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Quantitative HER2 tissue and plasma profiling predicts the activity of trastuzumab deruxtecan for breast cancer
(Springer Nature, 2026-03-13) Tarantino, Paolo; Kim, Se-Eun; Hughes, Melissa E.; Kusmick, Ross J.; Smith, Kalie; Brasó Maristany, Fara; Nyein Chan, Nay Nwe; Paré Brunet, Laia; Alder, Laura; Garcia Cortes, Diana; Gomez Tejeda Zanudo, Jorge; Pereslete, Alyssa M.; Noteware, Laura; Moore, Heather M.; Swearingen, Amanda E. D. Van; Li, Tianyu; Gupta, Hersh; D'Amico, Olivia; Martini, Alba; Morganti, Stefania; Spindel, Jennifer; Cook, Charmaine; McLaughlin, Christine; Dvir, Kathrin; Garrido Castro, Ana C.; Sammons, Sarah; Files, Janet L.; Sendrick, Kerry; Buck, Simone; Dillon, Deborah; Jeselsohn, Rinath; Li, Yvonne Y.; Cherniack, Andrew D.; LoRusso, Patricia; Lustberg, Maryam; Vega León, Rosario; Pardo, Francisco; Davis, Justin; Mueller, Claudius; Corgiat, Brian; Curigliano, Giuseppe; Anders, Carey K.; Petricoin, Emanuel F.; Rimm, David L.; Prat Aparicio, Aleix; Tayob, Nabihah; Lin, Nancy U.; Tolaney, Sara M.
Trastuzumab deruxtecan (T-DXd) is commonly used for treating metastatic breast cancer (MBC); however, traditional HER2 immunohistochemistry has largely failed to predict T-DXd activity. We reviewed survival outcomes and tested the reliability of multiple HER2 quantitative assays in predicting T-DXd's performance among 191 patients with MBC. We demonstrate that T-DXd's activity varies depending on the temporal evolution of HER2 immunohistochemical expression, with the longest activity observed among patients with HER2-positive disease or maintaining HER2-low disease across primary and metastatic settings. Quantitative HER2 assessment on pre-T-DXd samples showed that time-to-next treatment progressively increased by High Sensitivity-HER2 quartiles, Reverse Phase Protein Array HER2 quartiles, HER2DX ERBB2 mRNA scores and plasma-based DNADX HER2 signature tertiles (all with log-rank p < 0.05). Conversely, HER2 immunohistochemical subtypes showed limited predictive value for clinical outcomes. Additionally, elevated TOPO1 expression was associated with worse outcomes with T-DXd in HER2-negative breast cancer, suggesting potential relevance for payload-related markers in predicting T-DXd performance.
Talimogene laherparepvec and atezolizumab in HER2-negative breast cancer following neoadjuvant chemotherapy: a window-of-opportunity phase II trial (SOLTI-1503 PROMETEO)
(Nature Publishing Group, 2026-02-16) Pascual, Tomás; Vidal Losada, Maria Jesús; Cejalvo Andújar, Juan Miguel; Vega, Estela; Sanfeliu, Esther; Villacampa, Guillermo; Ganau, Sergi; Julve Parreño, Ana María; Zamora, Esther; Miranda, Ignacio; Delgado, Ana; Bermejo de las Heras, Begoña; Seguí, Elia; Brasó Maristany, Fara; Cruz Merino, Luis de la; Juan, Manel; Galván, Patricia; González Farré, Xavier; Chillara, Samyukta; Villagrasa, Patricia; Pfefferle, Adam D.; O'Connell, Constandina E.; Ferrero Cafiero, Juan Manuel; Oliveira, Mafalda; Perou, Charles M; Prat Aparicio, Aleix
This single-arm, phase II, preoperative window-of-opportunity trial (ClinicalTrials.gov Identifier: NCT03802604) investigated the efficacy and safety of talimogene laherparepvec (T-VEC), an oncolytic virus, with atezolizumab, an anti-PD-L1 antibody, in patients with breast cancer and radiologically and pathologically confirmed residual disease prior to surgery. Eligible patients had triple-negative breast cancer (TNBC) or hormone receptor-positive (HR+)/HER2-negative disease with a high proliferation index (Ki67 ≥ 20%) prior to neoadjuvant chemotherapy. Treatment consisted of one intratumoral injection of T-VEC (10⁶ plaque-forming units [PFU]/mL), followed by four biweekly T-VEC doses (10⁸ PFU/mL) plus atezolizumab (840 mg, intravenously). Among the 28 patients enrolled, 20 patients (71.4%) had HR+/HER2-negative and 8 patients (28.6%) had TNBC. At surgery, 7 patients (26.9%) achieved Residual Cancer Burden (RCB)-0/I (primary endpoint), 12 (46.2%) RCB-II and 7 (26.9%) RCB-III. Safety profile was favorable, with mostly low-grade adverse events and no serious events (secondary endpoint). Therapy induced immune modulation, including increased tumor-infiltrating lymphocytes, elevated PD-L1 expression, and enhanced immune-related gene signatures (exploratory endpoints). The trial met its pre-specified efficacy and safety endpoints. These findings support the feasibility of T-VEC plus atezolizumab as a preoperative immunotherapy approach for managing HER2-negative residual disease post-neoadjuvant chemotherapy and warrant further exploration in larger trials.
Real-world second- and third-line progression-free survival after progression on first-line CDK4/6 inhibitors in HR+/HER2- metastatic breast cancer by PAM50 intrinsic subtype: the SOLTI-1801 CDK-PREDICT study
(Springer Verlag, 2026-02-28) Tolosa, Pablo; Garcia Fructuoso, Isabel; Pascual, Tomás; Martínez Sáez, Olga; Cejalvo Andújar, Juan Miguel; Servitja, Sonia; Fernández Abad, María; Benitez Fuentes, Javier David; Brasó Maristany, Fara; Sanfeliu, Esther; Lema, Laura; Ruano, Yolanda; Parrilla, Lucía; Roncero, Ana María; Cobos-Fernandez, Maria Angeles; Díaz, Irene; Centelles López, Karla Alicia; Sánchez Bayona, Rodrigo; Alva, Manuel; Madariaga, Ainhoa; Villacampa, Guillermo; Salvador, Fernando; Sánchez Belmonte, Agustín; Malumbres, Marcos; Prat Aparicio, Aleix; Ciruelos, Eva
Purpose: Estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (MBC) shows variable outcomes after first-line CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET). The prognostic role of PAM50 intrinsic subtypes (IS) in this setting remains unestablished. We evaluated IS and biomarker profiles in the SOLTI-1801 CDK-PREDICT cohort, focusing on real-world second- and third-line progression-free survival (rwPFS-2L and rwPFS-3L). Methods: This multicenter observational study reports a post hoc secondary analysis of ER+ /HER2- MBC patients previously treated with first-line CDK4/6i plus ET. Baseline metastatic biopsies were molecularly profiled (PAM50, CCNE1, PDCD1) using the nCounter platform. rwPFS-2L and rwPFS-3L were defined from initiation of second- or third-line therapy to progression or death. Kaplan-Meier and Cox models assessed associations with clinical, molecular, and treatment variables. Results: Among evaluable patients (n = 125 for rwPFS-2L; n = 95 for rwPFS-3L), Luminal A/B subtypes represented most cases, while advanced lines showed more aggressive profiles. Median rwPFS-2L was 7.2 months in luminal IS vs. 6.1 in non-luminal (HR 1.40; 95% CI 0.86-2.30); the Basal-like (BL) subtype correlated with significantly shorter rwPFS-2L (HR 3.82; 95% CI 1.07-13.63). In rwPFS-3L, similar trends were seen (6.4 vs. 3.3 months; HR 1.74; 95% CI 0.98-3.08), with BL showing the poorest outcomes (HR 5.63; 95% CI 1.17-27.02). High CCNE1 expression was linked to shorter rwPFS-2L (HR 1.22; 95% CI 1.02-1.47). Targeted agents were frequent in 2L (51%) and capecitabine in 3L (36%), while endocrine monotherapy yielded poorest rwPFS. Conclusions: Outcomes after CDK4/6i progression differ by PAM50 IS, supporting its role in guiding post-progression treatment.
Validation of the HER2DX genomic test in first-line advanced HER2-positive breast cancer treated with trastuzumab, pertuzumab, and taxane
(Springer Nature, 2026-02-10) Kubeczko, Marcin; Cobo, Sandra; Sánchez Bayona, Rodrigo; Pycinski, Bartlomiej; Soberino, Jesús; Chmielik, Ewa; Sanfeliu, Esther; Rey, Maria; Pardo, Francisco; Aguirre, Ángela; Castillo, Oleguer; Lesniak, Aleksandra; Oczko-Wojciechowska, Malgorzata; Carcelero San Martin, Esther; Adamo, Barbara; Vidal Losada, Maria Jesús; Bergamino Sirvén, Milana; Maues, Julia; Villacampa, Guillermo; Paré, Laia; Villagrasa, Patricia; Ciruelos, Eva; Prat Aparicio, Aleix; Jarzab, Michal; Brasó Maristany, Fara
Trastuzumab, pertuzumab, and a taxane (THP) has been the standard first-line therapy for HER2+ advanced breast cancer for over a decade. With new regimens emerging, genomic tools like HER2DX may help identify patients who benefit durably from THP versus those requiring intensification. Here, baseline tumor tissue from 122 patients with HER2+ treated with THP in Poland was tested with HER2DX. A previously published Spanish real-world cohort (n = 93) was added to generate a combined cohort (n = 215). Univariable analyses were performed in the Polish cohort, and multivariable Cox and logistic regression models were applied to the combined cohort. A HER2DX metastatic prognostic score was trained on overall survival (OS) in the Spanish cohort and validated in the Polish cohort. In the Polish cohort, high ERBB2 mRNA scores were associated with significantly longer real-world progression-free survival (rwPFS) (33.8 vs. 17.9 months; hazard ratio [HR] 0.57; p = 0.022) and real-world overall survival (rwOS) (75.1 vs. 40.2; HR 0.48; p = 0.009). In the combined cohort, ERBB2 high-score tumors showed prolonged rwPFS (33.8 vs. 12.5; HR 0.50; p < 0.001) and rwOS (not reached vs. 37.1; HR 0.36; p < 0.001), and higher rwORR (84.4% vs. 52.0%; p < 0.001). Prognostic value was independent of clinical variables, including number of metastatic sites. Subgroup analyses showed particularly favorable outcomes in patients with <3 sites (median rwPFS 51.7 vs. 20.3 months). The HER2DX metastatic prognostic score outperformed ERBB2 alone in the validation cohort. In conclusion, the HER2DX ERBB2 mRNA score provides independent prognostic information in HER2+ advanced breast cancer treated with THP. The HER2DX metastatic prognostic score further improves prognostic accuracy.
Impact of cognitive reserve in clinical, neurocognitive and lifestyle factors in chronic schizophrenia and early stages of schizophrenia
(Elsevier España, 2024-07-01) Amoretti Guadall, Silvia; Arranz, Belén; Anmella, Gerard; Bernardo Arroyo, Miquel; Alfonso, Miqueu; Hernández, Carla; García-Portilla González, María Paz, 1962-; González-Blanco, Leticia; Safont, Gemma; Garrido, Ignacio; Sanchez Autet, Mónica
Introduction Although there is evidence that higher cognitive reserve (CR) is a protective factor and it has been related to better prognosis, there have been no studies to date that have explored the CR level and its impact in clinical, neurocognitive and lifestyle outcomes according to the stage of the disease: early stage of psychosis (ESP) or chronic schizophrenia (SCZ). Material and methods A total of 60 patients in the ESP and 225 patients with SCZ were enrolled in the study. To test the predictive capacity of CR for each diagnostic group, a logistic regression analysis was conducted. Hierarchical linear regression analyses were performed to explore the associations between CR and different outcomes. The mediation analyses were performed according to the principles of Baron and Kenny. Results Patients with SCZ showed lower CR than those in the ESP (p < 0.001). CR correctly classified 79.6% of the cases (p < 0.001; Exp(B) = 1.062). In ESP group, CR was related to working memory (p = 0.030) and negative symptoms (p = 0.027). CR (t = 3.925, p < 0.001) and cannabis use (t = 2.023, p = 0.048) explained 26.7% of the variance on functioning (p = 0.003). In patients with SCZ, CR predicted all cognitive domains, negative symptoms (R2 = 0.091, p = 0.001) and functioning (R2 = 0.074, p = 0.005). In both ESP and SCZ groups, higher CR was associated with lower body mass index and circumference. In ESP group, the effect of adherence to Mediterranean diet on functioning (p = 0.037) was mediated by CR level (p = 0.003).
Neoadjuvant palbociclib and endocrine therapy versus chemotherapy in ER + /HER2- breast cancer: a randomized phase II trial
(Nature Publishing Group, 2026-04-08) Pascual, Tomás; Gavilá, Joaquín; Prat Aparicio, Aleix; Perou, Charles M.; Brandberg, Yvonne; Bergh, Jonas; Hatschek, Thomas; Foukakis, Theodoros; Johansson, Hemming; Hellström, Mats; Agartz, Susanne; Grybäck, Per; Salgkamis, Dimitrios; Zerdes, Ioannis; Wang, Kang; Hartman, Johan; Acs, Balazs; Sun, Wenwen; Matikas, Alexios; Tzoras, Evangelos; Sarafidis, Michail; Sifakis, Emmanouil G.; Bjöhle, Judith; Barnekow, Elin; Margolin, Sara; Isaksson Friman, Erika; Edman Kessler, Luisa; Zouzos, Athanasios; Boyaci, Ceren; Villacampa, Guillermo
n PREDIX LumB patients with estrogen receptor positive and human epidermal growth factor receptor negative (ER + /HER2-) breast cancer > 20 mm and/or with lymph node metastasis were randomized 1:1 to receive either paclitaxel weekly for 12 weeks followed by palbociclib and endocrine therapy for 12 weeks (arm A), or the reverse sequence (arm B). Primary endpoint is objective radiologic response at 12 weeks (ORR12), and key secondary endpoints are ORR24, pathologic complete response, event-free survival, safety and correlative studies of tissue and circulating biomarkers. Whole exome sequencing and RNA sequencing were performed on baseline fresh frozen tissue samples. In total, 179 patients comprise the intention-to-treat population. There is no statistically significant difference between the two arms in ORR12 (59% vs 45%, p = 0.058). An exploratory gene expression analysis identified differentially expressed genes and gene sets between responders and non-responders at 12 weeks. A predictive signature, CDKPredX, comprising 31 genes related to proliferation, ER signaling and immune activity was developed to identify patients resistant to chemotherapy but responding to palbociclib plus endocrine therapy (pinteraction=0.03). The predictive signature was independently validated in the CORALLEEN trial (pinteraction=0.048). Clinicaltrials.gov identifier: NCT02603679
Emerging global patterns of COVID-19 vaccine information fatigue in 23 countries in 2023
(Elsevier B.V., 2024-12-02) White, Trenton M.; Lazarus, Jeffrey V.; Rabin, Kenneth; Ratzan, Scott; El-Mohandes, Ayman
Vaccine information fatigue, exacerbated by the infodemic, misinformation, and cultural influences, hampers public responsiveness to the uptake of vaccines for COVID-19 and other vaccine-preventable diseases. This cross-sectional study of 23,000 respondents surveyed in 23 countries in October 2023 analyzed trust in information sources, perceptions of the pandemic's conclusion, and confidence in one's ability to discern false information from true and the association of these factors with willingness to pay attention to COVID-19 vaccine information, adjusting for sociodemographic characteristics. Results revealed that satisfaction with health authority communication was positively associated with individuals' willingness to pay attention to COVID-19 vaccine information in all 23 countries. Confidence in one's own capacity to distinguish true information from false was associated with willingness in 20 countries. Belief that the pandemic is over was associated with unwillingness to pay attention to COVID-19 vaccine information in 14 countries. These findings underscore the need for tailored communication strategies that build trust in information sources, combat complacency, and enhance discernment skills to address vaccine and pandemic fatigue, aiming to sustain public engagement with vaccine information and, ultimately, support vaccination efforts.
Not all severe malaria cases are severe: Is it time to redefine severity criteria for malaria in non-endemic regions?
(Elsevier, 2024-07-01) Balerdi Sarasola, Leire; Muñoz Gutiérrez, José; Fleitas, Pedro E.; Rodriguez Valero, Natalia; Almuedo Riera, Alex; Antequera, Alba; Subirà, Carme; Grafia, Ignacio; Ortiz Fernández, Maria; Alba, Tessa de; Álvarez Martínez, Míriam; Valls Lolla, Ma. Eugenia; Parolo, Claudio; Castro Rebollo, Pedro; Camprubí Ferrer, Daniel
Background: The current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort. Methods: A cohort study of patients managed for malaria in a non-endemic setting (2005-2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2 % threshold was applied. Patients with SM were distinguished as very severe malaria (VSM) when presenting at least one of the following conditions: parasitemia >10 %, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria (LSM) was defined by: 2-10 % parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections. Results: Among 506 patients with malaria, 176 (34.8 %) presented with SM. A total of 37 (7.3 %) patients developed a life-threatening condition, namely death (n = 4) and/or the need for life-saving interventions (n = 34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28 (5.5 %) patients had a community-acquired co-infection, with no differences between groups (p = 0.763). Conclusions: Severity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics.
Spontaneous and perturbation-based EEG cortical excitability markers are associated with plasma p-tau181 concentration in healthy middle-aged adults
(Elsevier, 2024-12-30) Perellón Alfonso, Ruben; Abellaneda Pérez, Kilian; Pileckyte, Indre; Cabello Toscano, María del Rocío; Mulet Pons, Lídia; Vaqué Alcázar, Lídia; Cattaneo, Gabrielle; Redondo-Camós, María; España Irla, Goretti; Delgado Gallén, Selma; Solana Sánchez, Javier; Zetterberg, Henrik; Tormos, José María; Franzmeier, Nicolai; Pascual Leone, Álvaro, 1961-; Bartrés Faz, David
In early-stage Alzheimer's disease (AD) amyloid-β (Aβ) deposition can induce neuronal hyperactivity, thereby potentially triggering activity-dependent neuronal secretion of phosphorylated tau (p-tau), ensuing tau aggregation and spread. Therefore, cortical excitability is a candidate biomarker for early AD detection. Moreover, lowering neuronal excitability could potentially complement strategies to reduce Aβ and tau buildup. There is, however, a lack of understanding of the relationship between cortical excitability and p-tau increase in vivo. Therefore, in a sample of 658 healthy middle-aged (between the ages of 40 and 65) participants of the Barcelona Brain Health Initiative cohort study, we examined the relation of blood-based tau, phosphorylated at amino acid 181 (p-tau181), reflecting neuronal p-tau secretion; neurofilament light chain (NfL), as a passively released control for p-tau181; and electroencephalography (EEG) markers of cortical excitability. A subsample of 47 participants also completed a controlled brain perturbation approach via transcranial magnetic stimulation (TMS) with concurrent EEG. Results show that both spontaneous (i.e., resting-state) and perturbation-based TMS-EEG markers, are associated with blood p-tau181, particularly in older individuals. The perturbation-based marker was a significantly more sensitive predictor of p-tau181 concentration than the spontaneous resting state EEG-based marker. The relationships observed are not present for the NfL control. These results show that relationships between p-tau181 and cortical excitability are present in healthy middle-aged subjects and that p-tau181 increases may reflect activity-dependent secretion.
Uncovering the role of sociodemographic factors in sex/gender differences in emotional brain activation: an SDM-PSI meta-analysis of fMRI studies
(Elsevier B.V., 2026-02-03) Ariño-Braña, Paula; Vieira, Rita; Soriano Mas, Carles; Radua, Joaquim; Picó Pérez, Maria
Introduction: The study of sex/gender (S/G) differences in neuroscience, particularly in emotional processing, has been hindered by methodological inconsistencies, often producing biased conclusions that overgeneralize brain differences between males and females. Moreover, many studies fail to consider how other sociodemographic factors interact with S/G to influence the brain. This study aims to address these gaps by investigating whether potential S/G effects in brain activation during emotion-evoking functional magnetic resonance imaging (fMRI) tasks are influenced by those factors. Methods: This meta-analysis followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and was registered on PROSPERO. We searched for peer-reviewed studies on S/G differences in whole-brain activations during fMRI emotion-evoking tasks. Data analysis was conducted using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI). Subgroup analyses were performed based on the type of tasks and on race, and meta-regressions assessed the impact of age, education, and hormonal con- traceptive use on the main effects. Results: 63 studies were included for the meta-analysis, comprising a total of 5,436 individuals from the general population (2,635 females). The main meta-analysis showed no significant S/G activation differences at the whole-brain level. Subgroup analyses, however, revealed significant S/G differences depending on the type of task and the race subgroup, while meta-regression analyses showed significant associations between S/G effects and education and hormonal contraceptive use, with notable shifts in activation patterns across these variables. Discussion: Our findings highlight the need for more complex, intersectional models that consider the dynamic interplay of biological, psychological, and social factors in shaping S/G differences in brain function and mental health.
High-resolution kinetics and cellular determinants of SARS-CoV-2 antibody response over two years after COVID-19 vaccination
(Elsevier Masson SAS, 2025-02-01) Rubio Bodí, Rocío; Macià Bros, Dídac; Barrios, Diana; Vidal, Marta; Jiménez, Alfons; Molinos Albert, Luis M.; Díaz Garrido, Natalia; Canyelles, Mar; Lara Escandell, Maria; Planchais, Cyril; Santamaria, Pere; Carolis, Carlo; Izquierdo, Luis; Aguilar, Ruth; Moncunill, Gemma; Dobaño, Carlota, 1969-
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) studies usually rely on cross-sectional data of large cohorts but limited repeated samples, overlooking significant inter-individual antibody kinetic differences. By combining Luminex, activation-induced marker (AIM) and IFN-γ/IL-2 Fluorospot assays, we characterized the IgM, IgA, and IgG antibody kinetics using 610 samples from 31 healthy adults over two years after COVID-19 vaccination, and the T-cell responses six months post-booster. Antibody trajectories varied among isotypes: IgG decayed slowly, IgA exhibited an initial sharp decline, which gradually slowed down and stabilized above the seropositivity threshold. Contrarily, IgM rapidly dropped to undetectable levels after primary vaccination. Importantly, three vaccine doses induced higher and more durable anti-spike IgG and IgA levels compared to two doses, whereas infection led to the highest antibody peak and slowest antibody decay rate compared to vaccination. Comparing with ancestral virus, antibody levels recognizing Omicron subvariants had a faster antibody decay. Finally, polyfunctional T cells were positively associated with subsequent IgA responses. These results revealed distinctive antibody patterns by isotype and highlight the benefits of booster doses in enhancing and sustaining antibody responses.
Neuromodulation and meditation: A review and synthesis toward promoting well-being and understanding consciousness and brain
(Elsevier, 2024-11-01) Abellaneda Pérez, Kilian; Potash, Ruby M.; Pascual Leone, Álvaro, 1961-; Sacchet, Matthew D.
The neuroscience of meditation is providing insight into meditation's beneficial effects on well-being and informing understanding of consciousness. However, further research is needed to explicate mechanisms linking brain activity and meditation. Non-invasive brain stimulation (NIBS) presents a promising approach for causally investigating neural mechanisms of meditation. Prior NIBS-meditation research has predominantly targeted frontal and parietal cortices suggesting that it might be possible to boost the behavioral and neural effects of meditation with NIBS. Moreover, NIBS has revealed distinct neural signatures in long-term meditators. Nonetheless, methodological variations in NIBS-meditation research contributes to challenges for definitive interpretation of previous results. Future NIBS studies should further investigate core substrates of meditation, including specific brain networks and oscillations, and causal neural mechanisms of advanced meditation. Overall, NIBS-meditation research holds promise for enhancing meditation-based interventions in support of well-being and resilience in both non-clinical and clinical populations, and for uncovering the brain-mind mechanisms of meditation and consciousness.
Single-pill combination for treatment of hypertension: Just a matter of practicality or is there a real clinical benefit?
(Elsevier B.V., 2024-08-01) Coca, Antonio; Whelton, Seamus; Camafort Babkowski, Miguel; López López, José; Yang, Eugene
Abstract Elevated blood pressure (BP) is the largest contributor to the incident cardiovascular disease worldwide. Despite explicit guideline recommendations for the diagnosis and management of hypertension, a large proportion of patients remain undiagnosed, untreated, or treated but uncontrolled. Inadequate BP control is associated with many complex factors including patient preference, physician's inertia, health systems disparities, and poor adherence to prescribed antihypertensive drug treatment. The primary driver for reduced cardiovascular morbidity and mortality is lowering of BP ‘‘per se’’ and not class effects of specific pharmacotherapies. The recent ESH guidelines recommend the use of four major classes of drugs including renin‐angiotensin‐aldosterone system (RAS) blockers (angiotensin receptor blockers (ARB) or angiotensin‐converting enzyme inhibitors (ACEi)), calcium channel blockers (CCB), thiazide and thiazide‐like diuretics, and betablockers. Initiation of treatment for hypertension with a two-drug regimen, preferably in a single pill combination (SPC), is recommended for most patients. Preferred combinations should comprise a RAS blocker (either an ACEi or an ARB) with a CCB or thiazide/thiazide-like diuretic. These strategies are supported by robust evidence that combination therapy produces greater BP reductions than monotherapy, reduces side effects of the individual components, improves therapeutic adherence and long-term persistence on treatment, and permits achievement of earlier BP control.
Managing and discharging COPD patients hospitalized because of an exacerbation of respiratory symptoms: An opportunity to improve outcomes
(Elsevier B.V., 2024-10-01) Agustí García-Navarro, Àlvar; Celli, Bartolome R.; Fabbri, Leonardo M.; Vogelmeier, Claus F.
Many patients with chronic obstructive pulmonary disease (COPD) develop episodes of exacerbation of respiratory symptoms (ECOPD) that may require hospitalization (H-ECOPD). Long-term prognosis during and following an H-ECOPD is poor, with a five-year mortality rate of about 50 %
Implementation of the TALK© clinical self-debriefing tool in operating theatres: a single-centre interventional study
(Oxford University Press, 2024-10-01) Diaz Navarro, Cristina; Enjo Perez, Iago; León Castelao, Esther; Hadfield, Andrew; Nicolás Arfelis, Josep Maria; Castro Rebollo, Pedro
Background Debriefing in operating theatre environments leads to benefits in mortality, efficiency, productivity, and safety culture; however, it is still not regularly performed. TALK© is a simple and widely applicable team self-debriefing method to collaboratively learn and improve. Methods An interventional study introducing TALK© for voluntary clinical debriefing was carried out in operating theatre environments in a UK National Health Service hospital over 18 months. It explored compliance with the Five Steps to Safer Surgery and changes in behaviour in surgical teams regarding consideration and completion of debriefing. Results Team briefing and compliance with the WHO surgical safety checklist were performed consistently (>95% and >98%, respectively) throughout the study, which included 460 surgical lists. Consideration of debriefing increased at all data collection periods after intervention, from 35.6% to 60.3–97.4% (P≤0.003). Performance of debriefing, which was 23.3% at baseline, reached 39% at 6 months (P=0.039). Team planning of actions for improvement during debriefing also increased (P<0.001). A decline in performance of debriefing and subsequent improvement actions was observed after 6 months, albeit rates were above baseline at 18 months. The most reported reason not to carry out a debriefing was ‘lack of issues’. After implementation, nurses and allied healthcare professionals increased their contribution to initiating and leading debriefing. Reported barriers were <18% at baseline, and decreased after intervention. Conclusions A simple intervention introducing TALK© for voluntary debriefing in theatres prompted significant changes in team behaviour and sustained growth regarding consideration and performance of debriefing, especially in the first 6 months.
Walking one hour per day and the derived neutrophil-to-lymphocyte ratio are associated with outcome in palliative second-line immunotherapy for patients with recurrent and/or metastatic squamous cell carcinoma of head and neck
(Elsevier, 2024-11-01) Caballero Borrego, Miguel; Piedra Cascón, Aida; Gallego Rubio, Oscar; López Pousa, Antonio; Castillo, Paola; Navarrete Duran, Pilar; Prat, Alba; Grau, Juan José
Objectives To determine whether routinary walking activity and the derived neutrophil-to-lymphocyte ratio are associated with outcomes in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Methods This multicenter retrospective cohort study included 64 patients diagnosed with recurrent and/or metastatic squamous cell carcinoma of head and neck and treated with immunotherapy (Programmed Death-1 and Programmed Death-ligand-1 proteins inhibitors) at two tertiary centers. We compared a group that performed uninterrupted physical activity for 1 h per day and controls who performed no activity. The derived neutrophil-to-lymphocyte ratio was calculated as follows: [neutrophils / (leukocytes – neutrophils)]. Progression-free survival and overall survival were evaluated. Results We included 28 (44%) and 36 (56%) patients in the activity and non-activity groups, respectively. Patient characteristics, treatment details, and tumor Programmed Death-ligand-1 expression were not associated with either progression-free survival or overall survival. Physical activity was an independent beneficial factor for progression-free survival (p < 0.001) and overall survival (p < 0.001). By contrast, a derived neutrophil-to-lymphocyte ratio <3.5 was an independent beneficial factor for overall survival (p = 0.013), but not for progression-free survival (p = 0.328). Conclusions Walking one hour per day and having a high proportion of lymphocytes to neutrophiles (expressed as a low derived neutrophil-to-lymphocyte ratio) independently predict a better prognosis in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck treated with immunotherapy.
Reactivation of Trypanosoma cruzi infection in immunosuppressed patients: a systematic review and meta-analysis
(European Society of Clinical Microbiology and Infectious Diseases, 2024-08-01) Antequera, Alba; Molin Veglia, Agustina dal; López Alcalde, Jesús; Álvarez Díaz, Noelia; Muriel García, Alfonso; Muñoz Gutiérrez, José
Background: The risk of Trypanosoma cruzi reactivation is poorly understood. Previous studies evaluating the risk of reactivation report imprecise findings, and recommendations for monitoring and management from clinical guidelines rely on consensus opinion. Objectives: We conducted a systematic review and meta-analysis to estimate the cumulative T. cruzi reactivation incidence in immunosuppressed adults, summarize the available evidence on prognostic factors for reactivation, and examine its prognostic effect on mortality. Data sources: MEDLINE, Embase, LILACS, Clinical Trials, and CENTRAL from inception to 4 July 2022. Study eligibility criteria: Studies reporting the incidence of T. cruzi reactivation. Participants: Immunosuppressed adults chronically infected by T. cruzi. Methods: Two authors independently extracted data (including, but not limited to, incidence data, reactivation definition, follow-up, treatment, monitoring schedule, examined prognostic factors) and evaluated the risk of bias. We pooled cumulative incidence using a random-effects model. Results: Twenty-two studies (806 participants) were included. The overall pooled incidence of T. cruzi reactivation was 27% (95% CI, 19-36), with the highest pooled proportion in the sub-group of transplant recipients (36%; 95% CI, 25-48). The highest risk period was in the first 6 months after transplant (32%; 95% CI, 17-58), decreasing drastically the number of new cases later. People living with HIV and patients with autoimmune diseases experienced significantly lower cumulative reactivation incidences (17%; 95% CI, 8-29 and 18%; 95% CI, 9-29, respectively). A single study explored the independent effect of benznidazole and found benefits for preventing reactivations. No studies evaluated the independent association between reactivation and mortality, while sensitivity analysis results using unadjusted estimates were inconclusive. The heterogeneity of diagnostic algorithms was substantial. Conclusions: Reactivation occurs in three out of ten T. cruzi-seropositive immunosuppressed adults. These findings can assist clinicians and panel guidelines in tailoring monitoring schedules. There is a great need for an accurate definition of reactivation and targeted monitoring.
Preterm prelabor rupture of membranes: the use of amniocentesis to detect intraamniotic infection reduces maternal and neonatal duration of antibiotic exposure
(Elsevier, 2025-11-01) Cobo Cobo, Maria Teresa; Aldecoa Bilbao, Victoria; Ferrero Martinez, Sílvia ; Balcells, Judith; Contreras, Ana Lucia; Valenzuela Rodríguez, Andrea; Pastor Lorca, María; Boada, David; Herranz Barbero, Ana; Izquierdo Renau, Montserrat; Murillo Bravo, Clara; Río, Ana del; Hernández Meneses, Marta; Fidalgo, Berta; Rodriguez Reyes, Montserrat; Figueras Retuerta, Francesc; Gratacós Solsona, Eduard; Palacio, Montse
Current management guidelines for patients with preterm prelabor rupture of membranes at <32þ0 weeks of gestation recommend administering antibiotics, although evidence on their benefits for short- and long-term neonatal outcomes is poor. OBJECTIVE: This study aimed to evaluate whether the use of amniocentesis to detect intraamniotic infection reduces maternal and neonatal duration of antibiotic exposure. STUDY DESIGN: This was a retrospective observational cohort study (2014e2023) including patients diagnosed with preterm prelabor rupture of membranes at <32þ0 weeks of gestation who underwent amniocentesis at admission to assess the presence of intraamniotic infection. We compared 2 groups according to antenatal antibiotic management. From 2014 to 2019, patients received at least 5 days of broad-spectrum antibiotic treatment (including intravenous ampicillin and gentamicin and a single dose of oral azithromycin), regardless of intraamniotic infection status (standard management group). Beyond 2019, gentamicin was substituted for intravenous ceftriaxone and azithromycin for oral clarithromycin. Antibiotic treatment duration was optimized on the basis of amniotic fluid analysis (amniocentesis-based management): if amniotic fluid glucose concentrations were 14 mg/dL and Gram staining did not show the presence of bacteria, antibiotic treatment was discontinued at 48 hours. Otherwise, antibiotic therapy was prolonged at least until microbiological amniotic fluid results. Regardless of the management group, if intraamniotic infection was diagnosed, the type of antibiotic was individualized according to the bacteria isolated, and treatment was prolonged for 7 to 10 days unless delivery occurred earlier. There were no other differences in maternal management between the 2 periods. RESULTS: A total of 172 patients diagnosed with preterm prelabor rupture of membranes at <32þ0 weeks of gestation were included (122 in the standard management group and 50 in the amniocentesis-based management group). The prevalence of intraamniotic infection was 29% in both periods, with most cases (61%) being due to Ureaplasma species. There were no differences in maternal characteristics between the 2 groups. As expected, in the amniocentesis-based management group, maternal exposure to antibiotics was shorter (median [25th centilee75th centile] of 2 [2e3] days [amniocentesis-based management] vs 5 days [4e5] [standard management]; P<.0001). In line with the reduction of the duration of antibiotic therapy, we observed that maternal hospital stay was significantly shorter (5 [4e9] vs 11 [5e21] days; P¼.001) and outpatient management was more frequent (68% vs 47%; P¼.011) in the amniocentesis-based management group. No differences were observed in maternal morbidity. Similar results were found when neonatal outcomes were evaluated. In the amniocentesis-based management group, neonates received less antibiotic treatment at admission (odds ratio [95% confidence interval], 0.31 [0.15e0.61]; P<.001) and had less exposure to antibiotics during hospitalization (614 vs 1318 days in the standard management group; P¼.023). This did not translate into worse neonatal outcomes. CONCLUSION: Management of preterm prelabor rupture of membranes based on amniotic fluid analysis was associated with shorter maternal and neonatal antibiotic exposure and shorter maternal length of hospitalization, and allowed outpatient management without jeopardizing maternal or neonatal outcomes
Real-world use of terlipressin in cirrhosis and acute kidney injury: frequent use beyond hepatorenal syndrome
(Elsevier, 2026-04) Ma, Ann T.; Juanola Mayos, Adrià; Patidar, Kavish R.; Barone, Anna; Incicco, Simone; Kulkarni, Anand V.; Verma, Nipun; Lange, Christian Markus; Xie, Qing; Alessandria, Carlo; Cerda, Eira; Maiwall, Rakhi; Kim, Jeong Han; Marciano, Sebastián; Queiroz Farias, Alberto; Toledo, Claudio; Nardelli, Silvia; Vorobioff, Julio D.; Roblero, Juan Pablo; Thevenot, Thierry; Papp, Maria; Maan, Raoel; Solé, Cristina; Cordova Gallardo, Jacqueline; Simonetto, Douglas A.; Fouad, Yasser; Balcar, Lorenz; Raevens, Sarah; Nabilou, Puria; Merli, Manuela; Presa, José; Laleman, Wim; Krag, Aleksander; Bruns, Tony; Pereira, Gustavo; Mattos, Angelo Z.; Arab, Juan Pablo; Wentworth, Brian; Abdelaaty Abdelkader, Nadia; Wong, Yu Jun; Kim, Sung Eun; Roux, Olivier; Takkenberg, R. Bart; Galante, Antonio; Lofego Goncalves, Luciana; Pyrsopoulos, Nikolaos; Caraceni, Paolo; Pérez Hernández, José Luís; Asrani, Sumeet K.; Torre, Aldo; Díaz Ferrer, Javier; Orman, Eric S.; Perricone, Giovanni; Gadano, Adrian; Ivashkin, Vladimir; Fassio, Eduardo; Marino, Mónica; Vargas, Víctor; Rabinowich, Liane; Montes, Pedro; Mohammed, Abdulsemed; Carrera, Enrique; Cabrera, María Cecilia; Girala, Marcos; Samant, Hrishikesh; Madaleno, Joao; Kim, W. Ray; Ferreira, Carlos Noronha; Allegretti, Andrew S.; Sarin, Shiv K.; Ginès i Gibert, Pere; Angeli, Paolo; Solà, Elsa; Piano, Salvatore; International Club of Ascites GLOBAL AKI team
Background & Aims Terlipressin is indicated to treat hepatorenal syndrome (HRS)-acute kidney injury (AKI) but is likely used outside this primary indication in clinical practice. We aimed to investigate real-world practice patterns on the use of terlipressin in AKI in cirrhosis. Methods International prospective study including patients hospitalized for decompensated cirrhosis. This was a subgroup analysis of patients who received terlipressin to treat AKI. Primary outcome was AKI resolution. Secondary outcomes were respiratory failure and 28-day mortality. Results Among 1456 patients with AKI, 243 (17%) received terlipressin. Terlipressin was predominantly administered as a continuous infusion (75%). The AKI phenotype was HRS-AKI in 50%, acute tubular necrosis (ATN) in 17%, hypovolemic in 25%, and other in 8%. AKI resolution occurred in 49% of the patients, and was lowest in ATN (29%), followed by HRS-AKI (51%) and hypovolemic (63%). ATN was independently associated with lack of AKI resolution (odds ratio, 2.77; 95% confidence interval, 1.24–6.54; P = .02). De novo respiratory failure occurred in 20% of patients. There were no significant differences in the amount of albumin received nor acute-on-chronic liver failure grade between those who did and did not develop respiratory failure. The presence of pneumonia independently predicted respiratory failure (odds ratio, 7.80; 95% confidence interval, 2.43–26.95; P < .001). Mortality rate at 28 days was 36%; ATN and hospital-acquired AKI independently predicted 28-day mortality. Conclusions Terlipressin is often used for treatment of AKI outside its primary indication of HRS-AKI. Compared with patients with HRS-AKI, response to terlipressin is significantly lower in patients with ATN, in whom the risks may outweigh the benefits. Respiratory failure is common but does not seem to be driven by the amount of albumin received nor acute-on-chronic liver failure grade.
From peri-implant mucositis to peri-implantitis: Incidence and risk indicators in a university dental hospital sample with up to 10 years of follow-up
(Elsevier, 2026-01-06) Alahmari, Ahmad; Arsalan Askarizadeh, Amir; Barbosa de Figueiredo, Rui Pedro; García-García, Marta; Costa-Berenguer, Xavier; Sales Collado, Miquel; Valmaseda Castellón, Eduardo; Sánchez Torres, Alba
Objectives: To determine the proportion of patients with peri‑implant mucositis who develop peri‑implantitis over a 1- to 10-year follow-up period, and to identify the variables associated with this progression. Materials and Methods: A retrospective cohort study was conducted including 97 patients with 204 dental implants diagnosed with peri‑implant mucositis. Clinical and radiographic examinations were performed, and compliance with supportive peri‑implant care (SPIC) was recorded. A multilevel multinomial logistic regression model was developed to identify the predictors of disease progression. Results: After a mean follow-up of 49.8 months, 23.7% of patients initially diagnosed with peri‑implant mucositis became healthy, 57.7% showed no change and remained with peri‑implant mucositis, while 18.5% progressed to peri‑implantitis. A history of periodontitis significantly increased the odds of presenting peri‑implant disease at the last follow-up appointment (p < 0.001). Conversely, regular compliance with SPIC, prostheses with an adequate design, and single-unit restorations significantly reduced the risk of progression (p < 0.001). Conclusions: Almost one fifth of patients with dental implants with peri‑implant mucositis are likely to develop peri‑implantitis after a mean follow-up of 4 years. A history of periodontitis, irregular supportive peri‑implant care and inadequate prosthetic design increase the likelihood of bone loss and progression to peri‑implantitis. Clinical Significance: This study emphasizes the importance of regular supportive peri‑implant care and appropriate prosthetic design to prevent progression from peri‑implant mucositis to peri‑implantitis, especially in patients with a history of periodontitis

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