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PubMed1994

C-erbB-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk.

The prognostic value of c-erbB-2 protein overexpression has been evaluated in 463 patients with operable breast cancer after a median follow-up of 66 months. Overexpression was observed in 99/463 (21%) of the breast tumors. It showed significant positive correlation to histological grade (p < 0.0001) and tumor size (p < 0.02). A relationship of borderline significance was observed between c-erbB-2 protein overexpression and negative or low estrogen receptor (ER) content. No significant correlation was found to lymph node involvement or proliferating tumor cell fraction as determined by the proliferating cell nuclear antigen (PCNA). After a median follow-up of 66 months (range 6 to 109 months), the overall survival of all patients amounted to 63%. Multivariate analysis revealed lymph node involvement, tumor size, histological grade, histological type, c-erbB-2 protein overexpression, progesterone receptor (PR) content, and oral contraceptive use as independent prognostic factors. In an univariate analysis, the overall survival amounted to 72% and 38% of tumor patients with negative and positive c-erbB-2 protein overexpression, respectively. The most significant finding is that c-erbB-2 overexpression has been recognized as an independent predictive factor in subsets of tumor patients who would be expected to have a generally poor prognosis, such as those indicating axillary lymph node involvement, large tumor size (> 2 cm), and PR negativity.

Adult↗
PubMed1998

Bacterial pneumonia in HIV-infected patients: analysis of risk factors and prognostic indicators.

This case control study assessed risk factors and prognostic indicators of 350 episodes of bacterial pneumonia in 285 HIV-infected patients. On univariate analysis, intravenous drug abuse (i.v.DA; p < .001 versus controls), regular cigarette smoking (p < .001), cirrhosis (p = .04), and history of a previous episode of pneumonia (p = .04) were risk factors for community-acquired episodes of bacterial pneumonia, whereas length of hospitalization (p = .01) was a risk factor only for nosocomial bacterial pneumonia. The small amount of circulating T CD4+ cells (<100/ mm3) was a risk factor in both groups of pneumonia (p < .05). Stepwise logistic regression analysis revealed that i.v.DA in community-acquired episodes and low levels of circulating T CD4+ cells, both in community-acquired and hospital-acquired episodes, were independent risk factors for the development of bacterial pneumonia. The case-fatality rate observed in our study was 27%. On stepwise logistic regression analysis, T CD4+ cell counts < or = 100/mm3 (p = .02), neutropenia (p = .04), PO2 arterial level < or = 70 mm Hg (p = .01), and Karnofsky score < or = 50 (p = .04) were independent indicators of mortality. According to a personally developed prognostic score, 211 episodes of pneumonia (60%) were classified as mild, 63 (18%) as moderate, and 76 (22%) as severe. Clinicians must carefully evaluate those variables that can influence the prognosis of bacterial pneumonia to make early identification of affected patients and to promptly establish the most appropriate therapeutic strategy in each case.

AIDS-Related Opportunistic Infections↗
PubMed1998

Survival with bone marrow transplantation versus hydroxyurea or interferon for chronic myelogenous leukemia. The German CML Study Group.

Hydroxyurea, interferon, and HLA-identical sibling bone marrow transplantation are common therapies for chronic myelogenous leukemia (CML) in chronic phase. Which is best is controversial. The purpose of this study was to compare survival of patients with CML receiving HLA-identical sibling transplants versus hydroxyurea or interferon. The transplant cohort included 548 recipients of HLA-identical sibling transplants, reported to the International Bone Marrow Transplant Registry. The nontransplant cohort included 196 patients receiving hydroxyurea (n = 121) or interferon (n = 75) on a randomized trial of the German CML Study Group. Survivals were compared using proportional hazards regression with fixed and time-dependent variables to adjust for patient differences and changing risks over time. For the first 18 months after diagnosis, mortality was higher in the transplant than the nontransplant cohort (relative risk [RR], 5.85; P < .0001). From 18 to 56 months, mortality was similar (RR, 0.80; P = .38). After 56 months, mortality was lower in the transplant cohort (RR, 0.16; P < .0001). Seven-year survival probabilities (95% confidence interval) were 58% (50% to 66%) with transplant and 32% (22% to 41%) with hydroxyurea or interferon. There was a significant survival advantage for hydroxyurea or interferon in the first 4 years after diagnosis and for transplants starting 5.5 years after diagnosis. For transplants done within 1 year of diagnosis, the survival advantage for transplantation began earlier. Survival advantage for transplants was greater and occurred earlier in patients with intermediate- and high-risk prognostic features than in those with low-risk features. This study confirms higher early mortality, but a long-term survival advantage for HLA-identical sibling transplants over hydroxyurea or interferon in CML.

Adolescent↗
PubMed1990

Cellular DNA content and prognosis of high-grade soft tissue sarcoma: the Scandinavian Sarcoma Group experience.

The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.

Adolescent↗
PubMed1992

[An analysis on prognostic significance of histopathologic risk factor in uterine endometrial carcinoma].

Prognostic risk factors in histopathologic findings were analyzed in the data for one hundred and thirteen patients with uterine endometrial carcinoma who were treated surgically. Univariate survival analysis with Kaplan-Meier methods revealed that the nuclear grade (p less than 0.005), lymph-vascular space invasion (p less than 0.005), histologic grade (p less than 0.01) and histologic type (p less than 0.01) correlated with the patient's prognosis. Among surgical FIGO stages II and III, there was similar significance in the correlations in the nuclear grade (p less than 0.05), lymph-vascular space invasion (p less than 0.0001) and histologic type (p less than 0.05), although there was difference (p less than 0.05) only between grade 1 and grade 3 in the histologic grade. Multivariate survival analysis with a proportional hazard regression model showed that the nuclear grade (p less than 0.005) and lymph-vascular space invasion (p less than 0.01) correlated significantly with the prognosis. The hazard ratios with a 95% confidence interval for each of these factors were 19.2 (3.2-115.7) and 16.9 (2.1-135.3), respectively. The 3-year survival rate was 98% for a hazard ratio less than 64.7, and 45% for one more than 67.4, between which there was a significant difference (p less than 0.0001). And univariate survival analysis of this hazard ratio also revealed strong correlations with the patient's prognosis. These results suggest that it is of great importance to adopt the hazard model including such factors as the nuclear grade and lymph-vascular space invasion in estimating the patient's prognosis and proceeding to adequate post-operative therapy for individual patient.

Adenocarcinoma↗
PubMed2001

Independent contribution of myocardial perfusion defects to exercise capacity and heart rate recovery for prediction of all-cause mortality in patients with known or suspected coronary heart disease.

OBJECTIVES: The goal of this study was to determine the value of thallium201 single photon emission computed tomography (SPECT) imaging for prediction of all-cause mortality when considered along with functional capacity and heart rate recovery. BACKGROUND: Myocardial perfusion defects identified by thallium201 SPECT imaging are predictive of cardiac events. Functional capacity and heart rate recovery are exercise measures that also have prognostic implications. METHODS: We followed 7,163 consecutive adults referred for symptom-limited exercise thallium SPECT (mean age 60 +/- 10, 25% women) for 6.7 years. Using information theory, we identified a probable best model relating nuclear findings to outcome to calculate a prognostic nuclear score. RESULTS: There were 855 deaths. Intermediate- and high-risk prognostic nuclear scores were noted in 28% and 10% of patients. Compared with those with low-risk scans, patients with an intermediate-risk score were at increased risk for death (14% vs. 9%, hazard ratio: 1.67, 95% confidence interval [CI]: 1.44 to 1.95, p < 0.0001), while those with high-risk scores were at greater risk (24%, hazard ratio: 2.98, 95% CI: 2.49 to 3.56, p < 0.0001). In multivariable analyses that adjusted for clinical characteristics, functional capacity and heart rate recovery, an intermediate-risk nuclear score remained predictive of death (adjusted hazard ratio: 1.50, 95% CI: 1.28 to 1.76, p < 0.0001), as did a high-risk score (adjusted hazard ratio: 2.76, 95% CI: 2.13 to 2.56, p < 0.0001). Impaired functional capacity and decreased heart rate recovery provided additional prognostic information. CONCLUSIONS: Myocardial perfusion defects detected by thallium SPECT imaging are independently predictive of long-term all-cause death, even after accounting for exercise capacity, heart rate recovery and other potential confounders.

Activities of Daily Living↗
PubMed1997

Mortality in psychiatric hospital patients: a cohort analysis of prognostic factors.

BACKGROUND: This work followed a group of patients living in a psychiatric hospital in Central Italy in 1978 at the time of enforcement of the Italian reform law (No. 180) for closing down mental hospitals. The study had the following aims: a) to compare in terms of mortality patients discharged into the community with patients who did not experience deinstitutionalization; b) to determine the survival of the cohort of patients and to analyse prognostic risk factors for death; c) to analyse differences in mortality rates between psychiatric patients and the general population. METHODS: The study was designed as an historical follow-up investigation. Univariate (product limit) and multivariate (proportional hazards model) methods were used to estimate prognostic variables and related death risks. Mortality was assessed using standardized mortality ratios (SMR) on the entire cohort as well as after stratification according to age, sex, cause of death and discharge status, assuming the Abruzzo Region's population as standard. RESULTS: Length of hospitalization and discharge from hospital are prognostic variables for death risk, with relative risks respectively of 4.22 (95% confidence interval [CI]: 2.41-7.40) for a length of hospitalization of 10-25 years, and 8.13 (95% CI: 4.73-13.88) for non-discharge. The global SMR of the cohort was 2.68 (95% CI: 2.42-3.07). Non-discharged patients showed higher SMR than discharged. Excess mortality was found both in males and females for circulatory, respiratory and undefined diseases. A significantly lower mortality for cancer was observed in male patients. A strong excess mortality was observed in younger patients (20-29 years: SMRmales = 43.57; SMRfemales = 97.52). CONCLUSIONS: Longer periods of hospitalization and non-discharge from hospital are the main risk factors for death in psychiatric patients, who globally experience higher death rates than the general population for a wide spectrum of causes of death, whatever their diagnosis or gender. These findings strongly suggest positive actions in order to overcome the effects of institutionalization.

Adult↗
PubMed2000

Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups.

PURPOSE: We evaluated the prognostic factors of primary superficial bladder cancer that may predict a metachronous upper urinary tract tumor. We also determined whether the incidence of upper urinary tract disease varies according to risk group based on primary superficial bladder tumor classification. MATERIALS AND METHODS: We studied disease evolution in a cohort of 1,529 patients with a primary superficial bladder tumor. To determine the prognostic factors of upper urinary tract cancer we performed multivariate analysis using Cox regression. Independent variables were grade, T stage, multiplicity, tumor size, carcinoma in situ association, previous or synchronous upper urinary tract tumor and intravesical instillation. We also performed the chi-square test and Kaplan-Meier survival analysis to assess the variable incidence of upper urinary tract tumors according to primary superficial bladder tumor risk group classification. RESULTS: The incidence of upper urinary tract cancer was 2.6%. The only factor prognostic for an upper urinary tract tumor was multiplicity (relative risk 2.7, 95% confidence interval [CI] 1.06 to 6.84). All patients with an upper urinary tract tumor had a previously recurrent primary superficial bladder tumor. In the low, intermediate and high risk groups the incidence of upper urinary tract cancer was 0.6% (relative risk 1), 1.8% (relative risk 3.1, 95% CI 0.4 to 23.9) and 4.1% (relative risk 8.3, 95% CI 1.1 to 61.6), respectively (chi-square and log rank tests p = 0.007 and p <0.05, respectively). CONCLUSIONS: A higher risk of upper urinary tract cancer must be expected in cases of multiple primary superficial bladder tumors. This finding supports the multicentricity theory of transitional cell carcinoma. Primary superficial bladder tumor classification by risk group is also useful for predicting the various risks of metachronous upper urinary tract cancer.

Carcinoma, Transitional Cell↗
PubMed2002

Deletion of the Ink4-locus (the p16ink4a, p14ARF and p15ink4b genes) predicts relapse in children with ALL treated according to the Nordic protocols NOPHO-86 and NOPHO-92.

Inactivation of the Ink4 gene locus locus on 9p comprising the tumour suppressor gene p16ink4a and its neighbours p14ARF and p15ink4b is common in childhood acute lymphoblastic leukaemia (ALL), but the prognostic significance is controversial. DNA from 230 patients was retrospectively analysed by Southern blotting, single strand conformation polymorphism (SSCP) and sequencing techniques. The results were correlated with clinical characteristics and outcome. One hundred and ninety-four fully analysed patients, similarly treated using the Nordic NOPHO-86 or the current NOPHO-92 protocols, were included in the outcome analysis. Deletions approached a minimally deleted region between the p16ink4a and p15ink4b genes, making the p14ARF gene the most commonly deleted coding sequence. Bi-allelic deletion was associated with high white blood cell count (WBC) (P < 0.001), T cell phenotype (P < 0.001) and mediastinal mass (P < 0.001). Patients with Ink4 locus bi-allelic deletions had an inferior pEFS (P < 0.01) and multivariate analysis indicated that bi-allelic deletion of the p16ink4a and the p14ARF genes was an independent prognostic risk factor (P < 0.05). Sub-group analysis revealed a pronounced impact of deletion status for high-risk patients, ie with high WBC. Deletion-status and clinical risk criteria (WBC) could thus be combined to further differentiate risk within the high-risk group. The analysis of the Ink4 locus adds independent prognostic information in childhood ALL treated by Nordic protocols and may help in selection of patients for alternative treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Study of the autonomous nervous system with heart rate spectral analysis in acute myocardial infarction].

OBJECTIVES: Characterize power spectrum pattern of heart rate variability (HRV) and assessment of relative cardiac nervous system in patients with acute myocardial interaction of sympathetic and parasympathetic infarction. We also compared the spectral power with some known prognostic risk variables. STUDY DESIGN: Study of patients with acute myocardial infarction (AMI) and sedentary healthy subjects sex matched. SUBJECT AND METHODS: 19 postinfarction patients aged 55.7 +/- 10.5 years and 19 healthy subjects controls aged 53.9 +/- 11.0. ECG signals were recorded after 15 minutes of supine rest with controlled breathing at 15 cycles/min. Signal acquisition was done at 300 samples/sec. From 512 consecutive sinus beats, we calculated the average, standard deviation, maximum and minimum values and rate between the longest and shortest R-R interval (E/I). We also calculated, after computing the fast Fourier transform, the total spectrum power, low frequency component (LF, from 0.01 to 0.15 Hz), high frequency component (HF, from 0.15 to 0.50 Hz) and its ratio (LF/HF). Thereafter, we correlated these results with radionuclide ejection fraction, duration of treadmill test, Holter ventricular premature complex and localization of infarction. RESULTS: The average R-R interval was 757.9 +/- 116.3 and 850.9 +/- 133.9 msec (p less than 0.05), the R-R corrected standard deviation was 15.3 +/- 6.0 and 38.2 +/- 8.5 msec (p less than 0.001) and ratio E/I was 1.13 +/- 0.06 and 1.32 +/- 0.09 (p less than 0.001) in AMI and control group, respectively. In AMI group, low frequency spectral band was very decreased (LF = 0.03 +/- 0.02 sec2) and high frequency was virtually absent (HF = 0.01 +/- 0.01 sec2) compared with control group (LF = 0.13 +/- 0.06 and HF = 0.14 +/- 0.15 sec2), p less than 0.001; ratio LF/HF was increased in AMI group. There were no significant differences between groups for normalized LF (LF%) and HF (HF%). CONCLUSIONS: These results showed that spectral pattern in AMI patients had very low LF and HF power density. Decreased HRV in that group was mainly due to diminished parasympathetic influence in cardiac regulation; nevertheless ratio LF/HF was increased which represents an imbalance of sympatho-vagal activity with predominance of sympathetic tone. We found poor correlation between frequency domain indices and other risk variable; best correlation was between total spectral power and radionuclide ejection fraction (r = 0.642, p less than 0.01), which could express independent prognostic value in AMI patients risk stratification.

Autonomic Nervous System↗
PubMed2005

Infradiaphragmatic versus supradiaphragmatic Hodgkin lymphoma: a retrospective review of 1,114 patients.

Infradiaphragmatic Hodgkin lymphoma (IDH) accounts for 4-13% of cases of stage I-II Hodgkin lymphoma (HD). It has been associated with distinct pre-treatment characteristics and outcomes when compared with supradiaphragmatic HD (SDH). The comparison of IDH vs SDH can only be made in early and intermediate stages (I-II), such a comparison is not possible for advanced stages (III-IV). This study retrospectively compared two groups of 1013 patients with stage I-II SDH and 101 patients with IDH (10%). These two sub-groups of patients were treated in 1988-1993 in 2 prospective randomized clinical trials in Germany for early and intermediate stages of Hodgkin lymphoma. IDH-patients were older (median 39 vs 31 years; p < 0.001), predominantly male (73% vs 52%; p < 0.001) and more often had involvement of 3 lymph node areas (LNA) (80% vs 55%; p < 0.001). Histology in IDH was more likely to be mixed cellularity (46.5% vs 23.6%, p < 0.001) or lymphocyte predominant (20 vs 10%, p = 0.003) and less likely nodular sclerosis (25% vs 63%, p < 0.001). In early-stage unfavorable disease, IDH was associated with a higher treatment failure rate (unadjusted hazard ratio 2, 95% CI, 1.3-3.4; p = 0.003). After controlling for age, sex, stage, histology, B-symptoms and involvement of 3 LNA, the adjusted hazard ratio was 1.25 (95% CI, 0.65-2.4; p = 0.51) so that IDH was no longer associated with a statistically significant treatment failure rate. Poorer outcomes with IDH as compared to SDH are attributable to its association with known adverse prognostic risk factors, but IDH, in itself, is not an independent adverse prognostic factor for treatment failure or survival.

Adult↗
PubMed2002

Strong predictive value of TIMI risk score analysis for in-hospital and long-term survival of patients with right ventricular infarction.

BACKGROUND: While right ventricular myocardial infarction is associated with increased in-hospital morbidity and mortality, prognostic risk factors for in-hospital and long-term mortality are poorly defined. OBJECTIVES: To evaluate the prognostic value of TIMI (Thrombolysis in Myocardial Infarction) risk score analysis in patients with right ventricular myocardial infarction (RVI). DESIGN: Retrospective analysis of a community population. SETTING: Mayo Clinic Coronary Care Unit. PATIENTS: One hundred and two patients with RVI from 580 consecutive patients from Rochester, Minnesota admitted to the Coronary Care Unit with acute inferior or lateral wall myocardial infarction from January 1988 through March 1998. MEASUREMENT: Combined TIMI risk score analysis with in-hospital and long-term mortality. RESULTS: In-hospital morbidity (RVI: 54.9% vs non-RVI: 22.2%; P<0.001) and mortality (RVI: 21.6% vs non-RVI: 6.9%;P <0.001) were increased in patients with RVI. The TIMI risk score predicted risk (per one point increase in TIMI score) for in-hospital mortality (OR 1.23, 95% CI 1.02-1.51, P=0.037) and long-term mortality (OR 1.57, 95% CI 1.25-1.96, P<0.001). Patients with RVI whose TIMI risk score was >or=4 had significantly worse long-term survival compared to those patients with RVI and TIMI score <4 (P=0.006). CONCLUSIONS: In-hospital morbidity and mortality, and long-term mortality are increased by right ventricular infarction and can be accurately predicted by the initial TIMI risk score.

Aged↗
PubMed2000

Development and evaluation of models to predict death and myocardial infarction following coronary angioplasty and stenting.

Prior estimates of the risk death and myocardial infarction following percutaneous coronary intervention (PCI) may not be uniformly applicable due to recent significant changes in clinical practice. Accordingly, we studied 2,804 cases from January 1997 through February 1999, in order to develop risk models to predict death, and post-procedural myocardial infarction following PCI. Risk models were constructed using multivariate logistic regression, artificial neural networks and prognostic risk scoring systems. Composite logistic regression models and artificial neural networks performed similarly in predicting the risk of major acute complications (c-index for predicting death of 0.812 and 0.807, respectively). Risk scoring models, based on the composite logistic regression beta coefficients, performed only slightly worse (c-index death = 0.794). Risk score models appear to provide reasonable discrimination while offering the potential for simple clinical implementation in the estimation of the risk of death and myocardial infarction in interventional cardiology.

Angioplasty, Balloon, Coronary↗
PubMed1991

Prognostic indicators and risk factors for increased duration of acute diarrhoea and for persistent diarrhoea in children.

To identify the prognostic indicators and risk factors for increased duration of acute diarrhoea and for occurrence of persistent diarrhoea (i.e. acute episodes lasting longer than 14 days) in children under three years, a systematic sample (3690) of patients attending a large treatment centre in Bangladesh was analysed using multiple regression, logistic regression and stratified (Mantel-Haenszel) analysis. Significant prognostic indicators or risk factors for increase in duration of acute diarrhoea, after adjusting for confounders, include bloody or mucoid diarrhoea, concomitant signs of chest infection, presence of vitamin A deficiency signs, decreased weight for age, routine use of contaminated surface water, lack of breastfeeding and increasing age; presence of rotavirus or enterotoxigenic Escherichia coli or Vibrio cholerae 01 in stool had negative association. In logistic regression and stratified analysis these factors, except for lack of breastfeeding and age, were also found to be risk factors or prognostic indicators of persistent diarrhoea. Policy implications of these findings for programmes to reduce morbidity and mortality from persistent diarrhoea include development of effective vaccines against dysentery-causing Shigella, programmes to prevent vitamin A deficiency, protein energy malnutrition and acute respiratory infections in children, and long-term programmes to provide clean water for all day-to-day needs.

Acute Disease↗
PubMed1983

Partial blood oxygen pressure and pulmonary ventilation changes in patients with fractures with a view to traumatic fat embolism development.

The body's response to the effects of mechanical injury, taking the form of shock during the first hours and the onset of fat embolism in the subsequent period, is substantially higher in patients with multiple or associated injuries, both as regards the severity of manifestations and prognostic risk. Also the death rate due to this sort of complication is seen rising. Two groups of injured persons with isolated (n = 33) and multiple fractures (n = 33) were used to show that dynamic follow-up of PaO2 in the blood could serve as a criterion of the risk of fat embolism development in the body and, in particular, as a prognostic criterion for the progress of fat embolism. Special point was made of findings demonstrating a time relationship between PaO2 deterioration in the early post-injury period (up to 24-36 hours) as compared with the period of 48-72 hours after the injury. PaO2 is seen dropping rapidly in injured persons showing signs of fat embolism syndrome development. The decrease can be recorded as early as the free interval phase, i.e. prior to the manifestation of the clinical signs of fat embolism. The findings of low PaO2 levels in the blood are in accordance with respiratory ventilation disturbances and impaired diffusion documented in our investigation.

Adult↗
PubMed2026

Metabolism pathway-based subtyping in pancreatic adenocarcinoma: an integrated study by bulk RNA-sequence and machine learning algorithms.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is highly aggressive, and its tumor microenvironment has significant metabolic and immune microenvironment complexity and genomic instability. In this study, by integrating the metabolic pathway activity score and clinical data, we constructed a novel risk assessment model to reveal the unique biological behavior and clinical significance behind different PAAD subtypes. METHODS: In this study, the transcriptome and clinical data of TCGA and GSE57495 databases were integrated to explore the interaction between metabolic pathways. Based on unsupervised clustering analysis of pathway activity and survival prognosis, patients with PAAD were classified into metabolic subtypes with significant prognostic differences. Subsequently, we assessed the heterogeneity of these subtypes in terms of clinical outcomes, genomic characteristics, and immune microenvironment composition. Based on the differentially expressed genes (DEGs) among metabolic subtypes, a clinical prognostic risk model and nomogram were constructed, which were double-validated by GSE57495-independent cohort and GSE57495&#xa0;+&#xa0;TCGA-PAAD combined cohort. Finally, the correlations between risk scores (RSs) and signaling pathway activity and tumor immune microenvironment characteristics were evaluated. RESULTS: Based on metabolic pathway correlation and prognostic information, 240 patients in the TCGA-PAAD and GSE57495 datasets were divided into three subgroups. There were significant differences between subgroups in gene expression, pathway activity, clinical prognosis, and immune infiltration characteristics among the subtypes. Using machine learning algorithms, an RS model was constructed from DEGs among the subgroups, with the random forest method showing the best performance. A nomogram integrating the RS and clinical indicators demonstrated excellent predictive accuracy for 1-, 3-, and 5-year survival rates, confirming the RS as an independent prognostic factor. High- and low-risk groups exhibited significant differences in immune infiltration, pathway activity, and gene mutations. Drug sensitivity analysis showed that the high-risk group was more sensitive to AZD6244, ABT737, and other drugs. CONCLUSION: This study stratified patients with PAAD into three subgroups based on metabolic pathways and prognostic information, revealing significant differences in clinical outcomes, immune characteristics, and genetic mutations. The robust RS model developed from these findings demonstrated strong predictive power for patient survival and identified promising therapeutic strategies, providing valuable insights for advancing precision medicine in PAAD.

immune microenvironment↗
PubMed2026

GCH1, identified by a ferroptosis-related prognostic model, contributes to progression and drug resistance of esophageal cancer.

OBJECTIVE: Esophageal cancer has a poor prognosis and limited treatment options. Ferroptosis, an iron-dependent cell death pathway, is a promising therapeutic target; however, its significance in esophageal cancer remains largely unexplored. Here, we investigated the prognostic significance of ferroptosis-related genes in esophageal cancer and identified a key functional regulator that may serve as a therapeutic target. METHODS: We analyzed ferroptosis-related gene expression profiles with The Cancer Genome Atlas-Esophageal Carcinoma (TCGA-ESCA) cohort and constructed a prognostic risk model using LASSO Cox regression analysis. Among the genes in this model, GTP cyclohydrolase 1 (GCH1) was selected for functional investigation, based on its established role in antioxidant defense. Subsequently, in vitro experiments were performed to assess the effects of GCH1 knockdown on cell proliferation, migration, clonogenicity, and ferroptosis-related biochemical indicators. The role of GCH1 in antitumor immunity was evaluated through co-culture of esophageal cancer cells with activated T cells, and drug sensitivity was assessed using cytotoxicity assays. RESULTS: A prognostic model consisting of nine ferroptosis-related genes (STC2, TRIB3, HMGB3, CXCL8, GCH1, PARP10, APOE, MTIM, and GPER1) with reliable risk stratification was constructed. The prognostic model could reflect the differences in drug responses and immune cell infiltration. GCH1 knockdown suppressed esophageal cancer cell proliferation, migration, and clonogenicity. Furthermore, GCH1 knockdown increased the intracellular levels of reactive oxygen species, lipid peroxidation, and ferrous iron (Fe2+). Co-culture assays demonstrated that GCH1 knockdown in tumor cells increased the production of granzyme B and interferon-&#x3b3; by CD8+ T cells. Moreover, GCH1 silencing sensitized esophageal cancer cells to both sorafenib and cisplatin. CONCLUSIONS: This study established a ferroptosis-related prognostic model for esophageal cancer and identified GCH1 as a critical regulator that contributes to esophageal cancer progression and drug resistance. These findings suggest that targeting GCH1 may be a promising strategy to improve drug sensitivity and clinical outcomes in esophageal cancer.

Esophageal cancer↗
PubMed2002

The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty.

AIMS: The acute phase reactant C-reactive protein is an important prognostic risk factor in patients with both stable and unstable coronary artery disease. The potential prognostic implications of an abnormal pre-procedural C-reactive protein concentration in patients undergoing elective coronary angioplasty may be relevant for subsequent treatment. METHODS AND RESULTS: Pre-procedural plasma levels of C-reactive protein were measured in 501 patients with stable coronary artery disease undergoing elective coronary angioplasty. The incidence of death or myocardial infarction during a 2-year follow-up was 10.6% (24/227) in patients with an increased C-reactive protein level (>3 mg. l(-1)) and 2.9% (8/274) in patients with a normal C-reactive protein level (RR 3.9, 95% CI 1.7-8.9). Survival without death, myocardial infarction, urgent revascularization or hospital admission for unstable angina was significantly lower in patients with an increased C-reactive protein vs patients with a normal C-reactive protein (log-rank 14.62, P<0.0001). Logistic regression analysis identified an increased C-reactive protein level as a strong independent predictor of event-free survival (RR 2.54, 95% CI: 1.44-4.47, P=0.001). CONCLUSION: Pre-procedural C-reactive protein levels are increased in 45% of patients undergoing elective coronary angioplasty. An increased C-reactive protein level is a powerful independent prognostic indicator for subsequent cardiac events, suggesting that late clinical outcome is markedly influenced by pre-procedural systemic activation of inflammation.

Aged↗