Kaplan-Meier Survival Analysis Research Articles

Outcomes of advanced care management in home-based long-term care: A retrospective population-based observational study

BackgroundIn home-based long-term care, care management aims to facilitate the independence of community-dwelling older adults and mitigate the escalation of their care needs. We examined the association between the types of care management (advanced vs. conventional) and the progression of care needs among recipients with moderate care needs and compared care services offered in care plans between care management types. MethodsA retrospective, population-based observational study was conducted in Tsukuba City in Japan. The individual-level secondary data from the suburban municipal government was collected between May 2015 and March 2019. The primary outcome was the progression of care-need levels certificated in Japanese long-term care insurance. The exposure variable was advanced care management. First, we conducted propensity-score matching to adjust for differences in recipient characteristics. Second, we performed Kaplan–Meier survival analyses and log-rank tests, with the outcome measure being the progression of care-need levels. Third, Pearson's chi-square tests were performed to compare care services for recipients of advanced vs. conventional care management. ResultsOf the 1010 long-term care recipients, we selected 856 propensity score-matched recipients receiving advanced or conventional care management. The proportions of four-year cumulative progression-free survival in the groups receiving advanced and conventional care management were 82.2 % and 78.5 %, respectively (p = .69). The proportions of the groups with advanced and conventional care management were 17.1 % and 23.8 % using home-help services (p < .05), and 4.0 % and 8.2 % using community-based day care services (p < .05), respectively. ConclusionsAdvanced care management in home-based long-term care was not associated with a slowing of the progression of care needs among older adults with moderate care needs compared with conventional care management. There was a notable discrepancy in the use of care services, with the advanced care management group having lower rates of use of home-help services and community-based day care services compared with the conventional care management group.

Periostin Predicts All-Cause Mortality in Male but Not Female End-Stage Renal Disease Patients on Hemodialysis.

Periostin is a matricellular protein. Elevated serum concentrations of periostin have been reported in patients with various cardiovascular diseases, including heart failure. Patients with end-stage renal disease have a substantially increased risk for cardiovascular diseases. However, there is a lack of clinical studies to clarify the prognostic significance of systemic periostin on all-cause mortality in patients with end-stage renal disease on hemodialysis. 313 stable end-stage renal disease patients were recruited and followed for 5 years concerning all-cause mortality. At baseline, we collected blood samples and clinical data. Serum periostin concentrations were measured using a certified ELISA. The optimal cut-off value for serum periostin regarding all-cause mortality, calculated through receiver operating characteristic analysis, was 777.5 pmol/L. Kaplan-Meier survival analysis using this cut-off value demonstrated that higher periostin concentrations are linked to higher all-cause mortality (log-rank test: p = 0.002). Subgroup analysis revealed that serum periostin concentrations only affected all-cause mortality in male but not in female patients (p = 0.002 in male patients and p = 0.474 in female patients). Multivariate Cox regression analyses, adjusted for confounding factors, likewise showed that elevated serum periostin concentrations were positively associated with all-cause mortality in male (p = 0.028) but not in female patients on hemodialysis (p = 0.313). Baseline serum periostin is an independent risk factor for all-cause mortality in male patients with chronic renal disease on hemodialysis.

Identification of Immune Infiltration-related Molecular Features in Ovarian Cancer Patients and Experimental Validation of Immune Response Molecular Mechanisms through Integrated WGCNA, Machine Learning, and Single-cell Sequencing Analysis.

Ovarian cancer is one of the most common gynecological malignancies globally, and immunotherapy has emerged as a promising treatment strategy in recent years. However, the effectiveness of immunotherapy is often limited by immune escape mechanisms. To unravel the immune response mechanisms in ovarian cancer, this study aimed to employ integrated Weighted Gene Co-expression Network Analysis (WGCNA), machine learning, and single-- cell sequencing analysis to systematically investigate immune infiltration-related molecular features in ovarian cancer patients and experimentally validate the molecular mechanisms of the immune response. This research may provide a new theoretical foundation and treatment strategy for immune-based therapies in ovarian cancer. Relevant ovarian cancer datasets were collected from public databases. The ConsensusCluster- Plus and ggplot2 R packages were used to perform dimensionality reduction and clustering analysis of immune infiltration-related genes. Various algorithms were employed to select the best ovarian cancer prognostic model with OC consistency. The prognostic value of angiogenesis and immune-related gene expression was evaluated through Kaplan-Meier survival analysis, and the impact of immune infiltration on immune function in ovarian cancer patients was assessed. Functional pathways were identified using the Gene Set Enrichment Analysis (GSEA) method, and the infiltration abundance of immune and stromal components was inferred using the single-sample Gene Set Enrichment Analysis (ssGSEA) method. The influence of angiogenesis on the cellular level of Ovarian Cancer (OC) was explored in single- cell sequencing data, followed by in vitro cell experiments for further validation. The effect of the angiogenesis model on OC was evaluated through the above-mentioned research and experiments, aiming to investigate the mechanism of targeted therapy strategies in ovarian cancer. Immune-related data were collected from ovarian cancer patients in this study. Through WGCNA analysis, the MEturquoise module was identified, and a total of 1018 hub genes were determined. A prediction model was constructed using machine learning, with CoxBoost+StepCox selected as the best model, leading to the identification of 10 genes associated with ovarian cancer. Patients with high AIDPS had shorter survival time, and GSEA analysis revealed enrichment in immune-related pathways. Single-sample gene set enrichment analysis demonstrated increased immune cell infiltration and malignant stromal changes in the high AIDPS group. Results from in vitro cell experiments showed that silencing RPL31 inhibited the proliferation and migration of ovarian cancer cells while enhancing immune response capability. AIDPS holds significant clinical significance in Ovarian Cancer (OC) with poor prognosis observed in patients with high AIDPS. These patients exhibit more significant genomic variations, denser immune cell infiltration, and greater tolerance toward immune therapy. Importantly, inhibiting the expression of RPL31, a key component of AIDPS, can significantly suppress the proliferation, migration, and invasive properties of ovarian cancer cells, while stimulating the cytotoxicity of effector T cells and promoting immune response, thus slowing down the progression of ovarian cancer.

Prognostic impact of the high-sensitivity modified glasgow prognostic score on patients undergoing radical surgery for hepatocellular carcinoma : Authorship.

Our study aimed to assess the ability of high-sensitivity modified Glasgow prognostic Score (HS-mGPS) predicting survival in patients undergoing radical surgery for hepatocellular carcinoma (HCC) and to compare the impact with other Inflammation-Based prognostic scoring systems including Glasgow prognostic Score (GPS) and modified GPS (mGPS). Our study evaluated 293 patients with HCC who had undergone hepatectomy at the Third Affiliated Hospital of Soochow University between 2010 and 2018. The HS-mGPS, mGPS, and GPS were calculated based on particular cut-off values of preoperative C-reactive protein and albumin, and the correlations between HS-mGPS and clinicopathological parameters were evaluated. Univariate and multivariate survival analyses were conducted by Kaplan-Meier method and Cox proportional hazards model. To evaluate the discrimination ability of each prognostic score, the receiver operating characteristic (ROC) curve were generated and the areas under the curve (AUC) were measured and compared. The study results indicated a correlation between elevated HS-mGPS scores and adverse clinical factors, including higher BCLC stage, C-P grade, multiple tumors, and larger tumor diameter. Kaplan-Meier and univariate survival analyses revealed that higher scores of HS-mGPS, GPS, and mGPS were all associated with significantly reduced overall survival (OS) (all p < 0.001). In multivariate survival analysis, HS-mGPS emerged as an independent risk factor for poor OS in patients undergoing hepatectomy for HCC (p = 0.010), along with factors including maximal tumor diameter (p < 0.001), microvascular invasion (MVI) (p = 0.008), and BCLC stage (p = 0.001). The analysis of ROC curves and the AUC values indicated that HS-mGPS outperforms GPS and mGPS in predicting the long-term prognosis of patients with resectable HCC. Preoperative HS-mGPS proves superior in predicting adverse long-term outcomes in HCC patients undergoing radical surgery.

Improving Wound Healing and Infection Control in Long-term Care with Bacterial Fluorescence Imaging.

High bacterial burden stalls wound healing and can quickly progress to infection and sepsis in complex, older-adult patients in long-term care (LTC) or skilled nursing facilities (SNFs). To investigate the outcomes of point-of-care fluorescence (FL) imaging (MolecuLight i:X) of bacterial loads, which are frequently asymptomatic, to inform customized wound treatment plans for patients in LTC/SNFs. In this retrospective pre/postinterventional cohort study, the authors compared the healing and infection-associated outcomes of 167 pressure injuries from 100 Medicare beneficiaries before and after implementation of FL imaging. Most patient demographics and wound characteristics did not differ significantly between the standard-of-care (SOC; n = 71 wounds) and FL (n = 96 wounds) cohorts. Significantly more wounds (+71.0%) healed by 12 weeks in the FL cohort (38.5%) versus the SoC cohort (22.5%). Wounds in the FL cohort also healed 27.7% faster (-4.8 weeks), on average, and were 1.4 times more likely to heal per Kaplan-Meier survival analysis (hazard ratio = 1.40; 95% CI, 0.90-2.12). Infection-related complications decreased by 75.3% in the FL cohort, and a significant shift from largely systemic to topical antibiotic prescribing was evidenced. Fluorescence-imaging-guided management of wounds significantly improved healing and infection outcomes in highly complex and multimorbid patients in LTC/SNFs. Proactive bacterial infection management via local treatments was enabled by earlier, objective detection. These reported outcome improvements are comparable to randomized controlled trials and cohort studies from less compromised, selectively controlled outpatient populations. Fluorescence imaging supports proactive monitoring and management of planktonic and biofilm-encased bacteria, improving patient care in a complex, real-world setting.

Age at natural menopause and associated factors with early and late menopause among Chinese women in Zhejiang province: A cross-sectional study.

Menopause is a significant life transition for women, impacting their physical and psychological health. The age at natural menopause (ANM) and its associated factors have differed by race and region. This study aimed to investigate ANM and associated factors of early and late menopause among Chinese women in Zhejiang province. A cross-sectional study was conducted using a multi-stage stratified cluster sampling method to recruit 8,006 women aged 40-69 years who had resided in Zhejiang province for over 6 months between July 2019 and December 2021. Self-reported ANM and sociodemographics, lifestyle behaviors, reproductive history, and health-related factors were collected using questionnaires in face-to-face surveys. ANM were categorized into three groups: early menopause (<45 years), normal menopause (45-54 years), and late menopause (≥55 years). Kaplan-Meier survival analysis was utilized to calculate the median ANM. Multivariable multinomial logistic regression was employed to explore the associated factors of early menopause and late menopause. A total of 6,047 women aged 40-69 years were included for survival analysis, with 3,176 of them for the regression analysis. The overall median ANM was 51 years (Inter-quartile range [IQR]: 51-52). Women who were smokers (odds ratio [OR]:4.54, 95% confidence interval [CI]:1.6-12.84), had irregular menstrual cycles (OR:1.78, 95% CI:1.12-2.83) and hypertension (OR:1.55, 95% CI:1.09-2.21) had a higher odds ratio of early menopause, while central obesity (OR:1.33, 95% CI:1.03-1.73) and hyperlipidemia (OR:1.51, 95% CI:1.04-2.18) were factors associated with late menopause. This study revealed the associations between ANM and various factors among Chinese women. These factors included socio-demographic factors such as age; life behavior factors like current or prior smoking status; reproductive history factors such as irregular menstrual cycles, miscarriages, and breastfeeding; and health-related factors like central adiposity, hypertension, and hyperlipidemia. These findings provided a basis for understanding factors associated with ANM.

A novel treatment approach using vitamin B12-conjugated sericin for mitigating nanodiamond-induced toxicity in darkling beetles.

The escalating use of nanodiamonds (NDs) has raised concerns about their ecotoxicological impact, prompting exploration of therapeutic interventions. This paper pioneers the examination of Vitamin B12-conjugated sericin (VB12-SER) as a potential therapeutic approach against ND-induced toxicity in darkling beetles (Blaps polychresta). The study analyzes mortality rates and organ-specific effects, covering the testis, ovary, and midgut, before and after treatments. Following exposure to 10 mg NDs/g body weight, within a subgroup of individuals termed ND2 with a mortality rate below 50%, two therapeutic treatments were administered, including pure sericin (SER) at 10 mg/mL and VB12-SER at 10.12 mg/mL. Consequently, five experimental groups (control, SER, ND2, ND2+SER, ND2+SER+VB12) were considered. Kaplan-Meier survival analysis was performed to assess the lifespan distribution of the insects in these groups over a 30-d period. Analyses revealed increased mortality and significant abnormalities induced by NDs within the examined organs, including cell death, DNA damage, enzyme dysregulation, antioxidant imbalances, protein depletion, lipid peroxidation, and morphological deformities. In contrast, the proposed treatments, especially (ND2+SER+VB12), demonstrated remarkable recovery, highlighting VB12-conjugated SER's potential in mitigating ND-triggered adverse effects. Molecular docking simulations affirmed binding stability and favorable interactions of the VB12-SER complex with target proteins. This research enhances understanding of NDs' effects on B. polychresta, proposing it as an effective bioindicator, and introduces VB12-conjugated SER as a promising therapeutic strategy in nanotoxicological studies.

Analysis of cardiac arrest after coronary artery bypass grafting

BackgroundCardiac arrest after coronary artery bypass grafting (CABG) is a serious complication with low survival rate. The prognosis of patients with cardiac arrest in the general ward is worse than that in the intensive care unit (ICU) because of the delayed and poor rescue conditions.MethodsThis retrospective study included patients who experienced cardiac arrest after CABG surgery between January 2010 and December 2019 at the Fuwai Hospital. Differences in cardiac arrest between the ICU and the general ward were compared. The patients were divided into shockable and non-shockable rhythm groups, and the differences between the two groups were compared. Finally, we proposed a management protocol for cardiac arrest in the general ward.ResultsWe retrospectively analyzed 41,450 patients who underwent CABG only, of whom 231 (0.56%) experienced cardiac arrest post-surgery in the ICU (185/231) or in the general ward (46/231). The rescue success rate and 30-day survival rate of the patients with cardiac arrest in the general ward were 76.1% (35/46) and 58.7% (27/46), respectively. The incidence of the different arrhythmia types of cardiac arrest in the general ward compared with that in the ICU was different (P = 0.010). The 30-day survival rate of the non-shockable rhythm group was 31.8% (7/22), which was worse than that of the shockable rhythm group (83.3% [20/24]; P = 0.001). Kaplan–Meier survival analysis showed that the prognosis of the non-shockable group was poor (P < 0.001).ConclusionsThe incidence of cardiac arrest after CABG was low. The prognosis of patients in the general ward was worse than that of those in the ICU. The proportion of non-shockable rhythm type cardiac arrest was higher in the general ward than in the ICU, and patients in this group had a worse early prognosis.

Transforming growth factor-β1 and vascular endothelial growth factor levels in senile acute myeloid leukemia and correlation with prognosis.

Acute myeloid leukemia (AML) is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand, inhibiting hematopoiesis. The treatment and prognosis of this disease have always been unsatisfactory. To investigate the correlation between vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGFβ1) expression and prognosis in older adults with AML. This study enrolled 80 patients with AML (AML group), including 36 with complete response (AML-CR), 23 with partial response (AML-PR), and 21 with no response (AML-NR). The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls. Kaplan-Meier analysis was performed to assess overall survival (OS) and progression- or disease-free survival (DFS). Prognostic risk factors were analyzed using a Cox proportional hazards model. The AML group showed a VEGF level of 2.68 ± 0.16. VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR (P < 0.05). TGFβ1 expression in the AML group was 0.33 ± 0.05. Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR (P < 0.05). VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes, platelets, hemoglobin, and peripheral blood immature cells (P < 0.05); Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression (P < 0.05), whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels (P < 0.05). VEGF, TGFβ1, and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS (P < 0.05), while VEGF, TGFβ1, and white blood cell count were independent risk factors for DFS (P < 0.05). Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.

Risk Factors for Disease Progression in Glaucoma Patients with Disc Hemorrhage.

Glaucoma eyes with recurrent disc hemorrhage were associated with increased systolic blood pressure and diastolic blood pressure, and increased visit-to-visit diastolic blood pressure variability was associated with glaucoma progression. In this study, we investigated the effects of the clinical characteristics of disc hemorrhage (DH) and hemodynamic factors on glaucoma progression. This retrospective cohort study included 81 eyes with open angle glaucoma and non-recurrent or recurrent DH. Recurrent DH was further classified according to the DH location. Visual field (VF) progression was determined using event-based analysis and Guided Progression Analysis software. The coefficient of variation (CV) of systolic and diastolic blood pressure (SBP and DBP, respectively) was used to measure visit-to-visit variability. Kaplan-Meier survival analysis was used to compare the cumulative risk ratio of progression between groups. The recurrent DH group had significantly higher SBP and DBP (P=0.014 and=0.021, respectively) and a higher proportion of VF progression (P=0.019) than the non-recurrent DH group. In particular, females with recurrent DH had the highest cumulative probability of VF progression (P=0.047, log-rank test). Recurrent DH in a different quadrant was associated with the highest cumulative probability of VF progression than non-recurrent DH (P=0.038, log-rank test). In Cox regression analysis, higher visit-to-visit DBP variability, female sex, and recurrent DH in a different quadrant were significantly associated with glaucoma progression. In glaucomatous eyes with DH, increased visit-to-visit DBP variability was associated with glaucoma progression. Our results suggest that hemodynamic factors are involved in the recurrence of DH and progression of glaucoma.

Histologic Activity From Neoterminal Ileal Biopsies in Patients With Crohn's Disease in Endoscopic Remission is Associated With Postoperative Recurrence.

Following ileocolic resection (ICR), the clinical importance and prognostic implications of histologic activity on biopsies in Crohn's disease (CD) patients with endoscopic remission are not well defined. The aim of this study was to determine if histologic activity in patients with endoscopic remission is associated with future risk of endoscopic and/or radiologic postoperative recurrence (POR). In this multicenter retrospective cohort study, adult patients with CD who underwent ICR between 2009 and 2020 with endoscopic biopsies of ileal mucosa from Rutgeerts i0 on index colonoscopy were included. The composite rate of endoscopic (Rutgeerts score ≥i2b) and radiologic (active inflammation on imaging) recurrence was compared in patients with and without histologic activity using a Kaplan-Meier survival analysis. A multivariable Cox proportional hazard regression model including clinically relevant risk factors of POR, postoperative biologic prophylaxis, and histology activity was designed. A total of 113 patients with i0 disease on index colonoscopy after ICR were included. Of these, 42% had histologic activity. Time to POR was significantly earlier in the histologically active versus normal group ( P = 0.04). After adjusting for clinical risk factors of POR, histologic activity (HR 2.37, 95% CI 1.17-4.79; P = 0.02) and active smoking (HR 2.54, 95% CI 1.02-6.33; P = 0.05) were independently associated with subsequent composite POR risk. In patients with postoperative CD, histologic activity despite complete endoscopic remission is associated with composite, endoscopic, and radiographic recurrence. Further understanding of the role of histologic activity in patients with Rutgeerts i0 disease may provide a novel target to reduce disease recurrence in this population.

Development of a Cancer-associated Fibroblast Signature for Evaluating Immunotherapy Response and Prognosis of Hepatocellular Carcinoma.

Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), and hepatitis B and C are the main pathogenic factors of hepatocellular carcinoma (HCC). Though the current understanding of risk factors for HCC has been improved, patients with this type of cancer are normally diagnosed at advanced stages, posing significant challenges to effective treatment. This study analyzed the HCC datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database (GSE14520 and GSE116174). Stromal and immune cell infiltration in the tumor microenvironment (TME) was quantified by the ESTIMATE algorithm. To identify gene modules associated with cancer-associated fibroblasts (CAFs), weighted gene co-expression network analysis (WGCNA) was performed to develop gene co-expression networks. A CAF prognosis score (CAFPS) model was established based on the prognostic CAF genes screened by univariate and multivariate Cox regression analyses. To determine the role of the genes in the vital module in HCC, we conducted Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, the relationship between CAFPS and drug sensitivity was analyzed using Genomic Data for Cancer Drug Sensitivity (GDSC). In this study, we found significant differences in immune scores, stromal scores, CAFs scores, and CD4/8 T-cell scores between normal samples and samples with different TNM staging. In particular, the proportion of CAFs was higher than all other cells in normal samples. Gene modules related to CAFs were identified by developing a gene co-expression network using WGCNA analysis. The lightyellow and greenyellow modules showed the highest correlation with CAF scores. Univariate COX analysis identified 12 genes related to HCC prognosis from a total of 191 genes in the two modules. The Kaplan-Meier (KM) survival analysis revealed that a high expression of these genes was associated with a lower survival chance. Based on the 12 genes obtained by univariate COX analysis, multivariate COX analysis was performed to construct a risk score model for the characteristics of CAFs (CAFPS). The KM survival curves of patients in the high CAFPS and low CAFPS groups showed that patients in the low CAFPS group had better survival. CAFs played a crucial role in the pathogenesis and treatment response of HCC. Targeting the CAFs milieu may provide therapeutic benefits, highlighting the importance of CAFS in developing a personalized treatment for HCC patients. Further studies are required to verify the current findings and explore their implications in clinical settings.

Plasma Deoxycholic Acid Levels are Associated with Hemodynamic and Clinical Outcomes in Acute Pulmonary Embolism Patients.

This study aimed to evaluate the correlation of plasma deoxycholic acid (DCA) levels with clinical and hemodynamic parameters in acute pulmonary embolism (APE) patients. Total 149 APE adult patients were prospectively recruited. Plasma DCA levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to plasma DCA levels. The plasma DCA levels were significantly lower in APE patients than in those without APE (P < 0.001). APE patients with adverse events had lower plasma DCA levels (P < 0.001). Low DCA group patients presented more adverse cardiac function, higher NT-proBNP levels (P = 0.010), and higher WHO functional class levels (P = 0.023). Low DCA group also presented with an adverse hemodynamic status, with higher pulmonary vascular resistance levels (P = 0.027) and lower cardiac index levels (P = 0.024). Both cardiac function and hemodynamic parameters correlated well with plasma DCA levels. Kaplan-Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had a significantly higher event rate (P = 0.009). In the univariate and multivariate Cox regression analyses, the plasma DCA level was an independent predictor of clinical worsening events after adjusting for age, sex, WHO functional class, NT-proBNP level, pulmonary vascular resistance, and cardiac index (HR 0.370, 95% CI 0.161, 0.852; P = 0.019). Low plasma DCA levels predicted adverse cardiac function and hemodynamic collapse. A low DCA level was correlated with a higher clinical worsening event rate and could be an independent predictor of clinical outcomes in multivariate analysis.

Stanniocalcin-2 expression in glioblastoma - A novel prognostic biomarker: An observational study.

The objective of this study was to assess the prognostic relevance of Stanniocalcin-2 (STC2) expression, as determined via immunohistochemistry in tumor tissue, in a cohort of 83 patients diagnosed with glioblastoma who underwent maximal safe surgical resection followed by radiotherapy concurrent with adjuvant temozolomide. STC2 expression levels were categorized using a 3-tiered semiquantitative system: negative expression (level 0-), low expression (level 1+), and high expression (levels 2 + and 3+). Patients were categorized into 2 distinct groups according to their STC2 expression levels: negative STC2 (-/+) and positive STC2 (++/+++). The primary outcome measure was the relationship between STC2 expression and progression-free survival (PFS), with overall survival (OS) serving as the secondary endpoint. Kaplan-Meier survival analysis confirmed that patients exhibiting high STC2 expression had significantly shorter OS (8 vs 20 months, P < .001) and PFS (6 vs 18 months, P < .001) than those with low or negative STC2 expression. Multivariate analysis revealed that STC2 expression was an independent prognostic factor for both OS (hazard ratio: 0.4; 95% confidence interval: 0.2-0.8; P < .05) and PFS (hazard ratio: 0.3; 95% confidence interval: 0.2-0.4; P < .05) in patients with glioblastoma. Furthermore, elevated STC2 expression in GBM was correlated with several established aggressive clinicopathological characteristics, including advanced age (≥65 years), low ECOG PS (≥2), and isocitrate dehydrogenase mutation negativity. These findings underscore that heightened STC2 expression within the tumor tissue of GBM patients functions as an adverse prognostic marker, correlating with an elevated risk of progression and reduced OS. Therapeutic interventions targeting the AKT-mTOR, ERK1-2, and mitogen-activated protein kinase pathways as well as immune checkpoint inhibitors and vascular endothelial growth factor blockade, as well as potential forthcoming antibody-drug conjugates targeting the STC2 molecule, have the potential to broaden the scope of combined treatment strategies.

Comparison of allergy prevalence using brinzolamide 1.0% / brimonidine 0.2% fixed combination with and without β-blocker in glaucoma patients: a retrospective cohort study

BackgroundGlaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent β-blocker.MethodsOf these, 176 patients used a β-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent β-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan–Meier survival analysis.ResultsAllergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent β-blocker-usage groups, respectively. Kaplan–Meier survival analysis indicated that half of the allergies in the concurrent β-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent β-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent β-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent β-blocker-usage group.ConclusionsConcurrent use of β-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of β-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.

The Association between Patient Characteristics and Biochemical Recurrence after Radical Prostatectomy.

Background: Biochemical recurrence (BCR) represents the rise of prostate-specific antigen (PSA) levels after treatment with curative radical prostatectomy (RP) or radiation for prostate cancer. The objective of the current study was to test for the association between patient characteristics, namely age, body mass index (BMI), as well as prostate volume at surgery, and BCR after RP. Material and Methods: Within a tertiary care database, patients with prostate cancer treated with RP between January 2014 and June 2023 were included. Kaplan-Meier survival analyses and Cox regression models addressed BCR after RP according to patient characteristics. Results: Of 821 patients, the median age was 66 years (interquartile range [IQR] 61-71 years), BMI was 26.2 kg/m2 (IQR 24.3-28.8 kg/m2), and prostate volume was 40 cm3 (IQR 30-55 cm3). Median follow-up was 20 months. In survival analyses, the three-year BCR-free survival rates were 81 vs. 84 vs. 81% in patients aged ≤60 vs. 61-69 vs. 70 years (p = 0.1). In patients with BMI < 25.0 vs. 25.0-29.9 vs. ≥30.0 kg/m2, the three-year BCR-free survival rates were 84 vs. 81 vs. 84% (p = 0.7). In patients with prostate volume ≤40 vs. >40 cm3, the three-year BCR-free survival rates were 85 vs. 80% (p = 0.004). In multivariable Cox regression models accounting for patient and pathologic tumor characteristics and adjuvant radiation therapy, a higher prostate volume independently predicted BCR as continuous (hazard ratio 1.012, 95% confidence interval 1.005-1.019; p < 0.001), as well as categorized the variable based on the median (hazard ratio 1.66, 95% confidence interval 1.17-2.36; p = 0.005). Conversely, neither age nor BMI were significantly associated with BCR after RP. Conclusions: The higher prostate volume independently predicted BCR after RP, but not age or BMI at surgery. Consequently, patients with an elevated prostate volume should be considered for closer postoperative follow-up.

Comprehensive bioinformatic profiling of matrix metalloproteinases and their inhibitors: Expression and interaction patterns in head and neck cancer toward predictive biomarkers and personalized therapies

ObjectiveMatrix metalloproteinases (MMPs) and Tissue inhibitors of metalloproteinases (TIMPs) are involved in the turnover of extracellular matrix (ECM) components. Overexpression of MMPs facilitates tumour progression by promoting ECM turnover, angiogenesis, and cell migration. Head and neck squamous cell carcinoma (HNSCC) exhibits significant upregulation of multiple MMPs and TIMPs, correlating with poor prognosis, using bioinformatics tools to analyse the expression profiles and prognostic significance of MMPs and TIMPs in HNSCC. Materials and methodsGEPIA and UALCAN databases were used to analyse the expression of MMPs and TIMPs in HNSCC tissues. Immunohistochemistry confirmed high protein levels of several MMPs in tumour samples. GeneMANIA, STRING, and Metascape analyses highlighted key functional relationships and pathways enriched in MMPs and TIMPs. Kaplan-Meier survival analyses were conducted to assess the prognostic significance of TIMPs in HNSCC. ResultsThe study found significant overexpression of MMP1, MMP2, MMP3, MMP9, and MMP14 in HNSCC tissues. Immunohistochemistry confirmed elevated protein levels of these MMPs in tumour samples. PPI network analyses indicated crucial interactions among MMPs and their regulatory pathways. TIMP1 was significantly upregulated in HNSCC, while TIMP3 downregulation correlated with increased MMP activity and tumour progression. According to Kaplan-Meier survival analyses, higher TIMP expression was associated with poor overall survival in HNSCC patients. ConclusionThis comprehensive study emphasises the dysregulation of MMPs and TIMPs in HNSCC, proposing them as potential biomarkers for early diagnosis and prognostic evaluation and suggesting them as therapeutic targets to improve clinical outcomes in HNSCC patients.

ZBTB7A regulates LncRNA HOTAIR-mediated ELAVL1/SOX17 axis to inhibit malignancy and angiogenesis in endometrial carcinoma

BackgroundEndometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified.MethodsThe research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression.ResultsThe study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/β-catenin pathway, promoting malignant behaviors in EC cells.ConclusionHOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/β-catenin pathway underlines its potential as a therapeutic target.

Gene signatures of copper metabolism related genes may predict prognosis and immunity status in Ewing's sarcoma.

Cuproptosis is copper-induced cell death. Copper metabolism related genes (CMRGs) were demonstrated that used to assess the prognosis out of tumors. In the study, CMRGs were tested for their effect on TME cell infiltration in Ewing's sarcoma (ES). The GEO and ICGC databases provided the mRNA expression profiles and clinical features for downloading. In the GSE17674 dataset, 22prognostic-related copper metabolism related genes (PR-CMRGs) was identified by using univariate regression analysis. Subsequently, in order to compare the survival rates of groups with high and low expression of these PR-CMRGs,Kaplan-Meier analysis was implemented. Additionally, correlations among them were examined. The study employed functional enrichment analysis to investigate probable underlying pathways, while GSVA was applied to evaluate enriched pathways in the ES (Expression Set). Through an unsupervised clustering algorithm, samples were classified into two clusters, revealing significant differences in survival rates and levels of immune infiltration. Using Lasso and step regression methods, five genes (TFRC, SORD, SLC11A2, FKBP4, and AANAT) were selected as risk signatures. According to the Kaplan-Meier survival analysis, the high-risk group had considerably lower survival rates than the low-risk group(p=6.013e-09). The area under the curve (AUC) values for the receiver operating characteristic (ROC) curve were 0.876, 0.883, and 0.979 for 1, 3, and 5 years, respectively. The risk model was further validated in additional datasets, namely GSE63155, GSE63156, and the ICGC datasets. To aid in outcome prediction, a nomogram was developed that incorporated risk levels and clinical features. This nomogram's performance was effectively validated through calibration curves.Additionally, the study evaluated the variations in immune infiltration across different risk groups, as well as high-expression and low-expression groups. Importantly, several drugs were identified that displayed sensitivity, offering potential therapeutic options for ES. The findings above strongly indicate that CMRGs play crucial roles in predicting prognosis and immune status in ES.

The inflammatory markers combined with CA125 may predict postoperative survival in endometrial cancer

Background Endometrial cancer (EC) has a high latency, making prognosis difficult to predict. Cancer antigen 125 (CA125) is not specific as a tumour marker for EC; however, complete blood count (CBC) inflammatory markers are associated with prognosis in various malignancies. Thus, this study investigated the value of CBC inflammatory markers combined with CA125 levels in predicting the prognosis of patients with EC. Methods In this study, 517 patients with EC were recruited between January 2015 and January 2022, and clinical characteristics, CBC inflammatory markers, and CA125 levels were assessed. Differences in each index at different EC stages and the correlation between the index and EC stage were analysed, and the influence of the index on EC prognosis was evaluated. Results Platelet distribution width (PDW) levels were significantly lower in patients with advanced EC than in those with early EC, whereas the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and CA125 levels were significantly higher in patients with advanced EC (all P < 0.05). ROC curve and multivariate logistic regression analyses indicated that decreased PDW and increased CA125 levels were independent risk factors for EC staging progression. In addition, multivariate Cox regression analysis showed that the combination of low PDW and high CA125 (PDW + CA125 = 2) was an independent prognostic factor of survival in EC patients. Kaplan-Meier survival analysis indicated that patients with low PDW and high CA125 had worse overall survival. Conclusions The PDW and CA125 score may be an independent prognostic factor for postoperative overall survival in patients with EC and a useful marker for predicting the prognosis of these patients.