Search Results (669)

Background: Octogenarians constitute the fastest-growing segment within contemporary cardiac surgery, yet precise risk assessment in this age group remains challenging. Aims: This study aimed to evaluate EuroSCORE II reliability in octogenarians undergoing isolated coronary surgery and to create an adjustment formula if necessary. Patients and Methods: All octogenarians who had isolated coronary surgery in Poland from January 2012 to December 2023, recorded in the Polish National Registry of Cardiac Surgical Procedures (KROK registry), were retrospectively assessed. EuroSCORE II’s reliability was measured using the ROC curve area and observed-to-predicted mortality ratio, differentiating on-pump and off-pump cases. A nomogram was developed to enhance predictive accuracy. Results: Among 5771 octogenarians, 2729 (47.3%) underwent on-pump and 3042 (52.7%) underwent off-pump surgery. EuroSCORE II demonstrated reliability in off-pump patients (AUC:0.72, O/E ratio:0.98) but underestimated mortality for on-pump cases (AUC:0.73, O/E ratio:1.62). The lowest predicted mortality group (0.50–1.82%) showed the greatest discrepancies. Calibration was improved by adding a coefficient and creating a nomogram. Conclusions: EuroSCORE II was dependable in predicting outcomes for Polish octogenarians undergoing isolated coronary surgery. Observed mortality following on-pump surgeries was higher than expected, which was corrected by adding a coefficient to the initial EuroSCORE II calculation. Full article

Background: Chloride Intracellular Channel 4 (CLIC4) plays a versatile role in cellular functions beyond its role in primary chloride ion transport. Notably, many studies found an association between CLIC4 expression and cancers. However, the correlation between CLIC4 and glioma remains to be uncovered. Methods: A total of 3162 samples from nine public datasets were analyzed to reveal the relationship between CLIC4 expression and glioma malignancy or prognosis. Immunohistochemistry (IHC) staining was performed to examine the results in an in-house cohort. A nomogram model was constructed to predict the prognosis. Functional enrichment analysis was employed to find CLIC4-associated differentially expressed genes in glioma. Immune infiltration analysis, correlation analysis, and IHC staining were employed, aiming to examine the correlation between CLIC4 expression, immune cell infiltration, and ECM (extracellular matrix)-related genes. Results: The expression level of CLIC4 was correlated with the malignancy of glioma and the prognosis of patients. More aggressive gliomas and mesenchymal GBM are associated with a high expression of CLIC4. Gliomas with IDH mutation or 1p19q codeletion express a low level of CLIC4, and a high expression of CLIC4 correlates with poor prognosis. The nomogram model shows a good predictive performance. The DEGs (differentially expressed genes) in gliomas with high and low CLIC4 expression are enriched in extracellular matrix and immune functions. On the one hand, gliomas with high CLIC4 expression have a greater presence of macrophages, neutrophils, and eosinophils; on the other hand, a high CLIC4 expression in gliomas is positively associated with ECM-related genes. Conclusions: Compared to glioma cells with low CLIC4 expression, gliomas with high CLIC4 expression exhibit greater malignancy and poorer prognosis. Our findings indicate that a high level of CLIC4 correlates with high expression of ECM-related genes and the infiltration of macrophages, neutrophils, and eosinophils within glioma tissues. Full article

This research studies the potential of frozen low lunar orbits to be used in the design of constellations for global and regional communication or navigation. We introduce a robust two-stage approach to the frozen low lunar orbit design based on the successive application of non-gradient techniques, the Bayesian optimization and the Nelder–Mead method. The developed methodology has a number of advantages over existing numerical design techniques and allows revealing orbits with the periodic behavior of the eccentricity vector over long propagation intervals in the full dynamical model. By leveraging a convenient nomogram with constellation visibility parameters and lower bound coverage curves, we have identified most suitable low-altitude orbital configurations of Walker type and then adjust them to be frozen. The frozenness condition can be achieved without changing the orientation of orbital planes. Visibility and coverage metrics (multiplicity of continuous coverage for specified sites, polar regions, or the whole lunar surface; position dilution of precision) of candidate constellations are analyzed. Several promising designs of frozen constellations in near-circular low lunar orbits are singled out. The frozen orbit stability and the station-keeping cost are discussed. Full article

Background: Head and neck carcinosarcoma (HNCS) is a rare and highly aggressive malignancy with limited research, resulting in an incomplete understanding of disease progression and a lack of reliable prognostic tools. This study aimed to retrospectively analyze the clinical characteristics and outcomes of HNCS patients using data from the Surveillance, Epidemiology, and End Results (SEER) database and to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS). Methods: Patients diagnosed with HNCS from 1975 to 2020 were identified in the SEER database. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic indicators, with the optimal model selected using the minimal Akaike Information Criterion (AIC). The identified prognostic factors were incorporated into nomograms to predict OS and CSS. Model performance was assessed using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis (DCA). Survival curves were generated using Kaplan–Meier analysis and compared via the log-rank test. Results: A total of 152 HNCS patients were included, with 108 assigned to the training cohort and 44 to the validation cohort in a 7:3 ratio. Prognostic factors including age, primary tumor site, marital status, radiotherapy, chemotherapy, tumor size, pathological grade, and tumor stage were incorporated into the nomogram models. The models demonstrated strong predictive performance, with C-index values for OS and CSS of 0.757 and 0.779 in the training group, and 0.777 and 0.776 in the validation group, respectively. AUC values for predicting 3-, 5-, and 10-year OS were 0.662, 0.713, and 0.761, and for CSS the values were 0.726, 0.703, and 0.693. Kaplan–Meier analysis indicated significantly improved survival for patients with lower risk scores. The 3-, 5-, and 10-year OS rates for the entire cohort were 54.1%, 45.6%, and 35.1%, respectively, and the CSS rates were 62.9%, 57.5%, and 52.2%, respectively. Conclusions: This study provides validated nomograms for predicting OS and CSS in HNCS patients, offering a reliable tool to support clinical decision-making for this challenging malignancy. These nomograms enhance the ability to predict patient prognosis and personalize treatment strategies. Full article

Colon adenocarcinoma (COAD) is a frequently occurring and lethal cancer. Cuproptosis is an emerging type of cell death, and the underlying pathways involved in this process in COAD remain poorly understood. Transcriptomic and clinical data for COAD patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We investigated alterations in DNA and chromatin of cuproptosis-related genes (CRGs) in COAD. In order to identify predictive differentially expressed genes (DEGs) and various molecular subtypes, we used consensus cluster analysis. Through univariate, multivariate, and Lasso Cox regression analyses, four CRGs were identified. A risk prognostic model for cuproptosis characteristics was constructed based on four CRGs. This study also examined the association between the risk score and the tumor microenvironment (TME), the immune landscape, and drug sensitivity. We distinguished two unique molecular subtypes using consensus clustering analysis. We discovered that the clinical characteristics, prognosis, and TME cell infiltration characteristics of patients with multilayer CRG subtypes were all connected. The internal and external evaluations of the predicted accuracy of the prognostic model built using data derived from a cuproptosis risk score were completed at the same time. A nomogram and a clinical pathological analysis make it more useful in the field of medicine. A significant rise in immunosuppressive cells was observed in the high cuproptosis risk score group, with a correlation identified between the cuproptosis risk score and immune cell infiltration. Despite generally poor prognoses, the patients with a high cuproptosis risk but low tumor mutation burden (TMB), cancer stem cell (CSC) index, or microsatellite instability (MSI) may still benefit from immunotherapy. Furthermore, the cuproptosis risk score positively correlated with immune checkpoint gene expression. Analyzing the potential sensitivity to medications could aid in the development of clinical chemotherapy regimens and decision-making. CRGs are the subject of our in-depth study, which exposed an array of regulatory mechanisms impacting TME. In addition, we performed additional data mining into clinical features, prognosis effectiveness, and possible treatment medications. COAD’s molecular pathways will be better understood, leading to more precise treatment options. Full article

In the frame of the I-MOVE-COVID-19 project, a cohort of 2050 patients admitted in two Spanish reference hospitals between March 2020 and December 2021 was selected and a range of clinical factor data were collected at admission to assess their impact on the risk COVID-19 severity outcomes through a multivariate adjusted analysis and nomograms. The need for ventilation and intensive care unit (ICU) admission were found to be directly associated with a higher death risk (OR 6.9 and 3.2, respectively). The clinical predictors of death were the need for ventilation and ICU, advanced age, neuromuscular disorders, thrombocytopenia, hypoalbuminemia, dementia, cancer, elevated creatin phosphokinase (CPK), and neutrophilia (OR between 1.8 and 3.5), whilst the presence of vomiting, sore throat, and cough diminished the risk of death (OR 0.5, 0.2, and 0.1, respectively). Admission to ICU was predicted by the need for ventilation, abdominal pain, and elevated lactate dehydrogenase (LDH) (OR 371.0, 3.6, and 2.2, respectively) as risk factors; otherwise, it was prevented by advanced age (OR 0.5). In turn, the need for ventilation was predicted by low oxygen saturation, elevated LDH and CPK, diabetes, neutrophilia, obesity, and elevated GGT (OR between 1.7 and 5.2), whilst it was prevented by hypertension (OR 0.5). These findings could enhance patient management and strategic interventions to combat COVID-19. Full article

Background/Objectives: The aim of the study was to determine the clinical value of the sentinel lymph node ratio (SLN-R) in predicting additional positive lymph nodes during axillary lymph node dissection (ALND) in breast cancer patients following neoadjuvant chemotherapy (NAC). Methods: A cross-sectional study was performed at a single institution evaluating data from 1521 BC patients. Inclusion criteria comprised cT1/cT4, cN0/cN1 status with positive post-NAC axillary staging by SLN/TAD, respectively, and subsequent ALND. Results: The study included 118 patients, divided into two groups based on the presence or absence of additional node metastasis at ALND: 39 in the residual disease group (RD) and 79 in the non-residual disease group (nRD). Univariate logistic regression analysis of SLN-R was conducted to assess its predictive value, yielding an odds ratio (OR) of 7.79 (CI 1.92–29.5, p = 0.003). An SLN-R cut-off point of <0.35 was identified using ROC curve analysis, with a false-negative rate of 10.2%, as a predictor for no additional metastasis at ALND following post-NAC SLN/TAD positivity. Conclusions: The study concludes that SLN-R is a valuable predictor for determining the omission of ALND in cases where SLN/TAD is positive after NAC. This metric, in combination with other clinical variables, could help develop a nomogram to spare patients from ALND. Full article

Background and Objectives: We sought to investigate whether the 2012 Briganti nomogram may represent a potential prognostic factor of prostate cancer (PCa) progression after surgical treatment beyond European Association of Urology (EAU) risk categories. Materials and Methods: From January 2013 to December 2021, data on PCa patients treated with robot-assisted radical prostatectomy at a single tertiary referral center were extracted. The 2012 version of the Briganti nomogram assessing the risk of pelvic lymph node invasion was used. Here, the nomogram score was evaluated both as a continuous and a categorical variable. The association between variables and disease progression after surgery was evaluated through Cox regression models. Results: Overall, 1047 patients were identified. According to the EAU classification system, 297 (28.4%) patients were low-risk, 527 (50.3%) intermediate-risk, and 223 (21.3%) high-risk. The median (interquartile range) 2012 Briganti nomogram score within the investigated population was 3% (2–8%). Median (95% Confidence Interval [CI]) follow-up was 95 (91.9–112.4) months. Disease progression occurred in 237 (22.6%) patients, who were more likely to have an increasing 2012 Briganti nomogram score (Hazard Ratio [HR]: 1.03; 95%CI: 1.01–1.81; p = 0.015), independently of unfavorable issues at clinical presentation. Moreover, the nomogram score stratified according to tertiles (<3% vs. 3–8% vs. ≥8%) hold significance beyond EAU risk categories: accordingly, the risk of disease progression increased as the score increased from the first (reference) to the second (HR: 1.50; 95%CI: 1.67–3.72; p < 0.001) up to the third (HR: 3.26; 95%CI: 2.26–4.72; p < 0.001) tertile. Conclusions: Beyond EAU risk categories, the 2012 Briganti nomogram represented an independent predictor of PCa progression after surgery. Likewise, as the nomogram score increased so patients were more likely to experience disease progression. Accordingly, it may allow further stratification of patients within each risk category to modulate appropriate treatment paradigms. Full article

Objective: This study aimed to investigate the prognostic value of preoperative myosteatosis and the albumin–bilirubin (ALBI) grade in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) and develop a robust prognostic score based on these factors. Methods: Patients with HCC who underwent TACE between January 2009 and December 2020 were included. Multivariate Cox regression analysis identified prognostic factors. CT-based body composition parameters were acquired from baseline abdominal CT images at the level of the third lumbar vertebra. A prognostic score (Myo-ALBI) was developed based on the presence of preoperative myosteatosis and the ALBI grade, and its prognostic value was evaluated. Results: Of 446 patients, 63% were male, and the mean age was 62.4 years. Preoperative myosteatosis was present in 41.5% of patients. The BCLC stages were mostly B (67.9%). Multivariate analysis shows that preoperative myosteatosis, ALBI grade 2, and ALBI grade 3 were independent prognostic factors. The Myo-ALBI grade was incorporated into a prognostic model, including alpha-fetoprotein and up-to-seven criteria, to generate a nomogram. The C-index of the nomogram based on the Myo-ALBI grade (0.743) was significantly higher than the non-Myo-ALBI nomogram (0.677), the up-to-seven criteria (0.653), the ALBI grade (0.616), and the Child–Pugh class (0.573) (all p < 0.05). The t-ROC curve for the nomogram was consistently superior to the other models throughout the observation period in all patients and the BCLC-B subgroup. Conclusions: The combination of preoperative CT-derived myosteatosis and ALBI grade enhances prognostication for patients with unresectable HCC undergoing TACE. The Myo-ALBI nomogram constructed in this study could support individualized prognosis prediction, assisting in treatment decision-making for HCC patients. Full article

Background: The physical abilities of older adults decline with age, making them more susceptible to micronutrient deficiency, which may affect their sleep quality. Objectives: This study aimed to construct a risk correlative model for sleep disorders in Chinese older adults based on blood micronutrient levels. Methods: In this matched case-control study, we recruited 124 participants with sleep disorders and 124 matched controls from the Tianjin Elderly Nutrition and Cognition cohort in China. Micronutrient levels in whole blood were measured using the dried blood spot technique. We compared the differences in micronutrient levels between the two groups and also constructed a receiver operating characteristic (ROC) model and nomogram for sleep disorders. Results: In comparison to the control group, the sleep disorders group showed lower levels of blood vitamin A, vitamin E (VE), folate, magnesium, copper, iron, and selenium (Se) in the univariate analysis (p < 0.05). The ROC curve analysis indicated that the combination of VE + folate + Se may have an excellent diagnostic effect on sleep disorders, with an area under the curve of 0.964. This VE + folate + Se was integrated into a nomogram model to demonstrate their relationship with sleep disorders. The consistency index of the model was 0.88, suggesting that the model assessed sleep disorders well. Conclusions: The sleep disorders risk correlative model constructed by the levels of VE, folate, and Se in whole blood might show good performance in assessing the risk of sleep disorders in older adults. Full article

A Prognostic Index for Liver Radiation (PILiR) for improved patient selection for stereotactic liver-directed radiotherapy (SBRT) was developed. Using a large single-center database, 195 patients treated with SBRT for local control, including 66 with hepatocellular carcinoma (HCC) and 129 with metastatic liver disease, were analyzed. Only patients ineligible for alternative treatments were included. Overall survival was 11.9 months and 9.4 months in the HCC group and metastatic groups, respectively. In the combined dataset, Child–Pugh Score (CPS) (p = 0.002), serum albumin (p = 0.039), and presence of extrahepatic disease (p = 0.012) were significant predictors of early death on multivariable analysis and were included in the PILiR (total score 0 to 5). Median survival was 23.8, 9.1, 4.5, and 2.6 months for patients with 0, 1–2, 3, and 4–5 points, respectively. In the HCC dataset, CPS (p < 0.001) and gross tumor volume (p = 0.013) were predictive of early death. In the metastatic dataset, serum albumin (p < 0.001) and primary disease site (p = 0.003) were predictive of early death. The AUC for the combined, HCC, and metastatic datasets are 0.78, 0.84, and 0.80, respectively. Poor liver function (defined by CPS and serum albumin) and extrahepatic disease were most predictive of early death, providing clinically important expected survival information for patients and caregivers. Full article

Hepatocellular carcinoma (HCC) is a formidable challenge to global human health, while recent years have witnessed the important role of NAD+ in tumorigenesis and progression. However, the expression pattern and prognostic value of NAD+ in HCC still remain elusive. Gene expression files and corresponding clinical pathological files associated with HCC were obtained from the Cancer Genome Atlas (TCGA) database, and genes associated with NAD+ were retrieved from the GSEA and differentially analyzed in tumor and normal tissues. A consensus clustering analysis was conducted by breaking down TCGA patients into four distinct groups, while Kaplan–Meier curves were generated to investigate the disparity in clinical pathology and endurance between clusters. A prognostic model based on NAD+-associated genes was established and assessed by combining LASSO-Cox regression, uni- and multi-variate Cox regression, and ROC curve analyses. Investigations were conducted to determine the expression of distinct mRNAs and proteins in both HCC and non-tumor tissues. A novel two-gene signature including poly (ADP-Ribose) polymerase 2 (PARP2) and sirtuin 6 (SIRT6) was obtained through LASSO-Cox regression and was identified to have favorable prognostic performance in HCC patients from TCGA. Analyses of both single and multiple variables showed that the prognostic model was a distinct prognostic factor in the endurance of liver cancer patients in both the training and trial groups. The nomogram also exhibited clinical significance in the prognosis of HCC patients. Immunohistochemistry, qRT-PCR, and Western blotting revealed that HCC samples exhibited higher PARP2 and SIRT6 expression levels than those of normal controls. This study identified a robust prognostic model comprising two NAD+-associated genes using bioinformatic methods, which is accurate in predicting the survival outcome of HCC patients. This model might benefit the early diagnosis of HCC and further facilitate the management of individualized medical service and clinical decision-making. Full article

Background: Androgen deprivation therapy (ADT) is the mainstay of treatment for prostate cancer, yet dynamic molecular changes from hormone-sensitive to castration-resistant states in patients treated with ADT remain unclear. Methods: In this study, we combined the dynamic network biomarker (DNB) method and the weighted gene co-expression network analysis (WGCNA) to identify key genes associated with the progression to a castration-resistant state in prostate cancer via the integration of single-cell and bulk RNA sequencing data. Based on the gene expression profiles of CRPC in the GEO dataset, the DNB method was used to clarify the condition of epithelial cells and find out the most significant transition signal DNB modules and genes included. Then, we calculated gene modules associated with the clinical phenotype stage based on the WGCNA. IHC was conducted to validate the expression of the key genes in CRPC and primary PCa patients Results:Nomograms, calibration plots, and ROC curves were applied to evaluate the good prognostic accuracy of the risk prediction model. Results: By combining single-cell RNA sequence data and bulk RNA sequence data, we identified a set of DNBs, whose roles involved in androgen-associated activities indicated the signals of a prostate cancer cell transition from an androgen-dependent state to a castration-resistant state. In addition, a risk prediction model including the risk score of four key genes (SCD, NARS2, ALDH1A1, and NFXL1) and other clinical–pathological characteristics was constructed and verified to be able to reasonably predict the prognosis of patients receiving ADT. Conclusions: In summary, four key genes from DNBs were identified as potential diagnostic markers for patients treated with ADT and a risk score-based nomogram will facilitate precise prognosis prediction and individualized therapeutic interventions of CRPC. Full article

As a novel discovered mechanism of cell death, cuproptosis is copper-dependent and induces protein toxicity related to advanced tumors, disease prognosis, and human innate and adaptive immune response. However, it has not yet been fully established how the prognosis of lung adenocarcinoma (LUAD) is related to the immune microenvironment of cuproptosis-related lncRNAs using several bioinformatic techniques. In the study, 19 genes related to cuproptosis were collected. Subsequently, 783 lncRNAs related to the co-expression of cuproptosis were obtained. Moreover, the Cox model revealed and constructed four lncRNA (AC012020.1, AC114763.1, AL161431.1, AC010260.1) prognostic markers related to cuproptosis. Based on the median risk score (RS) values, patients were categorized into two groups: high risk and low risk. The Kaplan–Meier (KM) survival curve depicted a statistically significant overall survival (OS) rate among two groups. Principal component analysis (PCA) and receiver operator characteristic curve (ROC) proved that the model had promising ability in prognosis. The analysis of univariate and multivariate Cox regression revealed that RS served as an independent prognostic factor. Moreover, multivariate Cox regression was employed for the establishment of a nomogram of prognostic indicators. The tumor mutational burden (TMB) depicted a considerable difference between the two risk groups. The immunotherapy response of LUAD patients with high risk was improved compared to low risk patients. The study also revealed that drug sensitivity associated with LUAD was significantly linked to RS. The findings could be helpful to establish a good diagnosis, prognosis, and management regime for patients with LUAD. Full article

Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan–Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37–126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5–126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14–5.75; HR 2.94, 95% CI 1.42–6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms. Full article