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Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population. The β-galactoside binding protein Galectin-1 (Gal-1) is a protein with a wide range of pro-tumor functions such as proliferation, invasion, angiogenesis, and immune suppression. Here, we evaluated Gal-1 expression by immunohistochemistry in a homogenously treated cohort of GBM (the GLIOCAT project) and correlated its expression with clinical and molecular data. We observed that Gal-1 is a negative prognostic factor in GBM. Interestingly, we observed higher levels of Gal-1 expression in the mesenchymal/classical subtypes compared to the less aggressive proneural subtype. We also observed a Gal-1 expression correlation with immune suppressive signatures of CD4 T-cells and macrophages, as well as with several GBM established biomarkers, including SHC1, PD-L1, PAX2, MEOX2, YKL-40, TCIRG1, YWHAG, OLIG2, SOX2, Ki-67, and SOX11. Moreover, Gal-1 levels were significantly lower in grade 4 IDH-1 mutant astrocytomas, which have a better prognosis. Our results confirm the role of Gal-1 as a prognostic factor and also suggest its value as an immune-suppressive biomarker in GBM.

Height-adjusted total kidney volume (htTKV) is the best marker of disease progression in early autosomal dominant polycystic kidney disease (ADPKD) when renal function still remains normal. The usefulness of cystatin-C as a biomarker to assess renal function according to renal volume has not been studied in ADPKD patients. Observational and cross-sectional study of 62 ADPKD patients. htTKV, creatinine and cystatin-C estimated glomerular filtration rate (eGFR) were determined. Correlations between htTKV and eGFR were studied. A control group was used to determine the association between renal function differences and htTKV. htTKV significantly correlated with cystatin-C-eGFR (r = -0.384, p = 0.002) but not with creatinine-eGFR (r = -0.225, p = 0.078). With htTKV stratified into tertiles, a significant difference of cystatin-C-eGFR but not in creatinine-eGFR was detected in the third tertile when compared with the first tertile group (110.0±22.2 vs 121.3±7.2; p = 0.023 and 101.8±17.2 vs 106.9±15.1; p = 0.327 respectively). When cystatin-C-eGFR of the controls was used as the reference, htTKV above 605 ml/m identified with a 75% sensitivity and 84.9% specificity those patients with a significant worse kidney function. However, this cut-off value could not be identified using creatinine-eGFR. Cystatin-C-eGFR but not creatinine-eGFR correlated with htTKV in ADPKD patients in early stages of the disease. Differences in cystatin-C-eGFR but not in creatinine-eGFR have been identified through htTKV tertiles. A htTKV above 605 ml/m is associated with a worse renal function only if cystatin-C-eGFR is used. Cystatin-C-eGFR should be studied in prospective studies of early stages of ADPKD to determine its usefulness as an early marker of disease progression.

To assess whether serum osteoprotegerin (OPG) and/or fetuin-A predict mortality and cardiovascular (CV) morbidity and mortality in hemodialysis patients. Multicenter, observational, prospective study that included 220 hemodialysis patients followed up for up to 6 years. Serum OPG and fetuin-A levels were measured at baseline and their possible association with clinical characteristics, CV risk biomarkers, carotid ultrasonographic findings, as well as their association with overall and CV mortality and CV events were assessed. During a mean follow-up of 3.22 ± 1.91 years, there were 74 deaths (33.6%) and 86 new cardiovascular events. In the Kaplan-Meier survival analysis, the highest tertile of OPG levels was associated with higher overall mortality (p = 0.005), as well as a higher, although non-significant, incidence of CV events and CV mortality. In contrast, fetuin-A levels did not predict any of these events. OPG levels were directly associated with age, the Charlson comorbidity index (CCI), prevalent cardiovascular disease, carotid intima-media thickness, adiponectin, troponin-I and brain natriuretic peptide (BNP). OPG showed a negative correlation with left ventricular ejection fraction (LVEF) and phosphate levels. In the multivariate Cox proportional hazard analysis, all-cause mortality was associated with the highest tertile of OPG (HR:1.957, p = 0.018), age (HR:1.031, p = 0.036), smoking history (HR:2.122, p = 0.005), the CCI (HR:1.254, p = 0.004), troponin-I (HR:3.894, p = 0.042), IL-18 (HR:1.061, p < 0.001) and albumin levels (HR:0.886, p < 0.001). In the bootstrapping Cox regression analysis, the best cut-off value of OPG associated with mortality was 17.69 pmol/L (95%CI: 5.1-18.02). OPG, but not fetuin-A levels, are independently associated with overall mortality, as well as clinical and subclinical atherosclerosis and cardiac function, in prevalent hemodialysis patients. The online version of this article (10.1186/s12882-017-0701-8) contains supplementa

Alfonso Anton,1–4 Monica Fallon,3,5 Francesc Cots,2 María A Sebastian,6 Antonio Morilla-Grasa,4 Sergi Mojal,3 Xavier Castells2 1Medicine School, Universidad Internacional de Cataluña, 2Servei d’Estudies, Parc de Salut Mar, 3Instituto Hospital del Mar de Investigaciones Médicas (IMIM), 4Glaucoma Department, Instituto Catalán de Retina (ICR), 5Universidad Autónoma de Barcelona, 6Centro de Atención Primaria Larrard, Barcelona, Spain Purpose: To analyze the cost and detection rate of a screening program for detecting glaucoma with imaging devices. Materials and methods: In this cross-sectional study, a glaucoma screening program was applied in a population-based sample randomly selected from a population of 23,527. Screening targeted the population at risk of glaucoma. Examinations included optic disk tomography (Heidelberg retina tomograph [HRT]), nerve fiber analysis, and tonometry. Subjects who met at least 2 of 3 endpoints (HRT outside normal limits, nerve fiber index ≥30, or tonometry ≥21 mmHg) were referred for glaucoma consultation. The currently established (“conventional”) detection method was evaluated by recording data from primary care and ophthalmic consultations in the same population. The direct costs of screening and conventional detection were calculated by adding the unit costs generated during the diagnostic process. The detection rate of new glaucoma cases was assessed. Results: The screening program evaluated 414 subjects; 32 cases were referred for glaucoma consultation, 7 had glaucoma, and 10 had probable glaucoma. The current detection method assessed 677 glaucoma suspects in the population, of whom 29 were diagnosed with glaucoma or probable glaucoma. Glaucoma screening and the conventional detection method had detection rates of 4.1% and 3.1%, respectively, and the cost per case detected was 1,410 and 1,435€, respecti

Cardiovascular disease, closely related to an early appearance of hypertension, is the most common mortality cause among autosomal dominant polycystic kidney disease patients (ADPKD). The development of hypertension is related to an increase in renal volume. Whether the increasing in the renal volume before the onset of hypertension leads to a major cardiovascular risk in ADPKD patients remains unknown. Observational and cross-sectional study of 62 normotensive ADPKD patients with normal renal function and a group of 28 healthy controls. Renal volume, blood pressure, and renal (urinary albumin excretion), blood vessels (carotid intima media thickness and carotid-femoral pulse wave velocity), and cardiac (left ventricular mass index and diastolic dysfunction parameters) asymptomatic organ damage were determined and were considered as continuous variables. Correlations between renal volume and the other parameters were studied in the ADPKD population, and results were compared with the control group. Blood pressure values and asymptomatic organ damage were used to assess the cardiovascular risk according to renal volume tertiles. Even though in the normotensive range, ADPKD patients show higher blood pressure and major asymptomatic organ damage than healthy controls. Asymptomatic organ damage is not only related to blood pressure level but also to renal volume. Multivariate regression analysis shows that microalbuminuria is only associated with height adjusted renal volume (htTKV). An htTKV above 480 mL/m represents a 10 times higher prevalence of microalbuminuria (4.8% vs 50%, P < 0.001). Normotensive ADPKD patients from the 2nd tertile renal volume group (htTKV > 336 mL/m) show higher urinary albumin excretion, but the 3rd tertile htTKV (htTKV > 469 mL/m) group shows the worst cardiovascular risk profile. Normotensive ADPKD patients show in the early stages of the disease with slight increase in renal volume, higher cardiovascular risk than healthy controls. An htTK

[Abstract] Background. Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3–5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Methods. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. Results. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Conclusions. Circulating ACE2 and ACE activities ca

Olatz Urbina,1 Olivia Ferrández,1 Sònia Luque,1 Santiago Grau,1,2 Sergi Mojal,3 Rosa Pellicer,1 Marta Riu,4 Esther Salas,1 Josep Comin-Colet5 1Pharmacy Department, Hospital Universitari del Mar, Barcelona, Spain; 2Universitat Autònoma de Barcelona, Barcelona, Spain; 3Department of Statistics, Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain; 4Department of Epidemiology and Health Services Evaluation, CIBER de Epidemiología y Salud Pública (CIBERESP), Hospital Universitari del Mar, Barcelona, Spain; 5Heart Failure Unit, Cardiology Department, Hospital Universitari del Mar, Barcelona, Spain Background: Because of the high incidence of drug-related problems (DRPs) among hospitalized patients with cardiovascular diseases and their potential impact on morbidity and mortality, it is important to identify the most susceptible patients, who therefore require closer monitoring of drug therapy.Purpose: To identify the profile of patients at higher risk of developing at least one DRP during hospitalization in a cardiology ward.Method: We consecutively included all patients hospitalized in the cardiology ward of a teaching hospital in 2009. DRPs were identified through a computerized warning system designed by the pharmacy department and integrated into the electronic medical record.Results: A total of 964 admissions were included, and at least one DRP was detected in 29.8%. The variables associated with a higher risk of these events were polypharmacy (odds ratio [OR]=1.228; 95% confidence interval [CI]=1.153–1.308), female sex (OR=1.496; 95% CI=1.026–2.180), and first admission (OR=1.494; 95% CI=1.005–2.221).Conclusion: Monitoring patients through a computerized warning system allowed the detection of at least one DRP in one-third of the patients. Knowledge of the risk factors for developing these problems in patients admitted to hospital for

[EN] Purpose: To track the saline during infusion with a 15 G needle into healthy pig livers at high and low infusion rates for 300 s. Methods: In each experiment, the needle was inserted into a single lobe of the liver to a depth of at least 2 cm following its longer axis. Two sets of experiments were defined: 1) low infusion rate of 0.1 mL/min (n = 6) and 2) high infusion rate of 1 mL/min (n = 6). Cine CT scans were carried out and three transverse planes were defined around the infusion point (IP), which corresponds with needle tip. Two assessments were performed: 1) a dynamic plane study focused on the time progress of the saline distribution on a single plane, which provided the Mean Percentage of Grayscale Intensity (MPG!): and 2) a volumetric study focused on the three dimensional distribution of the saline around IP at the end of the experiment, which provided the High Intensity Volume Ratio (HIVR). Results: The saline solution was conspicuous around the IP and shortly after heterogeneously inside the vessels. At the high infusion rate, the saline became conspicuous not only much sooner (evident at 20 s) but farther away (mean value of MPGI over 2%, up to 17 mm from the IP) and at a much higher intensity (mean value of MPGI over 10% up to 4 mm from the IP). The lower the radial distance to the IP, the greater the difference in HIVR between both groups. Conclusions: The high infusion rate leads to a faster, wider and a more marked presence of saline than the low rate. The rapid drainage into the hepatic veins may explain the heterogeneous distribution. (C) 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

[EN] Purpose: To track the saline during infusion with a 15 G needle into healthy pig livers at high and low infusion rates for 300 s. Methods: In each experiment, the needle was inserted into a single lobe of the liver to a depth of at least 2 cm following its longer axis. Two sets of experiments were defined: 1) low infusion rate of 0.1 mL/min (n = 6) and 2) high infusion rate of 1 mL/min (n = 6). Cine CT scans were carried out and three transverse planes were defined around the infusion point (IP), which corresponds with needle tip. Two assessments were performed: 1) a dynamic plane study focused on the time progress of the saline distribution on a single plane, which provided the Mean Percentage of Grayscale Intensity (MPG!): and 2) a volumetric study focused on the three dimensional distribution of the saline around IP at the end of the experiment, which provided the High Intensity Volume Ratio (HIVR). Results: The saline solution was conspicuous around the IP and shortly after heterogeneously inside the vessels. At the high infusion rate, the saline became conspicuous not only much sooner (evident at 20 s) but farther away (mean value of MPGI over 2%, up to 17 mm from the IP) and at a much higher intensity (mean value of MPGI over 10% up to 4 mm from the IP). The lower the radial distance to the IP, the greater the difference in HIVR between both groups. Conclusions: The high infusion rate leads to a faster, wider and a more marked presence of saline than the low rate. The rapid drainage into the hepatic veins may explain the heterogeneous distribution. (C) 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Objective: Orthodontic mini-implants (OMIs) are increasingly used in orthodontics but can fail for various reasons. This study investigates the effects of OMI design characteristics on the mechanical properties in artificial bone. Material and Methods: Twelve self-drilling OMIs (2 small, 6 medium, 4 large) from 8 manufacturers were tested for their primary stability in simulated medium-high cancellous bone and the risk to fracture in high-density methacrylate blocks. For the assessments of the maximum insertion torque (IT) and torsional fracture (TF) 5 of each OMI were used and for the pull-out strength (POS) 10. The OMIs were inserted with a torque screwdriver (12 sec/360°) until the bottom at 8 mm depth was reached. OMI designs were analyzed with a scan electron microscope (SEM). Results: SEM images revealed a great variation in product refinement. In the whole sample, a cylindrical OMI shape was associated with higher POS (p<0.001) but lower IT (p=0.002) values. The outer and inner OMI diameters were design characteristics well correlated with POS, IT and TF values (ranging from 0.601 to 0.961). Greater thread depth was related to greater POS values (r= 0.628), although OMIs with similar POS values may have different IT values. Thread depth and pitch had some impact on POS. TF depended mainly on the OMI inner (r= 0.961) and outer diameters (r=0.892). A thread depth to outer diameter ratio close to 40% increased TF risk. Conclusion: Although at the same insertion depth the OMI outer and inner diameters are the most important factors for primary stability, other OMI design characteristics (cylindrical vs. conical, thread design) may significantly affect primary stability and torsional fracture. This needs to be considered when selecting the appropriate OMI for the desired orthodontic procedures., Peer Reviewed, Postprint (published version)