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Integrative analysis of single-cell sequencing identifies CD8+ TIM3+ CD101+ T cell-associated genes as prognostic biomarkers in breast cancer.

BACKGROUND: Breast cancer is a prevalent and deadly malignancy that significantly impacts women's quality of life and imposes financial burdens. Despite therapeutic advancements, tumour heterogeneity and frequent relapses remain major challenges. Accordingly, this study aimed to characterize immune features associated with CD8+ TIM3+ CD101+ T cells and develop a prognostic signature for breast cancer. METHODS: This study integrated single-cell and bulk transcriptomic datasets to characterize CD8+ TIM3+ CD101+ T cell (CCT)-related immune features and construct a prognostic signature in breast cancer. Single-cell RNA-seq data were sourced from the Gene Expression Omnibus (GEO) repository, and bulk transcriptomic data were from The Cancer Genome Atlas (TCGA) and GEO databases. Analytical methods included pseudo-time trajectory reconstruction (Monocle2), intercellular signalling analysis (CellChat), functional enrichment (ClusterProfiler), and immune profiling (ssGSEA). Prognostic modeling was conducted using least absolute shrinkage and selection operator (LASSO) Cox regression, with validation via Kaplan-Meier and time-dependent receiver operating characteristic (ROC) analyses. RESULTS: Single-cell analysis identified 17 clusters spanning seven cell types, including T cells, myeloid cells, and epithelial cells. T-cell sub-clustering revealed four subtypes. Pseudotime analysis suggested a potential state-transition relationship between CD8+ CD101- TIM3+ and CD8+ CD101+ TIM3+ T-cell states. A total of 121 differentially expressed genes were enriched in vital biological processes. An 11-gene prognostic model showed strong predictive power across cohorts. Single-cell T-cell reclustering identified a CD8+ CD101+ TIM3+ T-cell subpopulation, which was primarily characterized by the expression of markers such as CD101 and HAVCR2/TIM3. CONCLUSIONS: This study maps cellular heterogeneity and molecular networks in breast cancer, offering insights for targeted therapy and improved prognosis.

Breast invasive carcinoma↗

The prognostic value and molecular mechanisms of Porphyromonas gingivalis infection-associated differentially expressed genes in oral squamous cell carcinoma.

BACKGROUND: Increasing evidence suggests that Porphyromonas gingivalis (Pg) is associated with oral squamous cell carcinoma (OSCC) development and progression. This study aimed to identify Pg-associated genes with prognostic relevance in OSCC through integrated bioinformatics analysis. METHODS: OSCC-related differentially expressed genes (DEGs) were identified from the The Cancer Genome Atlas (TCGA)-OSCC cohort and intersected with Pg supernatant-associated DEGs from GSE192887. Raw count data were analyzed with DESeq2, whereas transcripts per million (TPM)-transformed expression values were used for downstream visualization and model construction. Weighted gene co-expression network analysis (WGCNA), univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariable Cox modeling were used to develop a seven-gene prognostic signature, which was externally evaluated in GSE41613. Additional analyses examined treatment-associated expression changes in the seven model genes, pairwise correlations among the model genes, and correlations between Pg supernatant-associated differentially expressed gene (PgSDEG)-derived module eigengenes and immune-cell fractions. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed in eight paired OSCC and adjacent non-tumor tissues and in supplemented-brain heart infusion (BHI) vehicle-control and Pg culture-supernatant-treated HOK, HSC-3, and CAL-27 cells. RESULTS: A prognostic signature comprising CXCL8, GAST, HBQ1, PADI3, STC1, TEX19, and TMEM92 was established. The signature showed limited-to-moderate discrimination in the TCGA training cohort, with 1-, 3-, and 5-year areas under the curve (AUCs) of 0.68, 0.69, and 0.69, respectively, and limited discrimination in the GSE41613 external cohort (AUCs: 0.66, 0.67, and 0.61). Kaplan-Meier analysis showed poorer survival in the high-risk group in both cohorts. The GSE192887 analysis showed significant treatment-associated expression changes in all seven genes after Pg culture-supernatant exposure. In paired tissues, CXCL8 and TMEM92 were significantly higher in OSCC tissues, whereas STC1 was not significant after Holm correction. In CAL-27 cells, CXCL8, STC1, and TMEM92 increased significantly after culture-supernatant treatment, whereas the corresponding comparisons were not significant in HOK or HSC-3 cells after adjustment. CONCLUSIONS: This study developed a seven-gene Pg-associated prognostic signature for OSCC and provided complementary transcriptomic, immune-correlation, tissue, and cell-based evidence that placed the signature in biological context. The model showed limited-to-moderate discrimination and is not ready for clinical use. The enrichment, gene-correlation, and immune-correlation findings are hypothesis-generating rather than mechanistic evidence. Further independent validation and dedicated functional studies are required.

Oral squamous cell carcinoma (OSCC)↗

Evaluation of the subtype-specific epigenetic prognostic association of HELLS in non-small cell lung cancer: integrated clinical and molecular insights.

BACKGROUND: Helicase, lymphoid-specific (HELLS) is an epigenetic chromatin remodeler implicated in several cancers, but its prognostic role in non-small cell lung cancer (NSCLC) subtypes remains unclear. We investigated the expression, prognostic significance, and subtype-specific associations of HELLS in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). METHODS: The Cancer Genome Atlas (TCGA) and independent Gene Expression Omnibus (GEO) datasets were analyzed. HELLS expression was compared between tumor and normal tissues, survival was evaluated separately in LUAD and LUSC, and gene set enrichment analysis (GSEA) was performed. Multivariable analyses were used to assess associations between HELLS and selected oncogenic and immune-related genes after adjustment for clinical variables. RESULTS: HELLS was significantly upregulated in both LUAD and LUSC compared with normal lung tissues (P<0.001). High HELLS expression was associated with shorter overall survival (OS) in LUAD (log-rank P=0.001) and in the TCGA-LUSC cohort (log-rank P=0.002); however, external validation in GSE42127 (LUSC, n=43) was not significant [log-rank P=0.12; hazard ratio (HR) =0.49, 95% confidence interval (CI): 0.20-1.22, P=0.13]. HELLS-high LUAD tumors showed enrichment trends enriched in proliferation-related pathways, whereas HELLS-low LUSC tumors were enriched in inflammatory and apoptotic pathways. HELLS expression remained associated with KRAS, BRAF, and CD274 in LUAD after adjustment for age, sex, and stage, while only limited associations were observed in LUSC. CONCLUSIONS: HELLS shows a subtype-dependent prognostic and molecular association in NSCLC, with the strongest and most reproducible signal in LUAD; however, its prognostic value is attenuated after multivariable adjustment and is not consistently reproduced across external cohorts.

Helicase, lymphoid-specific (HELLS)↗

Mutual Information-based Prognostic Biomarker Discovery in Cancer Genomics: Conceptual Framework and Representative Applications of MI-POG.

Mutual information (MI)-based approaches have increasingly been applied to cancer genomics; however, their use for genome-wide prognostic biomarker discovery remains relatively underexplored. The present article summarizes the conceptual workflow of Mutual Information-based Prognostic Omics Gene (MI-POG) based on previously published applications in breast cancer, lower-grade glioma, and other cancer datasets. The framework consists of clinical endpoint discretization, genome-wide MI-based screening, candidate ranking, and downstream validation using conventional survival-analysis approaches. Previous MI-POG applications identified solute carrier family 20 member 1 (SLC20A1) as a prognostic biomarker in hormone receptor-positive breast cancer. Elevated SLC20A1 expression was associated with unfavorable survival outcomes and was independently validated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. Methodological analyses demonstrated how survival endpoints can be integrated into an information-theoretic framework through fixed-time outcome discretization, enabling model-independent assessment of molecular-clinical dependencies. Applications across multiple cancer datasets suggested the potential applicability of the framework across biologically distinct tumor types, although further validation will be required to establish its robustness and generalizability. In conclusion, MI-POG can be formalized as an information-theoretic framework for genome-wide identification of prognostic biomarkers by quantifying molecular-clinical dependencies using mutual information. Representative applications from previously published studies suggest that MI-POG may complement conventional survival-analysis approaches and provide a useful strategy for biomarker discovery, although additional benchmarking and prospective validation will be required.

Humans↗

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↗

Integrated multi-omics analysis and functional experiments reveals PPAP2C as a potential prognostic biomarker and therapeutic target in breast cancer.

BACKGROUND: This study aims to systematically elucidate the clinical significance and biological function of the phospholipid phosphatase (PLPP) family member (PPAP2C) phosphatidic acid phosphatase type 2C in breast cancer, and to evaluate its potential as a prognostic biomarker and therapeutic target. METHODS: Gene expression data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were integrated to characterize the expression profile of PLPP family members, focusing on PPAP2C in breast cancer. The prognostic value of PPAP2C, initially identified at the mRNA level (TCGA, (METABRIC) Molecular Taxonomy of Breast Cancer International Consortium, Gene Expression Omnibus (GEO)), was confirmed at the protein level by immunohistochemistry (IHC) on tissue microarrays (TMA). The oncogenic functions of PPAP2C were investigated in triple-negative breast cancer (TNBC) cells through CRISPR-Cas9-mediated knockout and ectopic overexpression, with assessment of key phenotypes including proliferation, colony formation, migration, and invasion. In vivo validation was subsequently performed using an MDA-MB-231 xenograft model. RESULTS: PPAP2C exhibits the most significant overexpression pattern across 33 cancer types (upregulated in 16 cancers, downregulated in only 3). Compared with normal tissues, PPAP2C showed specific overexpression in breast cancer tissues and was significantly associated with advanced clinical stages and aggressive subtypes (HER2+ and TNBC). Survival analysis demonstrated that high PPAP2C expression correlated with significantly shorter overall survival and disease-free survival, which was further validated in METABRIC and GEO cohorts. Tissue microarray analysis confirmed higher PPAP2C protein positivity in tumor tissues (94.7%) than in adjacent normal tissues (59.7%), with worse OS and RFS in high-expression groups. Multivariate analysis identified PPAP2C as an independent prognostic factor for OS. Functional experiments revealed that PPAP2C knockout (via 5-bp/1-bp frameshift mutations) suppressed TNBC cell proliferation, colony formation, migration, and invasion, while overexpression enhanced these phenotypes. In vivo studies further demonstrated complete tumor regression in MDA-MB-231 xenografts upon PPAP2C knockout. CONCLUSION: This study identifies PPAP2C as a key oncogenic driver and a robust independent prognostic biomarker in breast cancer. The findings provide compelling evidence that PPAP2C represents a promising therapeutic target, offering a new strategic avenue for precision therapy, particularly for aggressive breast cancer subtypes.

PLPP2↗

Prognostic value of blood eosinophilia in primary cutaneous T-cell lymphomas.

OBJECTIVE: To investigate the prognostic value of initial characteristics including blood eosinophilia in patients with primary cutaneous T-cell lymphoma. DESIGN: A retrospective inception cohort, patients included from date of diagnosis (1982-1998). SETTING: Two dermatology departments of a university hospital. Patients A total of 104 patients with cutaneous T-cell lymphoma, including patients with mycosis fungoides (n = 69), Sézary syndrome (n = 13), and nonepidermotropic cutaneous lymphoma (n = 22). The following variables were recorded: age, sex, diagnosis according to the European Organization for Research and Treatment of Cancer (EORTC) classification, type of skin involvement at the time of diagnosis, initial eosinophil absolute count, lactate dehydrogenase value, date of disease progression, and cause and date of death or date of last contact. MAIN OUTCOME MEASURES: Time from diagnosis to disease progression and to disease-specific death. RESULTS: The median follow-up was 43 months (range, 7-197 months). Estimated rates of disease progression and disease-specific death for 3 years were 19.5% (95% confidence interval [CI],11.3%-27.6%) and 9.9% (95% CI, 2.8%-13.6%), respectively. Univariable analysis of initial variables possibly influencing disease progression revealed significant prognostic value for diagnosis according to EORTC classification (hazard ratio [HR], 2.77; 95% CI, 1.04-7.41; P =.04), type of skin involvement (HR, 2.70; 95% CI, 1.00-7.25; P =.04), raised blood eosinophil absolute count (HR, 7.33; 95% CI, 2.84-18.91; P<.001), and raised serum level of lactate dehydrogenase (HR, 3.72; 95% CI, 1.58-8.78; P =.001). Concerning disease-specific death, significant prognostic indicators were diagnosis according to the EORTC classification (HR, 6.62; 95% CI, 1.68-26.12; P =.007) and a raised blood eosinophil absolute count (HR, 10.57; 95% CI, 2.28-49.0; P<.001). In multivariable analysis, only blood eosinophilia was associated with disease progression and disease-specific death. CONCLUSION: These results strongly suggest that blood eosinophilia at baseline is a prognostic factor in patients with primary cutaneous T-cell lymphoma.

Adult↗

A prognostic factor study of disease-free interval and survival following enucleation for uveal melanoma.

Prognostic indicators of uveal melanoma disease-free interval and survival following enucleation were evaluated for 267 patients. The median follow-up time was 17 years. Analysis involved Kaplan-Meier survival curves based on time to tumor-related deaths and multivariate proportional hazards analysis, which provides an estimate of the "force of mortality." Prognostic indicators considered included demographic, clinical, and histopathological factors. Cell type was classified according to the number of epithelioid cells present per high-power field (HPF) on light microscopy. Various classifications of size of the tumor were compared for prognostic value. The five leading predictors of survival in order of importance were as follows: (1) number of epithelioid cells per HPF, (2) largest dimension of the tumor, (3) location of the anterior margin of the tumor, (4) invasion to the line of transection, and (5) degree of pigmentation. Risk categories for survival were constructed based on the three leading prognostic factors.

Epithelium↗

Prognostic value of CD44 variant 6 in laryngeal epidermoid carcinomas.

BACKGROUND: CD44 variant exon 6 (v6) belongs to a family of transmembrane glycoproteins involved in cell adhesion. OBJECTIVES: To determine the prognostic role of CD44v6 in laryngeal cancer and to examine its relation with other clinicopathologic prognostic factors. DESIGN: A retrospective cohort study was designed with 93 laryngeal cancer cases. They were selected randomly from patients treated with laryngectomy between January 1, 1983, and December 31, 1993. SETTING: Faculty of Medicine, Hacettepe University, Ankara, Turkey. PATIENTS: The ages of the patients ranged from 31 to 73 years. Eighty-eight patients were men and 5 were women. Three had stage I, 33 had stage II, 27 had stage III, and 30 had stage IV disease at the time of surgery. INTERVENTION: Histological sections of tumors and metastatic lymph nodes were reevaluated for several histopathological factors. Sections were stained using anti-CD44v6 monoclonal antibody by immunohistochemical methods. RESULTS: CD44v6 expression was seen only in the lower one third of the normal squamous epithelium but in all layers of dysplasia and in situ carcinoma. Besides a general evaluation of tumor staining, immunostaining was evaluated separately for cell groups located in the center of neoplastic islands (nonbasal cells), at the periphery of the neoplastic islands (basal cells), and at the infiltration zones (marginal cells). Decreased disease-free survival was noted when there was extensive staining in the general evaluation and in cases with extensive staining in marginal and nonbasal cells (P =.03). Using Cox regression analysis, the greatest dimension of the largest metastatic lymph node and extensive expression of CD44v6 in nonbasal tumor cells were independent prognostic factors. CONCLUSION: Our results suggest that CD44v6 expression is an important prognostic factor in laryngeal cancer.

Adult↗

Prognostic significance of p21WAF1/CIP1 expression in tongue squamous cell carcinomas.

OBJECTIVE: To investigate the prognostic significance of p21(WAF1/CIP1) expression and its relationship with p53 accumulation and other apoptotic markers such as Bax, Bcl-2, and apoptotic index in relation to disease-specific survival in oral tongue squamous cell carcinoma (SCC). DESIGN: A 10-year retrospective clinical study. Information about clinical findings, treatment, and follow-up has been recorded prospectively. PATIENTS AND METHODS: Diagnostic, formalin-fixed, paraffin-embedded sections taken from 80 randomly selected patients before treatment for T1 to T4 oral tongue SCC were stained immunohistochemically with p21(WAF1/CIP1). The percentages of positive nuclei that stained positive for tumor were determined. MAIN OUTCOME MEASURES: The significance of prognostic parameters was tested by log-rank and Kaplan-Meier methods for the univariate analysis. The Cox proportional hazards regression model was used for multivariate analysis. RESULTS: Expression of p21(WAF1/CIP1) correlated inversely with T classification and clinical stage (P =.02 and P =.006, respectively) but not with N classification, tumor differentiation, or apoptosis-related variables such as p53 accumulation, apoptotic index, and Bax and Bcl-2 expression. Patients with tumors expressing high p21(WAF1/CIP1) values had increased disease-specific survival time (P =.03). The correlation between p21(WAF1/CIP1) expression and disease-specific survival was even more significant when restricted to p53-negative tumors (P =.002). A 2-parameter combination between p21(WAF1/CIP1) expression and Bax expression or p21(WAF1/CIP1) expression and p53 accumulation, respectively, revealed an enhanced prognostic potential (P<.001) when compared with single parameters. CONCLUSION: The expression of p21(WAF1/CIP1), particularly in combination with p53 accumulation or Bax expression, has prognostic value in oral tongue SCC.

Adult↗

Prognostic value of histologic findings in neck dissections for squamous cell carcinoma.

BACKGROUND: Cervical node involvement is the most significant prognostic factor in head and neck squamous cell carcinoma. When histologic findings show node invasion, the number of positive nodes and the presence of extracapsular spread are commonly accepted as prognostic factors. OBJECTIVE: To confirm the findings of recent reports that there is no significant difference in outcome associated with extracapsular spread. SETTING: Referral center. DESIGN: Retrospective study. PATIENTS: Three hundred thirty-seven patients under-going 487 neck dissections for carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx from January 1, 1985, to December 31, 1992. For N3 node involvement, a radical neck dissection was performed; other patients underwent supraomohyoid or functional neck dissection. Two hundred forty-two patients underwent postoperative radiotherapy (mean dose, 59 Gy). OUTCOME MEASURES: Survival capabilities calculated by the Kaplan-Meier method and significance calculated by the log rank test. RESULTS: Overall 5-year survival was 50.8%. The study of prognostic factors showed no significance for extracapsular spread (P = 45). Conversely, the number of positive nodes had a significant value (P < .001). CONCLUSIONS: Extracapsular node spread per se might be considered as no longer having a definitive prognostic value. These results, consistent with those of previous reports, may be due to wider use of combined treatment modalities.

Carcinoma, Squamous Cell↗

Pathologic features of prognostic significance for adrenocortical carcinoma after curative resection.

OBJECTIVE: To identify the pathologic features of prognostic significance in patients with resectable adrenocortical carcinomas. DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Review of the Memorial Sloan-Kettering Cancer Center prospective adrenocortical carcinoma database from 1986 through 1996 identified 46 patients who underwent curative adrenalectomy for primary disease. All cases were reviewed by a single pathologist and each primary tumor was characterized by 16 separate pathologic parameters. MAIN OUTCOME MEASURE: Overall survival rates in the patient population. RESULTS: The 5-year overall survival rate for the entire cohort was 36% (median survival rate, 28 months). Of the pathologic factors analyzed, tumor size, number of mitotic figures, and the presence of intratumoral hemorrhage were independent prognostic factors. Patients presenting with primary tumors larger than 12 cm (n = 30) had a worse outcome compared with those with smaller tumors (n = 16) (5-year survival rate: 53% vs. 22%, P<.05). Mitotic count (> or =6 per 10 high-power fields) was a negative prognostic feature (n = 15) with a 5-year survival rate of 13% vs. 51% for 0 to 6 mitotic figures per 10 highpower fields (n = 31, P<.05). Intratumoral hemorrhage (n = 23) was also a negative prognostic factor compared with no evidence of intratumoral hemorrhage (n = 23) (5-year survival rate, 53% vs. 22%, P<.05). Overall survival rates were also calculated based on the number of pathologic risk factors. Patients with no risk factors had an 83% 5-year survival rate, which decreased to 42% with 1 factor, 33% with 2 factors, and 0% with all 3 risk factors. CONCLUSIONS: Tumor size, hemorrhage, and mitotic count correlate with survival rates for patients undergoing curative resection. Based on these pathologic factors, adrenocortical carcinomas may be divided into low- and high-risk groups.

Adrenal Gland Neoplasms↗

Prognostic significance of cellular immunity to autologous breast carcinoma and glycoprotein 55.

Using a skin window (SW) procedure, we evaluated post-operative cell-mediated immunity (CMI) to autologous breast cancer with reference to its prognostic significance, the nature of the immunogen, and the therapeutic implications. It appears that SW reactivity to autologous breast cancer is prognostically favorable per se and is independent of the prognostic significance of the nuclear grade of the cancer cells; SW reactivity to autologous breast cancer reflects CMI to a determinant(s) that is expressed by glycoprotein 55, the principal envelope glycoprotein of the RIII-murine mammary tumor virus; the glycoprotein 55-like CMi determinant(s) is more regularly expressed by preinvasive than by invasive breast cancers; tumor antigenicity and host reactivity may vary independently; and postoperative monitoring of CMI to autologous breast cancer is prognostically and therapeutically important.

Breast Neoplasms↗

Prognostic factors in meningococcal disease. Development of a bedside predictive model and scoring system. Barcelona Meningococcal Disease Surveillance Group.

CONTEXT: Meningococcal disease is associated with significant morbidity and mortality. Development of a prognostic model based on clinical findings may be useful for identification and management of patients with meningococcal infection. OBJECTIVES: To construct and validate a bedside model and scoring system for prognosis in meningococcal disease. DESIGN: Prospective, population-based study. SETTING: Twenty-four hospitals in the metropolitan area of Barcelona, Spain. PATIENTS: A total of 907 patients with microbiologically proven meningococcal disease. Patients diagnosed with meningococcal disease from 1987 through 1990 were used to develop the prognostic model, and those diagnosed in 1991 and 1992 were used to validate it. OUTCOME MEASURES: Clinical independent prognostic factors for mortality in meningococcal disease. The association between outcome and independent prognostic factors was determined by logistic regression analysis. A scoring system was constructed and tested using receiver operating characteristic curves. RESULTS: Among 624 patients in the derivation set, 287 (46%) were male, the mean age was 12.4 years, and 34 patients (5.4%) died. Among 283 patients in the validation set, 124 (43.8%) were male, the mean age was 12.7 years, and 17 patients (6.0%) died. In multivariate analysis, independent predictors of death were hemorrhagic diathesis (odds ratio [OR], 101; 95% confidence interval [CI], 30-333), focal neurologic signs (OR, 25; 95% CI, 7-83), and age 60 years or older (OR, 10; 95% CI, 3-34), whereas receipt of adequate antibiotic therapy prior to admission was associated with reduced likelihood of death (OR, 0.09; 95% CI, 0.02-0.4). Hemorrhagic diathesis was scored with 2 points, presence of focal neurologic signs with 1 point, age of 60 years or older with 1 point, and preadmission antibiotic therapy was scored as -1. The clinical scores of -1, 0, 1, 2, and 3 or more points were associated with a probability of death of 0%, 2.3%, 27.3%, 73.3%, and 100%, respectively. CONCLUSIONS: Hemorrhagic diathesis, focal neurologic signs, and age of 60 years or older were independent predictors of death in meningococcal disease, whereas receipt of adequate antibiotic therapy was associated with a more favorable prognosis. The scoring system presented is simple, is based on findings readily available at the bedside, and may be useful to help guide aggressive therapy.

Adolescent↗

Prognostic indicators for AIDS and infectious disease death in HIV-infected injection drug users: plasma viral load and CD4+ cell count.

CONTEXT: Plasma human immunodeficiency virus type 1 (HIV-1) viral load and CD4+ cell count are used to predict prognosis of persons infected with HIV. However, whether combining these markers improves prognostic accuracy and whether they predict prognosis for injection drug users (IDUs) and nonwhite persons infected with HIV has not been extensively investigated. OBJECTIVE: To evaluate plasma viral load and CD4+ cell count as prognostic indicators for the acquired immunodeficiency syndrome (AIDS) and infectious disease deaths. DESIGN: Cohort study initiated in 1988 and 1989 with follow-up for up to 7.9 years. PARTICIPANTS: Injection drug users infected with HIV recruited from the community in Baltimore, Md. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA and CD4+ cell count measured at baseline compared with time to first clinical AIDS diagnosis and death due to an infectious disease. RESULTS: Of 522 subjects, 96% were African American, 80% were male, 96% injected drugs within the past 6 months, and the median age was 33 years. A total of 146 cases of AIDS and 119 infectious disease deaths were seen during a median follow-up period of 6.4 years. Time-fixed baseline levels of viral load and CD4+ cell count were independent predictors of progression to AIDS and infectious disease deaths, but in proportional hazards models, viral load had better predictive value than CD4+ cell count. Kaplan-Meier analysis of time to AIDS and to infectious disease deaths by viral load (<500, 500-9999, 10000-29 999, > or =30000 copies/mL) at 3 levels of CD4+ cell count (<0.20, 0.20-0.49, and > or =0.50x10(9)/L [<200,200-499, and > or =500/microL]) was reduced to a 5-stage classification scheme using a backward stepwise regression procedure. The 5-year cumulative probabilities for AIDS and infectious disease deaths ranged from 0% and 0%, respectively, for group I (viral load, <500 copies/mL; CD4+ cell count, 0.50x10(9)/L) to 81.2% and 76.1% respectively, for group V (viral load, > or =10000 copies/mL; CD4+ cell count, 0.20x10(9)/L). CONCLUSIONS: In this study, plasma HIV-1 viral load independently and in combination with CD4+ cell count measurements provided powerful prognostic information for progression to AIDS and death caused by infectious disease in a population of predominantly African American IDUs. Combining categories of both markers provided a simple method for prognostically staging HIV disease.

AIDS-Related Opportunistic Infections↗

Differences in prognostic factors and outcomes between women and men undergoing coronary artery stenting.

CONTEXT: Women with coronary artery disease (CAD) are believed to have a higher risk for adverse outcomes than men after conventional coronary interventions. The increasing use of coronary stenting has improved the outcome of patients undergoing coronary interventions, but little is known about the nature of outcomes in men vs women after this procedure. OBJECTIVE: To examine whether there are sex-based differences in prognostic factors and in early and late outcomes among CAD patients undergoing coronary stent placement. DESIGN, SETTING, AND PATIENTS: Inception cohort study, at 2 tertiary referral institutions in Germany. Consecutive series of 1001 women and 3263 men with symptomatic CAD who were treated with stenting between May 1992 and December 1998. Patients who underwent stenting in the setting of acute myocardial infarction were excluded. MAIN OUTCOME MEASURE: The combined event rates of death and nonfatal myocardial infarction, assessed at 30 days and 1 year after stenting and compared by sex. RESULTS: Compared with men, women undergoing coronary stenting were significantly older (mean age, 69 vs 63 years) and more likely to present with diabetes, arterial hypertension, or hypercholesterolemia. Women had less extensive CAD, a less frequent history of myocardial infarction and better preserved left ventricular function than men. Women presented an excess risk of death or nonfatal myocardial infarction only during the early period after stenting: the 30-day combined event rate of death or myocardial infarction was 3.1% in women and 1.8% in men (P =.02) and the multivariate-adjusted hazard ratio (HR) for women was 2.02 (95% confidence interval [CI], 1.27-3.19). At 1 year, the outcome was similar for both women and men (combined event rate for women, 6.0%, and for men, 5.8% (P =.77); multivariate-adjusted HR for women, 1.06 [95% CI, 0.75-1.48]). There was a sex difference in the prognostic value of baseline characteristics: the strongest prognostic factors were diabetes in women and age in men. CONCLUSIONS: The results of this study indicate that 1-year outcomes of women with CAD undergoing coronary artery stenting are similar to those of men. Despite the similarity in outcomes, there are several sex-specific differences in baseline characteristics, clinical course after the intervention, and relative weight of prognostic factors. JAMA. 2000;284:1799-1805.

Aged↗

Development and validation of a prognostic index for 1-year mortality in older adults after hospitalization.

CONTEXT: For many elderly patients, an acute medical illness requiring hospitalization is followed by a progressive decline, resulting in high rates of mortality in this population during the year following discharge. However, few prognostic indices have focused on predicting posthospital mortality in older adults. OBJECTIVE: To develop and validate a prognostic index for 1 year mortality of older adults after hospital discharge using information readily available at discharge. DESIGN: Data analyses derived from 2 prospective studies with 1-year of follow-up, conducted in 1993 through 1997. SETTING AND PATIENTS: We developed the prognostic index in 1495 patients aged at least 70 years who were discharged from a general medical service at a tertiary care hospital (mean age, 81 years; 67% female) and validated it in 1427 patients discharged from a separate community teaching hospital (mean age, 79 years; 61% female). MAIN OUTCOME MEASURE: Prediction of 1-year mortality using risk factors such as demographic characteristics, activities of daily living (ADL) dependency, comorbid conditions, length of hospital stay, and laboratory measurements. RESULTS: In the derivation cohort, 6 independent risk factors for mortality were identified and weighted using logistic regression: male sex (1 point); number of dependent ADLs at discharge (1-4 ADLs, 2 points; all 5 ADLs, 5 points); congestive heart failure (2 points); cancer (solitary, 3 points; metastatic, 8 points); creatinine level higher than 3.0 mg/dL (265 micromol/L) (2 points); and low albumin level (3.0-3.4 g/dL, 1 point; <3.0 g/dL, 2 points). Several variables associated with 1-year mortality in bivariable analyses, such as age and dementia, were not independently associated with mortality after adjustment for functional status. We calculated risk scores for patients by adding the points of each independent risk factor present. In the derivation cohort, 1-year mortality was 13% in the lowest-risk group (0-1 point), 20% in the group with 2 or 3 points, 37% in the group with 4 to 6 points, and 68% in the highest-risk group (>6 points). In the validation cohort, 1-year mortality was 4% in the lowest-risk group, 19% in the group with 2 or 3 points, 34% in the group with 4 to 6 points, and 64% in the highest-risk group. The area under the receiver operating characteristic curve for the point system was 0.75 in the derivation cohort and 0.79 in the validation cohort. CONCLUSIONS: Our prognostic index, which used 6 risk factors known at discharge and a simple additive point system to stratify medical patients 70 years or older according to 1-year mortality after hospitalization, had good discrimination and calibration and generalized well in an independent sample of patients at a different site. These characteristics suggest that our index may be useful for clinical care and risk adjustment.

Aged↗

Prognostic importance of physical examination for heart failure in non-ST-elevation acute coronary syndromes: the enduring value of Killip classification.

CONTEXT: In acute myocardial infarction, the presence and severity of heart failure at the time of initial presentation have been formally categorized by the Killip classification. Although well studied in ST-elevation myocardial infarction, the prognostic importance of Killip classification in non-ST-elevation acute coronary syndromes is not well established. OBJECTIVES: To determine the prognostic importance of physical examination for heart failure analyzed according to Killip classification in non-ST-elevation acute coronary syndromes and to understand its predictive value relative to other variables. DESIGN, SETTING, AND PATIENTS: From April 2001 to September 2003, We analyzed information from 26 090 patients with non-ST-elevation acute coronary syndromes enrolled in the GUSTO IIb, PURSUIT, PARAGON A, and PARAGON B trials. Demographic information was categorized by Killip class. Killip classes III and IV were combined into 1 category. Multivariate Cox proportional hazard models were developed to determine the prognostic importance of Killip classification in comparison with other variables. MAIN OUTCOME MEASURE: Association between Killip classification and all-cause mortality at 30 days and 6 months. RESULTS: Patients in Killip class II (n = 2513) and III/IV (n = 390) were older than those in Killip class I (n = 23 187), with higher rates of diabetes, prior myocardial infarction, ST depression, and elevated cardiac enzymes (all P<.001). Higher Killip class was associated with higher mortality at 30 days (2.8% in Killip class I vs 8.8% in class II vs 14.4% in class III/IV; P<.001) and 6 months (5.0% vs 14.7% vs 23.0%, respectively; P<.001). Patients with Killip class II, III, or IV constituted 11% of the overall population but accounted for approximately 30% of the deaths at both time points. In multivariate analysis, Killip class III/IV was the most powerful predictor of mortality at 30 days (hazard ratio [HR], 2.35; 95% confidence interval [CI], 1.69-3.26; P<.001) and 6 months (HR, 2.12; 95% CI, 1.63-2.75; P<.001). Killip class II was predictive of mortality at 30 days (HR, 1.73; 95% CI, 1.44-2.09; P<.001) and 6 months (HR, 1.52; 95% CI, 1.31-1.76; P<.001). Five factors-age, Killip classification, heart rate, systolic blood pressure, and ST depression-provided more than 70% of the prognostic information for 30-day and 6-month mortality. CONCLUSIONS: Killip classification is a powerful independent predictor of all-cause mortality in patients with non-ST-elevation acute coronary syndromes. Age, Killip classification, heart rate, systolic blood pressure, and ST depression should receive particular attention in the initial assessment of these patients.

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