Survival Time Of Patients Research Articles

The impact of single and multiple occurrences, as well as the sequence of occurrences, of primary gastrointestinal cancer on overall survival: a comprehensive analysis based on the surveillance, epidemiology, and end results database in the United States from 2016 to 2019

IntroductionGastrointestinal cancers encompass malignant tumors of multiple digestive system organs in humans. Each type of digestive system cancer also contains different histological types, each of which has a distinct prognosis. The survival time of cancer patients has significantly extended with the development of modern medicine, allowing for primary cancers occurring more than once in a lifetime.MethodsThe study analyzed multiple primary gastrointestinal cancers, including esophagus, stomach, liver, gallbladder, small bowel, colon, rectum, and anus, based on the Surveillance, Epidemiology, and End Results (SEER) database from 2016 to 2019 in the United States. A total of 119,760 cases were included in this study. Each gastrointestinal cancer was analyzed separately based on the International Classification of Diseases for Oncology third edition (ICD-O-3) for the common histologic type. Meanwhile, based on the sequence of cancer occurrence in the patients, they were divided into the one primary (OP) group and the multiple primaries (MP) group. The multiple primaries group was further subdivided into the first of multiple primaries (FMP) group and the non-first of multiple primaries (NFMP) group. The Kaplan-Meier method with the log-rank test was used to analyze overall survival (OS), while the Cox regression model was used for univariate and multivariate analyses.ResultsThe study enrolled nine organs of the digestive system and twenty histologic types of primary gastrointestinal cancers. The characteristics of patients in different groups with various cancers, overall survival of these patients, and the risk factors for developing these cancers were comprehensively analyzed. The comprehensive analysis revealed the connection between the occurrence sequence of cancers and different outcomes for patients.ConclusionsDifferent prognoses were observed in patients with different sequences of various primary gastrointestinal cancers. Patients with high mortality cancers in the FMP group may have potential factors, such as high treatment sensitivity, that could lead to improved OS. Patients with low mortality cancers in the NFMP group could benefit from positive treatment therapies.

C-reactive protein, genetic susceptibility, and the long-term risk of venous thromboembolism in patients with past cancer.

Several studies indicated that C-reactive protein (CRP) is associated with the risk of venous thromboembolism (VTE) in general population. But CRP appears to be unrelated to VTE events in newly diagnosed cancer patients. However, as the survival time of cancer patients increases, the effect of CRP on the long-term risk of VTE may change. We aimed to investigate the association between CRP and VTE in cancer survivors, and further assess the modification effect of genetic susceptibility. Cox proportional hazards model was used to evaluate the association between serum CRP levels and VTE risk, as well as to investigate the joint effect of CRP and genetic susceptibility. The Kaplan-Meier curve and the restricted cubic spline were used to visualize the relationship between CRP and VTE. This study included 30,145 participants with cancer diagnosis at baseline in the UK Biobank. Over a follow-up period of 344,636 person-years, a total of 1,151 VTE events were recorded. Participants were divided into four groups based on the quartiles of CRP levels. The adjusted hazard ratios (95% CIs) of Q1, Q2, Q3, and Q4 were 1.00, 1.20 (0.99-1.44), 1.25 (1.04-1.50), and 1.51 (1.25-1.82), respectively. For those with high genetic risk of VTE, high CRP had an additional increased risk for VTE. CRP can be used as a predictive biomarker for VTE risk in cancer survivors, especially for those with high genetic risk. Future research can explore whether prevention and treatment strategies for VTE can be developed based on CRP for cancer survivors.

Factors influencing the survival time of patients with advanced cancer at the end of life: a retrospective study

BackgroundPredicting the survival time of patients at the end of life can provide more accurate treatment and care programs for patients. The purpose of this study was to investigate the factors impacting 14-day survival at the end of life.MethodThis was a retrospective study. Patients with advanced cancer admitted to the Department of Palliative Medicine in a tertiary hospital in China in 2021 were included and classified into group A (survival time ≤ 14 days) or group B (survival time > 14 days). Patient demographic characteristics, palliative performance scale (PPS) scores, Barthel index scores, Fracture Risk Assessment Scale (FRAIL) scale scores, clinical features and laboratory test results were extracted from medical records. Univariable and multivariable logistic regression analyses were used to identify predictors of death within 14 days. Survival time was compared between frail and nonfrail patients.ResultsA total of 261 patients were included (122 in group A and 139 in group B), with a median survival time of 17 (13.04, 20.96) days. There were significant differences in age, FRAIL score, PPS, Barthel index, dyspnea, edema, C-reactive protein and white blood cell count between the two groups. According to the multivariable logistic regression analysis, the PPS could predict the risk of death within 14 days (OR = 6.818, 95% CI = 3.944–11.785, p < 0.001). The median survival time was 48 (33.71, 62.29) days in the nonfrail group (n = 34) and 15 (12.46, 17.54) days in the frail group (n = 227) (p < 0.001).ConclusionsA lower PPS increases the risk of 14-day mortality in patients at the end of life. Frailty may shorten the survival time of patients at the end of life.

Mortality of chronic disorders of consciousness in adults and adolescents – a retrospective community based study from Salzburg, Austria

IntroductionEpidemiological data on disorders of consciousness (DoC) is rare and very heterogeneous due to difficulties in case ascertainment and differences in health care pathways between countries. This study reports data on mortality and survival time for DoC patients in Salzburg, Austria.MethodsAll patients with DoC were registered in the health care region of Salzburg North, Austria between 2007 and 2022 and their death data retrieved from the Statistik Austria. The 1- and 5-year mortality was calculated, also in relation to several explanatory variables (age, sex, etiology, diagnosis, CRS-R score, improvement). Furthermore, the incidence, survival functions using the Kaplan–Meier estimator and a Cox-Regression were calculated.ResultsThe mean annual incidence is 2.2 DoC/100.000 inhabitants in the Salzburg North region. The crude 1- and 5-year mortality rates were 25.9 and 55.1%, respectively, and the median survival of DoC patients based on the Kaplan–Meier estimator was 6.3 years. Moreover, the mortality was lower in women and in younger patients, those of traumatic etiology, and those with higher CRS-R scores, better diagnosis or an improvement of diagnosis until discharge from hospital.ConclusionThis article gives a rare insight into epidemiological data on DoC and shows which factors influence the mortality of these patients. Moreover, it is the first community based study on mortality of DoC in Salzburg, Austria.

The clinical features and prognostic implications of the co-mutated TP53 gene in advanced non-small cell lung cancer.

TP53 is a frequently mutated oncogene within non-small cell lung cancer (NSCLC). However, the clinical and prognostic significance of co-mutations in TP53 in patients with advanced NSCLC has not been fully elucidated. A total of 174 patients with advanced NSCLC were enrolled in this study. All patients were subjected to sequencing analysis of tumor-related genes and information such as PD-L1 expression, TMB, and co-mutation changes were collected. Patients were categorized into TP53 mutant and TP53 wild-type groups according to their TP53 mutation status and then statistically analyzed. TP53 mutations were the most common among all patients, accounting for 56.32%, followed by epidermal growth factor receptor mutations at 48.27%. The most common mutation sites in the TP53 mutation group were exons 5-8.TP53 mutations were significantly associated with PD-L1 and TMB levels. Univariate Cox analysis showed that gender and EGFR mutation affected the prognosis of TP53-mutated NSCLC patients, and multivariate Cox regression analysis identified EGFR mutation as an independent risk factor. The OS of NSCLC patients in the TP53 mutation group was significantly shorter than that of the TP53wt group. Survival curves in the TP53/EGFR combined mutation group showed that patients with combined EGFR mutation had a lower survival rate. TP53 mutations are associated with different clinical indicators and have important implications in clinical treatment. TP53 is a poor prognostic factor for NSCLC patients, and TP53/EGFR co-mutation will affect the survival time of patients. TP53/EGFR co-mutation may be a new prognostic marker for NSCLC.

A next generation probabilistic approach to analyze cancer patients data with inference and applications

This study addresses the critical challenges faced in cancer care, particularly in predicting survival times for patients with lung cancer and acute myeloid leukemia. Despite recent advancements in medical science, existing models often fall short in accurately capturing disease progression, leading to less effective clinical decision-making, and compromised patient outcomes. The need for advanced predictive models is urgent to improve survival time forecasts and enhance treatment strategies. In response to this, we introduce a novel probabilistic approach, the New Weibull (NEWE) model, which is part of a newly generated class designed to model cancer patient data more effectively. Our methodology includes using seven well-known estimation methods, each rigorously evaluated for consistency through Monte Carlo simulation studies focused on key metrics such as absolute bias, mean square error, and mean relative error. The datasets analyzed include survival times for twenty acute myeloid leukemia patients, 121 breast cancer patients from 1929 to 1938, 33 patients with acute myelogenous leukemia, data from eighteen individuals who died from causes unrelated to cancer, and survival times of advanced lung cancer patients undergoing standard chemotherapy. The NEWE model outperformed competing models, particularly in Anderson-Darling, Cramer-von Mises, and Kolmogorov-Smirnov tests, with significantly higher p-values. These findings highlight the NEWE model’s potential to transform predictive oncology by offering more precise survival time predictions, improving the quality of care and decision-making in cancer treatment.

Effects of Socio-Economic and Health Variables on Survival Time of HIV/AIDS Patients in Manipuir

Background: The survival time of patients with human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome (AIDS) is associated with many socio-economic, education, employment and socio-cultural factors. High prevalence rates of HIV/AIDS are observed in some Indian States including Manipur. Objectives: It is to examine the effects of socio-economic and health related variables on the survival time of HIV and Hepatitis-C virus (HCV) patients. Materials and Methods: Under simple random sampling without replacement (SRSWOR), it analysed a sample of 200 HIV+ patients attending the ART Centre of Jawaharlal Institute of Medical Science (JNIMS), Imphal during March – July 2016. Using multiple regression models, the significant covariates of the survival time of patients are explored. Findings: The five factors – sex of patient (P&lt;0.05), marital status (P&lt;0.05), family income (P&lt;0.05), patient type (P&lt;0.01) and CD4 count (P&lt;0.05) are found to be significantly influencing the dynamics of survival duration of the patients. Conclusion: In Manipur, the average survival time of the HIV/ AIDS patients is observed to be about six years varying with their sex, marital status, size of family, employment and CD4 count. Keywords: Manipur, regression model, sex, marital status, CD4

On prediction of future failure times based on bathtub-shaped type-II censoring samples

In this paper, we focus on predicting future failure times under Type-II right censoring samples with bathtub-shaped failure times. We first discuss the point and interval estimation of the unknown parameters using the maximum likelihood estimation and spacing-based methods. Various point predictors for future failure times are derived, using the best unbiased, maximum likelihood, conditional median, and median unbiased methods. Moreover, we establish the corresponding prediction intervals by applying different techniques including pivotal, Wald, highest conditional density, and shortest length methods. A simulation study is performed to assess the performance of the proposed prediction methods. Additionally, two real datasets are analyzed: one representing the survival times of patients treated for stomach cancer (Hand et al., 1994) and another from Lawless (2011), showing the duration in thousands of cycles until electrical appliances failed in a life test. These analyses illustrate the practical application of the proposed methods. Based on these numerical experiments, it is shown that the maximum likelihood predictor based on two-stage procedure and the conditional median predictor are the best point predictors for future failure times. Moreover, the highest conditional density method is identified as a strong candidate for establishing prediction intervals.

Mesothelioma of the Tunica Vaginalis Testis: Diagnostic and Therapeutic Management. A Comprehensive Review, 1982–2024

Background: Mesothelioma of the tunica vaginalis testis (MTVT) is an extremely rare and aggressive cancer. The diagnosis and management of MTVT is complex, and no standard treatment protocol is available. Methods: We conducted a systematic literature review from 1 January 1982 to 14 March 2024 using PubMed to collect all the available case reports and case series. A descriptive analysis of patient characteristics with clinical presentation, diagnostic work-up, therapeutic management, and past asbestos exposure was performed. Survival times of patients treated with different therapeutic approaches were evaluated. Results: Overall, 289 patients with MTVT were included in our analysis. The most common clinical presentations were scrotal/testicular swelling or mass (187 patients, 65%) and the presence of hydrocele (159, 55%). Imaging evaluation, mostly with ultrasonography or CT scan, was reported in two-thirds of cases. Radical surgery (216 patients, 75%) with orchiectomy and, in select cases, hemiscrotectomy and inguinal lymphadenectomy was the most frequent therapeutic approach. A minority of patients (49, 17%) received adjuvant therapy after surgery (radiotherapy, chemotherapy, or a combination of the two), with no evidence of survival improvement. Conclusions: No standard guidelines for MTVT are available so far. Radical surgery following accurate radiological staging should be the mainstay of treatment. The role of adjuvant treatments remains undefined. Due to its rarity, MTVT should be treated in referral centers, and patients’ data should be collected in a dedicated register in order to improve the knowledge of this exceedingly rare disease and establish optimal diagnostic and therapeutic management.

The impact of positive resection margin in perihilar cholangiocarcinoma, ductal margin vs radial margin.

Resection margin status is the important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the effect of positive RM on survival. Patients with pCCA underwent curative resection between 2013 and 2018 were retrospectively reviewed. Resection margin status was divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+). Of the 167 pCCA patients, 62 (37.1%) had R1 margin. Among 62 R1 patients; 17 (27.4%) had positive DM alone, 20 (32.3%) had positive RM alone and 25 (40.3%) had both positive DM and RM. The R1 patients had a significantly greater number of lymph node metastasis (LNM) and advanced tumor staging than R0 patients, however there was no difference between the RM + and DM + patients. The median survival time of patients with RM + was significantly poorer than R0 patients (13.8 vs. 24.5 months; p < 0.001, respectively) and similar to the DM + patients (9.1 months, p = 0.556). However, in patients with LNM, those who underwent R0 resection had no statistically significant difference in survival outcomes compared to those with R1 resection. Positive resection margin remains the important prognostic factor, and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM.

Duration Diabetes Survival Times Modelling Using Some Extended Lomax Distribution

The precise modeling of survival time in diabetes is essential for accurately estimating the potential lifespan of individuals diagnosed with diabetes. One of the key factors in assessing the potential survival times of diabetes patients in a specific region is the probability distribution of diabetes survival times. Therefore, data on diabetes survival times are necessary to conduct statistical modeling, particularly in determining the most suitable probability distribution. Statistical models are developed to draw conclusions about the probability distribution of diabetic patients at the Mandau Regional General Hospital (RSUD) in Bengkalis Regency, Riau Province. To achieve this, six distributions will be utilized and evaluated to identify the best model for describing diabetes survival times. The primary objective of this research is to identify the most appropriate distribution to represent the survival times of diabetes patients from 50 individuals in the Bengkalis region, using the Lomax (LM) distribution, three parameters modified Lomax distributions (Rayleigh Lomax (RL), Logistics Lomax (LL), New Rayleigh Lomax (NRL)) and four parameters modified Lomax Distribution (Odd Lomax Log Logistics (OL), Novel Extended Power Lomax (PL)). The maximum likelihood method will be employed to estimate the parameter values of the distributions used in this study. Additionally, graphical assessments (density-density plot) and numerical criteria (Akaike’s Information Criterion (AIC), -log likelihood (-l)) will be utilized to determine the best-fitting model. In most instances, the results obtained from graphical assessments were consistent but differed from the numerical criteria. The model with the lowest values of AIC and -l was selected as the best fit. Overall, the RL and OL distributions was identified as the most suitable model.

Recent efficacy and long-term survival of Astragalus polysaccharide combined with gemcitabine and S-1 in pancreatic cancer.

Pancreatic cancer is a highly malignant tumor with a rapid progression rate and a high susceptibility to infiltration and metastasis. Astragalus polysaccharide (APS), a pure Chinese medicine preparation primarily made from the traditional Chinese herb Astragalus, plays a positive role in the treatment of many malignant tumors. To explore the recent efficacy of APS combined with gemcitabine plus tegafur gimeracil oteracil potassium capsule (S-1) (GS) regimen in the treatment of pancreatic cancer and assess its effect on the immune function and long-term survival of patients. A total of 97 patients who were diagnosed with pancreatic cancer and received GS chemotherapy at The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) from March 2021 to December 2021 were included in the retrospective analysis. Among them, 41 patients received APS combined with GS chemotherapy, and 56 patients received GS chemotherapy only. The recent efficacy, immune function, adverse reactions, and long-term survival were compared among these patients. After 4 cycles of treatment, the objective response rate of patients receiving the combined therapy of APS and GS was 51.22%, and the disease control rate (DCR) was 56.10%, higher than those of patients receiving the monotherapy with GS alone (30.36% and 35.71%, respectively). Besides, the percentages of CD3+ T cells (50.18% ± 9.57%) and CD4+ T cells (31.52% ± 5.33%) in the peripheral blood of patients receiving the combined therapy of APS and GS were higher compared with those treated with GS regimen alone [(44.06% ± 8.55%) and (26.01% ± 7.83%), respectively]. Additionally, the incidences of leukopenia, thrombocytopenia, and fatigue in patients receiving the combined therapy of APS and GS were significantly lower than those in patients receiving the monotherapy of GS alone (17.07%, 9.76%, 31.71% vs 37.50%, 28.57%, 60.71%). Moreover, the median survival time of patients receiving the combined therapy of APS and GS was 394 days, significantly longer than that of patients receiving the monotherapy of GS alone (339 days) (hazard ratio: 0.66; 95%CI: 0.45-0.99; P = 0.036). All these differences were statistically significant (P < 0.05). The combined therapy of APS and GS improved the recent efficacy and long-term survival of patients with pancreatic cancer and alleviated chemotherapy-induced immune suppression and adverse reactions.

Oct4 promotes the progression and radioresistance of esophageal squamous cell carcinoma by regulating epithelial-mesenchymal transition

Objective: To explore the specific role and molecular mechanism of octamer-binding transcription factor 4 (Oct4) in promoting the progression of esophageal squamous cell carcinoma and radioresistance. Methods: The Gene Expression Profile Data Dynamic Analysis (GEPIA) database was used to analyze the expression differences of the Oct4 gene in different types of tumor tissues and their corresponding adjacent normal tissues. The clinical data and surgical resection tissue specimens of 196 patients with esophageal squamous cell carcinoma who received surgery combined with radiotherapy at Henan Provincial Chest Hospital from January 2013 to May 2022 were collected. Immunohistochemistry was used to detect the expression of Oct4 protein in the tumor and adjacent tissues. The lentiviral packaging system was used to construct esophageal squamous cell carcinoma cell lines that up-regulated or down-regulated Oct4. The cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, the scratch test was used to detect the cell migration ability, and the clone formation test was used to detect the cell radiosensitivity. Immunofluorescence experiment was used to detect DNA damage level, and Western blot was used to detect the expressions of Oct4, human phosphorylated histone (γ-H2AX), E-cadherin, N-cadherin, vimentin, and zinc finger E box binding homology box 1 (ZEB1). Results: The analysis of GEPIA database showed that the expression level of Oct4 mRNA in esophageal carcinoma was higher than that in paracancerous tissues. The expression level of Oct4 protein in tumor tissues was 78.35±1.42, which was higher than that in adjacent tissues (16.27±0.49). The survival time of patients with a high expression of Oct4 was significantly shorter than that of patients with a low expression of Oct4 (25.40 and 47.00 months). Compared with the control group, the proliferation ability of KYSE510 cells in the Oct4 up-regulated group was enhanced after 72-h culture, and the cell migration ability of these cells was also enhanced, with the migration rate being (41.67±1.20)% vs (23.67±1.86)% after 24-h culture. The radiosensitivity of cells in this group decreased, with the radiosensitivity enhancement ratio being 0.69±0.06 vs 1.00±0.02. After radiotherapy, the expressions of γ-H2AX and E-cadherin decreased, while the expressions of ZEB1, vimentin and N-cadherin increased. Compared with the control group, the proliferation ability of KYSE150 cells in the Oct4 down-regulated groups 1 and 2 decreased (absorbance being 2.51±0.17, 2.38±0.16, and 3.33±0.07, respectively, P＜0.01) after 72-h culture, and the migration ability also decreased, with the migration rate being (13.33±0.88)%, (13.00±1.00)%, and (40.33±2.03)%, respectively (all P＜0.001), after 24-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.34±0.11,1.24±0.07, and 1.00±0.02, respectively (all P＜0.05). After radiotherapy, the expressions of γ-H2AX and E-cadherin increased, while the expressions of ZEB1, vimentin and N-cadherin decreased. Compared with the control group, the proliferation ability of KYSE510 cells in the ZEB1 down-regulated group decreased [absorbance being 1.33±0.15 vs 1.81±0.16 (P=0.002)] after 72-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.37±0.11 vs 1.00±0.01 (P=0.037), and after radiotherapy the expression of γ-H2AX increased. Conclusion: Oct4 is involved in the regulation of epithelial-mesenchymal transformation of esophageal squamous cell carcinoma, which promotes the proliferation, migration, and radioresistance of esophageal squamous cell carcinoma.

Systematic pan-cancer analysis of the prognostic value of MECOM in human cancer

Recently, emerging evidence suggests an association between MECOM (MDS1 and EVI1 complex locus) and cancers. However, a comprehensive pan-cancer analysis to fully investigate this relationship is lacking. Herein, public platforms with large-scale genomics, including The Cancer Genome Atlas, Gene Expression Omnibus dataset, and the Human Protein Atlas were explored to investigate the prognostic and immunological roles of MECOM across certain cancer types. Our findings revealed differential expression of MECOM in various cancer types, indicating its potential to predict diverse clinical outcomes, such as overall survival time and disease-free survival time in patients with various malignancies. Additionally, we observed an association between the mutation burden in MECOM in various cancers and patient survival. Furthermore, the mechanism of MECOM-mediated oncogenesis was tentatively explored by immune infiltration analysis. This study provided a relatively comprehensive overview of the prognostic and immunological roles of MECOM in multiple cancers.

Targeted anti-cancer agents and risk of venous thromboembolism.

The incidence of one-year venous thromboembolism (VTE) after cancer diagnosis is reported to be increasing for several types of cancer. The introduction of targeted anti-cancer therapies and immunotherapy into the therapeutic armamentarium of medical oncologists contributed to the significantly improved response rates and survival times of cancer patients. In recent years, a potential prothrombotic effect of several targeted anti-cancer agents and immunotherapy drugs has been suggested; however, the methodological limitations of clinical trials evaluating the possible role of these classes of drugs on the VTE risk often make the interpretation of their results difficult. It is still not clear whether the increased risk of VTE is more closely correlated to the expression of specific oncogenic profiles than to the administration of specific therapies against these mutations. Furthermore, the increased survival rates observed with these agents could influence the prevalence of VTE events in cancer patients by the competing risk mortality on the risk of VTE. To date, the available data have suggested that the risk of VTE varies among different categories of targeted therapy, being most reported for anti-vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), monoclonal antibodies and immune checkpoint inhibitors, and less reported for tyrosine kinase inhibitors (TKI). The risk of VTE seems to significantly increase when targeted therapy is administered in combination with traditional anti-cancer agents. Considering the uncertainties in estimating the rate of thrombotic complications associated with targeted therapy, the need for antithrombotic prophylaxis in cancer patients receiving targeted therapies still needs to be specifically assessed. In this review, we examine available evidence of the literature and the methodological limitations of clinical trials, and we discuss the potential future perspectives.

DSN1 may predict poor prognosis of lower-grade glioma patients and be a potential target for immunotherapy

ABSTRACT DSN1 has been previously found to be positively correlated with various cancers. However, the effect of DSN1 or its methylation on the prognosis, molecular characteristics, and immune cell infiltration of low-grade glioma (LGG) has not yet been studied. We obtained 1046 LGG samples from the The Cancer Genome Atlas, The Chinese Glioma Genome Atlas (CGGA) microarray, and CGGA RNA-Seq databases. Bioinformatic methods (gene set enrichment analysis (GSEA), chi-square test, multivariate), and laboratory validation were used to investigate DSN1 in LGG. The expression levels of DSN1 mRNA and protein in LGG were substantially higher than those in normal brain tissue, and their expression was negatively regulated by methylation. The survival time of patients with low expression of DSN1 and cg12601032 hypermethylation was considerably prolonged. DSN1 was a risk factor, and of good diagnostic and prognostic value for LGG. Importantly, the expression of DSN1 is related to many types of tumor-infiltrating immune cells and has a positive correlation with PDL1. DSN1 promoted the activation of multiple cancer-related pathways, such as the cell cycle. Additionally, knockdown of DSN1 substantially inhibited the proliferation and invasion of LGG cells. To the best of our knowledge, this study is the first comprehensive analysis of the mechanism of DSN1 leading to poor prognosis of LGG, which provides a new perspective for revealing the pathogenesis of LGG. DSN1 or its methylation has diagnostic value for the prognosis of glioma, and may become a new biological target of anti-tumor immunotherapy.

Blood CD45+/CD3+ lymphocyte-released extracellular vesicles and mortality in hospitalized patients with coronavirus disease 2019.

The global pandemic of coronavirus disease 2019 (COVID-19) represented a major public health concern. Growing evidence shows that plasma of COVID-19 patients contains large numbers of circulating extracellular vesicles (cEVs) that correlate with disease severity and recovery. In this study, we sought to characterize the longitudinal cEV signature in critically ill COVID-19 patients during hospitalization and its relation to mortality risk. cEVs were quantitatively and phenotypically analysed in hospitalized non-surviving COVID-19 patients at baseline (n = 42) and before exitus (n = 40) and in 40 healthy volunteers as a reference group by high sensitivity nano flow cytometry using specific markers for parental cell sources and activation. Levels of cEV subtypes differed between patients with severe COVID-19 and healthy subjects, specifically those from platelets and endothelial, inflammatory and viral infected cells, which associate to high mortality risk. In the longitudinal analysis from baseline to the time point immediately preceding death, no changes were found for platelet, pan-leukocyte, and lung epithelial cell-shed cEVs, while endothelial cell releases of EVs (eEVs) significantly differed. Vascular endothelial growth factor receptor 2-positive eEVs were significantly increased before death compared to admission whereas endoglin and E-selectin-containing eEVs did not change. Conversely, lymphocyte (ℓEV), monocyte, macrophage, pericyte and progenitor cell-derived cEVs displayed significant reductions before exitus. Noteworthy, levels of CD45+/CD3+-ℓEVs were significantly associated to the patient's survival time. An evolving cEV profile able to discriminate prompt risk of death during hospitalization has been defined suggesting a role for circulating and vascular cell-derived EVs in COVID-19 pathogenesis.

CTNI-65. DETERMINANTS OF LONG-TERM SURVIVAL IN PATIENTS WITH IDH-MUTANT GLIOMAS

Abstract BACKGROUND Survival times of patients with IDH-mutant gliomas is variable and can extend to decades. Many studies only provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored clinical disease characteristics of long-term survivors within a large cohort of patients with extended follow-up. METHODS This single-center, retrospective analysis included 114 patients with IDH-mutant glioma that either died due to tumor-related causes or survived at least 15 years after first diagnosis. Patient characteristics, outcomes, and prognostic factors were stratified by short- (&amp;lt; 15 years) versus long-term (≥ 15 years) survival. Initial diagnosis was (re-)classified according to the WHO 2016 classification. Uni- and multivariate analyses were performed. RESULTS Overall, 66 patients (58%) were diagnosed with astrocytoma and 48 patients (42%) with oligodendroglioma. Median follow-up of the survivors was 16.6 years (range 15-28.9). 62 tumor-related deaths (54%) had been reported at database closure. Patients that died before reaching 15 years survival time had been diagnosed with astrocytoma in 41 (72%) and oligodendroglioma in 16 cases (28%). The long-term survivor cohort comprised 25 patients (44%) with astrocytoma and 32 patients (56%) with oligodendroglioma. Long-term survival was associated with grade 2 histology (p &amp;lt; 0.01), smaller tumor volumes (p &amp;lt; 0.01), and lack of contrast enhancement (p = 0.02). 41 long-term survivors (72%) were initially monitored by a wait-and-scan strategy as opposed to 16 patients (28%) in the cohort of short-term survival (p&amp;lt;0.01). In patients with oligodendroglioma, a higher KPS was associated with longer survival (HR 0.25; 95% CI 0.02-0.67; p = 0.05). Tumor resection (HR 0.43; 95% CI 0.22-0.86; p = 0.02) and wait-and-scan strategies (HR 0.34; 95% CI 0.14-0.79; p = 0.01) were associated with longer survival in patients with astrocytoma. CONCLUSION Tumor resection followed by a wait-and-scan strategy may yield excellent survival times, especially in patients with IDH-mutant grade 2 astrocytoma. Age appears not be an important predictor for survival in patients with IDH-mutant gliomas.

Fasciculation potentials are related to the prognosis of amyotrophic lateral sclerosis.

Some prognostic biomarkers of amyotrophic lateral sclerosis (ALS) have been described; however, they are inadequate for satisfactorily predicting individual patient outcomes. Fasciculation potentials (FPs) on electromyography (EMG) are useful for the early diagnosis of ALS, and complex FPs are associated with shorter survival in ALS. In this study, we investigated the relationship between the proportion of muscles with FPs, biochemical markers, and the prognosis of ALS. 89 Patients with ALS were retrospectively classified into three groups based on the interval from onset to death or tracheostomy (less than 1 year: fast progression; from 1 year to less than 3 years: average progression; 3 years or more: slow progression). We performed statistical analysis of the electrophysiological findings, including the percentage of examined muscles with FPs, and biochemical markers evaluated on admission. Patients with fast ALS progression had a higher percentage of muscles with FPs (93.1% vs. 37.9%, P<0.001) and lower uric acid (UA) levels (male: 4.19 mg/dl vs 5.55 mg/dl, P<0.001; female: 3.71 mg/dl vs 5.41 mg/dl, P<0.001) than patients with slow progression. Survival curves demonstrated a relationship between these factors and the survival time in patients with ALS. Furthermore, UA levels were correlated with the percentage of muscles with FPs. Our electrophysiological findings suggest that ALS presents with multisystem neurological manifestations, and these manifestations differed among the groups classified by disease progression. The percentage of muscles with FPs on EMG and serum UA levels were especially associated with the prognosis of ALS.

Hypernatremia is associated with mortality in severe elderly sepsis patients.

To explore the relationship between hypernatremia and 28-day mortality in elderly sepsis patients. A total of 179 elderly patients (age ≥65 years) with elevated serum sodium admitted to the Department of Critical Care Medicine of Nanjing Hospital affiliated with Nanjing Medical University from September 2021 to September 2022 were included in this retrospective observational study. The clinical data of all patients were collected, and the patients were divided into septic group and nonseptic groups according to the Sepsis 3.0 definition. The clinical features, acute physiological and chronic health II score (APACHE II score), mechanical ventilation time, serum sodium value and duration of serum sodium elevation were compared between the two groups. ROC curves were drawn to evaluate the predictive value of each index on the prognosis of sepsis patients, and Kaplan‒Meier survival analysis was carried out on patients with different serum sodium peaks. (1) The changes in serum sodium within 48 hours after admission in the sepsis group were small and statistically significant compared with those in the nonsepsis group (P = 0.039); however, the serum sodium elevation duration was longer (P = 0.018). (2) Compared with nonseptic patients, the 7-day mortality of septic patients was higher (15.8 vs. 7.7, P<0.001). The 28-day mortality of septic patients was higher than that of nonseptic patients, but there was no significant difference between the two groups (P = 0.086). (3) The serum sodium level in the sepsis group was higher than that in the nonsepsis group on the 1st, 3rd, 5th and 7th days (P<0.001). There was no significant difference in mechanical ventilation time or duration of stay in the ICU between the two groups. (4) The ROC curve analysis showed that the peak value of serum sodium had predictive value for the prognosis severity of elderly patients with sepsis. The area under the curve (AUC) was 0.753, the 95% confidence interval (95% CI) was 0.639~0.867, and the best cut-off value was 154.9 mmol/L. (5) According to the best cut-off value of the serum sodium peak, the septic patients were divided into two groups: the peak value of serum sodium was ≥154.9 mmol/L (group A), and the peak value of serum sodium was <154.9 mmol/L (group B). Among them, the case fatality rate was higher at 7 days and 28 days when the peak value of serum sodium was ≥154.9 mmol/L (group A) (22.0% vs. 8.6%); the χ2 value was 35.379, P<0.05; 75.6% vs. 37.1%, χ2 = 14.21, P = 0.003). There was no significant difference in mechanical ventilation time or duration of stay in the ICU between the two groups. (6) Kaplan‒Meier survival analysis showed that the median survival time of patients with a serum sodium peak ≥154.9 mmol/L (group A) was significantly shorter than that of patients with a serum sodium peak < 154.9 mmol/L (group B) (16.7±1.4 d vs. 24.8±1.2 d, P <0.05). The serum sodium increase in elderly sepsis patients lasts for a long time, and the serum sodium fluctuation is relatively small. The serum sodium peak value has predictive value for 28-day mortality.