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[Controversies in stress echocardiography: the indications, diagnostic accuracy and stratification of dobutamine stress echocardiography].

In recent years, stress echocardiography has become a valuable tool in the diagnosis, stratification and prognostic evaluation of coronary artery disease. Stress echocardiography has been performed with a variety of methods, including exercise, atrial pacing and pharmacological stress with the use of adenosine, dipyridamol and dobutamine. Either of these modalities of stress echo are a good choice in the evaluation of ischemic disease and the selection of one over another should depend on the patient's characteristics, experience of the stress echo laboratory and clinical needs (in the detection of viability there is greater experience in the use of dobutamine making this the most popular choice when evaluating myocardial hibernation). The aim of this paper is to review the indications, diagnostic accuracy and prognostic stratification of dobutamine stress echocardiography, comparing them with those obtained with other stress echo modalities and with nuclear techniques.

Cardiotonic Agents↗

Tumor budding as a prognostic marker in stage-III rectal carcinoma.

BACKGROUND AND AIM: Tumor budding along the invasive margin is known to be associated with biological behavior in colorectal carcinoma. The aims of this study were to explore if the semiquantitative assessment of tumor budding in rectal cancers correlates with oncological behavior and to appraise if the tumor budding is valid as a pathological parameter in distinguishing tumors with higher malignancy potential from those with lower one for prognostic stratification. MATERIALS AND METHODS: Surgical specimens from 244 patients with well- or moderately differentiated rectal carcinoma were retrieved to assess the intensity of tumor budding at the invasive margin. Intensities were divided semiquantitatively into four groups based on quartiles, and the 5-year disease-free survivals (DFS) were analyzed to search for a cutoff point of prognostic stratification. RESULTS: The cutoff of the intensity considered to be the best indicator for dividing patients into subgroups with different DFS was between quartiles 3 and 4, but this survival difference in subgroups in either side of the cutoff was significant only in stage-III disease [5-year DFS, 62.1 vs 35.1%; p = 0.0023; 95% confidence interval (CI), 0.1824-0.6919]. Based on multivariate analysis, the intensity of budding proved to be an independent variable associated with DFS (hazard ratio, 2.005; p = 0.0086; 95% CI, 1.021-3.934). When scores were given to grade of budding (lower, 0; higher, 1) and N stage (N1, 0; N2, 1) in stage III, a better prognostic stratification in terms of the 5-year DFS was obtained than the American Joint Committee on Cancer nodal staging only (0 vs 1 vs 2, 66.5 vs 42.6 vs 29.2%; p = 0.0101). CONCLUSIONS: Quantitative assessment of tumor budding is a reliable biological prognostic variable to identify higher malignancy potential. Scoring system using tumor budding and N stage showed better prognostic stratification in stage-III rectal carcinoma. A prospective evaluation would confirm the clinical significance of tumor budding for prognostic stratification.

Adult↗

Sentinel node biopsy before neoadjuvant chemotherapy for determining axillary status and treatment prognosis in locally advanced breast cancer.

BACKGROUND: Treatment of locally advanced breast cancer with neoadjuvant chemotherapy assesses an in vivo tumor response while increasing breast conservation. Axillary clearance of nodal disease after treatment defines prognostic stratification. Our study objective was to show that sentinel node staging before treatment can optimize posttreatment prognostic stratification in clinically N0 patients. METHODS: Eighty-nine patients with locally advanced breast cancer were treated with neoadjuvant chemotherapy. Of these, 42 (47%) clinically palpable or image-detected nodes (cN+) were histologically confirmed before treatment (group 1), and 47 (53%) patients without palpable lymph nodes (cN0) had a sentinel lymph node (SLN) biopsy before treatment (group 2). Survival analysis was conducted with the Kaplan-Meier method. RESULTS: In groups 1 and 2, 82 (92%) of 89 patients had node-positive disease before treatment. Seven (8%) of 89 had negative SLNs and no completion axillary lymph node dissection, 24 (27%) patients had a complete pathologic axillary response (pCRAX; 11 [26%] of 42 in group 1 and 13 [33%] of 40 in group 2), and 58 (65%) of 89 had residual disease in the axilla. Breast-conserving therapy was applied to 27 (30%) of 89 patients. The seven SLN-negative patients had no axillary recurrence at 25 months, and pCRAX patients had a significantly higher overall survival than patients with residual disease. CONCLUSIONS: This study validates the prognostic stratification of patients with a complete pathologic axillary response to neoadjuvant chemotherapy. The addition of SLN biopsy to cN0 patients before treatment increased accurate nodal staging by 53%, eliminated completion axillary lymph node dissection in 15%, and demonstrated an improved prognosis in 28% of pCRAX patients. SLN biopsy before treatment provides accurate staging of cN0 patients; allows acquisition of standard treatment markers, prognostic biomarkers, and microarray analysis; and affords prognostic stratification after treatment.

Axilla↗

Risk group stratification and prognostic factors in papillary carcinoma of thyroid.

BACKGROUND: Our understanding of the natural history of differentiated thyroid carcinoma has improved with the definition of prognostic factors. These prognostic factors have helped us identify patients in various risk groups. METHODS: A retrospective review of a consecutive series of 810 previously untreated patients with papillary carcinoma of the thyroid was undertaken to analyze the prognostic factors and risk groups. There were 403 patients in the low-risk group, 313 in the intermediate group, and 94 classified in the high-risk group. RESULTS: With a median follow-up of 20 years, 99% survival was achieved in the low-risk group, whereas only 43% survived in the high-risk group. The intermediate-risk group had a 20-year survival of 83%. The favorable prognostic factors included female sex, young age, absence of distant metastases and extrathyroidal extension of the disease, size < 4 cm, and low-grade histology. Focality, presence of lymph node metastasis, and pure papillary or mixed variant had no statistical significance on prognosis. CONCLUSIONS: Based on various prognostic factors, low-, intermediate-, and high-risk groups are identified. Patients in the low-risk group have excellent survival (99%). Appropriate selection of surgical and adjuvant treatment should therefore be used based on prognostic factors and risk group stratification.

Age Factors↗

Polytomography in Ménière's disease: an update.

In a previous article the use of polytomography of the vestibular aqueduct in Meniere's disease was described. The value of this procedure in the prognosis of surgery was evaluated by contrast of results with a non-radiographically examined population. Since then five more years of experience has been gained through routine radiographic examination of all patients with Meniere's disease. Within the above epoch, several efforts have been made to effectively separate patients into categories based on therapeutic expectations and prognostic stratifications. In addition X-ray studies, glycerol tests, hearing levels, frequency of vertigo and other clinical features have been suggested as offering suitable data for prognostic stratification. This upper updates the radiologic data previously presented, and reviews the efforts to date to accomplish significant prognostic stratification. Several clinical aspects of patients with Meniere's disease which may affect its severity are outlined.

Endolymphatic Sac↗

[Comparison of prognostic value of high-dose dobutamine stress-echocardiography and exercise testing in patients with idiopathic dilated cardiomyopathy].

INTRODUCTION: It is of the utmost importance to make an accurate assessment of prognosis in patients with idiopathic dilated cardiomyopathy. Both high-dose dobutamine stress-echocardiography and exercise testing have been used for prognostic stratification of these patients. OBJECTIVE: To make head-to-head comparison of high-dose dobutamine stress-echocardiography and exercise testing in prognostic stratification of patients with idiopathic dilated cardiomyopathy. METHODS: A total of 63 consecutive patients (55 men, mean age 50.1 +/- 9.6 years, mean ejection fraction 19.2 +/- 8.4%) with idiopathic dilated cardiomyopathy, left ventricular end-diastolic diameter >60mm, ejection fraction <35%, and adequate echocardiographic window have been studied. Dobutamine stress echocardiography was performed using 5, 10, 20, 30 and 40 mcg/kg/min infusions, in progressive stages lasting 5 minutes each. Wall motion score index and ejection fraction were considered the indices of the left ventricular contractility. Contractile reserve was defined as the difference between the values of these indices obtained at peak dobutamine dose during the test and the baseline values. Exercise testing was performed as supine bicycle ergometry in progressive stages of 25 W lasting 120 seconds each. Patients were followed one year for combined end-point consisting of cardiac death, partial left ventriculectomy and hospitalization for congestive heart failure. RESULTS: Out of 61, 19 (31%) patients met combined end-point during follow-up [cardiac death in 6/61 (10%), partial left ventriculectomy in 4/61 (7%) and hospitalization for heart failure in 9/61 (15%) patients]. Kaplan-Meier survival analysis demonstrated that dobutamine-induced change of wall motion score index was the best parameter for separation of patients in terms of prognosis during the follow-up (log rank=25.34, p<0.001), followed by change of ejection fraction (log rank=16.83, p<0.001) and duration of exercise testing (log rank 13.85, p=0.002). Cox model identified dobutamine-induced change of wall motion score index as the only independent predictor (p<0.001) of combined end-point during one-year follow-up. DISCUSSION: There is a number of studies dealing with the left ventricular contractile indices. These studies are different with respect to studied population, method used to elicit the left ventricular contractile response and the indices of contractile reserve. A number of studies has suggested that the amount of pharmacologically or physically induced change of wall motion score index and ejection fraction can identify patients with dismal prognosis. Peak oxygen consumption is traditionally considered the most accurate prognostic index, but its usefulness has been recently questioned. Our data suggest that high-dose dobutamine stress-echocardiography may be superior to exercise testing for prognostic stratification of patients with idiopathic dilated cardiomyopathy. The reasons for such observation are not clear, but it can be hypothesized that this may be due to multifactorial nature of the exercise tolerance. The most serious potential drawback of methodology is that, because of technical limitations, we did not test peak oxygen consumption in our patients, but since it has been shown that oxygen consumption correlates well with the duration of exercise, we believe that our methodology is valid. CONCLUSION: Both high-dose dobutamine stress-echocardiography and exercise testing can identify patients with dismal prognosis during one-year follow-up, but it appears that dobutamine stress-echocardiography may yield better prognostic significance.

Cardiomyopathy, Dilated↗

A method of clinical prognostic staging for patients with rectal cancer.

Methods of prognostic stratification for patients with rectal cancer currently rely solely on the extent of tumor penetration in the surgically excised rectum. Thus stratification according to prognostic factors can be performed only after treatment had been carried out and can play no role in pretherapeutic treatment decisions or in the design of trials of preoperative adjuvant treatment. To devise a method of clinical prognostic staging that could be applied to all patients with rectal cancer, regardless of therapy, the medical records were examined of an inception cohort of 282 patients treated by surgical and nonsurgical methods at three Toronto hospitals during the years 1968 to 1974. Six groups of clinical variables were identified that independently influenced prognosis: the presence or absence of metastatic disease, whether the rectal tumor was fixed or mobile, an annular rectal tumor, and the systemic symptoms of weight loss, anorexia, or weakness, and anemia. A composite method was developed for clinical prognostic staging from these variables and it was found that it created substantial gradients in survival. In patients treated by surgery, for whom comparisons of clinical staging with conventional anatomic staging were possible, clinical staging was as effective a method of prognostic staging as was anatomic staging. Furthermore, the prognostic impact of clinical staging persisted after adjustment for the effects of anatomic staging. This method of clinical prognostic staging should prove useful in making therapeutic decisions and in the design and analysis of clinical trials of alternative treatment for patients with rectal cancer.

Anemia↗

Echocardiographic correlates of survival in patients with chest pain.

OBJECTIVES: This study sought to identify echocardiographic predictors of survival in patients with chest pain and to assess the utility of qualitative echocardiographic data in the prognostic stratification of this cohort. BACKGROUND: The potential usefulness of echocardiographic data in prognostic stratification of patients with acute chest pain is unclear, in part because of the qualitative nature of routinely available echocardiographic readings. METHODS: The study group comprised 513 patients who underwent transthoracic two-dimensional and Doppler echocardiography within 1 month of emergency department visits for acute chest pain. Clinical and electrocardiographic (ECG) data were recorded for these patients at the time of their initial evaluations, and echocardiographic data were subsequently obtained from the official hospital reports. Follow-up survival rate data were obtained from medical records or the Massachusetts Bureau of Vital Statistics. RESULTS: A mean of 28.5 months after the index visit, 102 patients (20%) had died, including 58 (57%) for whom the primary cause of death was cardiovascular. In analysis of routinely available qualitative echocardiographic data, left ventricular size and function, the presence of regional wall motion abnormalities, mitral regurgitation and structural abnormalities of the mitral valve were significant univariate correlates of both overall mortality and death from cardiovascular causes. Severe left ventricular dysfunction (adjusted rate ratio 3.8, 95% confidence interval [CI] 1.9-7.5) and moderate or severe mitral regurgitation (adjusted rate ratio 2.4, 95% CI 1.5-3.7) were independent predictors of mortality in a multivariate Cox regression analysis that adjusted for clinical and ECG variables. Moderate or severe left ventricular dysfunction and mitral regurgitation were predictors of mortality in the subset of patients without acute myocardial infarction. CONCLUSIONS: Qualitative echocardiographic reports of left ventricular dysfunction and mitral regurgitation were independent correlates of prognosis in patients with acute chest pain, including patients without acute myocardial infarction. Further data are needed to assess the generalizability of these findings and the implications for use of this diagnostic technology.

Acute Disease↗

Response of the right ventricle to acute pulmonary vasodilation predicts the outcome in patients with advanced heart failure and pulmonary hypertension.

OBJECTIVES: This study was designed to assess whether testing of potential reversibility of pulmonary hypertension (PHT) may be a useful means of defining the short-term prognosis of patients with advanced heart failure and elevated pulmonary artery pressure. In such patients, the reversibility of PHT after acute vasodilator administration is associated with a low early mortality rate after heart transplantation. However, its short-term prognostic value has not yet been determined. METHODS AND RESULTS: Between 1994 and 1998, 76 patients with advanced heart failure and PHT underwent right heart cathetherization. The hemodynamic measurements, including thermodilution-derived right ventricular ejection fraction, were repeated after an intravenous bolus of nitroglycerin (NTG). During a median follow-up period of 8.2 months (25% and 75% centiles, 3.3 and 18.9 months), 47 patients had a cardiac event (death or urgent heart transplantation). With Cox survival analysis, a multivariate model that included the New York Heart Association class and the hemodynamic variables obtained after NTG administration allowed a better assessement of the short-term prognosis of the patients than a model including the baseline variables. The evaluation of right ventricular function during the acute NTG-induced pulmonary vasodilation was of critical importance in obtaining such a refinement in the prognostic stratification. CONCLUSIONS: The prognostic evaluation of patients with advanced heart failure and PHT should include the assessment of the changes of right ventricular ejection fraction after acute afterload reduction.

Aged↗

In industrialized nations, a low socioeconomic status represents an independent predictor of mortality in patients with acute myocardial infarction.

BACKGROUND: It has been widely demonstrated that in the general population a low socioeconomic status (SES) represents a risk factor for coronary heart disease (CHD). Both the incidence of and the mortality due to CHD are significantly higher in subjects with a low SES. Conventional risk factors only partly account for the social gradient in CHD. The aim of this study was to evaluate whether mortality was associated with SES in patients with acute myocardial infarction (AMI). METHODS: To this purpose the articles dealing with AMI and SES, having a prospective cohort design, total mortality or sudden death as primary endpoint and multivariate analysis as statistical approach, were analyzed. RESULTS: Among the patients hospitalized for AMI, a low SES was associated with more advanced disease, as shown by a significantly higher prevalence of heart failure and of recurrent ischemic events. The in-hospital treatment and prescriptions at discharge were similar among the various socioeconomic groups. The pre-hospitalization, in-hospital and long-term mortality were significantly higher in the most deprived subjects and a low SES represented an independent predictor (adjusted odds ratio ranging from 1.4 to 3.1). The few available data suggest the socioeconomic gradient as being a predictor even of sudden death. CONCLUSIONS: A low SES represents an independent predictor of mortality in patients with AMI. The current prognostic stratification of AMI patients is rather disappointing. In order to get a more precise prognostic stratification and to approach an adequate prophylaxis, a low SES should be utilized; however, the mechanisms mediating the adverse outcome of low socioeconomic groups should be further investigated.

Acute Disease↗

Role of stress echocardiography in risk stratification early after an acute myocardial infarction. EPIC (Echo Persantin International Cooperative) and EDIC (Echo Dobutamine International Cooperative) Study Groups.

Resting and stress echocardiography is a 'one-stop shop', which enables a wide range of information to be collected on resting function, myocardial viability, and induced ischaemia, all of which are useful for prognostic stratification. Large scale, multicentre, prospectively collected data show the prognostic failure of resting function and inducible ischaemia, both independently and combined, which are especially effective in predicting cardiac death. The GISSI data show that the increment of risk as a result of reduction in ventricular function has a hyperbolic trend, with a relatively moderate increase in mortality for ejection fraction values between 50 and 30%, but with marked increases below 30%. The EPIC data show that the 1-year risk of cardiac death is as low as 2% in patients with negative dipyridamole stress echocardiography: it doubles if the test is positive at a high dose, and is almost four times higher if it is positive at a low dose. In the field of prognostic stratification, in the absence of carefully controlled studies, the choice between coronary angiography as the only essential study, or use of a non-invasive test to discriminate access to catheterization currently reflect alternate philosophical approaches rather than scientifically based decisions. In the invasive approach, stress echocardiography offers relief from the vicious circle of chest pain-coronary angiography revascularization. In the non-invasive and physiological approach, stress echo is capable of offering, in one sitting, an insight into the main determinants of survival: function, viability, and ischaemia.

Echocardiography↗

A reassessment of bone scintigraphy and commonly tested pretreatment biochemical parameters in newly diagnosed osteosarcoma.

PURPOSE: In patients with an osteosarcoma, the prognosis is still poor. The aim of the present study was to investigate whether routinely tested biochemical parameters or additional parameters on bone scintigraphy could be identified which can select prognostic subgroups at the time of diagnosis. METHODS: A retrospective study was performed in 115 consecutive patients (70 male, 45 female) (mean age: 25.6 years; range: 3.50-78.0 years) who were referred for bone scintigraphy prior to treatment from March 1986 to September 2000 because of a newly diagnosed osteosarcoma. All bone scans were reassessed for the intensity and pattern of uptake and a bone-scan index. All pre-treatment general, histological, biochemical, and scintigraphic data were correlated with clinical outcome during follow-up. RESULTS: During follow-up 54 patients died. Tumour volume and GGT showed significance as independent variables for metastases. Patients with metastases demonstrated a significantly lower survival rate (23% 5-year survival) than patients without metastases (98% 5-year survival). Tumours of the humerus and femur had a significantly lower survival rate. With respect to significant biochemical parameters (ALP, GGT, ASAT), it was not possible to determine a cut-off value that could be used to differentiate between high- and low-risk patients. Additional parameters assessed on bone scintigraphy were not important for prognostic stratification. CONCLUSION: The strongest predictor of survival in osteosarcoma is the presence or absence of metastasis. Some biochemical parameters have prognostic value, but they cannot be used for the unequivocal identification of subgroups. Additional scintigraphic parameters are irrelevant for prognostic stratification.

Adolescent↗

A simple stratification factor prognostic for survival in advanced cancer: the good/bad/uncertain index.

PURPOSE: This article summarizes the third step of a research program to identify variables that supplement the predictive power of the the Eastern Cooperative Oncology Group (ECOG) performance status (PS) for survival. The objective was to produce a simple, practical, stratification factor for phase III oncology clinical trials involving patients with advanced malignant disease. PATIENTS AND METHODS: A questionnaire was administered to 729 patients with metastatic colorectal or lung cancers. Patients provided a Karnofsky index and appetite rating while physicians provided a survival estimate and the ECOG-PS. Scores for each item were categorized as having a positive, neutral, or negative indication for survival. A patient was classified as having a relatively good prognosis if three or more of the four items showed a positive indication, a bad prognosis if three or more items were negative, and an uncertain prognosis otherwise (Good/Bad/Uncertain [GBU] index). RESULTS: The GBU index improved on the prognostic power of a Cox model quartile index and PS alone and increased the accuracy of survival classification estimates by 5% to 10% more than ECOG-PS alone. For patients with PS of 0 or 1, significant survival patterns exist between GBU groups (P=.002 and.0001, respectively). CONCLUSION: The GBU index may be recommended as a supplementary stratification factor for certain future phase III trials in metastatic lung or colorectal cancer where patient heterogeneity is a particular concern. The GBU represents a relatively modest increase to the cost and patient burden of a clinical trial given the additional control that is achieved over the potentially confounding concomitant to the treatment variable.

Aged↗

Prognostic value of pulmonary venous flow Doppler signal in left ventricular dysfunction: contribution of the difference in duration of pulmonary venous and mitral flow at atrial contraction.

OBJECTIVES: We assessed the contribution of difference in duration of pulmonary venous and mitral flow at atrial contraction (ARd-Ad) for prognostic stratification of patients with left ventricular (LV) systolic dysfunction. BACKGROUND: Although pulmonary venous flow (PVF) variables may supplement mitral flow patterns in evaluating left ventricular (LV) diastolic function, their value to the prognostic stratification of patients has not been investigated. METHODS: Pulsed wave Doppler mitral and PVF velocity curves were recorded in 145 patients (mean age: 70 years) with LV systolic dysfunction secondary to ischemic or nonischemic cardiomyopathy who were followed for 15 +/- 8 months. In 38% of patients, PVF signal was enhanced by the intravenous (IV) administration of a galactose-based echo-contrast agent. Based on E-wave deceleration time < or = or >130 ms and ARd-Ad, patients were grouped into restrictive (group 1, n = 40), nonrestrictive with ARd-Ad > or =30 ms (group 2, n = 55) and nonrestrictive with ARd-Ad <30 ms (group 3, n = 50). RESULTS: During follow-up, 29 patients died from cardiac causes and 28 were hospitalized for worsening heart failure (HF). On multivariate Cox model, ARd-Ad > or =30 ms provided important prognostic information with regard to cardiac mortality and emerged as the single best predictor of cardiac events (cardiac mortality, hospitalization). The 24-month cardiac event-free survival was best (86.3%) for group 3; it was intermediate (37.9%) for group 2; and it was worst (22.9%) for group 1 (p < 0.0002 group 1 vs. 3; p < 0.0005 group 2 vs. 3; p < 0.0003 group 1 vs. group 2). CONCLUSIONS: Assessment of ARd-Ad exhibited an independent value in the prognostic evaluation of patients with LV systolic dysfunction. Moreover, it contributed to identify patients at low, intermediate and high risk of cardiac events.

Adult↗

Construction of molecular signatures based on the co-expression network of NECSO-related gene TRPM4 and its prognostic value in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) demonstrates significant prognostic variability that is not entirely accounted for by traditional staging systems. Necrosis by sodium overload (NECSO) is an emerging programmed cell death pathway, but its clinical relevance in HCC remains undefined. Therefore, this study aimed to identify TRPM4-associated core genes, develop and validate a prognostic signature, and investigate its relationship with the tumor immune microenvironment, tumor mutational burden, and single-cell expression patterns in HCC. METHODS: We integrated transcriptomic, clinical, and mutational datasets from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) (n=421) and Gene Expression Omnibus (GEO) cohorts (n=115) to identify genes co-expressed with TRPM4-a key NECSO mediator-and those differentially expressed in HCC. A prognostic signature was developed using least absolute shrinkage and selection operator (LASSO)-Cox regression and validated through survival analysis, time-dependent receiver operating characteristic (ROC) curves, and multivariate Cox regression analysis. The immune landscape was characterized using CIBERSORT, somatic mutation data were used to calculate tumor mutational burden (TMB) and assess its correlation with the risk score, and single-cell RNA sequencing (scRNA-seq) resolved cell-type-specific expression patterns. RESULTS: From 294 TRPM4-associated core genes, we identified an 11-gene signature (BRSK1, MMP1, GRIN2D, GP6, MYOM2, N4BP3, CCDC112, TSEN54, MAP3K9, SPP1, B3GNT4) that independently predicted overall survival (OS) (hazard ratio =5.419, P<0.001) with areas under the curve (AUCs) of 0.779, 0.693, and 0.701 at 1, 3, and 5 years. These values were superior or comparable to conventional clinicopathologic variables after direct comparison. High-risk patients exhibited an immunosuppressive microenvironment, characterized by enrichment of M0 macrophage, a higher M2/M1 ratio (P<0.001) and distinct immune checkpoint profiles. When integrated with TMB, the prognostic stratification was further refined: high-TMB/high-risk patients had poorest outcomes (median OS, 15.3 months), while low-TMB/low-risk patients had the most favorable survival (median OS, 68.7 months). Single-cell analysis revealed that MMP1 was induced in cancer-associated fibroblasts (CAFs) and SPP1 was downregulated in macrophages, single-cell risk scores confirmed TAFs and macrophages as the main contributors to the prognostic model. CONCLUSIONS: The TRPM4-centered 11-gene signature provides robust and independent prognostic stratification in HCC by integrating immune, mutational, and single-cell features. This signature serves as a potential tool for prognostic evaluation and may help inform immunotherapeutic strategies for HCC.

Hepatocellular carcinoma (HCC)↗

Lymphangiogenesis-related gene signature-based risk model for prognostic assessment of cervical cancer: immune-metabolic characterization and molecular subtype analysis.

BACKGROUND: Lymphangiogenesis promotes tumor dissemination and may shape the immune contexture of cervical cancer, yet lymphangiogenesis-related prognostic stratification and its immunometabolic implications remain insufficiently defined in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). METHODS: TCGA-CESC transcriptomes and clinical data were obtained from UCSC Xena and integrated with normal cervix tissues from the Genotype-Tissue Expression Project after batch correction. Prognostic LYMRGs were first identified from the differentially expressed set using univariable Cox proportional hazards analysis. Candidate genes were then reduced using an L1-regularized Cox model (Least Absolute Shrinkage and Selection Operator), and the remaining markers were entered into a multivariable Cox regression to obtain the final coefficients and compute an individualized risk score. The model's prognostic value was further assessed in an independent Gene Expression Omnibus dataset. In addition, expression patterns of the signature genes were leveraged for molecular subtyping of TCGA samples via non-negative matrix factorization (NMF). Immune infiltration and immunotherapy-associated characteristics were interrogated through a multi-algorithm strategy (single-sample gene set enrichment analysis, CIBERSORT, ESTIMATE, Tumor Immune Dysfunction and Exclusion (TIDE), and Immunophenoscore . Additional analyses included pathway enrichment (GSEA/GO/KEGG), drug sensitivity prediction (pRRophetic/CellMiner), and ceRNA network analysis. RESULTS: A six-gene LYMRG signature robustly stratified survival. High-risk patients had significantly worse overall survival in The Cancer Genome Atlas with AUCs of 0.819/0.801/0.801&#xa0;at 1/3/5 years, and in GSE52903 (P = 0.001) with AUCs of 0.733/0.719/0.725. NMF identified two subtypes with distinct prognosis (P = 0.01) and divergent immune landscapes. Risk groups and subtypes exhibited consistent differences in immune infiltration, checkpoint expression, TIDE/IPS patterns, and pathway enrichment. Predicted chemosensitivity differed by risk group, and the ceRNA network suggested candidate upstream lncRNA regulators of the signature. CONCLUSION: A lymphangiogenesis-related six-gene model enables clinically meaningful prognostic stratification of CESC and links lymphangiogenesis programs to distinct tumor immune phenotypes and therapeutic vulnerabilities.

cancer↗

A pragmatic adaptation of the RANO clinical risk score for IDH-Wildtype glioblastoma in the absence of MGMT promoter methylation testing.

BACKGROUND: The novel RANO risk score provides prognostic stratification for patients with IDH-wildtype glioblastoma(GBM) and includes age, Karnofsky Performance Scale(KPS), RANO resection class(RRC), and MGMT promoter methylation(MGMTm). However, MGMTm testing is unavailable in many countries. We aimed to explore the prognostic performance of a RANO-adapted clinical score excluding MGMTm. METHODS: We applied the same scoring system established by original RANO score, excluding MGMTm. Three risk classes were defined as numerical scores derived through tertiles. The primary endpoint was overall survival(OS), and the secondary exploratory endpoint was progression-free survival(PFS). RESULTS: One-hundred twenty patients were included. Three risk classes were identified:low-risk(0-1 points,n:47, 39.2%), intermediate-risk(2-3 points,n:27, 22.5%), and high-risk(&#x2265;4 points,n:46, 38.3%). The median OS was 35.5&#x2009;months(95% CI:21.1-49.9) for the low-risk group, 16&#x2009;months(95% CI:9.9-22.1) for the intermediate-risk group, and 5&#x2009;months(95% CI:3.6-6.3) for the high-risk group(p&#x2009;<&#x2009;0.001). Similarly, the median PFS was 16.3&#x2009;months(95% CI:12.3-20.3) for the low-risk group, 9.9&#x2009;months(95% CI:7.2-12.6) for the intermediate-risk group, and 4.1&#x2009;months(95% CI:3.5-4.7) for the high-risk group(p&#x2009;<&#x2009;0.001). CONCLUSION: This simplified RANO-adapted score demonstrated promising prognostic stratification using basic clinical parameters. As a pragmatic adaptation study, external validation is required before clinical application, particularly in settings where MGMTm testing is unavailable.

Humans↗

Prognostic impact of peak oxygen uptake and percentage of predicted value of peak oxygen uptake in patients with left ventricular dysfunction.

BACKGROUND: Comparing the prognostic value of peak oxygen uptake (VO2max) in absolute values and percentage of predicted VO2max (%PredVO2) in terms of prognostic stratification, contradictory references are found in the medical literature. In theory, the measurement of VO2max relative to a normal subject should improve its predictive capacity, because VO2max is influenced by gender, weight, physical activity and age. OBJECTIVES: To compare the prognostic value of VO2max and %PredVO2 (Jones equation) in an adult population (> or = 20 years) of patients with left ventricular systolic dysfunction and to study the influence of age on these parameters. POPULATION AND METHODS: We review data from the first cardiopulmonary stress test performed in 295 consecutive patients with left ventricular systolic dysfunction (ejection fraction < or = 40%); mean age was 52 +/- 10 years, 81% were male, and 76 aged > or = 60 years. In 52%, the etiology was ischemic. We evaluated demographic and clinical variables, the baseline ECG and the medication used before the test. We compared VO2max (ml/kg/min) and %PredVO2 in terms of prognostic stratification for the combined endpoint (death and/or heart transplant) for 2 years of follow-up. RESULTS: We detected 60 patients with events (42 deaths and 18 transplants). ROC curve analysis was used to determine the best cut-off value for VO2max and %PredVO2 to identify patients with events. The best cut-off for VO2max was < or = 19 ml/kg/min and < or = 49% for %PredVO2 in the total population, and in the event-free survival analysis, by log-rank test, we obtained p < 0.001 for both cut-offs. Considering the two extreme age groups (20-40 years and > or = 60 years), we found different cut-off values. In the youngest group we obtained VO2max of < or = 23 ml/kg/min and %PredVO2 of < or = 59%, and in the elderly < or = 12.5 ml/kg/min and < or = 64% respectively. For the intermediate group, the cut-off values were the same as for the total population. In the youngest patients, the new cut-offs did not offer an improvement in accuracy. In the elderly, for VO2max, we obtained an improvement in specificity from 28 to 86% and a reduction in sensitivity from 95 to 50%, with an improvement in accuracy from 46.8 to 75.9% (p = 0.05). With regard to %PredVO2, specificity fell from 86 to 61% and sensitivity increased from 50 to 82%, with similar accuracy (75.9 to 67%, p = 0.78). CONCLUSIONS: In the extreme age groups, we obtained different cut-off values, but only for the elderly (VO2max < or = 12.5 ml/kg/min and %PredVO2 < or = 64%). A benefit in terms of accuracy was only obtained in respect of VO2max, because for %PredVO2, there is already a correction for age through the Jones equation.

Adult↗