EV-Associated miRNAs from Peritoneal Lavage are a Source of Biomarkers in Endometrial Cancer

Endometrial cancer (EC) is the sixth most common cancer in women worldwide and is responsible for more than 89,000 deaths every year. Mortality is associated with presence of poor prognostic factors at diagnosis, i.e., diagnosis at an advanced stage, with a high grade and/or an aggressive histology. Development of novel approaches that would permit us to improve the clinical management of EC patients is an unmet need. In this study, we investigate a novel approach to identify highly sensitive and specific biomarkers of EC using extracellular vesicles (EVs) isolated from the peritoneal lavage of EC patients. EVs of peritoneal lavages of 25 EC patients were isolated and their miRNA content was compared with miRNAs of EVs isolated from the ascitic fluid of 25 control patients. Expression of the EV-associated miRNAs was measured using the Taqman OpenArray technology that allowed us to detect 371 miRNAs. The analysis showed that 114 miRNAs were significantly dysregulated in EC patients, among which eight miRNAs, miRNA-383-5p, miRNA-10b-5p, miRNA-34c-3p, miRNA-449b-5p, miRNA-34c-5p, miRNA-200b-3p, miRNA-2110, and miRNA-34b-3p, demonstrated a classification performance at area under the receiver operating characteristic curve (AUC) values above 0.9. This finding opens an avenue for the use of EV-associated miRNAs of peritoneal lavages as an untapped source of biomarkers for EC

EV-associated miRNAs from peritoneal lavage as potential diagnostic biomarkers in colorectal cancer

Background: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality worldwide. Current systematic methods for diagnosing have inherent limitations so development of a minimally-invasive diagnosis, based on the identification of sensitive biomarkers in liquid biopsies could therefore facilitate screening among population at risk. Methods: In this study, we aim to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the peritoneal lavage as a source of potential miRNA diagnostic biomarkers. We isolated EVs by ultracentrifugation from 25 ascitic fluids and 25 peritoneal lavages from non-cancer and CRC patients, respectively. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 371 miRNAs. Results: 210 miRNAs were significantly dysregulated (adjusted p value < 0.05 and abs(logFC) ≥ 1). The top-10 miRNAs, which had the AUC value higher than 0.95, were miRNA-199b-5p, miRNA-150-5p, miRNA-29c-5p, miRNA-218-5p, miRNA-99a-3p, miRNA-383-5p, miRNA-199a-3p, miRNA-193a-5p, miRNA-10b-5p and miRNA-181c-5p. Conclusions: This finding opens the avenue to the use of EV-associated miRNA of peritoneal lavages as an untapped source of biomarkers for CRC.EC hold a postdoctoral fellowship from the Departament de Salut of the Generalitat de Catalunya (SLT002/16/00274). This work was supported by grants: Discovery, validation and implementation of biomarkers for Precision Oncology (ISCIII PIE15/00029), CIBERONC (CB16/12/00231 and CB16/12/00328). Grups consolidats de la Generalitat de Catalunya (2017SGR1368 and 2017SGR1661). Work supported by IRBLleida BIOBANK (B.0000682) and Plataforma biobancos PT17/0015/0027

Characteristics and outcome of Streptococcus pneumoniae endocarditis in the XXI Century: a systematic review of 111 cases (2000-2013)

Streptococcus pneumoniae is an infrequent cause of severe infectious endocarditis (IE). The aim of our study was to describe the epidemiology, clinical and microbiological characteristics, and outcome of a series of cases of S. pneumoniae IE diagnosed in Spain and in a series of cases published since 2000 in the medical literature. We prospectively collected all cases of IE diagnosed in a multicenter cohort of patients from 27 Spanish hospitals (n = 2539). We also performed a systematic review of the literature since 2000 and retrieved all cases with complete clinical data using a pre-established protocol. Predictors of mortality were identified using a logistic regression model. We collected 111 cases of pneumococcal IE: 24 patients from the Spanish cohort and 87 cases from the literature review. Median age was 51 years, and 23 patients (20.7%) were under 15 years. Men accounted for 64% of patients, and infection was community-acquired in 96.4% of cases. The most important underlying conditions were liver disease (27.9%) and immunosuppression (10.8%). A predisposing heart condition was present in only 18 patients (16.2%). Pneumococcal IE affected a native valve in 93.7% of patients. Left-sided endocarditis predominated (aortic valve 53.2% and mitral valve 40.5%). The microbiological diagnosis was obtained from blood cultures in 84.7% of cases. In the Spanish cohort, nonsusceptibility to penicillin was detected in 4.2%. The most common clinical manifestations included fever (71.2%), a new heart murmur (55%), pneumonia (45.9%), meningitis (40.5%), and Austrian syndrome (26.1%). Cardiac surgery was performed in 47.7% of patients. The in-hospital mortality rate was 20.7%. The multivariate analysis revealed the independent risk factors for mortality to be meningitis (OR, 4.3; 95% CI, 1.4-12.9; P < 0.01). Valve surgery was protective (OR, 0.1; 95% CI, 0.04-0.4; P < 0.01). Streptococcus pneumoniae IE is a community-acquired disease that mainly affects native aortic valves. Half of the cases in the present study had concomitant pneumonia, and a considerable number developed meningitis. Mortality was high, mainly in patients with central nervous system (CNS) involvement. Surgery was protective

Predictors of clinically significant quality of life impairment in Parkinson’s disease

COPPADIS Study Group.Quality of life (QOL) plays an important role in independent living in Parkinson’s disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson’s disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months ± 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 ≥ 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 ± 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 ± 13 to 20.3 ± 16.4; p < 0.0001) at V2. Ninety-three patients (18.6%) presented a clinically significant HRQoL impairment at V2. To be younger (OR = 0.896; 95% CI 0.829–0.968; p = 0.006), to be a female (OR = 4.181; 95% CI 1.422–12.290; p = 0.009), and to have a greater increase in BDI-II (Beck Depression Inventory-II) (OR = 1.139; 95% CI 1.053–1.231; p = 0.001) and NMSS (Non-Motor Symptoms Scale) (OR = 1.052; 95% CI 1.027–1.113; p < 0.0001) total scores from V0 to V2 were associated with clinically significant HRQoL impairment at the 2-year follow-up (Hosmer–Lemeshow test, p = 0.665; R 2 = 0.655). An increase in ≥5 and ≥10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (OR = 5.453; 95% CI 1.663–17.876; p = 0.005) and 8 (OR = 8.217; 95% CI, 2.975–22.696; p = 0.002), respectively. In conclusion, age, gender, mood, and non-motor impairment were associated with clinically significant HRQoL impairment after the 2-year follow-up in PD patients.Mir P. has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB and Zambon and have received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña.Peer reviewe

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up

COPPADIS Study Group.[Background and Objective] Non-motor symptoms (NMS) progress in different ways between Parkinson’s disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group.[Material and Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable).[Results] After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = −0.52), change from V0 to V2 in PDSS (Parkinson’s Disease Sleep Scale) (β = −0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865).[Conclusions] Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.This research was funded by Fundación Española de Ayuda a la Investigación en Parkinson y otras Enfermedades Neuro-degenerativas (Curemos el Parkinson; www.curemoselparkinson.org).Peer reviewe

Provirus reactivation is impaired in HIV-1 infected individuals on treatment with dasatinib and antiretroviral therapy

The latent viral reservoir formed by HIV-1, mainly in CD4 + T cells, is responsible for the failure of antiretroviral therapy (ART) to achieve a complete elimination of the virus in infected individuals. We previously determined that CD4 + T cells from individuals with chronic myeloid leukemia (CML) on treatment with dasatinib are resistant to HIV-1 infection ex vivo. The main mechanism for this antiviral effect is the preservation of SAMHD1 activity. In this study, we aimed to evaluate the impact of dasatinib on the viral reservoir of HIV-infected individuals with CML who were on simultaneous treatment with ART and dasatinib. Due to the low estimated incidence of HIV-1 infection and CML (1:65,000), three male individuals were recruited in Spain and Germany. These individuals had been on treatment with standard ART and dasatinib for median 1.3 years (IQR 1.3-5.3 years). Reservoir size and composition in PBMCs from these individuals was analyzed in comparison with HIV-infected individuals on triple ART regimen and undetectable viremia. The frequency of latently infected cells was reduced more than 5-fold in these individuals. The reactivation of proviruses from these cells was reduced more than 4-fold and, upon activation, SAMHD1 phosphorylation was reduced 40-fold. Plasma levels of the homeostatic cytokine IL-7 and CD4 effector subpopulations TEM and TEMRA in peripheral blood were also reduced. Therefore, treatment of HIV-infected individuals with dasatinib as adjuvant of ART could disturb the reservoir reactivation and reseeding, which might have a beneficial impact to reduce its size

Monitorización del consumo de sustancias de abuso legales e ilegales en España a través de las aguas residuales en el marco de la red ESAR-Net

Trabajo presentado en el 4th Congreso Internacional y XLIX Jornadas Nacionales de Socidrogalcohol - VIII Congreso Nacional Patología Bio-Psicosocial, celebrado en Tenerife del 06 al 08 de octubre de 2022

Predictors of Loss of Functional Independence in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up and Comparison with a Control Group

COPPADIS Study Group.[Background and objective] The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson’s disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD).[Patients and Methods] PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%.[Results] In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen’s effect size = −0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2.[Conclusions] In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.Fundación Curemos el Parkinson (www.curemoselparkinson.org).Peer reviewe

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

Virally suppressed HIV-positive individuals on combination antiretroviral therapy who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality. The increased mortality was seen across different patient groups and for all causes of deat