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Readiness to change: Exploring clinical, cognitive and neural predictors of treatment efficacy following virtual reality-based cognitive remediation in mood and schizophrenia spectrum disorders
(Elsevier B.V., 2026-02-21) Elleby Jespersen, Andreas; Montejo Egido, Laura; Damgaard, Viktoria; Macoveanu, Julian; Fortea, Lydia; Vinberg. Maj; Glenthøj, Louise Birkedal; Nordentoft, Merete; Knudsen, Gitte Maegaard; Wæhrens, Eva Ejlersen; Lumbye, Anders; Vieta i Pascual, Eduard, 1963-; Miskowiak, K.W.
Background: Virtual reality-based cognitive remediation therapy (VR-CRT) offers an ecologically valid approach to enhance real-world cognitive functioning in mood disorders (MD) or schizophrenia spectrum disorders (SSD). This study investigated baseline cognitive, clinical, and neural predictors of VR-CRT response in MD and SSD. Methods: Sixty-two MD and SSD participants were randomized to receive four-week VR-CRT or control with assessments at baseline, treatment completion (week 5), and follow-up (week 17). Univariate general linear models examined predictors of VR-CRT improvement on daily-life cognitive skills, assessed using the Cognition Assessment in Virtual Reality (CAVIR). Predictors included age, diagnosis, baseline cognition, IQ-cognition discrepancy, dorsal prefrontal cortex (dPFC) activation during a working memory task, functional connectivity within the dorsal attention (DAN) and salience (SAL) networks, subjective cognition, and technological acceptance. Results: Higher IQ-cognition discrepancy at baseline (i.e., better cognitive performance than expected from premorbid IQ) predicted greater treatment efficacy at treatment completion (β = 0.17, p = 0.045) and follow-up (β = 0.21, p = 0.008), while baseline cognition was not associated with treatment response (ps ≥ 0.15). Higher baseline dPFC activity predicted more improvements at both times (β = 2.27 p = 0.03; β = 1.82; p = 0.048, respectively). Higher DAN-SAL connectivity predicted improvements at treatment completion (β = 2.81 p = 0.047), but not at follow-up (p = 0.38). Age, sex, diagnosis, subjective cognition, and technological acceptance were not associated with cognitive change. Conclusions: Better cognitive performance than expected based on IQ, possibly reflecting higher cognitive fitness, and greater task-related engagement of dPFC may enhance VR-CRT responsiveness. This profile may indicate greater readiness for change and propensity to translate cognitive strategies into daily life.
Commentary: Navigating symptom and diagnostic overlap in pneumonia and malaria: insights from the field from the PERCH Study
(Oxford University Press, 2025-05-29) Torres-Fernandez, D; Bassat Orellana, Quique
Every year, severe pneumonia and malaria still cause an unacceptably high burden of disease and mortality globally. These illnesses predominantly affect children <5 years of age in low- and middle-income countries (LMICs), particularly in Southeast Asia and sub-Saharan Africa. In malaria-endemic regions, distinguishing severe pneumonia from malaria with respiratory symptoms is an almost impossible task for clinicians in the absence of accurate diagnostic tools, which are often scarcely available in these settings. The symptom overlap is frequent; in hospital-admitted paediatric patients, >40% of malaria cases have severe respiratory findings and 24% of paediatric patients fulfil World Health Organization (WHO) criteria for both diseases]. The true coinfection (or dual diagnosis) proportion of severe pneumonia among paediatric patients with malaria is estimated at about one-fifth of patients [1]. Understanding this overlapping clinical epidemiology and performing a reliable differential diagnosis between the two entities has arisen as a public health priority.
Incidence and Impact of COVID-19 in MS: A Survey From a Barcelona MS Unit
(American Academy of Neurology, 2021-01-27) Sepúlveda, María; Llufriu Duran, Sara; Hernandez Martinez, Eugenia; Català, Martí; Artola, Montse; Hernando Andrés, Ana; Montejo González, Carmen; Pulido Valdeolivas, Irene; Martínez Heras, Eloy; Guasp, Mar; Solana, Elisabeth; Llansó, Laura; Escudero, Domingo; Aldea, Marta; Prats Soler, Clara; Graus Ribas, Francesc; Blanco Morgado, Yolanda; Saiz Hinarejos, Albert
Objective To investigate the incidence of coronavirus disease 2019 (COVID-19) in a single-center cohort of patients with MS and to explore the contribution of their comorbidities and therapies to the outcome. Methods A cross-sectional mixed-method study was conducted involving an email-based, self-administered questionnaire sent on May 21, 2020, to 586 patients with MS followed at the MS Unit of Hospital Clinic, University of Barcelona, along with telephone interview, and review of electronic medical records until June 18, 2020. The cumulative incidence of confirmed COVID-19 (positive PCR or antibody test) and all COVID-19 cases (confirmed and suspected) from the start of the pandemic was compared with the population estimates for Barcelona. Results A total of 407 patients (69.5%) completed the survey. Most of the responders (67%) were female. The responders had a median age of 48 years (range 19–86), relapsing-remitting disease (84%), at least 1 comorbidity (45%), and were on disease-modifying therapy (DMT; 74.7%). COVID-19 was confirmed in 5 patients (1.2%) and suspected in 46 (11.3%). The cumulative incidence of confirmed COVID-19 cases was similar to that of the general population but was almost 2-fold higher when all cases were considered (p < 0.001). Six patients (11.7%) were hospitalized, of which 5 had good recovery and 1 died. Hospitalized patients were more frequently male, had diabetes and had progressive forms of MS (p < 0.05). DMT was not associated with the risk of infection or the outcome. Conclusions In the studied MS cohort, the incidence of COVID-19 was higher than that of the general population; however, most patients did not require hospitalization and had a good outcome despite the frequent presence of comorbidities and treatment with DMT.
Clinical improvement within 24 hours from mechanical thrombectomy as a predictor of long-term functional outcome in a multicenter population-based cohort of patients with ischemic stroke
(BMJ Publishing Group, 2021-02-01) Rudilosso, Salvatore; Laredo Gregorio, Carlos; Amaro Delgado, Sergio; Renú, Arturo ; Llull Estrany, Laura; Obach, Víctor ; Moreno, Javier; Ribó Jacobi, Marc; Abilleira, Sònia; Cardona Portela, Pere; Martí Fàbregas, Joan; Pérez de la Ossa, Natalia; Ramos, Anna; Roquer, Jaume; Serena, Joaquín; Purroy, Francisco; Urra Nuin, Xabier; Chamorro, Ángel
Background: Single-center studies have suggested that the early clinical course after mechanical thrombectomy (MT) in patients with ischemic stroke is a clinical predictor of long-term outcome. Objective: To analyze the prognostic value of clinical improvement within 24 hours in a population-based multicenter cohort. Methods: From a total of 3792 patients with acute ischemic stroke in Catalonia (CICAT registry), 1951 patients were treated with MT. The National Institutes of Health Stroke Scale (NIHSS) score within 24 hours, and follow-up was available in 1666 patients. Percentage variation in the NIHSS score was calculated in relation to a baseline assessment. Good outcome was defined as a modified Rankin Scale score ≤2 at 90 days. Predictive values of clinical improvement and adjusted OR to predict good outcomes were assessed in the whole cohort and the subgroup of patients with posterior circulation stroke (n=166). Results: Good outcome was achieved in 656/1666 patients (39%) overall. Percentage improvements both at the end of MT and at 24 hours predicted good outcome, with higher predictive capacity at 24 hours (C-statistic, 0.85 vs 0.73, p<0.001). Positive and negative predictive values were 70% and 74% for the >30% cut-off point at the end of MT, and 69% and 84% for the >50% cut-off point at 24 hours, respectively. The adjusted OR for good outcome was 5.8 (95% CI 4.2 to 8.1) and 12.9 (95% CI 9.7 to 17.1), respectively. In patients with posterior circulation stroke, the predictive value of the improvement at 24 hours was similar (C-statistic 0.90). Conclusion: Clinical improvement of patients within 24 hours of MT is a reliable and robust predictor of long-term prognosis, including patients with posterior circulation occlusions.
NURSE-led care in Patients Undergoing CATheter Ablation for Atrial Fibrillation: The NURSECAT-AF randomized trial.
(American Heart Association, 2026-02-26) Cano-Valls, Alba; Martínez Momblán, Ma. Antonia; Carro Fernández, Esther; Niebla Bellido, Mireia; Domingo Criado, Rebeca; Hevia, Sara; Venturas Nieto, Montserrat; Borràs, Roger; Tolosana, José M. (José María); Porta Sánchez, Andreu; Guichard, Jean Baptiste; Althoff, Till; Roca Luque, Ivo; Mont Girbau, Lluís; Guasch i Casany, Eduard
Background: Atrial fibrillation (AF) is associated with reduced quality of life and frequent hospitalizations. Integrated nurse-led care has proven beneficial in unselected AF patients, but evidence specific to patients undergoing catheter ablation is limited. We aimed to assess the impact of a structured nurse-led intervention in patients undergoing first-time AF ablation. Methods: NURSECAT-AF was a single-center prospective randomized clinical trial comparing usual care (UC) with a nurse-led peri-ablation care (NLC) which incorporated an educational program on AF, peri-procedural support, and risk factor management. Consecutive patients without heart failure referred for first-time AF ablation were randomized to UC or NLC. Visits in NLC were scheduled at 15 days pre- ablation, and 15 days, 3 months and 6 months post-ablation. The primary endpoint was quality of life at 12 months post-ablation using the Arrhythmia-Specific Scale in Tachycardia and Arrhythmia (ASTA). Secondary outcomes included arrhythmia recurrence, readmissions and emergency visits, and symptom burden at one year, and AF knowledge and satisfaction at 3 months. Results: Of 116 patients screened, 66 were randomized (33 per group; mean age 63±10 years; 67% male). At 12 months, the NLC group showed statistically significant better quality of life (baseline-adjusted ASTA difference +4 points [95%CI 1.8-6.3], p=0.007) than UC, and presented with less arrhythmia recurrences (OR 0.2 [95%CI 0.05-0.78]) and emergency visits (OR 0.2 [95%CI 0.06-0.66]). Patients assigned to NLC also presented with a lower symptom burden, higher satisfaction and greater disease knowledge. Risk factor profile was improved in the NLC group, with higher rates of smoking cessation, engagement in regular physical activity, and weight optimization. Nurse-led management enabled more frequently diagnosing obstructive sleep apnea. Conclusion: Nurse-led, integrated care for patients undergoing AF ablation improves the quality of life, clinical outcomes and risk factor management at one year post- procedure. These findings support the incorporation of structured nurse-led interventions in the peri-ablation care pathway.
Successful treatment with daptomycin and ceftaroline of MDR Staphylococcus aureus native valve endocarditis: a case report
(Oxford University Press, 2019-09) Duss, François Régis; García de la Mària, Cristina; Croxatto, Antony; Giulieri, Stefano; Lamoth, Frédéric; Manuel, Oriol; Miró Meda, José M.
Objectives The best therapeutic approach for treating MRSA endocarditis remains unknown, particularly in cases of high vancomycin MICs. We report here a case of daptomycin-non-susceptible, ceftaroline-resistant and fosfomycin-resistant MRSA native left valve endocarditis that was successfully treated with valve repair and a combination of high-dose daptomycin and ceftaroline. Methods Antimicrobial testing of the clinical strain was performed using Etest and microdilution broth methods. Time–kill and chequerboard methodologies were used to test the activity of antibiotic combinations. Results By Etest, the MIC of vancomycin was 2 mg/L, the MIC of daptomycin was 2 mg/L, the MIC of fosfomycin was 1024 mg/L and the MIC of ceftaroline was 1.5 mg/L. At the standard inoculum (105 cfu/mL), the three combinations of daptomycin plus ceftaroline, cloxacillin or fosfomycin were synergistic and bactericidal. However, when these combinations were tested using a higher inoculum (108 cfu/mL), all combinations were synergistic, but only daptomycin plus ceftaroline had bactericidal activity. Conclusions These results confirmed a synergistic effect between daptomycin plus ceftaroline and increased bactericidal activity against MRSA, suggesting that this combination may be effective for the treatment of invasive MRSA infection. Our experience highlights the potential clinical use of synergy testing to guide difficult treatment decisions in patients with MDR MRSA infection.
In vitro exebacase (CF-301) activity against methicillin-susceptible or methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci strains isolated from patients with infective endocarditis
(Oxford University Press, 2026-01-06) Cañas, María Alexandra; Cuervo Requena, Guillermo; García González, Javier; Krivak, Filip; Hernández Meneses, Marta; Falces Salvador, Carles; Perissinotti, Andrés; Vidal, Bàrbara; Tolosana, José M. (José María); Sandoval, Elena; Quintana, Eduard; Llopis Pérez, Jaime; Moreno Camacho, Ma. Asunción; Schuch, Raymond; García de la Mària, Cristina; Miró Meda, José M.
Background: Infective endocarditis (IE) is a severe infection mainly caused by Staphylococcus aureus, Enterococcus faecalis and viridans streptococci. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are major pathogens in prosthetic valves and devices. Exebacase is a first-in-class, antistaphylococcal lysin with rapid bactericidal and antibiofilm activity. Objective: To assess the in vitro activity of exebacase and standard IE antibiotics against S. aureus and CoNS isolates from IE patients in a university hospital (2010-2020). Methods: A total of 211 consecutive strains were analysed: S. aureus [n = 103 (82 MSSA, 21 MRSA)], S. epidermidis [n = 76 (20 MSSE, 56 MRSE)] and other CoNS species (n = 32, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus schleiferi, Staphylococcus caprae, Staphylococcus pasteuri). Broth microdilution MICs were determined for exebacase and comparators (cloxacillin, ceftaroline, vancomycin, daptomycin, gentamicin, rifampicin). Results: Exebacase inhibited all S. aureus at ≤1 mg/L. Geometric mean (GM) MICs were 0.56 mg/L for MSSA and 0.49 mg/L for MRSA, with MIC50/90 of 0.5/1 mg/L. For S. epidermidis, GM MICs were 3.03 mg/L (MSSE) and 3.40 mg/L (MRSE), with MIC50/90 of 4/16 and 4/8 mg/L, respectively. Other CoNS showed GM MICs ranging from 0.49 mg/L (S. capitis) to 2.59 mg/L (S. lugdunensis), with intermediate values for S. haemolyticus (1.15), S. hominis (1.0) and S. schleiferi (0.79). Exebacase activity was comparable to β-lactams, vancomycin and daptomycin and remained unaffected by resistance. Conclusions: Exebacase activity was independent of methicillin resistance and consistently higher against S. aureus than S. epidermidis. Further research is warranted to explore lysins in combination against staphylococcal infections.
In Vitro Activity of Ampicillin Plus Ceftriaxone Against Non-faecalis and Non-faecium Enterococcal Isolates With/Without VanC Phenotype: Clinical Implications for Infective Endocarditis.
(MDPI, 2024-12-05) García González, Javier; Cañas, María Alexandra; Cuervo Requena, Guillermo; Hernández Meneses, Marta; Verdejo, Miguel Ángel; Bodro, Marta; Díez de los Ríos, Javier; Gasch, Oriol; Ribera, Alba; Falces Salvador, Carles; Perissinotti, Andrés; Vidal Hagemeijer, Bárbara; Quintana, Eduard; Moreno Camacho, Ma. Asunción; Piquet, Maria; Roca Subirà, Ignasi; Fernández Pittol, Mariana José; San José Villar, Sol María; García de la Mària, Cristina; Miró Meda, José M.; Hospital Clínic Endocarditis Study Group
1) Background: Alternative antibiotics are needed to treat infective endocarditis (IE) caused by non-faecalis/non-faecium enterococci; we aimed to assess the in vitro activity of ampicillin plus ceftriaxone (AMP + CTR) against these enterococci and to describe its clinical efficacy in IE cases. (2) Methods: Time–kill curves with standard (ISI) and high (IHI) inocula were performed to test VanC isolates [3 E. casseliflavus (ECAS) and 1 E. gallinarum (EGALL)] and non-VanC isolates [1 E. durans (EDUR), 1 E. hirae (EHIR) and 1 E. raffinosus (ERAF)]. The narrative literature review of IE cases treated with AMP + CTR was analyzed alongside three study cases. Clinical outcomes were relapse and death. (3) Results: Ampicillin plus gentamicin (AMP + GEN) showed synergistic and bactericidal activity against most isolates. AMP + CTR was synergistic at ISI for EGALL, EDUR, and EHIR and bactericidal against EHIR. At IHI, indifferent activity was observed for all isolates. In IE cases treated with AMP + CTR, it was only effective for EDUR and EHIR. Clinical information for EGALL IE is lacking. For IE caused by ECAS and ERAF, AMP + CTR seems suboptimal or ineffective, respectively. (4) AMP + CTR cannot be recommended for treating IE due to ECAS/ERAF. In contrast, this combination was effective in IE caused by EDUR/EHIR and could be recommended.
Development of High-Level Daptomycin Resistance in Abiotrophia and Granulicatella Species Isolates from Patients with Infective Endocarditis
(American Society for Microbiology, 2021-09-17) Cañas, María Alexandra; Téllez, Adrián; García de la Mària, Cristina; Dahl, Anders; García González, Javier; Hernández Meneses, Marta; Almela, M. (Manel); Ambrosioni, Juan; Falces Salvador, Carles; Quintana, Eduard; Vidal, Bàrbara; Perissinotti, Andrés; Tolosana, José M. (José María); Sandoval, Elena; Pericàs, Juan M.; Moreno Camacho, Ma. Asunción; Miró Meda, José M.; Hospital Clínic Endocarditis Team Investigator
Abiotrophia and Granulicatella species are fastidious organisms, representing the causative agents of ∼1% to 3% of cases of infective endocarditis (IE). Little is known about the optimal antibiotic treatment for these species, and daptomycin has been suggested as a therapeutic option. We describe the antimicrobial profiles of Abiotrophia and Granulicatella IE isolates, investigate high-level daptomycin resistance (HLDR) development, and evaluate daptomycin activity in combination therapy. In vitro studies with 16 IE strains (6 Abiotrophia defectiva strains, 9 Granulicatella adiacens strains, and 1 G. elegans strain) were performed using microdilution to determine MICs and time-kill methodology to evaluate combination therapy. Daptomycin nonsusceptibility (DNS) (MIC ≥ 2 mg/liter) and HLDR (MIC ≥ 256 mg/liter) were based on existing Clinical and Laboratory Standards Institute (CLSI) breakpoints for viridans group streptococci. All isolates were susceptible to vancomycin: G. adiacens was more susceptible to penicillin and ampicillin than A. defectiva (22% versus 0% and 67% versus 33%) but less susceptible to ceftriaxone and daptomycin (56% versus 83% and 11% versus 50%). HLDR developed in both A. defectiva (33%) and G. adiacens (78%) after 24 h of exposure to daptomycin. Combination therapy did not prevent the development of daptomycin resistance with ampicillin (2/3 strains), gentamicin (2/3 strains), ceftriaxone (2/3 strains), or ceftaroline (2/3 strains). Once developed, HLDR was stable for a prolonged time (>3 weeks) in G. adiacens, whereas in A. defectiva, HLDR reversed to the baseline MIC at day 10. This study is the first to demonstrate rapid HLDR development in Abiotrophia and Granulicatella species in vitro. Resistance was stable, and most combination therapies did not prevent it.
Identifying risk factors for predominant negative symptoms from early stages in schizophrenia: A longitudinal and sex-specific study in first-episode schizophrenia patients
(Elsevier España, 2023-01-26) Mezquida Mateos, Gisela; Amoretti, Silvia; Bioque Alcázar, Miquel; García Rizo, Clemente; Sánchez Torres, Ana M.; Pina-Camacho, Laura; López Pena, Purificación; Mané Santacana, Anna; Rodríguez-Jiménez, Roberto; Corripio, Iluminada; Sarró, Salvador; Ibáñez Cuadrado, Ángela; Usall i Rodié, Judith; García-Portilla González, María Paz, 1962-; Vieta i Pascual, Eduard, 1963-; Mas Herrero, Sergi; Cuesta, Manuel J.; Parellada Redondo, Mara; González-Pinto, Ana; Berrocoso, Esther; Bernardo Arroyo, Miquel
Background: People with schizophrenia and predominant negative symptoms (PNS) present a different clinical and functional profile from those without such symptomatology. Few studies have examined the risk factors and the incidence of PNS in first-episode schizophrenia patients (FES) and differentiating by sex. This study aims to assess prevalence, demographic and clinical characteristics related to PNS from early stages and to study if there are sex-specific features in terms of developing PNS. Methods: In a sample of 121 FES patients derived from a multicentre and naturalistic study, those who developed PNS at 12-months were identified. Environmental, clinical, functional, and cognitive ratings were examined longitudinally. Binary logistic regressions were applied to detect baseline risk factors for developing PNS at one-year follow-up. Results: In the present FES cohort, 24.8% of the patients (n=30) developed PNS (20% of the women, 27.6% of the men). Compared to non-PNS (75.2%, n=91), at baseline, PNS group had more negative (t=-6.347; p<0.001) and depressive symptoms (t=-5.026; p<0.001), poorer premorbid adjustment (t=-2.791; p=0.006) and functional outcome (t=-2.649; p<0.001), more amotivation (t=-7.333; p<0.001), more expressivity alterations (t=-4.417; p<0.001), worse cognitive reserve (t=2.581; p<0.011), a lower estimated intelligent quotient (t=2.417; p=0.017), worse verbal memory (t=2.608; p=0.011), and worse fluency (t=2.614; p=0.010). Regressions showed that the premorbid adjustment was the main predictor of PNS in females (p=0.007; Exp(B)=1.106) while in males were a worse verbal memory performance (p=0.031; Exp(B)=0.989) and more alterations in the motivation domain (p=0.001; Exp(B)=1.607). Conclusions: A different baseline clinical profile and notable risk factors differences in the development of PNS between males and females were found. Results suggest that sex may be an important confounder in studies comparing schizophrenia patients with predominant and non-predominant negative symptomatology.
Food-dependent NSAID-induced hypersensitivity (FDNIH) reactions: unraveling the clinical features and risk factors
(John Wiley & Sons, 2021-05) López Sánchez, Jaime; Araujo Sánchez, Giovanna; Cardona, Victoria; García Moral, Alba; Casas Saucedo, Rocio; Guilarte, Mar; Torres Jaén, María José; Doña, Inmaculada; Picado Vallés, César; Pascal i Capdevila, Mariona; Muñoz-Cano, Rosa; Bartra Tomàs, Joan
Background In up to 70%–80% of patients with a suspected non-steroidal anti-inflammatory drug hypersensitivity (NSAIDH), challenge tests with the culprit drug yield negative results. On the other hand, there could be a NSAIDH overdiagnosis when anaphylaxis is the clinical manifestation. We hypothesize that some negative NSAID challenge tests and an overdiagnosis of NSAIDH occur in patients with food-dependent NSAID-induced hypersensitivity (FDNIH). Methods We studied 328 patients with a suspected acute NSAIDH. FDNIH was diagnosed in patients meeting all the following: (1) tolerance to the food ingested more temporally closed before the reaction, later the episode, (2) respiratory or cutaneous symptoms or anaphylaxis related to NSAID, (3) positive skin prick test to foods and/or specific IgE to food allergens (Pru p 3, Tri a 19, Pen a 1) involved in the reaction, and (4) negative oral provocation test to the culprit NSAID. Results 199 patients (60%) were diagnosed with NSAIDH and 52 (16%) with FDNIH. Pru p 3 was involved in 44 cases (84.6%) and Tri a 19 in 6 cases (11%). FDNIH subjects were younger (p < .001), with a higher prevalence of rhinitis (p < .001) and previous food allergy (p < .001), together with a higher proportion of subjects sensitized to pollens (p < .001) and foods (p < .001). Using just four variables (Pru p 3 sensitization, Tri a 19 sensitization, anaphylaxis, and any NSAID different from pyrazolones), 95.3% of cases were correctly classified, with a sensitivity of 92% and specificity of 96%. Conclusion Evaluation of FDNIH should be included in the diagnostic workup of NSAIDH.
Prediagnostic motor and non-motor symptoms in progressive supranuclear palsy: The step-back PSP study
(Elsevier B.V., 2020-03-13) Painous Martí, Cèlia; Martí Domènech, Ma. Josep; Simonet, Cristina ; Garrido Pla, Alicia; Valldeoriola Serra, Francesc; Muñoz, Esteban; Cámara Lorenzo, Ana; Compta, Yaroslau
Background: Improved knowledge of the prediagnostic phase of progressive supranuclear palsy (PSP) might provide information on when and how the disease starts, along with the opportunity to test therapies in disease stages with lesser neurodegeneration. Objective: To explore the symptoms in years preceding the PSP diagnosis. Methods: This is a single-center retrospective case-control study based on clinical charts review and a structured interview to PSP patients and their caregivers. Prediagnostic symptoms were defined as those present more than one year before the diagnosis. We explored 35 symptoms in the following domains: visual, dizziness, motor, mood/apathy, cognitive, behavioral, sleep, gastrointestinal/urinary and miscellaneous. Non-parametric statistics were applied, with significance set at <0.05 (FDR-corrected). Results: We included 150 subjects: 50 PSP patients (38% females, age 75.8) and an age- and sex-matched control group of 50 Parkinson's disease (PD) and 50 subjects (CS) without neurodegenerative disease. The frequencies of visual, motor, cognitive, behaviour and dizziness domains were significantly higher in PSP vs. PD, and so were the motor, mood/apathy, cognitive, behaviour and dizziness ones in PSP vs. CS. Over 50% of prediagnostic falls, apathy and anxiety, depression and memory-attention-executive symptoms, and over 30% of gait disturbances started more than three and up to ten years before the diagnosis. PSP patients had more consultations to ENT and ophthalmologists than PD patients. Conclusion: PSP patients present a broad variety of motor and non-motor symptoms several years before the diagnosis. The definition of a prediagnostic PSP phase might be helpful to identify patients in early disease stages.
Peripheral insulin and amylin levels in Parkinson's disease
(Elsevier B.V., 2020-08-25) Sánchez Gómez, Almudena; Alcarraz Vizán, Gema; Fernández Sánchez, Manel; Fernández Santiago, Rubén; Ezquerra Trabalón, Mario; Cámara Lorenzo, Ana; Serrano Clerencia, Mònica; Novials, Anna; Muñoz, Esteban; Valldeoriola Serra, Francesc; Compta, Yaroslau; Martí Domènech, Ma. Josep
Background: Type-2-diabetes (T2D) has surfaced as a potential risk factor for Parkinson's disease (PD) in some epidemiological studies. Evidence of glucose metabolism alterations in PD from molecular studies remains conflicting. Amylin, the T2D amyloid protein, has been implicated in PD in pathological studies. We aimed to assess peripheral levels of amylin and insulin in PD patients and control subjects (Cs). Methods: We conducted an observational cross-sectional study of 111 participants: 73 PD and 38 Cs, similar in age, sex and body mass index. All underwent motor (UPDRS-MDS-III), non-motor (NMSS) and cognitive (MDRS) scales as well as determination of four parameters: fasting glycaemia, glycated haemoglobin, fasting plasma insulin (FPI) and fasting plasma amylin (FPA). Results: FPI was significantly lower in PD than Cs (p = 0.034). In participants with age above cohort-median-age, FPA was higher in PD than Cs (p = 0.046). The FPA/FPI ratio (FPAIR) was significantly higher in PD than Cs (p = 0.024). In PD, modest correlation was found between higher insulin-resistance and NMSS scores. Conclusions: PD patients had lower FPI and increased FPAIR. In older PD subgroup, FPA was increased. The more the insulin resistance, the higher the non-motor scores. These findings provide an additional link between pathophysiology of diabetes and PD. This might be related to a dissociated insulin and amylin secretion in PD, in line with recent evidence of endocrine pancreas role in PD pathogeny.
Combined CSF α-SYN RT-QuIC, CSF NFL and midbrain-pons planimetry in degenerative parkinsonisms: From bedside to bench, and back again.
(Elsevier B.V., 2022-06) Compta, Yaroslau; Painous Martí, Cèlia; Soto Gimeno, Marta; Pulido Salgado, Marta; Fernández Sánchez, Manel; Cámara Lorenzo, Ana; Sánchez, V.; Bargalló Alabart, Núria; Caballol, Núria; Pont-Sunyer, Claustre; Buongiorno, Maria Teresa; Martín, Nuria; Basora Macaya, Misericordia; Tió, Montserrat; Giraldo, Darly M.; Pérez Soriano, Alexandra; Zaro, I.; Muñoz, Esteban; Martí Domènech, Ma. Josep; Valldeoriola Serra, Francesc
Introduction Differential diagnosis between Parkinson's disease (PD) and atypical parkinsonisms (APs: multiple system atrophy[MSA], progressive supranuclear palsy[PSP], corticobasal degeneration[CBD]) remains challenging. Lately, cerebrospinal fluid (CSF) studies of neurofilament light-chain (NFL) and RT-QuIC of alpha-synuclein (α-SYN) have shown promise, but data on their combination with MRI measures is lacking. Objective (1) to assess the combined diagnostic ability of CSF RT-QuIC α-SYN, CSF NFL and midbrain/pons MRI planimetry in degenerative parkinsonisms; (2) to evaluate if biomarker-signatures relate to clinical diagnoses and whether or not unexpected findings can guide diagnostic revision. Methods We collected demographic and clinical data and set up α-SYN RT-QuIC at our lab in a cross-sectional cohort of 112 participants: 19 control subjects (CSs), 20PD, 37MSA, 23PSP, and 13CBD cases. We also determined CSF NFL by ELISA and, in 74 participants (10CSs, 9PD, 26MSA, 19PSP, 10CBD), automatized planimetric midbrain/pons areas from 3T-MRI. Results Sensitivity of α-SYN RT-QuIC for PD was 75% increasing to 81% after revisiting clinical diagnoses with aid of biomarkers. Sensitivity for MSA was 12% but decreased to 9% with diagnostic revision. Specificities were 100% against CSs, and 89% against tauopathies raising to 91% with diagnostic revision. CSF NFL was significantly higher in APs. The combination of biomarkers yielded high diagnostic accuracy (PD vs. non-PD AUC = 0.983; MSA vs. non-MSA AUC = 0.933; tauopathies vs. non-tauopathies AUC = 0.924). Biomarkers-signatures fitted in most cases with clinical classification. Conclusions The combination of CSF NFL, CSF RT-QuIC α-SYN and midbrain/pons MRI measures showed high discriminant ability across all groups. Results opposite to expected can assist diagnostic reclassification.
Leukoaraiosis May Confound the Interpretation of CT Perfusion in Patients Treated with Mechanical Thrombectomy for Acute Ischemic Stroke
(Lippincott, Williams & Wilkins, 2019-08-01) Rudilosso, Salvatore; Laredo Gregorio, Carlos; Vivancos Sánchez, Catalina; Urra Nuin, Xabier; Llull Estrany, Laura; Renú, Arturo ; Obach, Víctor ; Zhao, Yashu; Moreno, Javier; Lopez-Rueda, Antonio; Amaro Delgado, Sergio; Chamorro, Ángel
Background and purpose: Leukoaraiosis frequently coexists in patients with acute stroke. We studied whether leukoaraiosis could confound the interpretation of CTP findings in patients treated with mechanical thrombectomy. Materials and methods: We analyzed 236 patients with stroke treated with mechanical thrombectomy and studied with CTP, of whom 127 (53.8%) achieved complete reperfusion. Periventricular white matter hyperintensities on MR imaging and hypodensities on NCCT were assessed through the Fazekas score. CTP-predicted nonviable tissue was defined as relative CBF <30%, and final infarct volume was quantified in DWI. We estimated mean MTT, CBV, and CBF in the asymptomatic hemisphere. In patients achieving complete reperfusion, we assessed the accuracy of nonviable tissue to predict final infarct volume using the intraclass correlation coefficient across periventricular hyperintensity/hypodensity Fazekas scores and variable relative CBF cutoffs. Results: MTT was longer (Spearman ρ = 0.279, P < .001) and CBF was lower (ρ = -0.263, P < .001) as the periventricular hyperintensity Fazekas score increased, while CBV was similar across groups (ρ = -0.043, P = .513). In the subgroup of patients achieving complete reperfusion, nonviable tissue-final infarct volume reliability was excellent in patients with periventricular hyperintensity Fazekas score grade 0 (intraclass correlation coefficient, 0.900; 95% CI, 0.805-0.950), fair in patients with periventricular hyperintensity Fazekas scores 1 (intraclass correlation coefficient, 0.569; 95% CI, 0.327-0.741) and 2 (intraclass correlation coefficient, 0.444; 95% CI, 0.165-0.657), and poor in patients with periventricular hyperintensity Fazekas score 3 (intraclass correlation coefficient, 0.310; 95% CI, -0.359-0.769). The most accurate cutoffs were relative CBF <30% for periventricular hyperintensity Fazekas score grades 0 and 1, relative CBF <25% for periventricular hyperintensity Fazekas score 2, and relative CBF <20% for periventricular hyperintensity Fazekas score 3. The reliability analysis according to periventricular hypodensity Fazekas score grades on NCCT was similar to that in follow-up MR imaging. Conclusions: In patients with stroke, the presence of leukoaraiosis confounds the interpretation of CTP despite proper adjustment of CBF thresholds.
Time to Reappraise the Antibiotic Treatment for Methicillin-Susceptible Staphylococcus aureus Infective Endocarditis: Data From the Experimental Model
(Oxford University Press, 2025-09-15) García de la Mària, Cristina; Gasch, Oriol; Cañas, María Alexandra; García González, Javier; Marco Reverté, Francesc; Hernández Meneses,Marta; Quintana, Eduard; Ambrosioni, Juan; Falces Salvador, Carles; Tolosana, José M. (José María); Vidal, Bàrbara; Pericàs, Juan M.; Perissinotti, Andrés; Llopis Pérez, Jaime; Moreno Camacho, Ma. Asunción; Cuervo Requena, Guillermo; Miró Meda, José M.; Hospital Clinic Endocarditis Study Group
Background Traditional treatment of methicillin-susceptible Staphylococcus aureus (MSSA) native valve endocarditis is based on cloxacillin/cefazolin monotherapy. Antibiotics with high activity against MSSA, such as ceftaroline and daptomycin, have been marketed for years, but there are no clinical trials evaluating them as monotherapy or combination therapy in patients with MSSA endocarditis. The objective of this study was to compare the efficacy of cloxacillin, ceftaroline, and daptomycin monotherapies and daptomycin combinations with β-lactams in a rabbit model of MSSA endocarditis. Methods Endocarditis was induced in rabbits with 2 strains of MSSA. After 24 hours of infection, they received human-like doses of cloxacillin, ceftaroline, or daptomycin or combinations of daptomycin plus either cloxacillin or ceftaroline. Isolates recovered from vegetation, spleen, and kidney were retested for daptomycin nonsusceptibility (DNS) posttreatment. Results MSSA vancomycin minimum inhibitory concentration did not influence the efficacy of any antibiotic treatment. Cloxacillin, ceftaroline, and daptomycin had similar activity (25%–50%) in sterilizing vegetations. However, 13% of rabbits treated with daptomycin developed DNS. The addition of daptomycin to cloxacillin or ceftaroline was synergistic and bactericidal, showing significantly more activity and higher rates of sterile vegetations (≥90%) than any monotherapy. Combinations also showed better activity in spleens and kidneys as compared with daptomycin monotherapy and prevented the development of DNS in all tissues. There were no differences between the daptomycin combinations. Conclusions In the MSSA experimental endocarditis model, daptomycin combinations with β-lactams had significantly better activity than any of the monotherapies in sterilizing valve vegetations and preventing DNS development. These findings support their use in clinical practice and to perform clinical trials.
Value of Vascular and Non-Vascular Pattern on Computed Tomography Perfusion in Patients With Acute Isolated Aphasia Stroke.
(American Heart Association, 2020-07-20) Rudilosso, Salvatore; Rodríguez Vázquez, Alejandro; Amaro Delgado, Sergio; Obach, Víctor ; Renú, Arturo ; Llull Estrany, Laura; Laredo Gregorio, Carlos; Marín Suárez, Ángel Alberto; Vargas Solano, Alberto; Urra Nuin, Xabier; Chamorro Sánchez, Ángel
Background and purpose: Acute onset aphasia may be due to stroke but also to other causes, which are commonly referred to as stroke mimics. We hypothesized that, in patients with acute isolated aphasia, distinct brain perfusion patterns are related to the cause and the clinical outcome. Herein, we analyzed the prognostic yield and the diagnostic usefulness of computed tomography perfusion (CTP) in patients with acute isolated aphasia. Methods: From a single-center registry, we selected a cohort of 154 patients presenting with acute isolated aphasia who had a whole-brain CTP study available. We collected the main clinical and radiological data. We categorized brain perfusion studies on CTP into vascular and nonvascular perfusion patterns and the cause of aphasia as ischemic stroke, transient ischemic attack, stroke mimic, and undetermined cause. The primary clinical outcome was the persistence of aphasia at discharge. We analyzed the sensitivity, specificity, positive and negative predictive values of perfusion patterns to predict complete clinical recovery and ischemic stroke on follow-up imaging. Results: The cause of aphasia was an ischemic stroke in 58 patients (38%), transient ischemic attack in 3 (2%), stroke mimic in 68 (44%), and undetermined in 25 (16%). CTP showed vascular and nonvascular perfusion pattern in 62 (40%) and 92 (60%) patients, respectively. Overall, complete recovery occurred in 116 patients (75%). A nonvascular perfusion pattern predicted complete recovery (sensitivity 75.9%, specificity 89.5%, positive predictive value 95.7%, and negative predictive value 54.8%), and a vascular perfusion pattern was highly predictive of ischemic stroke (sensitivity 94.8%, specificity 92.7%, positive predictive value 88.7%, and negative predictive value 96.7%). The 3 patients with ischemic stroke without a vascular perfusion pattern fully recovered at discharge. Conclusions: CTP has prognostic value in the workup of patients with acute isolated aphasia. A nonvascular pattern is associated with higher odds of full recovery and may prompt the search for alternative causes of the symptoms.
The multiomics blueprint of the individual with the most extreme lifespan
(Cell Press, 2025-10-21) Torrubiano, Marta; Massip Salcedo, Marta; Khidir, Kamal A.; Cao, Thong Huy; Quinn, Paulene A.; Jones, Donald J. L.; Macip, Salvador; Brigos Barril, Eva; Moldes, Mauricio; Barteri, Fabio; Ferrer, Gerardo; Muntané, Gerard; Davalos, Veronica; Laayouni, Hafid; Mereu, Elisabetta; Navarro, Arcadi; Pluvinet, Raquel; Esteller, Manel; Arribas, Carles; Torre, Carolina de la; Villavicencio Goula, Francisco; Sumoy, Lauro; Granada, Isabel; Coles, Natalie S.; Santos Pujol, Eloy; Noguera Castells, Aleix; Casado Pelaez, Marta; García Prieto, Carlos A.; Vasallo, Claudia; Campillo Marcos, Ignacio; Quero Dotor, Carlos; Crespo García, Eva; Bueno Costa, Alberto; Setién, Fernando; Acha, Pamela; Solé, Francesc; Mallo, Mar; Mata, Caterina; Peregrina, Sara; Gabaldón, Toni; Llirós, Marc; Pujolassos, Meritxell; Carrera Torres, Robert; Lluansí, Aleix; García Gil, Librado Jesús; Aldeguer, Xavier; Samino, Sara; Torné, Pol; Ribalta, Josep; Guardiola, Montse; Amigó, Núria; Yanes, Oscar; Martínez, Paula; Sánchez Vázquez, Raúl; Blasco, Maria A.; Oviedo, Jose; Lemos, Bernardo; Rius Bonet, Julia
Extreme human lifespan, exemplified by supercentenarians, presents a paradox in understanding aging: despite advanced age, they maintain relatively good health. To investigate this duality, we have performed a high-throughput multiomics study of the world's oldest living person, interrogating her genome, transcriptome, metabolome, proteome, microbiome, and epigenome, comparing the results with larger matched cohorts. The emerging picture highlights different pathways attributed to each process: the record-breaking advanced age is manifested by telomere attrition, abnormal B cell population, and clonal hematopoiesis, whereas absence of typical age-associated diseases is associated with rare European-population genetic variants, low inflammation levels, a rejuvenated bacteriome, and a younger epigenome. These findings provide a fresh look at human aging biology, suggesting biomarkers for healthy aging, and potential strategies to increase life expectancy. The extrapolation of our results to the general population will require larger cohorts and longitudinal prospective studies to design potential anti-aging interventions.
Hepatitis C-related cirrhosis will be a marginal cause of hospital admissions by 2025
(Elsevier, 2020-12-01) Rodriguez-Tajes, Sergio; Pocurull Aparicio, Anna; Castillo Iturra, Joaquín; Casanova, Gherzon; Vega, Laia; Lens García, Sabela; Mariño, Zoe; Londoño, María Carlota; Forner González, Alejandro; Torres, Ferran; Forns, Xavier
Background & Aims Complications of cirrhosis are the main cause of hospital admissions in liver units. In areas where HCV is prevalent, most of these admissions are attributable to HCV-related cirrhosis (HCV-cirrhosis). This study assessed the impact of direct-acting antivirals (DAA) in the profile of patients with liver disease admitted to a referral liver unit from a university hospital. Methods We registered hospital admissions resulting from cirrhosis to the Liver Unit of the Hospital Clinic of Barcelona, from 2011 to 2014 (pre-DAA period) and from 2015 to 2019 (post-DAA period). Results From a total of 14,865 hospital admissions, 10,053 resulted from cirrhosis (corresponding to 6,272 patients). The number and proportion of hospital admissions because of HCV-cirrhosis remained stable during the period 2011–2014 (525 per year, 48.8% of the total), but decreased progressively after 2015 (p <0.001), reaching <300 (27.1%) admissions in 2019. Similarly, HCV-cirrhosis accounted for 3,885 inpatient days per year (44.9%) during the pre-DAA period and decreased steadily after 2015 (p >0.001), reaching only 1,909 inpatient days (22%) in 2019. The figures for intensive care unit admissions followed a similar pattern. By means of a slope analysis (binomial regression model), we predicted that HCV-cirrhosis hospital admissions will be residual by 2025 (2.3%, 95% CI 0–10.9%). By contrast, we observed a significant increase in hospital admissions because of metabolic-associated fatty liver disease (5-fold) and autoimmune hepatitis (4-fold) during the study period. Conclusions In summary, our data showed a profound reduction in HCV-cirrhosis hospitalisation burden since 2015, coincident with the wide use of DAAs in Spain. Our predictions suggest that, by 2025, HCV-cirrhosis will be a marginal cause of hospital admissions for patients with liver disease. Lay summary Over the past few years, the wide use of antiviral drugs that cure HCV has had a significant effect on patients being admitted to hospital. Most patients with HCV and cirrhosis are treated (and often cured) in the community and, thus, the number of hospital admissions because of severe forms of HCV has decreased drastically. HCV is no longer the first cause of admission into liver units and, in only a few years from now, it is likely to be only a residual cause of hospitalisation.
Gastrointestinal Symptoms: Under the Tip of the Iceberg in Lipid Transfer Protein Food Allergy
(Esmon Publicidad S.A., 2024-07-30) Ruano Zaragoza, Maria; Araujo Sánchez, Giovanna; Gelis, Sònia; Loli Ausejo, David Enrique; Mir Ihara, Patricia Karina; Mascaró Hereza, Berta; Sánchez Fernández, M.C.; Pascal i Capdevila, Mariona ; Muñoz-Cano, Rosa; Bartra Tomàs, Joan
Gastrointestinal symptoms (GIS) have been reported to be a manifestation of IgE-mediated food allergy (FA), although epidemiologic data are limited. Patients with FA caused by lipid transfer proteins (LTP-FA) may react to many different plant foods, present a broad spectrum of clinical symptoms (ranging from oral allergy syndrome to anaphylaxis), and develop GIS.

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