Risultati per: Scoperto nuovo biomarker per il cancro al colon-retto

E’ partner del progetto ‘European cancer imaging – Eucaim’

Ast Pesaro-Urbino presenta i numeri del territorio

‘Gli strumenti ci sono ma bisogna applicarli’

Lungo post della modella che sarà sul palco di Sanremo

Oncologi,ma meno del 50% cittadini riceve consigli su stili vita

Per diagnosi precoce del tumore tra i 70 e 74 anni

Stroke, Volume 56, Issue Suppl_1, Page A33-A33, February 1, 2025. Introduction:Net water uptake (NWU) is a novel biomarker which measures edema and tissue injury from the degree of hypoattenuation on non-contrast CT and may serve as a precision tool for predicting outcomes after acute ischemic stroke (AIS). Using our recently developed algorithm, this study aimed to evaluate the relationship between NWU and post-stroke neurologic outcomes, including language impairment and motor weakness.Methods:Consecutive patients treated for AIS at certified stroke centers in Houston, TX were included. Patients’ precise functional outcomes at hospital discharge were recorded including decreased level of consciousness, presence of language impairment, visual deficit, arm and leg weakness, need for walking assistance, and gastrostomy placement. The primary outcome for this study was the performance of calculated NWU and clinical variables to predict language impairment at discharge. Baseline characteristics were compared, and then univariate and multivariate logistic regression were used to evaluate the association between clinical variables, imaging data, and the precise neurological outcomes.Results:Among 776 patients with AIS, average age was 67.0 +/- 14.8, 47.8% were female, median NIHSS was 10 [5,18], median ASPECTS was 9 [7,10], 42.6% received tPA, and 67.1% had a large vessel occlusion (see Table 1). In univariate logistic regression, higher NWU (OR 1.45, CI 1.30-1.63) and lower ASPECTS (OR 0.68, CI 0.63-0.74) were both significantly associated with higher likelihood of language impairment and other deficits at discharge (see Table 2). Additionally, higher NWU in all ten regions was significantly associated with deficit at discharge. In multivariate logistic regression, certain clinical and imaging variables remained significantly associated as described in Table 3. The ASPECTS and NWU-based regression models were directly compared when predicting language impairment using ROC curve analysis, and areas under the curve were 0.838 vs. 0.851 respectively (p = 0.152 with Delong test, see Figure 1).Conclusion:The novel NWU biomarker was significantly associated with precise post-AIS outcomes at discharge. When controlling for confounders, NWU was non-inferior to ASPECTS. Moving forward, region-based and overall NWU will need to be studied with long-term patient outcomes. Ultimately, this novel and open-access imaging biomarker could be used in the emergency setting to guide treatment decision-making and patient counseling.

Stroke, Volume 56, Issue Suppl_1, Page A74-A74, February 1, 2025. Introduction:Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the reduction in final infarct volume only accounts for a minority of the treatment effect. There is a need for surrogate imaging biomarkers that more strongly associate with functional outcome, to refine prognostication and facilitate development of EVT-adjuvant neuroprotective therapies. Our group recently developed a straightforward ADC-based metric of post-EVTinfarct density(i.e. a measure of infarct severity). We aimed to validate this novel metric in a multicenter study of EVT patients.Methods:A retrospective cohort included consecutive patients with anterior circulation LVO who underwent EVT at two stroke centers. MRI was performed 12–48 hours post-EVT. Good functional outcome was defined as a 90-day modified Rankin Scale score ≤2. MR imaging was processed via RAPID, and final infarct volume was based on the standard ADC

Stroke, Volume 56, Issue Suppl_1, Page ATP377-ATP377, February 1, 2025. Introduction:Intracranial aneurysms (IAs) are weak outpouchings on cerebral vessels that can rupture, causing subarachnoid hemorrhage. Timely and accurate risk stratification of IAs is paramount.Objective:Aneurysm wall enhancement (AWE) is a potential imaging biomarker for risk stratification. We propose to combine this with whole blood RNA sequencing to improve IA risk stratification.Methods:We retrospectively collected images and blood of patients who had undergone vessel wall imaging. We performed RNA sequencing and radiomics analysis on the IA sacs on pre- and post-contrast T1 MRI scans. Using univariate analysis, we selected significantly different radiomic features (RFs). We removed all collinear features, and pooled radiomic and expression features. We classified each IA as symptomatic or asymptomatic based on symptoms at presentation. We then built separate machine learning models: one based solely on the radiomics features and another with combined features. We performed principal component analysis (PCA) and a leave-one-out (LOO) cross validation to quantify models’ performances.Results:Our final cohort consisted of 7 patients. We found 34 significantly different RFs between symptomatic and asymptomatic IAs. The final feature set consisted of 9 RFs and 6 genes. PCA of whole dataset using the RFs alone reflected variances of 38% and 29% on the best principal components. We trained a random forest model using LOO cross validation and observed an accuracy of 57.1% (33.3% sensitivity, 75% specificity). With the addition of the gene expression features, we found the PCA explained variance to be 41% and 26%. The LOO accuracy improved to 85.7% (66.6% sensitivity, 100% specificity).Conclusion:In this study, we demonstrated that radiomics from the aneurysm wall alone have a low predictive value in identifying symptomatic IAs. However, adding gene expression levels improves the predictive value. Future work will be aimed at adding more cases.

Stroke, Volume 56, Issue Suppl_1, Page AWP35-AWP35, February 1, 2025. Neutrophils are reported to be critical mediators of to poor outcome after subarachnoid hemorrhage (SAH). Following SAH, neutrophils cause vascular occlusion via neutrophil extracellular traps (NETs) and NETs have been identified as a therapeutic target to prevent delayed cerebral ischemia in mice (DCI) with SAH. In this study, our hypothesis was that markers of NETs are higher in aneurysmal SAH patients developing DCI compared to SAH patients not developing DCI. Moreover, we hypothesized NETs occlude blood vessels in the brain of SAH patients developing DCI. Using aneurysmal SAH patient blood collected at 1, 2, 4, 7, and 10 days post-SAH, we used ELISA kits to measure three markers of NETs: neutrophil elastase, citrullinated histone H3, and H3.1 nucleosome. We collected autopsy samples to examine for the presence of NETs in the brain vessels. Finally, as neutrophil counts (and the ratio of neutrophils to lymphocytes) are reported to be a biomarker for DCI, we assessed these measures too. Two hundred and sixty-nine aneurysmal SAH patients were included in our analyses: 193 patients did not develop DCI and 76 patients developed DCI. In our study, neutrophil elastase and citrullinated histone H3 were NETs markers that were able to distinguish between SAH patients who developed DCI and those who did not develop DCI. Specifically, neutrophil elastase was elevated in SAH patients developing DCI (compared to that of patients not developing DCI) and neutrophil elastase levels could predict which SAH patients were at high-risk for developing DCI as early as day 2 post-SAH. Citrullinated histone H3 displayed an elevated level in DCI patients vs no DCI patients on day 10. Moreover, NETs were observed occluding the brain blood vessels in SAH patients. None of the other measures had any predictive value for identifying which SAH patients were likely to develop DCI: neutrophil count, neutrophil to lymphocyte ratio, H3.1 nucleosome. The findings of this study suggest NETs factors may be useful biomarkers to predict which aneurysmal SAH patients are at-risk for DCI. As NETs were observed occluding brain vessels, NETs may also be a therapeutic target.

Stroke, Volume 56, Issue Suppl_1, Page AWP359-AWP359, February 1, 2025. Background:Mechanical thrombectomy has been associated with improved outcomes in patients with acute ischemic stroke. However, not all patients with successful reperfusion experience good functional outcomes. Investigating the post-reperfusion inflammatory milieu could provide valuable insights into the mechanisms that influence stroke outcomes. We hypothesized that successful reperfusion may cause distinct cytokine/ chemokine profiles.Methods:Plasma samples were collected from patients with ischemic stroke that were admitted to Memorial Hermann Hospital, Houston within 24 hours of admission. Multiplex was used to analyze the plasma samples for levels of 48 cytokines and chemokines. The relationship between thrombectomy (TICI 2b and above) and analytes was assessed using ANOVA and then adjusted association was examined using multilinear regression models after adjusting for patient demographics and comorbidities.Results:The mean age of patients was 63.3 years, 54% were women, 87% had hypertension, 44% had diabetes mellitus, and 54% had hyperlipidemia. Only two out of the 48 cytokines demonstrated differences with thrombectomy. CCL4 levels were significantly higher in patients that underwent thrombectomy, 55.7±17.4 pg/ml vs. 39.5±20.6 pg/ml in the ones that did not undergo this procedure, p=0.01. Similarly, CCL-5 (RANTES) levels were elevated in patients with acute ischemic stroke that underwent thrombectomy 368.6±275.1 vs. others, 216.5±156.3, p=0.01. These remained significant after adjusting for co-morbidities.Conclusions:Our study suggests that MIP-1β (CCL4) and RANTES (CCL5) are significantly elevated in ischemic stroke patients that underwent successful reperfusion by mechanical thrombectomy. CCL4 or MIP-1β (macrophage inflammatory protein -1) is a chemoattractant for monocytes in injured tissue. CCL5 or RANTES (regulated onactivation,normalT-cellexpressed andsecreted) is also a chemokine secreted by T cells and monocytes and directly interacts with CCL4. CCL4 and CCL5 may contribute to the post-ischemia reperfusion inflammatory response, potentially influencing outcomes after reperfusion therapies such as mechanical thrombectomy. Longitudinal analysis of these chemokines and other cytokines after mechanical thrombectomy, along with their correlation with functional outcomes may provide deeper insights into the underlying mechanisms and also identify potential biomarkers of successful mechanical thrombectomy in stroke patients.

Stroke, Volume 56, Issue Suppl_1, Page AWP356-AWP356, February 1, 2025. Introduction:Blood-based biomarker investigations for neurological diseases such as ischemic stroke are commonly used in clinical practice and traditionally have focused on measuring alterations in cytokine quantity and composition. An emerging area has been the use of microRNA studying the effects of gene expression after ischemic stroke. There has been extensive evidence that gene expression changes after ischemic injury, especially in gene pathways related to inflammatory response, vascular injury, and cellular degeneration. Establishing a reliable blood-based biomarker used to quantify clinical indications is necessary for emergent treatment. With a blood-based assessment that utilizes transcriptomics, healthcare providers can better understand post-stroke molecular changes more rapidly, which is crucial during this acute phase.Methods:Peripheral blood samples were collected from ischemic stroke patients (N=100) during the acute onset of disease, 24 hours after the last known well. In this study, we investigated possible differences among the stroke population based on risk factors including age, sex, race, social isolation status, and presence of cognitive impairment. For this analysis, overall social isolation status was defined by a mixed model matrix comprised of Lubben Social Network score and UCLA Loneliness score. We used whole transcriptomic sequencing to assess these variables.Results:Overall, there were 8 miRNA sequences significantly upregulated in socially isolated patients. There were no significant differences found among patients based on sex or age variability. Interestingly, we found that circulatory miR-24-3p (FDR adjusted p-value

Stroke, Ahead of Print. Background:Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the final infarct volume (FIV) on MRI only accounts for a minority of the treatment effect. An imaging biomarker that more strongly correlates with post-EVT functional outcome would be helpful for clinical prognosis and serve as a surrogate outcome measure in trials of EVT-adjuvant therapies. Here, we aimed to validate a novel MRI-based metric, infarct density, which leverages post-EVT apparent diffusion coefficient (ADC) as a marker of infarct severity.Methods:A retrospective cohort was derived from a single-center prospective EVT registry. Consecutive anterior circulation EVT patients were included from 2018-2019 who achieved successful reperfusion (mTICI ≥2b). MRI was performed 12-48 hours post-EVT and processed via RAPID to quantify FIV using the ADC

Stroke, Volume 56, Issue Suppl_1, Page ATP85-ATP85, February 1, 2025. Background and Purpose:Due to limitations associated with the symptom-based tools currently used for triage, up to 35% of strokes are missed at initial clinician contact in emergency medicine settings. As a result, there has been a decades-long push to identify blood biomarkers with utility for stroke recognition. Despite numerous studies reporting candidates with seemingly high levels of diagnostic performance, none have made their way into clinical use. It is possible this discrepancy is linked to translational limitations in how these prior biomarker discovery investigations have been designed and implemented. Thus, we performed a nontraditional systematic review and meta-analysis spanning 30 years of published acute stroke blood biomarker data in which we sought to explicitly quantify the effects of study design and reporting considerations on diagnostic performance estimates, and correct said estimates for such effects in order to provide better projections of how the candidate biomarkers that have been studied to date would perform in a true clinical use scenario.Methods and Results:A electronic database search was performed to identify previously reported human acute stroke blood biomarker investigations, which yielded 14,253 potential articles. 189 were included in our final analysis based on subsequent abstract and full-text screening. From each article, detailed methodological information for all reported diagnostic comparisons was manually extracted. Collectively, data from 705 different diagnostic comparisons involving 355 unique single analytes or multi-analyte panels were captured. The raw diagnostic performance estimates reported in the literature inferred that as high as 40% of previously investigated candidate biomarkers could be clinically useful for stroke recognition. However, multiple regression revealed that 47.2% of the variance in these diagnostic performance estimates could be attributed to a small number of confounding study design and reporting factors related to population sampling, timing of blood collection, blinding, and conflicts of interest. After using the model residuals to correct for these factors, not a single candidate biomarker displayed adequate evidence to suggest true clinical utility.Conclusions:Our results clarify the current state of the search for an acute stroke blood biomarker, and identify several translational limitations that need to addressed in future investigations if one is to be realized.