Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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Improved prognostic stratification with the FIGO 2023 endometrial cancer staging system. A multicenter Spanish cohort study.
(2026-03-19) Díaz Feijoo, Berta; Veiga N; Padilla-Iserte P; Oliver R; Arencibia O; Diaz-Feijoo B; Gil-Moreno A; Coronado P; Martin-Salamanca MB; Pantoja-Garrido M; Marcos-Sanmartin J; Gilabert-Estelles J; Lorenzo C; Cazorla E; Cabezas E; RoldÁn-Rivas F; RodrÍguez-HernÁndez JR; Alvarez S; Sánchez L; Enguita-Germán M; Muruzabal JC
To evaluate the impact of applying the FIGO 2023 staging system compared with FIGO 2009 in a real-world cohort of patients with early-stage endometrial cancer who underwent surgery. This multicenter retrospective cohort study included patients with apparent early-stage endometrial cancer diagnosed between 2000 and 2020 across 18 Spanish centers. All patients underwent primary surgery and were classified according to both FIGO 2009 and FIGO 2023 criteria. Stage migration was assessed, and the characteristics of newly defined subgroups were described. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were compared between classifications. A total of 4566 patients were included. Application of the FIGO 2023 system resulted in stage migration in 909 patients (19.9%) compared with FIGO 2009. The FIGO 2023 system showed a higher 5-year OS for Stage I patients than the 2009 classification (91.3% vs. 88.2%). Within the new substages, 5-year OS was 93.9% in Stage IA1 and 91.9% in Stage IA2, and Stage IA3 demonstrated distinct survival outcomes. Overall survival for Stage III remained comparable between classifications, although outcomes varied across subcategories. In a simplified classification (Stages I-III), the FIGO 2023 system showed improved prognostic discrimination for both PFS and OS according to Harrell's C-index. The FIGO 2023 staging system leads to substantial reclassification of early-stage endometrial cancer patients and introduces new prognostic subgroups. This increased granularity improves prognostic stratification and may support individualized treatment decisions, even when molecular testing is limited.
Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona; Spain.
(Springer Verlag, 2024-05-27) Monzó Gallo, Patricia; Alastruey Izquierdo, Ana; Chumbita, Mariana; Aiello, Tommaso Francesco; Gallardo Pizarro, Antonio; Peyrony, Olivier; Teijon Lumbreras, Christian; Alcázar Fuoli, Laura; Espasa, Mateu; Soriano Viladomiu, Alex; Marco Reverté, Francesc; García Vidal, Carolina
Objectives We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months. Methods Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. Results Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. Conclusion We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.
Cortex folding by combined progenitor expansion and adhesion-controlled neuronal migration
(Nature Publishing Group, 2025-08-28) Chun, Seung Hee; Yoon, Da Eun; Diaz Almeida, Daniel Santiago; Todorov, Mihail Ivilinov; Straub, Tobias; Ruff, Tobias; Shao, Wei; Yang, Jianjun; Seyit Bremer, Gönül; Shen, Yi-Ru; Ertürk, Ali; Toro Ruiz, Daniel del; Shi, Songhai; Klein, Rüdiger
Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we show in mice that combining the Flrt1/3 double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 leads to a relative increase in Flrt-mutant neurons resulting in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 leads to a relative reduction in Flrt-mutant neurons resulting in enhanced formation of gyri. These results together with computational modeling identify key developmental mechanisms, such as adhesive properties, cell densities and migration of cortical neurons, that cooperate to promote cortical gyrification.
Identification of a crosstalk between ClC-1 C-terminal CBS domains and the transmembrane region
(The Physiological Society, 2025-02-07) Gaitán-Peñas, Héctor; Pérez González, Anna Priscil·la; González Subías, Marc; Zdebik, Anselm A.; Gasull Casanova, Xavier; Buey, Ruben M.; Errasti-Murugarren, Ekaitz; Estévez Povedano, Raúl
CLC channels and transporters have large C-terminal regions which contain two cystathionine β-synthetase (CBS) domains. It has been hypothesized that conformational changes in these domains upon nucleotide binding modulate the gating of the CLC dimer. It is not clear how rearrangements that occur in the CBS domains are transmitted to the ion pathway, as CBS domains interact with the rest of the channel at multiple locations and some of these sites are not visible in recent solved cryogenic electron microscopy structures or are difficult to model using the AlphaFold server. Using ClC-1 as a model, we started working with a described ClC-1 mutation (H835R) located in the first alpha helix of the CBS2 domain which changes the voltage dependence of gating. We then identified several residues located in the disorganized loop after helix R (R-linker) that revert the phenotype of this mutation. We additionally proved that R-linker's function is connected to the CBS2 domain as current intensity, plasma membrane levels and gating defects of several R-linker variants were corrected by adding the mutation H835R. Furthermore, cross-linking studies using newly developed split-cysless ClC-1 channels containing specific cysteine mutants in the R-linker and the CBS2 domain indicate that these two regions are in close contact. Considering these new results, we propose that conformational changes occurring in the CBS domains could be transmitted to the CLC intracellular chloride binding site by means of its interaction with the R-linker.
Low-dose cannabidiol treatment prevents chronic stress-induced phenotypes and is associated with multiple synaptic changes across various brain regions
(Elsevier Ltd., 2025-05-21) Borràs Pernas, Sara; Sancho Balsells, Anna; Patterer, Lisa; Wang, Maoyu; Toro Ruiz, Daniel del; Alberch i Vié, Jordi, 1959-; Schibano, Daniele; Espel, Joan; Heybeck, Maya; Scheidel, Bernhard; Giralt Torroella, Albert
Major Depressive Disorder (MDD) is a heterogeneous and debilitating mood disorder often associated with stress. Although current treatments are available, they remain ineffective for approximately 30 % of affected individuals and are frequently accompanied by undesirable side effects. Cannabidiol (CBD) has emerged as a potential and safe therapeutic option for alleviating depressive symptoms; however, the underlying molecular mechanisms through which this compound exerts its beneficial effects are not yet fully understood. In this study, we demonstrate that a very low dose of CBD (1 mg/kg) can partially reverse some sequelae induced by chronic stress, a well-established mouse model used to simulate depressive-like symptoms. Using mass spectrometry to analyze different brain regions, we observed several improvements following CBD treatment, particularly in the medial prefrontal cortex (mPFC), across multiple neurotransmission systems (including glutamatergic and serotonergic pathways). Microstructural experiments, utilizing double-labeling of F-Actin and VGlut1-positive clusters, revealed a complete restoration of mature synapses in the mPFC of mice treated with CBD. In conclusion, our findings indicate that a very low dose of CBD is effective in counteracting the adverse effects of chronic stress, possibly through the synaptic remodeling of excitatory synapses in the mPFC.
Consensus on Subdomains and Measures of Relevance to Affective and Social Cognition Research on Bipolar Disorder (CAS-BD); Outcomes and Recommendations From an International Society for Bipolar Disorders Targeting Cognition Taskforce Study
(John Wiley & Sons, 2026-03-01) Van Rheenen, Tamsyn E Van; Lewandowski, Kathryn E; Pinkham, Amy; Varo, Cristina; Caruana, Georgia F.; Gruber, J.; Zarp, Jeff; Young, Allan H.; Yatham, Lakshmi N.; Vieta i Pascual, Eduard, 1963-; Torres, Ivan J.; Tsapekos, Dimosthenis; Sumiyoshi, Tomiki; Stokes, Paul R. A.; Schaffer, Ayal; Purdon, Scot E.; Porter, Richard J.; McIntyre, Roger S.; Martínez-Arán, Anabel, 1971-; López Jaramillo, Carlos; Lafer, Beny; Kessing, Lars Vedel; Kjærstad, Hanne Lie; Hasler, Gregor; Gallagher, Peter; Douglas, Katie; Dols, Annemiek; Carvalho, André F.; Burdick, Katherine E.; Bowie, Christopher R.; Bonnín Roig, Caterina del Mar; Balanzá-Martínez, Vicent; Miskowiak, Kamilla W.
Background The Consensus on subdomains and measures of Affective and Social cognition for research on Bipolar Disorder (CAS-BD) project aimed to formulate preliminary consensus-based recommendations for assessing affective and social cognition in BD. Methods Three sequential surveys administered to experts on affective and social cognition in BD were conducted using the Delphi process. Experts responded to questions regarding affective and social cognition subdomains and rated their importance to research on BD. Experts also nominated measures, rated them for suitability, and ranked them by preference for use. Consensus was defined as ≥ 80% agreement. Results 31 experts completed the initial survey, with 20–23 completing subsequent surveys. Consensus was obtained for the subdomain structure of both affective cognition and social cognition, and the definition of each subdomain within. Explicit emotion regulation was ranked as being of highest priority for further research on affective cognition, and theory of mind as highest priority for further research on social cognition. The top-preferenced measures of all affective cognition subdomains were considered by consensus to be suitable for use in BD research. Agreement that the top-preferenced measures of social cognition were suitable ranged from 71.5% to 95.3%. Discussion Expert consensus on subdomains and measures of affective and social cognition for research on BD was obtained via a staged approach. Prior familiarity may have influenced some experts' rankings, but generally there was a notable lack of consistency in the use of available measures by BD experts. This reaffirms the need for more specific guidance and validated batteries of social and affective cognition to direct the field and allow for more consistency and replication of research in the future.
Psychosocial functional recovery in patients with bipolar disorder in remission: Which symptoms hold them back?
(Elsevier B.V., 2026-02-14) Bonnín Roig, Caterina del Mar; Montejo Egido, Laura; Torrent Font, Carla; Sánchez-Moreno, José; Diego-Adeliño, Javier de; Solé Cabezuelo, Brisa; Roca Tutusaus, Xavier; Hidalgo Mazzei, Diego; Borràs, Roger; Clougher, Derek; Valentí Ribas, Marc; Martínez-Arán, Anabel, 1971-; Cardoner, N. (Narcís); Vieta i Pascual, Eduard, 1963-
Background: Subthreshold depressive symptoms significantly hinder functional recovery in bipolar disorder (BD). While most studies use a global score to assess the impact of these symptoms on functioning, this study examines which specific subthreshold depressive symptoms mostly impede functional recovery in patients with BD in remission. Method: The sample comprised a total of 413 patients with BD. Subthreshold depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAM-D), and psychosocial functioning was measured with the Functioning Assessment Short Test (FAST). Bivariate analyses were performed to identify items from the HAM-D as well as other clinical and demographic variables associated with functional impairment. Multivariate linear regression analyses were conducted including the variables that demonstrated significant associations in the bivariate analyses. Results: The linear regression model for the FAST total score demonstrated that "psychomotor retardation" (item 8) had the strongest association on psychosocial functioning (β = 6,9; p < 0,001), followed by "feelings of guilt" (item 2) (β = 5,75; p < 0,001) "work and activities" (item 7) (β = 5,38; p < 0,001) and "somatic anxiety" (item 11) (β = 3,45; p < 0,001). Other significant clinical variables included antipsychotic use, older age, fewer years of education and male sex. This model explained 39,6% of the variance in the FAST total score (R2 = 0,396; Adjusted R2 = 0,375; F(399,13) = 20,04; p < 0,001). Conclusions: Specific subthreshold symptoms, including psychomotor retardation, apathy, guilt and somatic anxiety significantly influence psychosocial functioning. These findings highlight the importance of specifically targeting these symptoms to achieve functional recovery, even when patients are clinically stable.
Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression. Multicenter Study
(MDPI, 2025-06-28) García de Herreros, Marta; Jiménez, Natalia; Padrosa, Joan; Aversa, Caterina; Ferrer Mileo, Laura; García Esteve, Samuel; Rodriguez Carunchio, Leonardo; Trias Puigsureda, Isabel; Fernández Mañas, Laia; Marín Aguilera, Mercedes; Altamirano, Mariana; Mazariegos, Manuel; Font, Albert; Rodriguez Vida, Alejo; Climent, Miguel Ángel; Cros, Sara; Chirivella González, Isabel; Figols Gorina, Mariona; Sala González, Núria; Ruiz de Porras, Vicenç; Pardo, Juan Carlos; Prat Aparicio, Aleix; Reig Torras, Oscar; Mellado González, Begoña
Alterations in the PTEN tumor suppressor gene are common in prostate cancer. They have been associated with a more aggressive disease and poor outcomes and potential benefit of targeted therapies. The purpose of this work is to study the clinical and transcriptional landscapes associated to low PTEN mRNA expression in metastatic hormone-sensitive prostate cancer (mHSPC) patients. A multicenter biomarker ambispective study was performed in mHSPC patients. PTEN mRNA expression was assessed by nCounter in formalin-fixed paraffin-embedded tumor samples. PTENlow status was defined by a previously validated cut-off and was correlated with castration-resistant prostate cancer (CRPC)-free survival (CRPC-FS) (primary endpoint) and overall survival (OS). RNA-Seq was performed to molecularly characterize PTENlow vs. PTENwt tumors. A total of 380 patients were included, 350 eligible. PTENlow was observed in 28.2% of patients and was independently associated with shorter CRPC-FS (HR 1.6, 95% CI 1.2–2.1, p = 0.002) and OS (HR 1.5, 95% CI 1.1–2, p = 0.014). PTENlow tumors showed overexpression of neuroendocrine, cell cycle, and DNA repair gene signatures, reduced expression of the androgen receptor pathway, and a distinct immune microenvironment. Using microarray data from the CHAARTED trial, we developed a PTEN-low related signature, independently associated with CRPC-FS (HR 1.5, 95% CI 1–2.3, p = 0.036) and OS (HR 1.9, C1 1.2–2.9, p = 0.005), and identified targets for potential therapies in PTEN-altered tumors. We conclude that PTENlow correlates with an aggressive clinical outcome in mHSPC patients and is associated with a unique transcriptional profile. These findings further support the investigation of novel therapeutic strategies for patients with PTEN alterations.
Murine typhus as the leading cause of non-focalized fever in the Canary Islands
(Springer Verlag, 2024-11-29) Vélez-Tobarias, Mónica; Torres-Vega, Ana María; Carmelo Pascual, Emma; Morais-Martín, Julio; Pérez, José Antonio; Gonzalo-Hernández. C.; Clot Razquin, Guillem; Ascaso Terrén, Carlos
Purpose and methods: This prospective study aims to diagnose the etiology of non-focalized fever lasting between 5 and 28 days in the islands of La Palma and El Hierro (Canary Islands, Spain) during 2021, using serology and PCR. Results: The etiological profile described in this study aligns with that of fever of intermediate duration (FID), with zoonoses being the primary cause. Murine typhus (MT) is identified as the leading cause, followed by Q fever (QF). The incidence of MT is the highest reported nationally and comparable to the highest in Europe, with 39.6 cases per 100,000 inhabitants in La Palma and 79.7 cases per 100,000 inhabitants in El Hierro. Q fever, known to be endemic to the Canary Islands, presents incidences of 26.5 cases per 100,000 inhabitants in La Palma and 15.6 cases per 100,000 inhabitants in El Hierro. MT shows no gender differences and has a homogeneous geographical distribution. In contrast, QF is more prevalent in men and has a heterogeneous geographical distribution. Conclusions: The high incidence of MT found in both urban and peri-urban areas is particularly noteworthy. Its potential connection with climate change and/or the growth of the reservoir population in the Canary Islands remains unknown. MT's similarity to QF in terms of clinical signs and treatment, coupled with the absence of a specific protocol for early diagnosis, may have contributed to its underdiagnosis. MT can lead to significant health concerns, including risk of hospitalization, complications, and even death. Therefore, the registration of cases for epidemiological control is deemed essential.
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.
Protocol for tailored in vitro neuronal networks on high-density microelectrode arrays with polydimethylsiloxane microstructures
(Elsevier B.V., 2026-03-20) Haeb, Anna-Christina; Yamamoto, Hideaki; Roach, Paul; Merryweather, Daniel; Sato, Y.; Tornero, Daniel; Soriano i Fradera, Jordi
Complementary metal-oxide-semiconductor (CMOS)-based high-density microelectrode arrays (HD-MEAs) enable neuronal recordings with high spatiotemporal resolution. However, integrating polydimethylsiloxane (PDMS) microstructures onto HD-MEA surfaces to control network architecture is currently challenging and platform specific. Here, we present a protocol for PDMS fabrication, HD-MEA chip preparation, PDMS-HD-MEA microstructure alignment, and cell culture, including alternatives. Our results show reproducible formation of modular networks with characteristic activity patterns across different systems. This protocol supports engineering of defined neuronal architectures while maintaining compatibility with various HD-MEA systems.
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.
Sentinel node detection and imaging concordance in Early-Stage ovarian cancer: A MELISA trial analysis of tracer, timing, and intraoperative gamma camera
(2025-09-05) Agustí, Núria; Paredes Barranco, Pilar; Vidal Sicart, Sergi; Migliorelli, Federico; Celada Castro, Cristina; Carreras-Dieguez, Nuria; Campos Rodríguez, Francisco; Marina, Tiermes; Romero, Inmaculada; Glickman, Ariel; Fritsch, Andrea; Navarro, Nahir; Fuste, Pere; Torne, Aureli; Díaz Feijoo, Berta
PurposeTo evaluate the detection rate of sentinel lymph node (SLN) mapping in early-stage ovarian cancer using [99mTc]Tc-nanocolloid and indocyanine green (ICG), and the added value of an intraoperative gamma camera.MethodsThis was a prospective single-center trial of 63 patients with suspected early-stage epithelial ovarian cancer who underwent SLN mapping with combined tracers. [99mTc]Tc-nanocolloid was injected into the ovarian ligaments before adnexectomy, and if malignancy was confirmed on intraoperative frozen section, ICG was administered after adnexectomy in immediate staging cases. SLNs were identified using a handheld gamma probe, the gold standard, and a portable gamma camera for radiotracer localization, alongside near-infrared imaging for ICG. We calculated SLN detection rates for each tracer and concordance between the tracers (reflecting the impact of injection timing), including identification of the same SLN- as well as between detection modalities. Cohen's kappa and PABAK were used to assess concordance between detection modalities. Patients with confirmed malignancy underwent complete pelvic and aortic lymphadenectomy.ResultsAmong 63 patients, sentinel lymph nodes (SLNs) were detected in 79.4% using [99mTc]Tc-nanocolloid. In the 30 patients who also received ICG, the combined use of both tracers achieved a detection rate of 93.3%, with higher detection in the aortic region compared to the pelvic region (83.3% vs. 43.3%). The intraoperative gamma camera showed 83.3% concordance with the gamma probe, including 87.5% concordance in the aortic region and 66.7% in the pelvic region. Among patients who received both tracers, 14 had drainage in at least one region by both, and 12 of these (85.7%) showed concordant detection of the same SLN. Concordance was 100% in re-staging and 77.8% in immediate surgeries.ConclusionSLN mapping in ovarian cancer using a dual tracer approach is feasible and yields a higher detection rate than single tracers. The gamma camera identified SLN localization mainly in aortic regions. This combination may improve nodal staging in early ovarian cancer and reduce the need for systematic lymphadenectomy. Post-adnexectomy injection is a practical alternative to injection before adnexectomy for immediate surgeries, although caution is needed due to potential variations in lymphatic drainage.
Haematopoietic stem cell transplant versus immune-reconstitution therapy in relapsing multiple sclerosis.
(Oxford Academic, 2025-08-04) Kalincik, Tomas; Sharmin, Sifat; Roos, Izanne; Freedman, Mark S.; Atkins, Harold; Massey, Jennifer; Sutton, Ian; Withers, Barbara; Blanco Morgado, Yolanda; RESCUE-MS Group; MSBase Group
In the treatment of relapsing-remitting multiple sclerosis, autologous hematopoietic stem cell transplant and immune-reconstitution therapies show several similarities. These treatment strategies have not yet been compared head-to-head. This study emulated pairwise trials of comparative effectiveness of stem cell transplant vs. immune-reconstitution therapies cladribine and alemtuzumab. This cohort/registry study of comparative treatment effectiveness included data from 7 specialist multiple sclerosis centres with autologous hematopoietic stem cell programs (RESCUE-MS) and international MSBase registry during 2006-2023. The study included patients with relapsing-remitting multiple sclerosis treated with autologous hematopoietic stem cell transplant, cladribine or alemtuzumab, with a minimum of 2-month follow-up before commencing study therapy and ≥2 disability assessments after commencing the study therapy. Patients were matched on a propensity score derived from their clinical and demographic characteristics. The matched groups were compared on annualised relapse rates freedom from relapses and 6-month confirmed disability worsening and improvement (measured with Expanded Disability Status Scale). The matching of 143 (stem cell) to 283 cladribine-treated patients and of 134 (stem cell) to 562 alemtuzumab-treated patients reduced the measured differences between the groups by 98% and 96%, respectively. The matched patients had high mean disease activity (>0.8 relapses in the prior 2 years), mean Expanded Disability Status Scale scores of 3-4, and were followed-up for a mean of 3.8-3.9 (stem cell), 1.9 (cladribine) or 4.5 years (alemtuzumab). Compared to cladribine, stem cell transplant was associated with a lower risk of relapses (mean annualised relapse rate ± standard deviation 0.05±0.28 vs. 0.16±0.39, respectively; hazard ratio 0.24, 95% confidence interval 0.15-0.41), similar risk of disability worsening (hazard ratio 0.70, 95% confidence interval 0.34-1.43) and higher probability of disability improvement (hazard ratio 2.19, 95% confidence interval 1.31-3.66). Compared to alemtuzumab, stem cell transplant was associated with a lower risk of relapses (mean annualised relapse rate ± standard deviation 0.04±0.23 vs. 0.09±0.21, respectively; hazard ratio 0.52, 95% confidence interval 0.29-0.93), similar risk of disability worsening (hazard ratio 0.95, 95% confidence interval 0.53-1.72) and higher probability of disability improvement (hazard ratio 2.03, 95% confidence interval 1.23-3.34). 34% of patients treated with stem cell transplant experienced delayed complications, mainly infections. No treatment-associated deaths were reported. Among patients with active relapsing-remitting multiple sclerosis and moderate disability, autologous hematopoietic stem cell transplant is superior to cladribine and alemtuzumab at suppressing relapses and enabling recovery of neurological function. The high effectiveness of stem cell transplant is likely attributable to a complex interplay of immune suppression and reconstitution.
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 Sánchez, 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.
Effect of a bundle intervention on adherence to quality-of-care indicators and on clinical outcomes in patients with Staphylococcus aureus bacteraemia hospitalized in non-referral community hospitals
(Oxford University Press, 2024-11-04) Escrihuela-Vidal, Francesc ; Chico, Cristina; Borjabad, Beatriz; Vázquez Sánchez, Daniel Antonio; Lérida, Ana; Blas Escudero, Elisa de; Sanmartí Vilamala, Montserrat ; Linares González, Laura; Simonetti, Antonella Francesca; Coloma Conde, Ana; Muelas Fernandez, Magdalena; Díaz Brito, Vicens; Horna, Gertrudis ; Oriol, Isabel; Berbel, Dàmaris; Càmara Mas, Jordi ; Grillo, Sara; Pujol Rojo, Miquel; Cuervo Requena, Guillermo; Carratalà, Jordi; PROMISE Study Group
Background: Although a significant number of cases of Staphylococcus aureus bacteraemia (SAB) are managed at non-referral community hospitals, the impact of a bundle-of-care intervention in this setting has not yet been explored. Methods: We performed a quasi-experimental before-after study with the implementation of a bundle of care for the management of SAB at five non-referral community hospitals and a tertiary care university hospital. Structured recommendations for the five indicators selected to assess quality of care were provided to investigators before the implementation of the bundle and monthly thereafter. Primary endpoints were adherence to the bundle intervention and treatment failure, defined as death or relapse at 90 days of follow-up. Results: One hundred and seventy patients were included in the pre-intervention period and 103 in the intervention period. Patient characteristics were similar in both periods. Multivariate analysis controlling for potential confounders showed that performance of echocardiography was the only factor associated with improved adherence to the bundle in the intervention period (adjusted OR 2.13; 95% CI 1.13-4.02). Adherence to the bundle, performance of follow-up blood cultures, and adequate duration of antibiotic therapy for complicated SAB presented non-significant improvements. The intervention was not associated with a lower rate of 90 day treatment failure (OR 1.11; 95% CI 0.70-1.77). Conclusions: A bundle-of-care intervention for the management of SAB at non-referral community hospitals increased adherence to quality indicators, but did not significantly reduce rates of 90 day mortality or relapse.
Effect of long-term adherence on faecal immunochemical test positivity rate, positive predictive value and detection rate in organised population-based colorectal cancer screening.
(BMJ Publishing Group, 2026-01-30) Ladabaum, Uri ; Font Marimon, Rebeca; Castells Olivera, Xavier; Balaguer, Francesc; Pellíse, María; Solà, Judit ; Espinàs Piñol, Josep Alfons ; Castells, Antoni (Castells Oliveres)
Long-term adherence and results with faecal immunochemical test (FIT)-based colorectal cancer (CRC) screening are poorly characterised. To characterise adherence and results through seven rounds in an organised biennial FIT-based CRC screening programme. We determined per-round FIT-completion, FIT-positivity, CRC and high-risk-CRC precursor positive predictive values (PPVs) and CRC detection/1000-FIT-participants for all invitees versus an adherent cohort (entry 50-51 years; 66-100% rounds completed) versus comparable-age first-ever screenings from 2010 to 2023. Joinpoint and multivariable logistic regression analyses identified trends. Adherence was consistent, frequent, occasional, infrequent and never (defined as 100%, 66-99%, 33-65%, 1-32%, 0% of rounds offered) in 29.2%, 8.6%, 11.5%, 4.5% and 46.2% of 2.81 million individuals, respectively. In both the all-invitee population and the adherent cohort, the first round yielded the highest FIT positivity (5.8%, 4.4%), PPVs for CRC (5.1%, 3.3%) and high-risk precursors (20.4%, 13.1%), and CRC detection rates (2.65, 1.30 per 1000 participants), respectively. Beyond three rounds, outcomes stabilised at levels substantially lower than those observed in first-time screeners of the same age (eg, CRC-PPV in seventh round: 1.6-2.2% at median age 62-65 vs 6.6% for new screeners aged 62-63). Colonoscopy completion after a positive FIT was high (87.3%). After an initial round with the highest FIT-positivity and detection rates, screening outcomes stabilise at lower levels reflecting neoplasia removal and subsequent selection of a lower-risk population. Because detection rates remain clinically relevant even in an adherent cohort, early screening cessation after a sequence of normal biennial FITs is not justified.
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. (José María), 1956-
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 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. (José María), 1956- ; 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.

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