Artículos (Instituto de Biomedicina de Sevilla (IBIS))

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Epidemiological and Clinical Characteristics of Streptococcus Tigurinus Endocarditis
(BioMed Central, 2019) Ercibengoa, María; Goenaga, Miguel Ángel; Ardanuy, Carmen; Grau, Immaculada; García de la María, Cristina; Almela, Manuel; Miro, José María; Navas, Enrique; Fariñas, María Carmen; Ruiz de la Alegría, Carlos; Lepe Jiménez, José Antonio; Marimón, Jose María; Universidad de Sevilla. Departamento de Microbiología
Background: Streptococcus tigurinus was recently described as a new streptococcal species within the viridans group streptococci (VGS). The objectives of the present work were to analyse the clinical and microbiological characteristics of S. tigurinus isolated from patients with bacteraemias, to determine the prevalence of S. tigurinus among VGS endocarditis in Spain, and to compare the clinical characteristics and outcomes of endocarditis caused by S. tigurinus and other VGS. Methods: Retrospective nationwide study, performed between 2008 and 2016 in 9 Spanish hospitals from 7 different provinces comprising 237 cases of infective endocarditis. Streptococcal isolates were identified by sequencing fragments of their 16S rRNA, sodA and groEL genes. Clinical data of patients with streptococcal endocarditis were prospectively collected according to a pre-established protocol. Results: Patients with endocarditis represented 7/9 (77.8%) and 26/86 (30.2%) of the bacteraemias caused by S. tigurinus and other VGS, respectively (p < 0.001), in two of the hospital participants. Among patients with streptococcal endocarditis, 12 different Streptococcus species were recognized being S. oralis, S. tigurinus and S. mitis the three more common. No relevant statistical differences were observed in the clinical characteristics and outcomes of endocarditis caused by the different VGS species. Conclusions: In this multicenter study performed in Spain, S. tigurinus showed a higher predilection for the endocardial endothelium as compared to other VGS. However, clinical characteristics and outcomes of endocarditis caused by S. tigurinus did not significantly differ from endocarditis caused by other oral streptococci.
Sorafenib-associated translation reprogramming in hepatocellular carcinoma cells
(Taylor and Francis Ltd., 2025-03-17) Contreras Bernal, Laura; Rodríguez Gil, Alfonso; Muntané Relat, Jordi; Cruz Díaz, Jesús de la; Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica; Universidad de Sevilla. Departamento de Genética; European Cooperation in Science and Technology; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC); Instituto de Salud Carlos III; Junta de Andalucía; Universidad de Sevilla
Sorafenib (Sfb) is a multikinase inhibitor regularly used for the management of patients with advanced hepatocellular carcinoma (HCC) that has been shown to increase very modestly life expectancy. We have shown that Sfb inhibits protein synthesis at the level of initiation in cancer cells. However, the global snapshot of mRNA translation following Sorafenib-treatment has not been explored so far. In this study, we performed a genome-wide polysome profiling analysis in Sfb-treated HCC cells and demonstrated that, despite global translation repression, a set of different genes remain efficiently translated or are even translationally induced. We reveal that, in response to Sfb inhibition, translation is tuned, which strongly correlates with the presence of established mRNA cis-acting elements and the corresponding protein factors that recognize them, including DAP5 and ARE-binding proteins. At the level of biological processes, Sfb leads to the translational down-regulation of key cellular activities, such as those related to the mitochondrial metabolism and the collagen synthesis, and the translational up-regulation of pathways associated with the adaptation and survival of cells in response to the Sfb-induced stress. Our findings indicate that Sfb induces an adaptive reprogramming of translation and provides valuable information that can facilitate the analysis of other drugs for the development of novel combined treatment strategies based on Sfb therapy.
Virtual 3D models, augmented reality systems and virtual laparoscopic simulations in complicated pancreatic surgeries: state of art, future perspectives, and challenges
(Ovid Technologies, 2025-01-24) Laga Boul-Atarass, Imán; Cepeda Franco, Carmen; Sanmartín Sierra, José Domingo; Castell Monsalve, Javier; Padillo Ruiz, Francisco Javier; Universidad de Sevilla. Departamento de Cirugía
Pancreatic surgery is considered one of the most challenging interventions by many surgeons, mainly due to retroperitoneal location and proximity to key and delicate vascular structures. These factors make pancreatic resection a demanding procedure, with successful rates far from optimal and frequent postoperative complications. Surgical planning is essential to improve patient outcomes, and in this regard, many technological advances made in the last few years have proven to be extremely useful in medical fields. This review aims to outline the potential and limitations of 3D digital and 3D printed models in pancreatic surgical planning, as well as the impact and challenges of novel technologies such as augmented/virtual reality systems or artificial intelligence to improve medical training and surgical outcomes.
Performance of a Non-Invasive System for Monitoring Blood Glucose Levels Based on Near-Infrared Spectroscopy Technology (Glucube®)
(MDPI, 2024-12) Gómez-Peralta, Fernando; Luque Romero, Luis Gabriel; Puppo Moreno, Antonio; Riesgo, Jesús; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Instituto de Biomedicina de Sevilla (IBIS)
Background: The need for frequent blood glucose (BG) monitoring and the inconveniences associated with self-monitoring of BG (SMBG) have driven the development of non-invasive approaches. Methods: This prospective study aimed to investigate the accuracy of glucose level calculation using the near-infrared spectroscopy (NIRS) technology Glucube® system. People with Type 1 diabetes, Type 2 diabetes, prediabetes, and normal glucose metabolism were included. Over one week, individuals performed glucose measurements with the Glucube® system and capillary blood fingersticks with a standard glucometer (Ascensia Contour® Next). To assess the impact of the improvement in dexterity, the accuracy variables were compared with the point-of-care (POC) glucometer Accu-Chek® Inform II in a one-week sub-study. Results: Overall, 105 subjects (mean age 53.8 ± 13.8 years, 50.5% female) participated, resulting in 1914 paired glucose measurements between 49 and 331 mg/dL. Total mean absolute relative difference (MARD) was 20.3%, MARD for values >100 mg/dL was 18.3%, and mean absolute deviation (MAD) for values <100 mg/dL was 24.9%. A total of 97.3% of measurements fell within A+B Parkes zones, and 58.8%, 76.9%, and 88.1% within +−20%, +−30%, or +−40% error, respectively. On completion, 62 participants (59%) fulfilled the one-week prospective sub-study. In this subgroup, the total MARD was reduced between day 1 and day 8 from 22.8 to 18.3% (p = 0.068). The percentages within Zone A were 51.6 vs. 61.2%, Zone B 46.8 vs. 33.9%, and Zone C 1.6 vs. 4.8%, and the sum of Parkes Zones A+B was 98.4 vs. 95.2% (p = 0.311) for day 1 and day 8, respectively. Conclusions: Glucube® is a novel non-invasive system based on NIRS technology for monitoring blood glucose levels. Its promising capabilities support further research.
Pneumocystis infection in pregnant women: a scoping review
(MDPI, 2025-04-25) Calderón-Baturone, Irene; Salsoso, R; Charpentier, Eléna; de Armas, Yaxsier; Guadix, Pilar; Morilla Romero de la Osa, Rubén; Friaza, Vicente; Calderón Sandubete, Enrique José; Universidad de Sevilla. Departamento de Cirugía; Universidad de Sevilla. Departamento de Enfermería; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS607: Salud Reproductiva de la Mujer
Pneumocystis jirovecii is an opportunistic fungus that causes severe pneumonia in immunosuppressed individuals. While Pneumocystis colonization, a subclinical form of infection, has been studied in different populations, its implications during pregnancy remain poorly understood. Given the immune modulation of pregnancy, maternal colonization or infection may contribute to vertical transmission and neonatal respiratory complications. This scoping review aims to map the existing evidence on Pneumocystis colonization/infection during pregnancy, identifying knowledge gaps, prevalence, risk factors, and potential neonatal outcomes. A systematic literature search was conducted in three databases following PRISMA-ScR guidelines. A total of 26 studies were included, covering Pneumocystis pneumonia cases (n = 19) and Pneumocystis colonization (n = 7). The review found that most Pneumocystis pneumonia cases in pregnant women were associated with HIV before antiretroviral therapy. More recent cases were related to hematologic malignancies. Pneumocystis colonization rates varied widely (5.4–46.5%). Evidence of vertical transmission was observed, but neonatal impact remains underexplored. This review highlights the need for HIV screening in pregnant women and the need to include Pneumocystis in the diagnosis of pregnant women with pneumonia. Increased awareness and research on Pneumocystis in pregnancy are necessary to improve maternal and neonatal outcomes. Future studies should focus on vertical transmission and neonatal respiratory health.
Editorial: Microglia in Neurodegenerative Diseases
(Frontiers Media SA, 2024) Li, Ting; Espinosa Oliva, Ana María; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
Editorial: 15 years of Frontiers in Cellular Neuroscience: the dual role of microglia in (neuro)inflammation
(Frontiers Media, 2025) Herrera Carmona, Antonio José; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular
Age-dependent Progression from Clearance to Vulnerability in the Early Response of Periventricular Microglia to α-synuclein Toxic Species
(BioMed Central, 2025) Sirerol Piquer, Mª Salomé; Pérez Villalba, Ana; Duart Abadía, Pere; Belenguer, Germán; Gómez Pinedo, Ulises; Blasco Chamarro, Laura; Carrillo Barberà, Pau; Pérez Cañamás, Azucena; Navarro Garrido, Victoria; Dehay, Benjamin; Vitorica Ferrández, Francisco Javier; Fariñas, Isabel; Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular; Ministerio de Ciencia e Innovación (MICIN). España
Cytoplasmic alpha-synuclein (αSyn) aggregates are a typical feature of Parkinson’s disease (PD). Extracellular insoluble αSyn can induce pathology in healthy neurons suggesting that PD neurodegeneration may spread through cell-to-cell transfer of αSyn proteopathic seeds. Early pro-homeostatic reaction of microglia to toxic forms of αSyn remains elusive, which is especially relevant considering the recently uncovered microglial molecular diversity. Here, we show that periventricular microglia of the subependymal neurogenic niche monitor the cerebrospinal fluid and can rapidly phagocytize and degrade different aggregated forms of αSyn delivered into the lateral ventricle. However, this clearing ability worsens with age, leading to an increase in microglia with aggregates in aged treated mice, an accumulation also observed in human PD samples. We also show that exposure of aged microglia to aggregated αSyn isolated from human PD samples results in the phosphorylation of the endogenous protein and the generation of αSyn seeds that can transmit the pathology to healthy neurons. Our data indicate that while microglial phagocytosis rapidly clears toxic αSyn, aged microglia can contribute to synucleinopathy spreading.
Correction: Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype
(PLOS, 2017-04) Huertas, Ismael; Jesús, Silvia; Lojo, José Antonio; García-Gómez, Francisco Javier; Cáceres-Redondo, María Teresa; Oropesa-Ruiz, Juan Manuel; Martín Rodríguez, Juan Francisco; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Psicología Experimental; Instituto de Biomedicina de Sevilla (IBIS); Instituto de Salud Carlos III; Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía. Consejería de Salud y Bienestar Social; Sociedad Andaluza de Neurología; Jacques and Gloria Gossweiler Foundation; Fundación Alicia Koplowitz; Fundación Mutua Madrileña; Programa "PFIS"; Programa Río Hortega; Programa Sara Borrell; Programa Miguel Servet
There are errors in the funding section.
Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype
(PLOS, 2017-03) Huertas, Ismael; Jesús, Silvia; Lojo, José Antonio; García-Gómez, Francisco Javier; Cáceres-Redondo, María Teresa; Oropesa-Ruiz, Juan Manuel; Martín Rodríguez, Juan Francisco; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Psicología Experimental; Instituto de Biomedicina de Sevilla (IBIS); Junta de Andalucía. Consejería de Salud y Bienestar Social; Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo; Fundación Alicia Koplowitz; Fundación Mutua Madrileña; Instituto de Salud Carlos III; Jacques and Gloria Gossweiler Foundation; Sociedad Andaluza de Neurología
Parkinson’s disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.
TMEM230 in Parkinson's disease in a southern Spanish population
(PLOS, 2018-05) Tejera-Parrado, Cristina; Jesús, Silvia; López-Ruíz, Adrián; Buiza Rueda, Dolores; Bonilla Toribio, Marta; Bernal Bernal, Inmaculada; Periñán Tocino, María Teresa; Vargas González, Laura; Gómez Garre, Pilar; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo; Junta de Andalucía. Consejería de Salud y Bienestar Social; Fundación Alicia Koplowitz; Fundación Mutua Madrileña; Jacques and Gloria Gossweiler Foundation; Sociedad Andaluza de Neurologia to Pablo Mir; Instituto de Salud Carlos III; Universidad de Sevilla
TMEM230 has been associated with autosomal dominant Parkinson’s disease (PD). Subsequent studies have remained negative, and none of previous described mutation has been reported anymore. We investigated the implication of this gene in the PD in a population of 703 PD patients and 695 unrelated healthy controls from southern Spain. Thirteen variants were found, twelve of them observed only in controls or in patients and controls, and one (c.190A>G) observed only in one patient. Subsequent analysis of this variant indicates that probably it is not pathogenic. In addition, we found a variation in the 3’-UTR (rs183551373) and related with the miRNA hsa-miR-4299 but it was observed only in healthy controls. Our results suggest that variants in TMEM230 gene are not associated with the development of PD.
Abnormal cerebellar connectivity and plasticity in isolated cervical dystonia
(PLOS, 2019-01) Porcacchia, Paolo; Álvarez de Toledo, Paloma; Rodríguez-Baena, Antonio; Martín Rodríguez, Juan Francisco; Palomar, Francisco J.; Vargas González, Laura; Jesús, Silvia; Koch, Giacomo; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. Departamento de Psicología Experimental; Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empresa; Junta de Andalucía. Consejería de Salud y Bienestar Social; Fundacion Alicia Koplowitz; Fundacion Mutua Madrilena; Instituto de Salud Carlos III; Jaques and Gloria Gossweiler Foundation; Ministerio de Economía y Competitividad (MINECO). España; Sociedad Andaluza de Neurología
There is increasing evidence that supports the role of the cerebellum in the pathophysiology of dystonia. We used transcranial magnetic stimulation to test the hypothesis that patients with cervical dystonia may have a disrupted cerebellar cortical connectivity at rest, and that cerebellar plasticity is altered too. We enrolled 12 patients with isolated cervical dystonia and 13 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right cerebellum and the left primary motor area. Changes in the amplitude of motor evoked potentials were analysed. Continuous and intermittent Theta Burst Stimulation over the cerebellum was also applied. The effects of these repetitive protocols on cortical excitability, on intra-cortical circuits and on cerebellar cortical inhibition were analysed. In healthy subjects, but not in dystonic patients, a conditioning stimulus over the cerebellum was able to inhibit the amplitude of the motor evoked potentials from primary motor cortex. In healthy subjects continuous and intermittent cerebellar Theta Burst Stimulation were able to decrease and increase respectively motor cortex excitability. Continuous Theta Burst Stimulation was able to abolish the cerebellar cortical inhibition observed in basal condition. These effects were not observed in patients with cervical dystonia. Cerebellar cortical connectivity and cerebellar plasticity is altered at rest in patients with cervical dystonia.
Imaging biomarkers of cortical neurodegeneration underlying cognitive impairment in Parkinson’s disease
(Springer Nature, 2025-01) Silva Rodríguez, Jesús; Labrador Espinosa, Miguel Ángel; Castro-Labrador, Sandra; Muñoz Delgado, Laura; Franco-Rosado, Pablo; Castellano Guerrero, Ana María; Carrillo García, Fátima María; Martín Rodríguez, Juan Francisco; Mir Rivera, Pablo; Grothe, Michel J.; Universidad de Sevilla. Departamento de Psicología Experimental; Universidad de Sevilla. Departamento de Medicina; Junta de Andalucía. Consejería de Economía, Innovación, Ciencia y Empleo; Junta de Andalucía. Consejería de Salud y Familias; Universidad Carlos III de Madrid; Universidad de Sevilla; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Purpose: Imaging biomarkers bear great promise for improving the diagnosis and prognosis of cognitive impairment in Parkinson’s disease (PD). We compared the ability of three commonly used neuroimaging modalities to detect cortical changes in PD patients with mild cognitive impairment (PD-MCI) and dementia (PDD). Methods: 53 cognitively normal PD patients (PD-CN), 32 PD-MCI, and 35 PDD underwent concurrent structural MRI (sMRI), diffusion-weighted MRI (dMRI), and [18F]FDG PET. We extracted grey matter volumes (sMRI), mean diffusivity (MD, dMRI), and standardized uptake value ratios ([18F]FDG PET) for 52 cortical regions included in a neuroanatomical atlas. We assessed group differences using ANCOVA models and further applied a cross-validated machine learning approach to identify the modality-specific brain regions that are most indicative of dementia status and assessed their diagnostic accuracy for group separation using receiver operating characteristic analyses. Results: In sMRI, atrophy of temporal and posterior-parietal areas allowed separating PDD from PD-CN (AUC = 0.77 ± 0.07), but diagnostic accuracy was poor for separating PD-MCI from PD-CN (0.57 ± 0.10). dMRI showed most pronounced diffusivity changes in the medial temporal lobe, which provided excellent diagnostic performance for PDD (AUC = 0.87 ± 0.06), and a more modest but still significant performance for PD-MCI (AUC = 0.71 ± 0.09). Finally, [18F]FDG PET revealed pronounced hypometabolism in posterior-occipital regions, which provided the highest diagnostic accuracies for both PDD (AUC = 0.89 ± 0.05) and PD-MCI (AUC = 0.78 ± 0.05). In statistical comparisons, both [18F]FDG PET (p < 0.001) and dMRI (p < 0.031) outperformed sMRI for detecting PDD and PD-MCI. Conclusion: Among the tested modalities, [18F]FDG PET was most accurate for detecting cortical changes associated with cognitive impairment in PD, especially at early stages. Diffusion measurements may represent a promising MRI-based alternative.
Changes in Principal Caregiver Mood Affects the Mood of the Parkinson’s Disease Patient: The Vicious Cycle of Illness
(Sage Journals, 2023-03) Santos-García, Diego; de Deus Fonticoba, Teresa; Cores Bartolomé, Carlos; Feal Painceiras, María J.; Íñiguez-Alvarado, María Cristina; García Díaz, Iago; Jesús, Silvia; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Background: Although many studies have analyzed what factors contribute to caregiver burden in Parkinson’s disease (PD), there is currently no knowledge about how the status of the caregiver could impact the patient. Objective: The aim of this study was to analyze how the change in the caregiver’s status influences PD patients. Methods: PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers in Spain from the COPPADIS cohort were included in the study (V0). They were evaluated again at 2-year follow-up (V2). Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), and EUROHIS-QOL 8-item index (EUROHIS-QOL8) at V0 and V2. Multivariate models were used to analyze the impact of the change from V0 to V2 (Δ) on the caregiver’s status over the change in the patient’s status. Results: ΔBDI-II and ΔEUROHIS-QOL8 in the caregiver predicted ΔBDI-II (β = 0.32; p < 0.0001; R^2 = 0.71) and ΔEUROHIS-QOL8 (β = 0.39; p < 0.0001; R^2 = 0.68) in the patient, respectively. Variables related to the caregiver were not associated with changes in the patient´s health-related QoL (ΔPDQ-39 [39-item Parkinson’s disease Questionnaire]) or autonomy for activities of daily-living (ΔADLS [Schwab & England Activities of Daily Living Scale]). Conclusion: The change in the caregiver’s mood and global QoL was associated with the change in the patient’s mood and global QoL, respectively, independently of other variables of the disease influencing both patient´s aspects. Based on this finding, it could be of great importance to detect depression in the principal caregiver of a patient and act on it as earlier as possible.
Author Correction: Peripheral inflammatory immune response differs among sporadic and familial Parkinson’s disease (npj Parkinson's Disease, (2023), 9, 1, (12), 10.1038/s41531-023-00457-5)
(Springer Nature, 2023-02) Muñoz-Delgado, Laura; Macías-García, Daniel; Periñán Tocino, María Teresa; Jesús, Silvia; Adarmes-Gómez, Astrid D.; Bonilla Toribio, Marta; García Díaz, Sergio; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS)
In this article the affiliation details for Author Pablo Mir were incorrectly given as ‘Departamento de Medicina, Universidad de Sevilla, Seville, Spain’ but should have been ‘Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Seville, Spain’. The original article has been corrected.
Staging Parkinson's disease according to the MNCD (Motor/Non-motor/Cognition/Dependency) classification correlates with disease severity and quality of life
(Sage Journals, 2023-03) Santos-García, Diego; de Deus Fonticoba, Teresa; Cores Bartolomé, Carlos; Feal Painceiras, Maria J.; Íñiguez-Alvarado, Maria Cristina; García Díaz, Iago; Jesús, Silvia; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Background: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). Objective: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. Methods: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). Results: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. Conclusion: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.
Prevalence and factors associated with drooling in Parkinson's disease: results from a longitudinal prospective cohort and comparison with a control group
(Wiley, 2023-01) Santos-García, Diego; de Deus Fonticoba, Teresa; Cores Bartolomé, Carlos; Feal Painceiras, María J.; Íñiguez-Alvarado, María Cristina; Jesús, Silvia; Buongiorno, Maria Teresa; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Economía y Competitividad (MINECO). España
Introduction: Drooling in Parkinson’s disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results: (e frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR . 1.032; p . 0.012), being male (OR . 2.333; p < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR. 1.020; p < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR. 1.012; p < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with >_2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR . 1.121; p . 0.007) as a predictor of drooling at V2. Conclusion: Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden. associated with a greater motor severity and NMS burden
Peripheral immune profile and neutrophil-to-lymphocyte ratio in progressive supranuclear palsy: Case–control study and meta-analysis
(Wiley, 2024-12) Muñoz-Delgado, Laura; Luque-Ambrosiani, A.; Zamora, B. B.; Macías-García, D.; Jesús, S.; Adarmes-Gómez, Astrid; Ojeda-Lepe, Elena; Carrillo García, Fátima María; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Junta de Andalucía. Consejeria de Economia, Innovacion, Ciencia y Empleo; Junta de Andalucía. Consejería de Salud y Bienestar Social; Junta de Andalucía. Consejería de Salud y Consumo; Junta de Andalucía. Consejería de Transformación Económica, Industria, Conocimiento y Universidades
Background and purpose: Peripheral inflammation is probably involved in the pathogenesis of progressive supranuclear palsy (PSP) and it may be a common feature with Parkinson's disease (PD). The peripheral immune profile in PSP remains unclear, as well as whether the inflammatory pathways differ from those in PD. The neutrophil-to-lymphocyte ratio (NLR) has been proven to be a well-established biomarker of systemic inflammation. This study aimed to evaluate the peripheral immune profile in PSP compared with PD. Methods: A cross-sectional study was conducted including patients with PSP and PD and healthy controls (HCs). Leukocyte subpopulations and the NLR were measured in peripheral blood. Multivariate linear regression and post hoc tests were applied. Electronic databases were searched in November 2023 to perform meta-analyses to clarify the peripheral immune profile in PSP. Results: Our cohort included 121 patients with PSP, 127 patients with PD and 266 HCs. The NLR was higher in PSP and PD compared with HCs. PSP had a higher neutrophil count compared with HCs. Whilst a lower lymphocyte count was found in PD compared with HCs, the lymphocyte count did not differ between PSP and HCs. The meta-analyses supported this immune profile. Conclusions: PSP and PD show an increased peripheral inflammation and a higher NLR compared with HCs. Different pathogenic inflammatory mechanisms are probably involved in PSP and PD, since in PSP this altered peripheral immune profile is mainly driven by neutrophils. Understanding the neutrophils' role in PSP may allow for the development of targeted therapies.
Dysphagia in Parkinson´s disease. A 5-year follow-up study
(Springer Nature, 2025-02) Santos-García, Diego; Deus Fonticoba, Teresa de; Jesús, Silvia; Cosgaya, Marina; García Caldentey, Juan; Caballol, Nuria; Legarda, Inés; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS); Ministerio de Economía y Competitividad (MINECO). España
Background and objective: Dysphagia at time of diagnosis suggests atypical parkinsonism instead Parkinson´s disease (PD). Our aim was to analyze the frequency of dysphagia in patients with early PD comparing with a control group and to identify related factors. Patients and methods Patients with early PD (≤ 2 years from symptoms onset) who were recruited from January/2016 to November/2017 (baseline visit; V0) and evaluated annually for 5 years from the Spanish cohort COPPADIS were included in this prospective study. Controls were assessed at baseline and at 2-, 4-, and 5-year follow-up. Dysphagia was defined as a score ≥ 1 in the item 20 of the Non-Motor Symptoms Scale (NMSS). Results: Dysphagia was more frequent at baseline in PD patients (19.6% [36/184]; 62.3 ± 8.3 years old; 56.8% males) than in controls (5.3% [11/206]; 60.9 ± 8.3 years old; 50% males) (p < 0.0001) and in all visits as well (p < 0.0001). A worse quality of sleep (Parkinson´s Disease Sleep Scale; OR = 0.974; p = 0.005), a greater impulse-control behavior (ICB) (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale; OR = 1.066; p = 0.014), and non-motor symptoms burden (Non-Motor Symptoms Scale; OR = 1.016; p = 0.021) were independent factors associated with dysphagia at baseline. In those subjects with dysphagia, no differences were observed between patients and controls in the mean NMSS-item 20 overtime, and it didn´t change throughout the follow-up. Conclusion: Dysphagia was frequent in early PD patients compared to controls. However, it was minor and did not progress over time. Sleep, ICB, and non-motor symptoms burden were related to dysphagia.
Dopamine agonist therapy in Parkinson's disease: Spanish expert consensus on its use in different clinical situations
(ScienceDirect, 2025-03) Santos García, D.; Pagonabarraga Mora, J.; Escamilla Sevilla, F.; García Ruiz, P. J.; Infante Ceberio, J.; Kulisevsky Bojarski, J.; Linazasoro Cristóbal, G.; Mir Rivera, Pablo; Universidad de Sevilla. Departamento de Medicina; Instituto de Biomedicina de Sevilla (IBIS)
Background: Different types of therapies were proven effective for the medical management of motor and non-motor symptoms in Parkinson’s disease (PD). We aimed to gain consensus on the dopamine agonist (DA) therapy use in different clinical scenarios of Parkinson’s disease (PD) patients. Methods: This consensus study was based on the nominal group technique. Initially, a consensus group comprising 12 expert neurologists in the PD field identified the topics to be addressed and elaborated different evidence-based preliminary statements. Next, a panel of 48 Spanish neurologists expressed their opinion on an internet-based systematic voting program. Finally, initial ideas were reviewed and rewritten according to panel contribution and were ranked by the consensus group using a Likert-type scale. The analysis of data was carried out by using a combination of both qualitative and quantitative methods. The consensus was achieved if the statement reached ≥ 3.5 points in the voting process. Results: The consensus group produced 76 real-world recommendations. The topics addressed included 12 statements related to DA therapy in early PD, 20 statements concerning DA treatment strategy in patients with motor complications, 11 statements associated with DA drugs and their side effects, and 33 statements regarding DA therapy in specific clinical scenarios. The consensus group did not reach a consensus on 15 statements. Conclusion: The findings from this consensus method represent an exploratory step to help clinicians and patients in the appropriate use of DA in different stages and clinical situations of PD.

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