This model was evaluated using multi-omics data to investigate its associations with patient prognosis, clinical features, tumor microenvironment, tumor-infiltrating immune cells (TIICs), and immunotherapy response. Furthermore, scRNA-seq analysis and TIMER algorithm were applied to determine the correlation between the hub gene (ABL2) in the DE-KGsM and Macrophages. Finally, in vitro experiments were performed to explore the immune-related mechanisms of ABL2 in GC.ResultsWe identified two molecular subtypes of GC patients based on 64 DE-KGs expression. Significant differences were observed in overall survival and TIIC characteristics between Cluster 1 and Cluster 2. Among these 64 DE-KGs, we identified an optimal DE-KGsM that could be a prognostic indicator in GC. TIICs and TIDE analyses exhibited that GC patients in the high-DE-KGsM score group had a higher proportion of M2 macrophages and lower response rates to ICI treatment. scRNA-seq analysis indicated that ABL2 might play an indispensable role in tumor immunity. Furthermore, in vitro experiments demonstrated that ABL2 accelerated the proliferation, migration, and invasion of GC cells, as well as the polarization of M2 macrophages.ConclusionsThe DE-KGsM could be a powerful predictor of GC patients’ survival and might facilitate the development of personalized therapy. Furthermore, as a hub gene in the DE-KGsM, ABL2 could be an immunological biomarker that modulates the polarization of M2 macrophages, thereby promoting GC progression.Clinical trial numberNot applicable.

PI3K and PINK1 Immunoexpression as Predictors of Survival in Patients Undergoing Resection of Brain Metastases from Lung Adenocarcinoma

Phosphoinositide 3-kinase (PI3K) and PTEN-induced kinase 1 (PINK1) are key regulators of metabolism and mitochondrial quality control. This study assessed their immunoexpression in 22 patients with lung adenocarcinoma and resected brain metastases who underwent curative treatment between 2007 and 2017 and evaluated their prognostic significance. Tissue microarrays of primary tumors and matched metastases were analyzed using the H-score method. PI3K expression was significantly higher in primary tumors (96.8 ± 57.9 vs. 43.5 ± 62.3; p = 0.003) and in stage IV adenocarcinomas (113.3 ± 56.3 vs. 61.4 ± 47.1; p = 0.043). PINK1 expression showed no significant variation across disease stages. Univariate analysis identified older age (>55 years), PI3K overexpression (HR = 7.791, 95% CI 1.718–36.432; >50 points), and PINK1 overexpression (>100 points) in primary tumors as predictors of poor overall survival (HR = 2.236, 95% CI 1.109–4.508; p = 0.025). Multivariate analysis confirmed PINK1 overexpression in primary tumors as an independent prognostic factor (HR = 4.328, 95% CI 1.264–14.814; p = 0.020). These findings suggest that PI3K and PINK1 may serve as prognostic biomarkers in lung adenocarcinoma with resected brain metastases, emphasizing the need for research on their role in tumor progression and therapeutic response.

Malignancy can present as acute liver failure – a case report of B-cell lymphoma with acute liver failure as its first presentation

Malignant infiltration of the liver is a rare cause of acute liver failure and is associated with an exceedingly high mortality rate. We describe the case of an elderly woman presenting with fulminant hepatitis and simultaneous type B lactic acidosis, with near-normal imaging findings, who was later demonstrated to have non-Hodgkin lymphoma. The presence of acute liver failure, hepatomegaly, markedly elevated lactate dehydrogenase and/or lactic acidosis should raise suspicion for lymphoma infiltration of the liver and prompt liver biopsy early in the course of disease. We hope to raise awareness for this uncommon and elusive presentation of lymphoma, in the hope that it will help achieve earlier diagnoses and improvements in patient survival.

Identification and functional characterization of key biomarkers in diffuse large B-cell lymphoma: emphasis on STYX as a prognostic marker and therapeutic target

Diffuse large B-cell lymphoma (DLBC) is the most common subtype of non-Hodgkin lymphoma, characterized by its aggressive nature and poor prognosis in advanced stages. Despite advances in treatment, the molecular mechanisms driving DLBC progression remain incompletely understood, necessitating the identification of novel biomarkers for diagnosis and prognosis. In this study, we analyzed two publicly available datasets (GSE32018 and GSE56315) from the Gene Expression Omnibus database (GEO) to identify overlapping differentially expressed genes (DEGs). Later on, a comprehensive in silico and in vitro methodology was adopted to decipher the role of identify DEGs in DLBC. DEGs analysis of GSE32018 and GSE56315 datasets identified five overlapping gene: SP3, CSNK1A1, STYX, SIRT5, and MGEA5. Expression validation using the GEPIA2 database confirmed the upregulation of SP3, CSNK1A1, STYX, and SIRT5, and the downregulation of MGEA5 in DLBC tissues compared to normal controls. Furthermore, mutational analysis revealed that CSNK1A1 was the only gene among these DEGs to exhibit mutations, with a 2.7% mutation frequency in DLBC patients. Methylation analysis highlighted a negative correlation between DEGs methylation levels and mRNA expression, while survival analysis identified high STYX expression as significantly associated with poorer overall survival in DLBC patients. Functional assays demonstrated that STYX knockdown in U2932 cells led to reduced cell proliferation, colony formation, and enhanced wound healing, indicating STYX’s pivotal role in DLBC cell survival and migration. Additionally, gene enrichment analysis revealed the involvement of these DEGs in key biological processes, including intracellular trafficking and myeloid progenitor cell differentiation. These findings emphasize the potential of SP3, CSNK1A1, STYX, SIRT5, and MGEA5 as biomarkers and therapeutic targets in DLBC, particularly highlighting STYX as a promising prognostic marker and potential target for therapeutic intervention.

Clinical benefit of PD-1/PD-L1 inhibitors for poor performance status patients with advanced non-small cell lung cancer.

The benefit of programmed cell death protein-1 (PD-1)/programmed cell death protein ligand-1 (PD-L1) inhibitors remains unclear in non-small cell lung cancer (NSCLC) patients with poor performance status (PS). In the current multi-centre retrospective cohort study, advanced or recurrent NSCLC patients treated with PD-1/PD-L1 inhibitors were enrolled. Of the 219 patients enrolled, 44 had PS 2-4. The objective response rate (ORR) of patients with PS 2-4 in 1st line was 33%. Among 1st line group, median progression-free survival (PFS) in patients with PS 2 was significantly longer compared to that in patients with PS 3-4 (15.3 months vs. 0.9 months, P = 0.039, Log-rank test). Among previously treated patients, the ORR of patients with PS 2-4 was only 4%, and PFS and overall survival was poor even in patients with PS 2. PD-1/PD-L1 inhibitors can be an option for PS 2 NSCLC patients in 1st line setting.

Nociceptor neurons promote PDAC progression and cancer pain by interaction with cancer-associated fibroblasts and suppression of natural killer cells.

The emerging field of cancer neuroscience has demonstrated great progress in revealing the crucial role of the nervous system in cancer initiation and progression. Pancreatic ductal adenocarcinoma (PDAC) is characterized by perineural invasion and modulated by autonomic (sympathetic and parasympathetic) and sensory innervations. Here, we further demonstrated that within the tumor microenvironment of PDAC, nociceptor neurons interacted with cancer-associated fibroblasts (CAFs) through calcitonin gene-related peptide (CGRP) and nerve growth factor (NGF). This interaction led to the inhibition of interleukin-15 expression in CAFs, suppressing the infiltration and cytotoxic function of natural killer (NK) cells and thereby promoting PDAC progression and cancer pain. In PDAC patients, nociceptive innervation of tumor tissue is negatively correlated with the infiltration of NK cells while positively correlated with pain intensity. This association serves as an independent prognostic factor for both overall survival and relapse-free survival for PDAC patients. Our findings highlight the crucial regulation of NK cells by nociceptor neurons through interaction with CAFs in the development of PDAC. We also propose that targeting nociceptor neurons or CGRP signaling may offer a promising therapy for PDAC and cancer pain.

Transmembrane channel-like 5 drives hepatocellular carcinoma progression by regulating epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is a difficult cancer to manage due to its highly invasive and metastatic nature. To investigate the molecular function of transmembrane channel-like 5 (TMC5) in vitro and in vivo, with the objective of identifying novel diagnosis and treatment targets for HCC. The expression of TMC in cancer and normal tissues, along with its correlation with HCC prognosis, was analyzed using the GENT2, GEPIA database, and Human Protein Atlas. COX analysis was conducted to assess the relationship between TMC5 expression and overall survival in TCGA-LIHC patients. Further experiments were conducted to investigate the effect of TMC5 in cancer progression through loss- and gain-of-function assays in vitro and in vivo. Bioinformatics revealed that TMC5 expression was generally higher in tumors than in normal tissues, and its expression was associated with poorer patient survival outcomes. TMC5 expression in HCC tissues and cells was consistent with the results of the bioinformatics analysis. Suppression of TMC5 expression reduced migration, invasion, and proliferation, while also decreasing the expression of epithelial-mesenchymal transition (EMT)-associated molecules in MHCC97-LM3 cells. Conversely, higher TMC5 expression significantly increased cell migration, invasion, proliferation, and EMT in MHCC97 L cells. TMC5 knockdown significantly decreased both the formation and spread of nodules in liver tissue, whereas TMC5 overexpression promoted them. Our study provides compelling evidence that TMC5 is highly expressed in HCC and drives cancer progression through the activation of EMT-mediated invasion. TMC5 could represent a valuable molecular target for the diagnosis and treatment of HCC.

The Role of Gut Microbiome on Glioblastoma Oncogenesis and Malignant Evolution

Glioblastoma (GBM) remains the most aggressive primary brain tumor, with poor survival outcomes and treatment limited to maximal safe surgical resection, chemotherapy with temozolomide, and radiotherapy. While immunotherapy and targeted treatments show promise, therapeutic resistance and disease progression remain major challenges. This is partly due to GBM’s classification as a “cold tumor” with low mutational burden and a lack of distinct molecular targets for drug delivery that selectively spare healthy tissue. Emerging evidence highlights the gut microbiota as a key player in cancer biology, influencing both glioma development and treatment response. This review explores the intersectionality between the gut microbiome and GBM, beginning with an overview of microbiota composition and its broader implications in cancer pathophysiology. We then examine how specific microbial populations contribute to glioma oncogenesis, modulating immune responses, inflammation, and metabolic pathways that drive tumor initiation and progression. Additionally, we discuss the gut microbiome’s role in glioma therapeutic resistance, including its impact on chemotherapy, radiotherapy, and immunotherapy efficacy. Given its influence on treatment outcomes, we evaluate emerging strategies to modulate gut flora, such as probiotics, dietary interventions, and microbiota-based therapeutics, to enhance therapy response in GBM patients. Finally, we address key challenges and future directions, emphasizing the need for standardized methodologies, mechanistic studies, and clinical trials to validate microbiota-targeted interventions in neuro-oncology. By integrating gut microbiome research into GBM treatment paradigms, we may unlock novel therapeutic avenues to improve patient survival and outcomes.

Trimetallic PtPdCo nanoalloy on hollow porous N-doped carbon fibers: A high-performance electrochemical immunosensor for procalcitonin detection in SIRS diagnosis.

Systemic inflammatory response syndrome (SIRS) poses a serious threat that influences patient survival and lifequality. Its early and accurate diagnosis is paramount in clinics, where procalcitonin (PCT) is recognized as a key serological biomarker. Herein, well-dispersed PtPdCo nanoalloy was efficiently anchored on hollow porous N-doped carbon fibers (termed PtPdCo HPCNFs) through a sequential process involving electrospinning, pyrolysis, etching, and co-reduction. The morphology, structure, and physicochemical properties of PtPdCo HPCNFswere characterized by a set of techniques. Subsequently, the synthesized PtPdCo HPCNF nanocomposite was applied to build a label-free electrochemical amperometric immunosensor for ultrasensitive detection of PCT. Its performance was evaluated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). Notably, the biosensor demonstrated a wide dynamic linear range (0.0001-1000ngmL-1) and a low detection limit (0.20pgmL-1). Furthermore, the sensor achieved the bioassay of PCT in clinical samples, yielding acceptable results. This work offers a promising approach for synthesizing superior nanomaterials for bioanalytical applications, highlighting their potential in development of sensing devices, especially for early and sensitive diagnosis of SIRS through PCT detection.

Distribution of M1 and M2 macrophages and their impact on survival in non-small cell lung cancer

Tumor-associated macrophages play an essential role in carcinogenesis and metastasis. Our study aimed to evaluate the distribution of M1 and M2 macrophages in tumor islets and stroma and establish the impact on recurrence-free survival and overall survival in patients with surgically resected non-small cell lung cancer (NSCLC). 42 surgically treated NSCLC patients were recruited from the Sumy Regional Clinical Oncology Center. The inclusion criteria were age over 18, stages IA–IIIB of NSCLC, and absence of severe cardiovascular, pulmonary, or autoimmune diseases. Antibodies against CD68+ and CD163+ were used to determine the macrophage phenotype and their distribution in tumor islets and stroma. For each sample, six fields of view with a diameter of 1 mm were analyzed, focusing on the “hot spots” in the tumor stroma and islets. The average values method determined the cut-off value for macrophages M1 and M2. The cut-off values for total macrophages M1 was 28 cells/mm2, macrophages М1 in tumor islets – 18 cells/mm2, macrophages М1 in the stroma – 11 cells/mm2, total macrophages М2 – 38 cells/mm2, macrophages М2 in tumor islets – 13 cells/mm2, macrophages М2 in the stroma – 24 cells/mm2. All data about the clinicopathological characteristics of patients were collected from the medical records. The long-term follow-up period continued for at least 60 months. The difference between the studied groups was assessed using the Student's t-test and the Mann-Witney test. The Cox proportional hazards model was used to assess the impact of several clinicopathological characteristics on patient survival. Most M1 and M2 macrophages accumulated in the stroma (p<0.001). The total number of M1 macrophages was higher in men than women (p=0.0082). Pro-inflammatory macrophages were more prevalent in men than women in both the tumor islets (p=0.0192) and stroma (p=0.0226). Patients with the T1a–2a category had more total M1 macrophages than those with the T2b-4 category (p=0.0486). The tumor stroma also observed this trend (p=0.0205). Current and former smokers had a significantly higher number of M1 macrophages in tumor islets (p=0.0485). In squamous cell carcinomas, the total number of M2 macrophages was higher than in adenocarcinomas (p=0.0343), especially in the tumor stroma (p=0.0006). In conclusion, high M1 macrophage infiltration of tumor islets is associated with better recurrence-free survival. A low total number of M2 macrophages and their low expression in the stroma are associated with better overall survival in surgically treated NSCLC patients.

Evolution of grading for solitary fibrous tumors of the central nervous system: a clinical pathological and prognostic analysis

Objective: The 5th edition of the WHO classification of central nervous system (CNS) tumors in 2021 made significant revisions to the nomenclature and grading system of solitary fibrous tumors (SFT). This study aimed to explore the changes in the grading of CNS SFT and its relationship with clinical pathological features and prognosis. Methods: This study retrospectively reviewed the clinical and pathological data of 82 patients with CNS SFT diagnosed at the First Affiliated Hospital of Fujian Medical University from March 2006 to June 2021, reassessed their grading according to the WHO 5th edition CNS tumor classification, and conducted a comprehensive analysis of their histological morphology, immunohistochemical characteristics, and clinical imaging data. Results: The age of the patients ranged from 21 to 83 years, with a median age of 48 years. Follow-up was completed for 82 patients, during which 10 patients died, 24 recurred, and 5 metastasized. MRI imaging showed that SFT exhibited isointense signals on T1-weighted imaging (T1WI) and complex signals on T2-weighted imaging (T2WI), with signal intensity decreasing as the content of collagen fibers increased. According to the 2021 grading criteria, there was a significant change in the grading of SFT, with the number of grade 1 SFT increasing from 10 cases under the 2016 standard to 39 cases, while the number of grade 2 and 3 SFT decreased accordingly. The 2016 grading system was significantly correlated with the overall survival (OS) of patients (P=0.009), while the 2021 grading system did not reach statistical significance. Both grading systems were correlated with histological phenotype, Ki-67 index, mitotic figures, and necrosis (P＜0.05). All cases expressed STAT6, and showed varying degrees of expression of vimentin, CD99, BCL-2, and CD34. The staining intensity of type Ⅳ collagen fibers, as analyzed semi-quantitatively, was correlated with the OS of the patients (P=0.017). Conclusions: The new grading system for CNS SFT has undergone significant changes, and its association with OS requires further validation. In-depth study of the content and fine structure of collagen fibers in SFT may have important clinical significance for the prognosis assessment and the formulation of treatment plans for patients. Moreover, quantitative analysis of T2WI signal intensity may provide a new method for preoperative preliminary assessment of the collagen fiber content in SFT.

Rare‐Earth‐Based Nanomaterials for Cancer Therapy

ABSTRACTCancer is one of the leading causes of death worldwide, making the pursuit of effective treatments to prolong patient survival a major concern in modern medicine. Rare‐earth‐based nanomaterials (RENMs) possess unique optical properties, catalytic properties, and high X‐rays absorption capabilities, offering diverse approaches for cancer therapy. Herein, this review highlights various strategies for cancer treatment by exploiting the physical and chemical properties of RENMs. Their fluorescent properties can be harnessed for fluorescence image‐guided tumor resection, as well as for light‐triggered photothermal therapy (PTT), photodynamic therapy (PDT) and gas therapy. Additionally, the catalytic properties of RENMs enable the development of novel nanoenzymes for enzyme‐catalyzed therapies. Their high X‐rays absorption capabilities allow for enhanced radiotherapy. Moreover, rare earth ions can be applied to create novel functional nanoformulations for drug delivery and immunotherapy through coordinating with functional biomolecules. Furthermore, the challenges and further prospects of utilizing RENMs in cancer treatment are briefly discussed.

Cardiotoxicity induced by chemotherapy and immunotherapy in cancer treatment: a bibliometric analysis

ObjectiveNew chemotherapy and immunotherapy agents have revolutionized cancer treatment, significantly improving patient survival rates and quality of life while extending lifespans. However, these therapies often come with severe side effects, particularly cardiotoxicity. Over the past few decades, this field has seen steady growth. To better understand current trends, research hotspots, and collaborative networks in this area, a bibliometric analysis of relevant literature was conducted.MethodsA comprehensive search was performed in the Web of Science for articles on cardiotoxicity induced by chemotherapy and immunotherapy in cancer treatment, published in SSCI and SCI-EXPANDED up to October 21, 2024. Using software tools such as GraphPad Prism, CiteSpace, and VOSviewer, we analyzed various parameters including publication year, countries, institutions, journals, authors, and references. Additionally, co-occurrence analyses, cooperation relationship assessments, co-citation networks, keyword maps, clustering analyses, and keyword emergence evaluations were conducted.ResultsAs of October 21, 2024, a total of 5290 articles from 5674 institutions and 27,528 authors across 114 countries and regions were collected. The annual publication frequency and rate steadily increased. The United States emerge as the leading country in terms of publication volume, with the University of Texas System being the most prolific and frequently cited institution. “Breast Cancer Research and Treatment” was among the journals with revelant publications. Notable contributors included Ky bonnie and Thavendiranathan Paaladinesh, while Cardinale D achieved the highest average citation count per publication. Current research hotspots included echocardiography, trastuzumab, doxorubicin, radiotherapy, myocarditis, and 5-fluorouracil. The trend suggests that cardiotoxicity is expected to play an increasingly critical role in chemotherapy and immunotherapy for cancer treatment.ConclusionThis study provides a bibliometric visualization analysis of cardiotoxicity induced by chemotherapy and immunotherapy in the cancer treatment. It highlights current developments, collaborative efforts, and research hotspots within this field, offering essential scientific reference value for Cardio-Oncology.

Immunosuppressive JAG2+ tumor-associated neutrophils hamper PD-1 blockade response in ovarian cancer by mediating the differentiation of effector regulatory T cells.

Tumor-associated neutrophils (TANs) play a critical role in modulating immune responses and exhibit significant heterogeneity. Our previous study demonstrated that jagged canonical Notch ligand 2 (JAG2)+ TANs were associated with an immunosuppressive microenvironment in high-grade serous ovarian cancer (HGSOC), but the underlying mechanism remains unclear. This study aimed to elucidate the role of JAG2+ TANs in tumor immunosuppressive microenvironment in HGSOC. HGSOC samples were collected, with 274 samples constituting two independent cohorts (training and validation cohorts) and an additional 30 samples utilized to establish patient-derived tumor organoids (PDTOs). We characterized the number and phenotype of JAG2+ TANs by multiplex immunohistochemistry, flow cytometry, and single-cell RNA sequencing (scRNA-seq). We investigated the biological functions of JAG2 in immune evasion using in vitro co-culture systems, flow cytometry, tumor-bearing mouse models, and PDTOs. JAG2+ TANs expressed elevated levels of immunosuppressive molecules, including programmed cell death ligand 1 and CD14, and had independent prognostic value for the overall survival of patients with HGSOC. scRNA-seq analysis revealed that JAG2+ TANs exhibited a terminally mature phenotype. The infiltration of JAG2+ TANs was positively correlated with the abundance of effector regulatory T cells (eTregs). Interaction with JAG2+ TANs skewed CD4+ T cells towards an eTreg phenotype, a process that was suppressed by the Notch inhibitor LY3039478 and induced by recombinant Jagged2. Furthermore, we demonstrated that JAG2+ TANs enhanced Notch signaling activation, ultimately promoting recombination signal binding protein for immunoglobulin kappa J region (RBPJ)-induced differentiation of naïve CD4+ T cells into eTregs. Clinically, JAG2+ TANs could serve as a biomarker for assessing immunotherapy resistance in various solid tumors. Pharmacological targeting of Notch signaling with LY3039478 or JAG2 neutralization antibodies enhanced the efficacy of programmed cell death protein 1 (PD-1) monoclonal antibodies (mAbs) in both xenograft and PDTO models. The emergence of JAG2+ TANs is crucial for the differentiation of eTregs, which triggers immune evasion and resistance to anti-PD-1 therapy. Inhibiting Notch signaling with LY3039478 or JAG2 neutralization antibodies may overcome this anti-PD-1 resistance in HGSOC.

An Analysis of the Influence of Social Determinants of Health on Treatment and Survival among Adult Patients with High-Grade Glioma in Utah

Abstract Background Social determinants of health (SDOHs) may impact outcomes of patients with high-grade glioma (HGG). We examined the effect of rurality and socioeconomic status on treatment and survival of patients with newly diagnosed HGG. Methods This retrospective analysis used 2 cohorts from the Utah Cancer Registry including all patients diagnosed with HGG (2000-2019) (cohort 1) and all HGG patients who underwent surgery (2000-2020) (cohort 2). Patient demographics were evaluated descriptively. Kaplan-Meier curves, logrank tests, and multivariate Cox regression analysis were used for survival analyses. Results Patients from cohort 1 living in Frontier (n=60), Rural (n=363), and Urban (n=1502) Utah traveled mean distances of 95.9±69.7, 50.0±66.5, and 10.7±11.3 miles, respectively, for treatment (p<0.001). Urban patients were diagnosed at a younger age (54.2±20.2 years) than patients from Frontier (56.8±20.3 years) and Rural (57.3±17.6 years) areas (p<0.019). Frontier patients were more likely to have lower income than Urban patients (30.7% vs. 65.5%, p<0.001). Rural patients (13.0 months [95% CI 11.2-14.8]) experienced shorter median survival than Urban patients (16 months [95% CI 14.3-17.7]) (p=0.049). Among patients undergoing surgery, those with private insurance (54.2%, p<0.001) and in high-income (60.2%, p=0.007) and socioeconomic (60.4% p=0.005) quartiles received adjuvant chemotherapy and radiation more frequently. Conclusion HGG patients from Frontier and Rural counties in Utah encountered greater SDOH barriers without experiencing delays in resection. Rural patients had shorter survival than Urban patients. Further investigation is needed to determine whether additional SDOHs (income and insurance status) may intersect and contribute to shorter survival and less access to adjuvant therapy.