Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Clinical significance of bap1 in malignant pleural mesothelioma

Introduzione: il ruolo prognostico della proteina BRCA-associated protein 1 (BAP1) nel mesotelioma maligno della pleura (MPM) è ancora oggetto di discussione. In questo studio l’obbiettivo è quello di chiarire il ruolo prognostico del BAP1 nel MPM. Inoltre, abbiamo combinato lo status del BAP1 con i livelli di espressione tissutali del miR-31 con lo scopo di incrementare la sua performance prognostica. Metodi: è stata condotta una ricerca sistematica della letteratura ed è stata valutata l’espressone del BAP1 e del miR-31 in 60 tessuti di MPM. Il valore prognostico dei biomarcatori è stato valutato in termini di overall survival (OS) e di progression-free survival (PFS). Risultati: nella nostra popolazione, BAP1 era espresso nel 38% dei campioni e non espresso nel 62% dei campioni e la sua mancata espressione era significativamente associata all’istotipo epitelioide (e-MPM). Non sono state identificate differenze significative in termini di OS tra i due gruppi (BAP1 espresso/BAP1 non espresso). L’analisi multivariata mostrava che l’istologia non-epitelioide era l’unico fattore prognostico indipendente. Anche dalla meta-analisi non sono state osservate differenze in termini di OS in base allo status del BAP1. Sono stati misurati bassi livelli di espressione del miR-31 nei pazienti e-MPM rispetto ai sottotipi non-epitelioidi e sono risultati associati alla perdita di espressione del BAP1. Nei pazienti e-MPM bassi livelli di miR-31 erano associati ad una PFS migliore. Infine, pazienti e-MPM con BAP1 non espresso e bassi livelli di miR-31 presentavano una prognosi migliore rispetto a quelli con BAP1 espresso e alti livelli di miR-31. Conclusione: il BAP1 preso singolarmente non è in grado di stratificare i pazienti in base alla sua espressione quando si considera l’istotipo. Tuttavia, nei pazienti e-MPM, la stratificazione prognostica può essere migliorata combinando lo status del BAP1 con i livelli di miR-31. Questo score dei due marcatori è utile per identificare un sottogruppo di tumori e-MPM che presentano un outcome clinico peggiore.Introduction: The prognostic role of BRCA1 associated protein-1 (BAP1) expression in malignant pleural mesothelioma (MPM) is still a matter of discussion. In this study we aimed to clarify the prognostic role of BAP1 in MPM. Moreover, we combined BAP1 status with the tissue expression levels of miR-31 in order to improve its prognostic performance. Methods: A systematic literature search was conducted and the expression of BAP1 and miR-31 was analyzed in 60 MPM tissues. The prognostic value of the biomarkers was evaluated in terms of overall survival (OS) and progression-free survival (PFS). Results: In our cohort, BAP1 was positive/retained in 38% of samples and negative/loss in 62% of samples. BAP1 loss was significantly associated with epithelioid histotype. At univariate analysis, there were no significant difference in terms of OS between BAP1 retained group and BAP1 loss group. Multivariate analysis showed that non-epithelioid histology was the only independent prognostic factor. Even from meta-analysis, no differences were observed in term of OS according to BAP1 status. Lower miR-31 levels were detected in epithelioid MPM (e-MPM) compared to the non-epithelioid subtypes and resulted associated with BAP1 loss. By looking at the e-MPM subgroup, loss of BAP1 was not able to predict clinical outcome. Conversely, miR-31 levels were significantly associated with PFS. By combining the two biomarkers, e-MPM patients with BAP1 loss/low miR-31 levels showed a better prognosis compared to the ones with BAP1 retained/high miR-31 levels. The BAP1 and miR-31 combination was confirmed at multivariate analysis as an independent prognostic factor for e-MPM patients. Conclusion: BAP1 alone is unable to stratify MPM patients based on its expression when histotype was considered. Otherwise, in e-MPM patients, prognostic stratification may be improved by simultaneously assessing of BAP1 status and miR-31 levels. The two-biomarker score is useful to identify a subgroup of e-MPM tumors with worse clinical outcome

Validation strategy of reduced-order two-fluid flow models based on a hierarchy of direct numerical simulations

International audienceWhereas direct numerical simulation (DNS) have reached a high level of description in the field of atomization processes, they are not yet able to cope with industrial needs since they lack resolution and are too costly. Predictive simulations relying on reduced order modeling have become mandatory for applications ranging from cryotechnic to aeronautic combustion chamber liquid injection. Two-fluid models provide a good basis in order to conduct such simulations, even if recent advances allow to refine subscale modeling using geometrical variables in order to reach a unified model including separate phases and disperse phase descriptions based on high order moment methods. The simulation of such models has to rely on dedicated numerical methods and still lacks assessment of its predictive capabilities. The present paper constitutes a building block of the investigation of a hierarchy of test-cases designed to be amenable to DNS while close enough to industrial configurations, for which we propose a comparison of two-fluid compressible simulations with DNS data-bases. We focus in the present contribution on an air-assisted water atomization using a planar liquid sheet injector. Qualitative and quantitative comparisons with incompressible DNS allow us to identify and analyze strength and weaknesses of the reduced-order modeling and numerical approach in this specific configuration and set a framework for more refined models since they already provide a very interesting level of comparison on averaged quantities

Expectations and psychological issues before genetic counseling: analysis of distress determinant factors

Hereditary non-polyposis colorectal cancer (HNPCC) and Hereditary Breast and Ovarian Cancer Syndrome (HBOC) are the most common hereditary cancer syndromes in which a genetic test is available. Potential risks associated with testing include psychological harm, emotional distress and insurance problems

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents

Clinical impact of different exosomes' protein expression in pancreatic ductal carcinoma patients treated with standard first line palliative chemotherapy.

IntroductionPancreatic ductal adenocarcinoma is associated to dismal prognosis despite the use of palliative chemotherapy, partly due to the lack of knowledge of biological processes underlying disease progression. Exosomes have been identified as biomarkers sources in different cancer types. Aim of the study was to analyse the contents of circulating exosomes in patients with pancreatic cancer who received palliative chemotherapy.Patients and methodsPatients were submitted to blood sample collection before chemotherapy (T0) and after 3 months (T3). We quantified by an ELISA-based technique specific proteins of cancer-derived exosomes (CD44,CD44v6,EpCAM,CD9,CD81,Tspan8,Integrin α6,Integrin β4,CD24,CXCR4). We correlated the baseline levels of these factors and changes between T3 and T0 and survival outcomes. Survival analyses were performed by Kaplan-Meier method. Correlation was assessed by log-rank test and level of statistical significance was set at 0.05. Multivariate analysis was performed by logistic regression analysis.ResultsNineteen patients were enrolled. EpCAM T0 levels and increased EpCAM levels from T0 to T3 were those mostly associated with differences in survival. Patients having higher EpCAM had median progression free survival (PFS) of 3.18vs7.31 months (HR:2.82,95%CI:1.03-7.73,p = 0.01). Overall survival (OS) was shorter for patients having higher EpCAM (5.83vs16.45 months,HR:6.16,95%CI:1.93-19.58,p = 0.0001) and also response rates (RR) were worse (20%vs87%,p = 0.015). EpCAM increase during treatment was associated with better median PFS (2.88vs7.31 months,HR:0.24,95%CI:0.04-1.22,p = 0.003). OS was also better (8.75vs11.04 months, HR:0.77,95%CI:0.21-2.73,p = 0.66) and RR were 60%vs20% (p = 0.28). Among clinical factors that might determine changes on PFS and OS, only ECOG PS was associated to significantly worse PFS and OS (p = 0.0137andConclusionsPancreatic cancer patients exosomes express EpCAM, whose levels change during treatment. This represents a useful prognostic factor and also suggests that future treatment modalities who target EpCAM should be tested in pancreatic cancer patients selected by exosome EpCAM expression

Lynch syndrome-associated lung cancer: pitfalls of an immunotherapy-based treatment strategy in an unusual tumor type

: Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved for the treatment of NSCLC patients and represents a promising treatment option for patients with advanced metastatic MMR-deficient cancer, regardless of tumor origin. This case report describes the clinical presentation and management of a 74-year-old female with a history of rectal adenocarcinoma and ovarian cancer, who has a documented frameshift pathogenic variant in the exon 8 of MSH6 gene and an intronic variant in the BRCA2 gene (classified as a variant of uncertain significance), affected by NSCLC with brain metastases. Despite these premises, the patient was treated with pembrolizumab and she did not benefit from this kind of treatment

Patients’ characteristics.

<p>Patients’ characteristics.</p