Renin Feedback Is an Independent Predictor of Outcome in HFpEF.
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ABSTRACT:
SUBMITTER: Binder C
PROVIDER: S-EPMC8147649 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeGap junctions are specialized membrane structures that form channels between adjacent cells allowing cell communication. Gap junctions and specifically Connexin 43 (Cx43) are down-regulated in cancer; however, there are contrasting reports on how this effects breast cancer patient survival. This paper is the first large-scale tissue microarray analysis of Cx43 expression in breast cancer patients with an associated clinical long-term follow-up.MethodsUsing a validated TMA of 1118 primary breast cancers, coupled to a comprehensive database of clinicopathological variables, the expression levels and subcellular localisation of Cx43 was assessed by immunohistochemistry. Its impact in terms of survival, distant metastasis-free survival, and clinicopathological variables was determined.ResultsPatients whose tumors expressed high levels of Cx43 had significantly better survival (p < 0.001) than patients with low levels. High Cx43 expression within tumors was associated with an 18-month survival advantage. Loss of Cx43 expression was associated with markers of poor prognosis, namely large tumor size, high grade, high proliferation status, high pleomorphism, high mitosis, poor Nottingham Prognostic Index (NPI), and triple negative tumors. Cx43 expression was independent of tumor size, grade, stage and ER-status in predicting poor survival on multivariate analysis (p = 0.004).ConclusionConnexin 43 (Cx43) is an independent predictor of breast cancer survival and distant metastasis-free survival. High expression of Cx43 was seen in only 13% of tumors, suggesting that drugs to increase Cx43 expression may result in prolonged patients survival.
| S-EPMC6418069 | biostudies-literature
Project description:Purpose of the studyWe explored potential predictive variables associated with outcomes using baseline clinical parameters of 500 hospitalised patients with COVID -19 in a single centre, UK.MethodsRetrospective study collecting demographic and clinical characteristics of patients admitted at Southend University Hospital from 20th February to 7th May 2020.ResultsThe mean age of the cohort admitted to hospital with Covid-19 was 69.4 and 58% were over 70. Comorbidities were more frequently observed in non-survivors, whose mean Clinical Frailty Scale was significantly higher (5 vs 3) than survivors, p < 0.001. In addition, mean C-reactive protein was significantly higher.ConclusionOlder and frailer patients with high inflammatory markers were at risk of poor outcomes. Integrated frailty and age-based risk stratification is essential, in addition to monitoring saturation /FiO2 ratio (SFR) and inflammatory markers throughout the disease course to allow for early intervention to improve patient outcomes. A frailty-based risk-stratification approach, rather than age may prove more valuable when considering interventions in patients with multiple comorbidities.
| S-EPMC8175234 | biostudies-literature
Project description:Recently, expression profiling of breast carcinomas has revealed gene signatures that predict clinical outcome, and discerned prognostically relevant breast cancer subtypes. Measurement of the degree of genomic instability provides a very similar stratification of prognostic groups. We therefore hypothesized that these features are linked. We used gene expression profiling of 48 breast cancer specimens that profoundly differed in their degree of genomic instability and identified a set of 12 genes that defines the two groups. The biological and prognostic significance of this gene set was established through survival prediction in published datasets from patients with breast cancer. Of note, the gene expression signatures that define specific prognostic subtypes in other breast cancer datasets predicted genomic instability in our samples. This remarkable congruence suggests a biological dependency of poor-prognosis gene signatures, breast cancer subtypes, genomic instability, and clinical outcome. Keywords: disease state analysis 44 samples
2009-11-30 | E-GEOD-11901 | biostudies-arrayexpress
Project description:Recently, expression profiling of breast carcinomas has revealed gene signatures that predict clinical outcome, and discerned prognostically relevant breast cancer subtypes. Measurement of the degree of genomic instability provides a very similar stratification of prognostic groups. We therefore hypothesized that these features are linked. We used gene expression profiling of 48 breast cancer specimens that profoundly differed in their degree of genomic instability and identified a set of 12 genes that defines the two groups. The biological and prognostic significance of this gene set was established through survival prediction in published datasets from patients with breast cancer. Of note, the gene expression signatures that define specific prognostic subtypes in other breast cancer datasets predicted genomic instability in our samples. This remarkable congruence suggests a biological dependency of poor-prognosis gene signatures, breast cancer subtypes, genomic instability, and clinical outcome. Keywords: disease state analysis
2009-12-01 | GSE11901 | GEO
Project description:PurposeAtrial fibrillation (AF) is a significant independent risk factor for 1-year mortality in patients with first acute ischemic stroke (AIS). The CHA2DS2-VASc score was initially developed to assess the risk of stroke in patients with AF. Recently, this scoring system has been demonstrated to have clinical value for predicting long-term clinical outcomes in AIS but the evidence is insufficient. This large-scale prospective cohort study investigated the independent predictive value of the score in such patients.MethodsWe included patients with AIS from the Taiwan Stroke Registry (TSR) during 2006-2016 as the present study population. Patients were divided into those with high (≥2) and low (<2) CHA2DS2-VASc scores. We further analyzed and classified patients according to the presence of AF. The clinical endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year after the index AIS.ResultsA total of 62,227 patients with AIS were enrolled. The median age was 70.3 years, and 59% of the patients were women. After confounding factors were controlled, patients with high CHA2DS2-VASc scores had significantly higher incidence of 1-year MACCEs (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI] = 1.52, 1.76), re-stroke (adjusted HR = 1.28; 95% CI = 1.16, 1.42), and all-cause mortality (adjusted HR = 2.03; 95% CI = 1.83, 2.24) than those with low CHA2DS2-VASc scores did. In the comparison between AF and non-AF groups, the AF group had increased MACCEs (adjusted HR = 1.74; 95% CI = 1.60, 1.89), myocardial infarction (adjusted HR = 4.86; 95% CI = 2.07, 11.4), re-stroke (adjusted HR = 1.47; 95% CI = 1.26, 1.71), and all-cause mortality (adjusted HR = 1.90; 95% CI = 1.72, 2.10). The Kaplan-Meier curve revealed that both CHA2DS2-VASc scores and AF were independent risk predictors for 1-year MACCEs and mortality.ConclusionsThe CHA2DS2-VASc score and AF appeared to consistently predict 1-year MACCEs of AIS patients and provide more accurate risk stratification. Therefore, increased use of the CHA2DS2-VASc score may help improve the holistic clinical assessment of AIS patients with or without AF.
| S-EPMC9278736 | biostudies-literature
Project description:BackgroundBreast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early-stage BC can help understand the risk of metastasis and guide treatment decisions. Myxovirus resistance 1 (MX1), which is involved in the cellular antiviral mechanism, plays a role in some solid tumours; however, its role in invasive BC remains unknown. In this study, we aimed to explore the clinicopathological and prognostic significance of MX1 in BC.MethodsMX1 was assessed at the protein level using tissue microarrays from a large well-annotated BC cohort (n = 845). The expression of MX1 mRNA was assessed at the transcriptomic level using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1980) and validated using three publicly available cohorts on Breast Cancer Gene-Expression Miner (bc-GenExMiner version 4.4). The associations between MX1 expression and clinicopathological factors, and outcome were evaluated.ResultsHigh MX1 protein expression was associated with features of aggressiveness, including large tumour size, high tumour grade, high Nottingham prognostic index scores, hormone receptor negativity and high Ki67 expression. High MX1 expression showed an association with poor patient outcome and it was an independent predictor of short BC-specific survival (p = 0.028; HR = 1.5; 95% CI = 1.0-2.2). Consistent with the protein results, high MX1 mRNA levels showed an association with features of aggressive behaviour and with shorter survival.ConclusionThis study identified MX1 as an independent predictor of poor outcome in patients with BC. Further functional studies are needed to investigate the biological role of MX1 in BC and its potential value as a therapeutic target.
| S-EPMC7220876 | biostudies-literature
Project description:BackgroundDuodenal cytochrome b (DCYTB) is a ferrireductase that functions together with divalent metal transporter 1 (DMT1) to mediate dietary iron reduction and uptake in the duodenum. DCYTB is also a member of a 16-gene iron regulatory gene signature (IRGS) that predicts metastasis-free survival in breast cancer patients. To better understand the relationship between DCYTB and breast cancer, we explored in detail the prognostic significance and molecular function of DCYTB in breast cancer.MethodsThe prognostic significance of DCYTB expression was evaluated using publicly available microarray data. Signaling Pathway Impact Analysis (SPIA) of microarray data was used to identify potential novel functions of DCYTB. The role of DCYTB was assessed using immunohistochemistry and measurements of iron uptake, iron metabolism, and FAK signaling.ResultsHigh DCYTB expression was associated with prolonged survival in two large independent cohorts, together totaling 1610 patients (cohort #1, p = 1.6e-11, n = 741; cohort #2, p = 1.2e-05, n = 869; log-rank test) as well as in the Gene expression-based Outcome for Breast cancer Online (GOBO) cohort (p < 1.0e-05, n = 1379). High DCYTB expression was also associated with increased survival in homogeneously treated groups of patients who received either tamoxifen or chemotherapy. Immunohistochemistry revealed that DCYTB is localized on the plasma membrane of breast epithelial cells, and that expression is dramatically reduced in high-grade tumors. Surprisingly, neither overexpression nor knockdown of DCYTB affected levels of ferritin H, transferrin receptor, labile iron or total cellular iron in breast cancer cells. Because SPIA pathway analysis of patient microarray data revealed an association between DCYTB and the focal adhesion pathway, we examined the influence of DCYTB on FAK activation in breast cancer cells. These experiments reveal that DCYTB reduces adhesion and activation of focal adhesion kinase (FAK) and its adapter protein paxillin.ConclusionsDCYTB is an important predictor of outcome and is associated with response to therapy in breast cancer patients. DCYTB does not affect intracellular iron in breast cancer cells. Instead, DCYTB may retard cancer progression by reducing activation of FAK, a kinase that plays a central role in tumor cell adhesion and metastasis.
| S-EPMC5341190 | biostudies-literature
Project description:BackgroundPrevious studies have suggested body composition as a predictor of sorafenib toxicity and outcome in patients with advanced hepatocellular carcinoma (HCC). Large studies on the impact of body composition parameters in European HCC patients are lacking. Our aim was to validate the prognostic value of body composition parameters in Dutch patients with HCC treated with sorafenib.Patients and methodsA retrospective analysis was performed in a cohort of HCC patients treated with sorafenib at two Dutch tertiary referral centers between 2007 and 2016. Body composition (adipose and skeletal muscle tissue) was measured at baseline by computed tomography (CT). Low skeletal muscle mass (SMM) and density were defined using published cut-offs. Body composition parameters were correlated with overall survival (OS), time to progression, response rate, and toxicity.ResultsA total of 278 patients were included, mostly Child-Pugh class A (85%) and Barcelona Clinic Liver Cancer (BCLC) stage C (73%), with a median OS of 9.5 months (95% CI 8.1-11.0). Patients with combined low SMM and low total adipose tissue index (TATI) (n = 68, 25%) had a poor median OS (5.8, 95% CI 4.8-6.8) compared with other patients (11.7, 95% CI 9.4-14.0). Combined low SMM and low TATI remained an independent predictor of OS (HR 1.56, 95% CI 1.15-2.11, p = 0.004) after adjusting for known prognostic factors. There was no association between body composition and sorafenib toxicity.ConclusionsIn Dutch HCC patients treated with sorafenib, the combined presence of low SMM and low TATI was associated with impaired survival, independent of known prognostic factors. CT assessment of body composition may provide additional prognostic information prior to sorafenib treatment.
| S-EPMC6738194 | biostudies-literature
Project description:The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient's hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome.
| S-EPMC8217169 | biostudies-literature
Project description:BackgroundPreoperative PSA, ISUP grade group (GG), prostate examination and multiparametric MRI (mpMRI) form the basis of prostate cancer staging. Unlike other solid organ tumours, tumour volume (TV) is not routinely used aside from crude estimates such as maximum cancer core length. The aim of this study is to assess the role of TV as a marker for oncological outcomes in high-risk non-metastatic prostate cancer.MethodsA prospectively maintained database of patients undergoing minimally invasive (laparoscopic or robot-assisted laparoscopic) radical prostatectomy at a UK centre between 2007 and 2019 were analysed. A total of 251 patients with NCCN high or very high-risk prostate cancer were identified. Primary outcome measure was time to biochemical recurrence (BCR) and the secondary outcome was time to treatment failure (TTF). TV was measured on the pathological specimen using the stacking method. Multivariable cox regression analysis was used to identify factors predicting BCR and TFF. TV as a predictor of BCR and TFF was further analysed through time-dependent receiver operating characteristic (ROC) curves. Kaplan-Meier survival estimates were used to evaluate TV cut-off scores.ResultsMedian follow up was 4.50 years. Four factors were associated with BCR and TFF on multivariable analysis (TV, pathological GG, pathological T stage, positive margin >3 mm). Area under the Curve (AUC) for TV as a predictor of BCR and TTF at 5 years was 0.71 and 0.75, respectively. Including all 4 variables in the model increased AUC to 0.84 and 0.85 for BCR and TFF. A 2.50 cm TV cut off demonstrated a significance difference in time to BCR, p < 0.001.ConclusionsPathological tumour volume is an independent predictor of oncological outcomes in high risk prostate cancer but does not add significant prognostic value when combined with established variables. However, the option of accurate TV measurement on mpMRI raises the possibility of using TV as useful marker for preoperative risk stratification.
| S-EPMC10247356 | biostudies-literature