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  • Publication
    Role of S100B protein in urine and serum as an early predictor of mortality after severe traumatic brain injury in adults
    (Elsevier, 2012-09-29) Rodriguez-Rodriguez, Ana; Egea-Guerrero, Juan Jose; Leon-Justel, Antonio; Gordillo-Escobar, Elena; Revuelto-Rey, Jaume; Vilches-Arenas, Angel; Carrillo-Vico, Antonio; Dominguez-Roldan, Jose Maria; Murillo-Cabezas, Francisco; Guerrero, Juan Miguel; [Rodriguez-Rodriguez,A; Leon-Justel,A; Guerrero,JM] Department of Clinical Biochemistry, Virgen del Rocio University Hospital, IBIS/CSIC/University of Seville, Spain. [Egea-Guerrero,JJ; Gordillo-Escobar,E; Revuelto-Rey,J; Carrillo-Vico,A; Domínguez-Roldán,JM; Murillo-Cabezas,F] NeuroCritical Care Unit, Virgen del Rocío University Hospital, IBIS/CSIC/University of Seville, Seville, Spain. [Vilches-Arenas,A] Department Preventive Medicine and Public Health, University of Seville, Spain.
    S100B is a calcium-binding protein released into the blood from astroglial cells due to brain injury. Some authors have described a correlation between S100B serum concentration and severity of brain damage. There is not much information about the accuracy of urinary S100B for predicting outcome after severe traumatic brain injury (TBI). 55 patients with severe TBI were included in the study. Blood and urine samples were drawn to determine S100B levels on admission and on the subsequent 24, 48, 72 and 96 h. S100B concentrations (serum and urine) were significantly higher in patients who were dead a month after the accident compared to survivors. ROC-analysis showed that S100B at 24 h post-severe TBI is a useful tool for predicting mortality (serum: AUC 0.958, urine: AUC 0.778). The best cut-offs for S100B were 0.461 μg/L and 0.025 μg/L (serum and urine respectively), with a sensitivity of 90% for both measurements and a specificity of 88.4% (serum) and 62.8% (urine). We can state that the determination of S100B levels both in urine and serum acts as a sensitive and an effective biomarker for the early prediction of mortality after severe TBI.
  • Publication
    A Probabilistic Model for Cushing’s Syndrome Screening in At-Risk Populations: A Prospective Multicenter Study
    (Oxford University Press, 2016-08-14) Leon-Justel, Antonio; Madrazo-Atutxa, Ainara; Alvarez-Rios, Ana I.; Infantes-Fontan, Rocio; Garcia-Arnes, Juan A.; Lillo-Muñoz, Juan A.; Aulinas, Anna; Urgell-Rull, Eulalia; Boronat, Mauro; Sanchez-de-Abajo, Ana; Fajardo-Montañana, Carmen; Ortuño-Alonso, Mario; Salinas-Vert, Isabel; Granada, Maria L.; Cano, David A.; Leal-Cerro, Alfonso; CRISALIDA Study Group
    Context: Cushing’s syndrome (CS) is challenging to diagnose. Increased prevalence of CS in specific patient populations has been reported, but routine screening for CS remains questionable. To decrease the diagnostic delay and improve disease outcomes, simple new screening methods for CS in at-risk populations are needed. Objective: To develop and validate a simple scoring system to predict CS based on clinical signs and an easy-to-use biochemical test. Design: Observational, prospective, multicenter. Setting: Referral hospital. Patients: A cohort of 353 patients attending endocrinology units for outpatient visits. Interventions: All patients were evaluated with late-night salivary cortisol (LNSC) and a low-dose dexamethasone suppression test for CS. Main Outcome Measures: Diagnosis or exclusion of CS. Results: Twenty-six cases of CS were diagnosed in the cohort. A risk scoring system was developed by logistic regression analysis, and cutoff values were derived from a receiver operating characteristic curve. This risk score included clinical signs and symptoms (muscular atrophy, osteoporosis, and dorsocervical fat pad) and LNSC levels. The estimated area under the receiver operating characteristic curve was 0.93, with a sensitivity of 96.2% and specificity of 82.9%. Conclusions: We developed a risk score to predict CS in an at-risk population. This score may help to identify at-risk patients in non-endocrinological settings such as primary care, but external validation is warranted.
  • Publication
    Budget impact of using midnight salivary cortisol in the diagnosis of hypercortisolism
    (Elsevier, 2011-08-16) Leon-Justel, Antonio; Mangas, Miguel Angel; Infante-Fontán, Rocío; Castro-Luque, Jovanna; Venegas-Moreno, Eva; Madrazo-Atutxa, Ainara; Herrera del Rey, Teresa; Martin-Rodriguez, Juan Francisco; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; [Leon-Justel,A; Infante Fontán,R; Castro Luque,J; Herrera del Rey,T] Department of Clinical Biochemistry, Virgen del Rocío University Hospital, Seville, Spain. [Mangas,MA; Venegas Moreno,E; Madrazo Atutxa,A; Martin-Rodriguez,JF; Soto-Moreno,A; Leal-Cerro,A] Division of Endocrinology, Virgen del Rocío University Hospital, Seville, Spain. [Castro Luque,J; Venegas Moreno,E; Madrazo Atutxa,A; Herrera del Rey,T; Martin-Rodriguez,JF; Soto-Moreno,A; Leal-Cerro,A] Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Spain.
    Background: A single midnight serum cortisol (MSC) test has been reported to possess the best sensitivity and specificity for diagnosing Cushing's syndrome (CS). However, this test requires patient hospitalization, making it costly. This paper aims to compare the hospital budget impact and accuracy of using midnight salivary cortisol (MSVC), as opposed to MSC, in the diagnosis of hypercortisolism. Methods: 77 patients with at least two high urinary free cortisol (UFC) values (N360 nmol/24 h) were selected from 611 patients with clinical symptoms of CS. The costs of the method to confirm the diagnosis of hypercortisolism was calculated comparing Option A using MSC (UFCx2, low-dose dexamethasone suppression test [LDDST]) that requires patient hospitalization versus Option B using MSVC (UFCx2, LDDST) in which the evaluation is done outside the Hospital. A budget impact analysis for one year was developed, and a sensitivity analysis in different scenarios was performed. Reproducibility and diagnostic performance of MSVC and MSC were also measured. Results: Salivary cortisol is a sound analytical method for evaluating free serum cortisol due to its classification accuracy, good imprecision, linearity, and stability. AUCROC comparison between MSVC and MSC shows no significant differences. The substitution of the MSC for MSVC in our hospital could save between €16,762 and €132,804 in one year. Conclusions: The use of MSVC in the diagnosis of hypercortisolism can result in a substantial decrease in the budget impact, without losing diagnosis accuracy and reliability, a significant advantage considering the current emphasis on reducing the financial burden of health care.
  • Publication
    Alcohol use disorders among surgical patients: Unplanned 30-days readmissions, length of hospital stay, excessive costs and mortality
    (Elsevier, 2014-01-30) Gili-Miner, Miguel; Bejar-Prado, Luis; Gili-Ortiz, Enrique; Ramirez-Ramirez, Gloria; Lopez-Mendez, Julio; Lopez-Millan, Jose Manuel; Sharp, Brett; [Gili-Miner,M; Ramirez-Ramirez,G; Lopez-Mendez,J] a Unidad de Gestión Clínica de Medicina Preventiva, Vigilancia y Promoción de la Salud, Hospital Universitario Virgen Macarena, Seville, Spain. [Gili-Miner,M; Béjar-Prado,L; Ramírez-Ramírez,G; Lopez-Mendez,J] Departamento de Medicina Preventiva y Salud Pública, Universidad de Sevilla, Seville, Spain. [Gili-Ortiz,E] Unidad de Gestión Clínica de Anestesiología y Bloque Quirúrgico, Hospital Universitario Virgen Macarena, Seville, Spain. [Sharp,B] Unidad de Gestión Clínica de Diagnóstico por la Imagen, Hospital Universitario Virgen de Rocío, Seville, Spain.
    Aims: Alcohol use disorders (AUD) have been associated with an increased risk of unplanned hospital readmissions (URA). We analyzed in a sample of 87 Spanish Hospitals if surgical patients with AUD had a higher risk of URA and if among patients with URA, those with AUD had an excess length of hospital stay, higher hospital expenses and increased risk of mortality. Method: We analyzed data of patients who underwent surgical operations during the period between 2008 and 2010. URA was defined as unplanned readmissions during the first 30 days after hospital departure. The primary outcome was risk of URA in patients with AUD. Secondary outcomes were mortality, excess length of stay and over expenditure. Results: A total of 2,076,958 patients who underwent surgical operations were identified: 68,135 (3.3%) had AUD, and 62,045 (3.0%) had at least one URA. Among patients with AUD 4212 (6.2%) had at least one URA and among patients without AUD 57,833 (2.9%) had at least one URA. Multivariable analysis demonstrated that AUD was an independent predictor of developing URA (Odds ratio: 1.56; 95% CI: 1.50–1.62). Among surgical patients with URA, those with AUD had longer lengths of hospital stay (2.9 days longer), higher hospital costs (2885.8 Euros or 3858.3 US Dollars), higher risk of death (OR: 2.16, 95% CI: 1.92–2.44) and higher attributable mortality (11.2%). Conclusions: Among surgical patients, AUD increase the risk of URA, and among patients with URA, AUD heighten the risk of in-hospital death, and cause longer hospital stays and over expenditures.
  • Publication
    Point-of-care haemostasis monitoring during liver transplantation is cost effective
    (De Gruyter, 2019) Leon-Justel, Antonio; Alvarez-Rios Ana I; Noval-Padillo, Miguel A; Gómez-Bravo, Miguel Ángel; Porras, Manuel; Gomez-Sosa, Laura; Lopez-Romero, Juan L; Guerrero, Juan M; [Leon-Justel,A] Laboratory Medicine Department, Huelva University Hospital, Huelva, Spain. [Alvarez-Rios,A; Noval-Padillo,JA; Guerrero,JM] Department of Clinical Biochemistry, Virgen del Rocío University, Hospital, Seville, Spain; and Instituto de Biomedicina de Sevilla, IBIS (Universidad de Sevilla, HUVR, Junta de Andalucía, CSIC), Seville, Spain. [Gomez-Bravo,MA] Department of Hepatobiliary Surgery, Virgen del Rocío University Hospital, Seville, Spain. [Porras,M] Department of Intensive Care Medicine, Virgen del Rocío University Hospital, Seville, Spain. [Gomez-Sosa,L; Lopez-Romero,JL] Department of Anaesthesiology, Virgen del Rocío University Hospital, Seville, Spain.
    Background: Optimal haemostasis management in orthotropic liver transplant (OLT) could reduce blood loss and transfusion volume, improve patient outcomes and reduce cost. Methods: We performed a study including 336 OLTs to evaluate the clinical and cost effectiveness of a new pointof- care (POC)-based haemostatic management approach in OLT patients. Results: In terms of health benefit we found that the new approach showed a significant reduction in transfusion requirements (red blood cell transfusion units were reduced from 5.3 ± 4.6 to 2.8 ± 2.9 [p < 0.001], free frozen plasma from 3.1 ± 3.3 to 0.4 ± 1.0 [p < 0.001] and platelets from 2.9 ± 3.9 to 0.4 ± 0.9 [p < 0.001], transfusion avoidance, 9.7% vs. 29.1% [p < 0.001] and massive transfusion, 14.5% vs. 3.8% [p = 0.001]); we also found a significant improvement in patient outcomes, such, reoperation for bleeding or acute-kidney-failure (8.3% vs. 2.4%, p = 0.015; 33.6% vs. 5.4%, p < 0.001), with a significant reduction in the length of the hospital total stay (40.6 ± 13.8 days vs. 38.2 ± 14.4 days, p = 0.001). The lowest cost incurred was observed with the new approach (€73,038.80 vs. €158,912.90) with significant patient saving associated to transfusion avoidance (€1278.36), ICU-stay (€3037.26), total-stay (€3800.76) and reoperation for bleeding (€80,899.64). Conclusions: POC haemostatic monitoring during OLT is cost effective.
  • Publication
    S100B protein may detect brain death development after severe traumatic brain injury
    (Mary Ann Liebert, 2013-10-15) Egea-Guerrero, Juan J.; Murillo-Cabezas, Francisco; Gordillo-Escobar, Elena; Rodriguez-Rodriguez, Ana; Enamorado-Enamorado, Judy; Revuelto-Rey, Jaume; Pacheco-Sanchez, Maria; Leon-Justel, Antonio; Dominguez-Roldan, Jose M.; Vilches-Arenas, Angel; [Egea-Guerrero,JJ; Murillo-Cabezas,F; Gordillo-Escobar,E; Enamorado-Enamorado,J; Revuelto-Rey,J; Pacheco-Sanchez,M; Dominguez-Roldan,JM] NeuroCritical Care Unit, Virgen del Rocío University Hospital.; [Rodriguez-Rodriguez,A; Leon-Justel,A] Department of Clinical Biochemistry, Virgen del Rocı´o University Hospital.; [Vilches-Arenas,A] Department of Preventive Medicine and Public Health, IBIS/CSIC/University of Seville, Seville, Spain.
    Despite improvements in the process of organ donation and transplants, the number of organ donors is progressively declining in developed countries. Therefore, the early detection of patients at risk for brain death (BD) is a priority for transplant teams seeking more efficient identification of potential donors. In the extensive literature on S100B as a biomarker for traumatic brain injury (TBI), no evidence appears to exist on its prognostic capacity as a predictor of BD after severe TBI. The objective of this study is to assess the value of including acute S100B levels in standard clinical data as an early screening tool for BD after severe TBI. This prospective study included patients with severe TBI (Glasgow Coma Scale score [GCS] ≤8) admitted to our Neurocritical Care Unit over a 30 month period. We collected the following clinical variables: age, gender, GCS score, pupillary alterations at admission, hypotension and pre-hospital desaturation, CT scan results, isolated TBI or other related injuries, Injury Severity Score (ISS), serum S100B levels at admission and 24 h post-admission, and a final diagnosis regarding BD. Of the 140 patients studied, 11.4% developed BD and showed significantly higher S100B concentrations (p<0.001). Multivariate analysis showed that bilateral unresponsive mydriasis at admission and serum S100B at 24 h post-admission had odds ratios (ORs) of 21.35 (p=0.005) and 4.9 (p=0.010), respectively. The same analysis on patients with photomotor reflex in one pupil at admission left only the 24 h S100B sample in the model (OR=15.5; p=0.009). Receiver operating characteristics (ROC) curve analysis on this group showed the highest area under the curve (AUC) (0.86; p=0.001) for 24 h S100B determinations. The cut off was set at 0.372 μg/L (85.7% sensitivity, 79.3% specificity, positive predictive value [PPV]=18.7% and negative predictive value [NPV]=98.9%). This study shows that pupillary responsiveness at admission, as well as 24 h serum S100B levels, could serve as screening tools for the early detection of patients at risk for BD after severe TBI.
  • Publication
    Mobile Laboratory Unit: a disruptor solution for hemostasis management during major surgery. Usage in the context of face transplantation
    (De Gruyter, 2022-03-16) Leon-Justel, Antonio; Noval-Padillo, Jose Angel; Polonio, Francisco; Gomez-Cia, Tomas; Hinojosa, Rafael; Porras, Manuel; De-Blas, Jose M.; Solomon, Cristina; Guerrero, Juan M.; [Leon-Justel,A; Noval-Padillo,JA; Guerrero,JM] Department of Clinical Laboratory Sciences, Virgen del Rocío University Hospital, Seville, Spain.; [Polonio,F] Department of Anaesthesiology , Virgen del Rocío University Hospital, Seville, Spain.; [Gomez-Cia,T] Department of Plastic and Reconstructive Surgery and Burn Unit , Virgen del Rocío University Hospital, Seville, Spain.; [Hinojosa,R; Porras,M] Department of Intensive Care Medicine , Virgen del Rocío University Hospital, Seville, Spain.; [De-Blas,JM] Department of Haematology and Haemotherapy , Virgen del Rocío University Hospital, Seville, Spain.; [Solomon,C] Department of Anaesthesiology and Intensive Care Medicine , Salzburger Landeskliniken SALK, Salzburg, Austria.
    Background: The management of surgical bleeding during a face transplant in a patient diagnosed with bilateral neurofibromatosis is quite complex. With the actual methods and technology for hemostasis management, it may not always be possible to give the clinician the support needed to manage operative associated bleeding. Bedside hemostasis monitors are needed urgently to assist clinicians in making the correct diagnosis in a timely manner. Methods: Our Mobile Laboratory Unit is a disruptive solution for hemostasis management during major surgery as it allows real-time monitoring, the predominant mechanism of bleeding and goal-direct coagulation therapy. The unit is an autonomous mobile platform that can be moved immediately to anywhere its service is needed and offers a complete flexible laboratory test which includes biochemistry, hematology and coagulation studies as standard equipment. Results: In our case the test performed by the unit allowed us to identify the reason for our patient’s bleeding at the bedside. Severely decreased clot firmness of the fibrin-based clot and a less impaired firmness of the whole blood clot, suggested an acceptable contribution of platelets to the clot quality, but decreased polymerization of fibrinogen into fibrin. Conclusions: In our opinion new insights into the pathophysiology of coagulopathy, the availability of technology such as our Mobile Laboratory Unit, and awareness of side effects of intravenous fluids should encourage the idea that perhaps it is time to change hemostasis management in operation-related bleeding.
  • Publication
    Influence of reduction in the elution times on HPLC glycohaemoglobin results
    (Elsevier, 2009-07-16) Leon-Justel, Antonio; Santotoribio, Jose D.; Dominguez-Pascual, Inmaculada; Delgado, Ana L.; Macias, Carlos; Herrera, Maria T.; Leal, Alfonso; Mangas, Miguel A.; Acosta, Domingo; Guerrero, J.M.; [Leon-Justel,A; Santotoribio,JD; Dominguez-Pascual,I; Delgado,AL; Macias,C; Herrera,MT; Guerrero,JM] Department of Clinical Biochemistry, Virgen del Rocío University Hospital, IBIS/CSIC/University of Seville, Seville, Spain.; [Leal,A; Mangas,MA; Acosta,D] Clinical Management Unit for Endocrinology and Nutrition, Virgen del Rocío University Hospital, IBIS/CSIC/University of Seville, Seville, Spain.
    Objectives To compare HPLC methods with short and long elution times for HbA1c measurement in blood. Methods Comparison between G7-Tosoh (1.2 min); Bio-Rad-Variant-II-Turbo (1.3 min) and Arkray-HA-8160 (2.9 min). Results Passing–Bablok regression equations were: Y = 0.17 + 0.96X; Y = − 0.39 + 1.01X; Y = − 0.40 + 1.0X and the means of the differences using Bland–Altman Plot were 0.02; − 0.34; 0.32 for HA-8160/G7-Tosoh, HA-8160/Variant-II-Turbo and G7-Tosoh/Variant-II-Turbo, respectively. Conclusions Faster elution methods had no problems on reproducibility of results obtained by slower elution methods.
  • Publication
    A clinical profile of memory impairment in humans due to endogenous glucocorticoid excess
    (Wiley, 2009-01-19) León-Carrión, José; Atutxa, Ainara Madrazo; Mangas, Miguel Angel; Soto-Moreno, Alfonso; Pumar, Alfonso; Leon-Justel, Antonio; Martín-Rodriguez, Juan Francisco; Venegas, Eva; Domínguez-Morales, Mª Rosario; Leal-Cerro, Alfonso; [León-Carrión,J; Martín-Rodriguez,JF] Human Neuropsychology Laboratory, University of Seville.; [Atutxa, AM; Venegas, E] Division of Endocrinology, University Hospital Virgen del Rocío, Sevilla, Spain.; [Mangas, MA; Soto-Moreno,A; Pumar,A; Leal-Cerro,A] Institute of Biomedicine Seville (IBiS).; [Leon-Justel,A] Division of Chemical Analysis, University Hospital Virgen del Rocío, Sevilla, Spain.; [Domínguez-Morales, MR] Center for Brain Injury Rehabilitation (CRECER), Sevilla, Spain.
    Objective Glucocorticoid excess is commonly related to neuropsychiatric and neurological disorders, with memory impairment typically found among these disorders. The objective of this study is to offer a clinical profile of memory deficits resulting from exposure to chronic stress-level elevations of endogenous glucocorticoids in patients with Cushing's Syndrome (CS). Study subjects Thirty female participants of matching age and education level were studied: 15 had untreated CS (mean age 38 ± 14) and 15 were healthy. In all patients, CS was confirmed by histology of the lesion after surgery. Design Different learning and memory processes were assessed using an adapted version of Luria's Memory Words-Revised task (LMW-R). Participants’ performances were measured in an immediate condition and, 30 min later, in a delayed condition. Attentional and executive functions were also evaluated. Results Our data show that chronic exposure to elevated levels of cortisol is clinically associated with significant working memory deficits, which included less shot-term memory volume, slow learning rate, memory contamination and no accurate perception of own performance. Patients also show impairment in the delayed recall task. No relation was detected between learning and delayed conditions. CS group did not differ significantly from control group in basic attentional and executive functioning. Conclusions Our clinical profile of memory deficits related to CS relates chronic exposure to hypercortisolemia to impaired attentional-dependent working memory and delayed recall process, suggesting that cortisol levels play a critical role in the modulation of learning and memory. Possible damage to hippocampus and extrahippocampal areas is discussed.
  • Publication
    Indicación de tratamiento con tubo de drenaje endotorácico en derrames pleurales paraneumónicos, según la presión parcial de anhídrido carbónico de líquido pleural
    (Elsevier, 2008-06) Santotoribio, José Diego; Delgado-Pecellín, Carmen; Leon-Justel, Antonio; Guerrero, Juan Miguel; Servicio de Bioquímica Clínica, Hospital Universitario Virgen del Rocío, Sevilla, España.
    Fundamento y objetivo: Los derrames pleurales paraneumónicos (DPP) con un pH menor de 7,20 o glucosa menor de 0,40 g/l o lactatodeshidrogenasa (LDH) mayor de 1.000 U/l tienen indicación de tratamiento con tubo de drenaje endotorácico (TDE). El objetivo del presente estudio ha sido medir la exactitud que presenta la determinación de la presión parcial de anhídrido carbónico (pCO2) del líquido pleural para la indicación de tratamiento con TDE en los DPP mediante el cálculo del área bajo la curva (ABC) de eficacia diagnóstica, además de determinar su punto de corte óptimo. Pacientes y método: Se analizaron 207 líquidos pleurales, en los que se determinaron pCO2, pH, glucosa y LDH. Se recogió asimismo el diagnóstico etiológico del derrame pleural con que se dio el alta hospitalaria al paciente y si fue necesario tratamiento con TDE. Resultados: De los 207 líquidos pleurales estudiados, 46 fueron DPP, de los que 32 requirieron tratamiento con TDE. La ABC obtenida de la pCO2 fue 0,888 (p < 0,0001); la del pH, 0,890 (p < 0,0001); la de la glucosa, 0,816 (p < 0,0001), y la de la LDH, 0,801 (p < 0,0001). Las diferencias de las ABC carecieron de significación estadística. El punto de corte óptimo de la pCO2 resultó un valor superior a 48,6 mmHg, con una sensibilidad del 90,6% y una especificidad del 78,6%. Todos los DPP con una pCO2 mayor de 60,9 mmHg fueron tratados con TDE. De los 46 DPP, 3 (6,5%) serían tratados incorrectamente según el pH, la glucosa o la LDH; en cambio, hubieran sido correctamente tratados según la pCO2. Conclusiones: La pCO2 de líquido pleural presenta una exactitud para la indicación de tratamiento con TDE similar al pH, la glucosa y la LDH, y mejora el criterio de indicación de tratamiento con TDE en los DPP.
  • Publication
    Profiles of adult people in a Spanish sample with chronic pain: Cluster analysis.
    (2022-03-14) Cáceres-Matos, Rocío; Gil-García, Eugenia; Lopez-Millan, Jose Manuel; Martínez-Navas, Ángel; Peña, Isaac; Cabrera-León, Andrés
    To establish groups of people with chronic non-cancer pain according to the impairment caused by pain and to identify factors associated with the group with a higher level of impairment. Knowing the profiles of people who suffer from chronic non-cancer pain could make it possible to direct their treatment and to detect associated risks. A cross-sectional study. A sample of 395 people with chronic non-cancer pain was collected in Pain Units and Primary Healthcare Centres in southern Spain (January to March 2020). A cluster analysis was performed to divide the population into groups and a binary logistic regression model was established to determine factors associated with the group with a higher level of impairment. Two groups were identified: lower level of impairment due to pain, characterized by being 45-65 years old, not medicated with opioids or anxiolytics, employed and with a mild level of impact on daily life; and higher level of impairment characterized by being older than 65 years old, medicated with opioids and anxiolytics, retired or on medical leave and with a severe impact on daily life. In addition, among women, being widowed, single or a smoker are risk factors for belonging to the group with a higher level of impairment; being smokers or consuming alcohol three or less times a week would be risk factors in men. Age, chronic non-cancer pain impact on daily life, work situation and the consumption of opioid drugs and/or anxiolytics are factors that appear to influence the level of impairment due to chronic pain. These findings could help detect impairment due to pain in its early stages, determining the specific needs of each person.
  • Publication
    Gene set enrichment analysis of pathophysiological pathways highlights oxidative stress in psychosis.
    (2022-09-21) Pistis, Giorgio; Vázquez-Bourgon, Javier; Fournier, Margot; Jenni, Raoul; Cleusix, Martine; Papiol, Sergi; Smart, Sophie E; Pardiñas, Antonio F; Walters, James T R; MacCabe, James H; Kutalik, Zoltán; Conus, Philippe; Crespo-Facorro, Benedicto; Q Do, Kim
    Polygenic risk prediction remains an important aim of genetic association studies. Currently, the predictive power of schizophrenia polygenic risk scores (PRSs) is not large enough to allow highly accurate discrimination between cases and controls and thus is not adequate for clinical integration. Since PRSs are rarely used to reveal biological functions or to validate candidate pathways, to fill this gap, we investigated whether their predictive ability could be improved by building genome-wide (GW-PRSs) and pathway-specific PRSs, using distance- or expression quantitative trait loci (eQTLs)- based mapping between genetic variants and genes. We focused on five pathways (glutamate, oxidative stress, GABA/interneurons, neuroimmune/neuroinflammation and myelin) which belong to a critical hub of schizophrenia pathophysiology, centred on redox dysregulation/oxidative stress. Analyses were first performed in the Lausanne Treatment and Early Intervention in Psychosis Program (TIPP) study (n = 340, cases/controls: 208/132), a sample of first-episode of psychosis patients and matched controls, and then validated in an independent study, the epidemiological and longitudinal intervention program of First-Episode Psychosis in Cantabria (PAFIP) (n = 352, 224/128). Our results highlighted two main findings. First, GW-PRSs for schizophrenia were significantly associated with early psychosis status. Second, oxidative stress was the only significantly associated pathway that showed an enrichment in both the TIPP (p = 0.03) and PAFIP samples (p = 0.002), and exclusively when gene-variant linking was done using eQTLs. The results suggest that the predictive accuracy of polygenic risk scores could be improved with the inclusion of information from functional annotations, and through a focus on specific pathways, emphasizing the need to build and study functionally informed risk scores.
  • Publication
    Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium.
    (2022-09-07) van Velzen, Laura S; Dauvermann, Maria R; Colic, Lejla; Villa, Luca M; Savage, Hannah S; Toenders, Yara J; Zhu, Alyssa H; Bright, Joanna K; Campos, Adrián I; Salminen, Lauren E; Ambrogi, Sonia; Ayesa-Arriola, Rosa; Banaj, Nerisa; Başgöze, Zeynep; Bauer, Jochen; Blair, Karina; Blair, Robert James; Brosch, Katharina; Cheng, Yuqi; Colle, Romain; Connolly, Colm G; Corruble, Emmanuelle; Couvy-Duchesne, Baptiste; Crespo-Facorro, Benedicto; Cullen, Kathryn R; Dannlowski, Udo; Davey, Christopher G; Dohm, Katharina; Fullerton, Janice M; Gonul, Ali Saffet; Gotlib, Ian H; Grotegerd, Dominik; Hahn, Tim; Harrison, Ben J; He, Mengxin; Hickie, Ian B; Ho, Tiffany C; Iorfino, Frank; Jansen, Andreas; Jollant, Fabrice; Kircher, Tilo; Klimes-Dougan, Bonnie; Klug, Melissa; Leehr, Elisabeth J; Lippard, Elizabeth T C; McLaughlin, Katie A; Meinert, Susanne; Miller, Adam Bryant; Mitchell, Philip B; Mwangi, Benson; Nenadić, Igor; Ojha, Amar; Overs, Bronwyn J; Pfarr, Julia-Katharina; Piras, Fabrizio; Ringwald, Kai G; Roberts, Gloria; Romer, Georg; Sanches, Marsal; Sheridan, Margaret A; Soares, Jair C; Spalletta, Gianfranco; Stein, Frederike; Teresi, Giana I; Tordesillas-Gutiérrez, Diana; Uyar-Demir, Aslihan; van der Wee, Nic J A; van der Werff, Steven J; Vermeiren, Robert R J M; Winter, Alexandra; Wu, Mon-Ju; Yang, Tony T; Thompson, Paul M; Rentería, Miguel E; Jahanshad, Neda; Blumberg, Hilary P; van Harmelen, Anne-Laura; ENIGMA Suicidal Thoughts and Behaviours Consortium; Schmaal, Lianne
    Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen's d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.
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    Correction: Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals.
    (2022) McWhinney, Sean R; Brosch, Katharina; Calhoun, Vince D; Crespo-Facorro, Benedicto; Crossley, Nicolas A; Dannlowski, Udo; Dickie, Erin; Dietze, Lorielle M F; Donohoe, Gary; Du Plessis, Stefan; Ehrlich, Stefan; Emsley, Robin; Furstova, Petra; Glahn, David C; Gonzalez-Valderrama, Alfonso; Grotegerd, Dominik; Holleran, Laurena; Kircher, Tilo T J; Knytl, Pavel; Kolenic, Marian; Lencer, Rebekka; Nenadić, Igor; Opel, Nils; Pfarr, Julia-Katharina; Rodrigue, Amanda L; Rootes-Murdy, Kelly; Ross, Alex J; Sim, Kang; Škoch, Antonín; Spaniel, Filip; Stein, Frederike; Švancer, Patrik; Tordesillas-Gutiérrez, Diana; Undurraga, Juan; Vázquez-Bourgon, Javier; Voineskos, Aristotle; Walton, Esther; Weickert, Thomas W; Weickert, Cynthia Shannon; Thompson, Paul M; van Erp, Theo G M; Turner, Jessica A; Hajek, Tomas
  • Publication
    Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals.
    (2022-06-14) McWhinney, Sean R; Brosch, Katharina; Calhoun, Vince D; Crespo-Facorro, Benedicto; Crossley, Nicolas A; Dannlowski, Udo; Dickie, Erin; Dietze, Lorielle M F; Donohoe, Gary; Du Plessis, Stefan; Ehrlich, Stefan; Emsley, Robin; Furstova, Petra; Glahn, David C; Gonzalez-Valderrama, Alfonso; Grotegerd, Dominik; Holleran, Laurena; Kircher, Tilo T J; Knytl, Pavel; Kolenic, Marian; Lencer, Rebekka; Nenadić, Igor; Opel, Nils; Pfarr, Julia-Katharina; Rodrigue, Amanda L; Rootes-Murdy, Kelly; Ross, Alex J; Sim, Kang; Škoch, Antonín; Spaniel, Filip; Stein, Frederike; Švancer, Patrik; Tordesillas-Gutiérrez, Diana; Undurraga, Juan; Vázquez-Bourgon, Javier; Voineskos, Aristotle; Walton, Esther; Weickert, Thomas W; Weickert, Cynthia Shannon; Thompson, Paul M; van Erp, Theo G M; Turner, Jessica A; Hajek, Tomas
    Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive. Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia.
  • Publication
    Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: a large patient data set study from European registries.
    (2021-11-13) Récher, Christian; Röllig, Christoph; Bérard, Emilie; Bertoli, Sarah; Dumas, Pierre-Yves; Tavitian, Suzanne; Kramer, Michael; Serve, Hubert; Bornhäuser, Martin; Platzbecker, Uwe; Müller-Tidow, Carsten; Baldus, Claudia D; Martínez-Cuadrón, David; Serrano, Josefina; Martínez-Sánchez, Pilar; Arbolí, Eduardo Rodríguez; Gil, Cristina; Bergua, Juan; Bernal, Teresa; de la Fuente Burguera, Adolfo; Delabesse, Eric; Bidet, Audrey; Pigneux, Arnaud; Montesinos, Pau
    The outcome of acute myeloid leukemia patients aged 70 years or older is poor. Defining the best treatment option remains controversial especially when choosing between intensive chemotherapy and hypomethylating agents. We set up a multicentric European database collecting data of 3 700 newly diagnosed acute myeloid leukemia patients ≥70 years. The primary objective was to compare overall survival in patients selected for intensive chemotherapy (n = 1199) or hypomethylating agents (n = 1073). With a median follow-up of 49.5 months, the median overall survival was 10.9 (95% CI: 9.7-11.6) and 9.2 months (95% CI: 8.3-10.2) with chemotherapy and hypomethylating agents, respectively. Complete remission or complete remission with incomplete hematologic recovery was 56.1% and 19.7% with chemotherapy and hypomethylating agents, respectively (P 
  • Publication
    An Updated View of the Trypanosoma cruzi Life Cycle: Intervention Points for an Effective Treatment.
    (2022-06-02) Martín-Escolano, Javier; Marín, Clotilde; Rosales, María J; Tsaousis, Anastasios D; Medina-Carmona, Encarnación; Martín-Escolano, Rubén
    Chagas disease (CD) is a parasitic, systemic, chronic, and often fatal illness caused by infection with the protozoan Trypanosoma cruzi. The World Health Organization classifies CD as the most prevalent of poverty-promoting neglected tropical diseases, the most important parasitic one, and the third most infectious disease in Latin America. Currently, CD is a global public health issue that affects 6-8 million people. However, the current approved treatments are limited to two nitroheterocyclic drugs developed more than 50 years ago. Many efforts have been made in recent decades to find new therapies, but our limited understanding of the infection process, pathology development, and long-term nature of this disease has made it impossible to develop new drugs, effective treatment, or vaccines. This Review aims to provide a comprehensive update on our understanding of the current life cycle, new morphological forms, and genetic diversity of T. cruzi, as well as identify intervention points in the life cycle where new drugs and treatments could achieve a parasitic cure.
  • Publication
    Bioactive Peptides from Lupin (Lupinus angustifolius) Prevent the Early Stages of Atherosclerosis in Western Diet-Fed ApoE-/- Mice.
    (2022-06-29) Santos-Sánchez, Guillermo; Cruz-Chamorro, Ivan; Álvarez-Ríos, Ana Isabel; Álvarez-Sánchez, Nuria; Rodríguez-Ortiz, Beatriz; Álvarez-López, Ana Isabel; Fernández-Pachón, María-Soledad; Pedroche, Justo; Millán, Francisco; Millán-Linares, María Del Carmen; Lardone, Patricia Judith; Bejarano, Ignacio; Carrillo-Vico, Antonio
    We have previously reported the in vitro hypocholesterolemic, anti-inflammatory, and antioxidant effects of Alcalase-generated lupin protein hydrolysate (LPH). Given that lipoprotein deposition, oxidative stress, and inflammation are the main components of atherogenesis, we characterized the LPH composition, in silico identified LPH-peptides with activities related to atherosclerosis, and evaluated the in vivo LPH effects on atherosclerosis risk factors in a mouse model of atherosclerosis. After 15 min of Alcalase hydrolysis, peptides smaller than 8 kDa were obtained, and 259 peptides out of 278 peptides found showed biological activities related to atherosclerosis risk factors. Furthermore, LPH administration for 12 weeks reduced the plasma lipids, as well as the cardiovascular and atherogenic risk indexes. LPH also increased the total antioxidant capacity, decreased endothelial permeability, inflammatory response, and atherogenic markers. Therefore, this study describes for the first time that LPH prevents the early stages of atherosclerosis.
  • Publication
    Personal Beliefs about Illness Questionnaire-Revised (PBIQ-R): Spanish adaptation in a clinical sample with psychotic disorders.
    (2022-06-15) Vázquez Morejón, Antonio J; Jackson, Chris; Vázquez-Morejón, Raquel; Leon-Perez, Jose M
    The way people with psychosis psychologically adapt and manage the diagnosis of such a mental disorder has been considered a key factor that contributes to the emergence and aggravation of emotional problems. These beliefs about illness can be very important due to their possible association with stigma and its implications in terms of loss of roles and social status. Given the importance of these personal beliefs about the specific diagnosis of psychosis, the Personal Beliefs about Illness Questionnaire (PBIQ) and PBIQ-R have been developed. The present study aims to explore the psychometric characteristics of the Spanish version of the PBIQ-R in a sample of patients with a diagnosis of psychosis-related disorders. Participants were 155 patients (54.8% male) of the Public Health Service in Andalusia (Spain). Those who consented to participate filled in the PBIQ-R, the Social Comparison Scale, and the PHQ-9 and GAD-7 to measure emotional symptoms. All dimensions showed adequate internal consistency values: Cronbach's alpha extends between .81 and .88; and McDonald's omega ranges between .87 and .92. The temporal reliability for an interval of 3-4 weeks was high. The correlations between the PBIQ-R dimensions and the other variables included in the study were significant and in the expected direction. The factor analysis of the principal components of the PBIQ-R dimensions revealed a single factor in each of the dimensions that explained 64-74%. The results support the reliability and validity of the Spanish version of the PBIQ-R.
  • Publication
    Molecular epidemiology of paediatric invasive pneumococcal disease in Andalusia, Spain.
    (2022-08-22) de Felipe, Beatriz; Obando Pacheco, Pablo; Carazo Gallego, Begoña; López Martín, David; Santos Pérez, Juan Luis; González Jiménez, Yolanda; Muñoz Vilches, María José; Cardelo Autero, Nerea; González Galán, Verónica; Morón, Francisco José; Cordero Varela, Juan Antonio; Torres Sánchez, María José; Medina Claros, Antonio; Moreno Pérez, David; Obando, Ignacio
    This study aimed to assess the impact of the introduction of pneumococcal conjugate vaccine 13 (PCV13) on the molecular epidemiology of invasive pneumococcal disease (IPD) in children from Andalusia. A population-based prospective surveillance study was conducted on IPD in children aged