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HPV Vaccination in Women with Cervical Intraepithelial Neoplasia Undergoing Excisional Treatment: Insights into Unsolved Questions.
(MDPI, 2022-06-01) Henere, Carla; Torné Bladé, Aureli; Llupià Garcia, Anna; Aldea, Marta; Martí Delgado, Cristina; Glickman, Ariel; Saco, Adela; Marimon, Lorena; Manzotti, Carolina; Rakislova, Natalia; Ordi Maja, Jaume; Pino Saladrigues, Marta del
Several questions regarding the role of vaccination in women treated for high-grade cervical intraepithelial lesion (HSIL) have not been clarified. One of the main queries is whether the time at which the vaccine is administered (before or after treatment) influences the protection against post-treatment HSIL. A second unanswered question is whether the vaccine has any effect in women with persistent HPV after treatment. We aimed to address these questions in a study of 398 women undergoing excisional treatment from July 2016 to December 2019. Vaccination was funded and offered to all women undergoing treatment. A total of 306 women (76.9%) accepted HPV vaccination (vaccinated group): 113 (36.9%) received the first dose before excision and 193 (63.1%) after the procedure. A total of 92 women (23.1%) refused the vaccine (non-vaccinated group). Women vaccinated before treatment showed a lower rate of post-treatment HSIL compared with non-vaccinated women (0.9% vs. 6.5%; p = 0.047). Among women with persistent HPV infection after treatment, those who had received the vaccine showed a lower prevalence of post-treatment HSIL than non-vaccinated women (2.6% vs. 10.5%; p = 0.043). In conclusion, this study shows that HPV vaccination before treatment reduces the prevalence of post-treatment HSIL and suggests that vaccination might even benefit women with persistent HPV after treatment.
Risk stratification and anal cancer screening in immunocompetent women with genital HPV: Value of multicentric HSIL and performance of HPV-based screening
(Wiley, 2026-08-15) Matas, Isabel; Torné Bladé, Aureli; Saco, Adela; Martí Delgado, Cristina; Cardiel, Ada; Rakislova, Natalia; Marimon, Lorena; Glickman, Ariel; Victoria, Ingrid; Alos, Silvia; Lopez-Diaz, Jesús; Fusté, Pere; Ordi i Majà, Jaume; Pino Saladrigues, Marta del
The incidence of anal squamous cell carcinoma (ASCC) is rising, and women with genital human papillomavirus (HPV) infection or HPV-associated high-grade squamous intraepithelial lesions (HSIL) are at high risk of developing ASCC. We conducted a cross-sectional study including 354 immunocompetent women referred for anal evaluation because of HPV infection or HSIL of the lower genital tract between 2019 and 2024. Participants were categorized according to the genital site affected by HSIL (uterine cervix, vagina, vulva/perineum/perianal region, or multicentric disease), and a control group of 99 immunocompetent women with genital HPV infection and/or low-grade SIL was included. All patients underwent anal high-risk HPV testing, liquid-based cytology, and high-resolution anoscopy when indicated. Overall, high-risk HPV infection and HSIL were identified in the anal canal in 62.5% and 5.6% of women, respectively. Women with multicentric disease showed a higher prevalence of anal HSIL compared with the control group (6/29, 20.7%, vs. 2/99, 2.0%; p = .031), and the other genital HSIL groups (11/182, 6.0% for cervical; 0/13, 0%, for vaginal; 1/31, 3.2% for vulvar HSIL; p = .003). Genital HSIL, particularly multicentric disease, was a strong marker of anal involvement. No HSIL/AIN occurred among women with a negative anal high-risk HPV test. Anal high-risk HPV testing alone showed optimal sensitivity (100%) and negative predictive value (100%) for the diagnosis of HSIL/AIN, whereas cytology alone had lower sensitivity (68.4%). Combining both tests did not improve accuracy and resulted in excessive referrals. High-risk HPV testing alone appears to be the most efficient approach for anal screening in women with genital HSIL.
Human Papillomavirus Infection and Cytological Atypia in Female Allogeneic Hematopoietic Stem Cell Transplantation Recipients.
(Lippincott, Williams & Wilkins, 2025-07-01) Saco, Adela; Carbonell Ordeig, Sara; Rakislova, Natalia; Matas, Isabel; Alos, Silvia; Hoya, Sandra; Suárez-Lledó Grande, María; Darecka, Katarzyna; Sisuashvili, Lia; Marimon, Lorena; Vega, Naiara; Esteve, Roser; Martínez Muñoz, Ma. Carmen; Martí Delgado, Cristina; Glickman, Ariel; Balagué, Olga; Torné Bladé, Aureli; Ordi i Majà, Jaume; Pino Saladrigues, Marta del
Background. Female recipients of allogeneic hematopoietic stem cell transplantation are at high risk of developing human papillomavirus (HPV)-associated lesions and (pre)cancer. We describe the results of a cervical cancer screening program in these women. Methods. From 2010 to 2022, 70 female recipients of allogeneic hematopoietic stem cell transplantation in our institution entered a standardized protocol of gynecological evaluation. HPV testing, Papanicolaou smear, and thorough gynecological examinations were conducted in all the women. Results. The cumulative prevalence of HPV infection was 21.4% (15/70). Ten of 70 women (14.3%) had a positive HPV test result in the first gynecological evaluation and 5 additional women (7.1%) became positive during follow-up. Thirteen women (18.5%) presented cytohistological lesions (3 high-grade lesions and 10 low-grade lesions). Twenty-nine women (41.4%) showed HPV-negative reactive atypical abnormalities related to the conditioning treatment, which closely mimicked HPV-associated lesions, which spontaneously disappeared during follow-up. Conclusions. Gynecological evaluation should be maintained over time, as a significant proportion of these women may become HPV positive during follow-up. Reactive benign, atypical changes related to the treatment, which closely mimic HPV-associated lesions, are a frequent finding in these women. HPV testing is a key tool for the evaluation of these patients, as it allows for identifying women at risk and excluding cytological mimickers.
Robust framework for adaptive field-of-view automatic segmentation in vaginal brachytherapy for endometrial cancer
(sciencedirect, 2026-05-18) Casamitjana, Adrià; Gómez Fresco, Ana María; Candela Juan, Cristian; Tudela Fernández, Raúl; Sala Llonch, Roser; Moreno López, Sara; Noorian, Faegheh; Rovirosa Casino, Angeles; Niñerola Baizán, Aida; Herreros, Antonio
Background and purpose: The lack of robust automatic tools for segmentation in vaginal brachytherapy (VBT) limits efficiency and reproducibility in clinical practice. We aimed to develop a framework for automatic segmentation of the clinical target volume (CTV) and organs of interest (OOIs) for endometrial cancer patients that undergo vaginal cuff brachytherapy. Material and methods: We developed a three-step framework based on nnUNet and adapted to our context to segment the CTV/OOIs on pre-treatment computed tomography (CT) scans. Our method was adaptive to different contouring protocols used in clinical practice, where images were partly labelled, by either providing labels within a region of interest and/or considering only a subset of present structures. A dataset of 289 patients treated between 2014 and 2021 was used for model development (139/35/115 for training, validation and testing). Results: The Dice similarity coefficient of the CTV was 87.7%, while OOI Dice coefficients were 72.6%, 88.9%, 86.3% for the small bowel, bladder and rectum, respectively. The average absolute D2cm3 deviations were 27.5(±58.7), 25.5(±21.0), and 21(±19.1) cGy for the small bowel, bladder and rectum, respectively. The average absolute D90 % deviation was 17.0(±19.6) cGy. Clinical transferability was assessed using a 1-4 scale, achieving a median of 4 for the CTV, 3 for bladder and rectum, and 2 for the small bowel. Conclusions: Our method segmented the CTV and OOIs from CT scans with high quality and reliable dose calculations within the relevant range. Our framework outperformed state-of-the-art methods and potentially could help reduce complexity and time in VBT protocols. Keywords: Artificial intelligence in oncology; Automatic segmentation; Dosimetry evaluation; Endometrial cancer; Vaginal cuff brachytherapy.
Immunomodulatory therapy, risk factors and outcomes of hospital-acquired bloodstream infection in patients with severe COVID-19 pneumonia: a Spanish case-control matched multicenter study (BACTCOVID)
(European Society of Clinical Microbiology and Infectious Diseases, 2021-07-07) Abelenda Alonso, Gabriela; Rombauts, Alexander; Gudiol González, Carlota; Oriol, Isabel; Simonetti, Antonella Francesca; Coloma Conde, Ana; Rodríguez-Molinero, Alejandro; Izquierdo, Elisenda; Díaz Brito, Vicens; Sanmartí Vilamala, Montserrat; Padullés Zamora, Ariadna; Grau, Inmaculada; Ras, Mar; Bergas, Alba; Guillem, Lluïsa; Blanco Arévalo, Alejandro; Alvarez-Pouso, Claudia; Pallarès, Natàlia; Videla, Sebastià; Tebé, Cristian; Carratalà, Jordi
Objectives The effect of the use of immunomodulatory drugs on the risk of developing hospital-acquired bloodstream infection (BSI) in patients with COVID-19 has not been specifically assessed. We aim to identify risk factors for, and outcomes of, BSI among hospitalized patients with severe COVID-19 pneumonia. Methods We performed a severity matched case–control study (1:1 ratio) nested in a large multicentre prospective cohort of hospitalized adults with COVID-19. Cases with BSI were identified from the cohort database. Controls were matched for age, sex and acute respiratory distress syndrome. A Cox proportional hazard ratio model was performed. Results Of 2005 patients, 100 (4.98%) presented 142 episodes of BSI, mainly caused by coagulase-negative staphylococci, Enterococcus faecalis and Pseudomonas aeruginosa. Polymicrobial infection accounted for 23 episodes. The median time from admission to the first episode of BSI was 15 days (IQR 9–20), and the most frequent source was catheter-related infection. The characteristics of patients with and without BSI were similar, including the use of tocilizumab, corticosteroids, and combinations. In the multivariate analysis, the use of these immunomodulatory drugs was not associated with an increased risk of BSI. A Cox proportional hazard ratio (HR) model showed that after adjusting for the time factor, BSI was associated with a higher in-hospital mortality risk (HR 2.59; 1.65–4.07; p < 0.001). Discussion Hospital-acquired BSI in patients with severe COVID-19 pneumonia was uncommon and the use of immunomodulatory drugs was not associated with its development. When adjusting for the time factor, BSI was associated with a higher mortality risk.
Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease.
(Elsevier, 2021-10) Hernández Gea, Virginia; Campreciós Figueras, Genís; Betancourt, Fabian; Pérez Campuzano, Valeria; Seijo, Susana; Díaz, Alba; Duran Gallego, Ruth; Olivas, Pol; Orts, Lara; Magaz M.; Baiges Aznar, Anna; Turon, Fanny; Sidorova, Julia; Romero Gómez, Mercè; Lozano Salvatella, Juan José; García Pagán, Juan Carlos
Background & Aims Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD. Methods We obtained liver tissue samples from 20 consecutive patients with PSVD and 21 sex- and age-matched patients with cirrhosis and 13 histologically normal livers (HNL) (initial cohort) and performed transcriptomic analysis. Microarray data were analyzed using weighted gene correlation network analysis to identify clusters of highly correlated genes differently expressed in patients with PSVD. We next evaluated the molecular pathways enriched in patients with PSVD and the core-related genes from the most significantly enriched pathways in patients with PSVD. Our main findings were validated using RNA sequencing in a different cohort of PSVD, cirrhosis and HNL (n = 8 for each group). Results Patients with PSVD have a distinctive genetic profile enriched mainly in canonical pathways involving hemostasis and coagulation but also lipid metabolism and oxidative phosphorylation. Serpin family (SERPINC1), the apolipoproteins (APOA, APOB, APOC), ATP synthases (ATP5G1, ATP5B), fibrinogen genes (FGB, FGA) and alpha-2-macroglobulin were identified as highly connective genes that may have an important role in PSVD pathogenesis. Conclusion PSVD has a unique transcriptomic profile and we have identified deregulation of pathways involved in vascular homeostasis as the main pathogenic event of disease development. Lay summary Porto-sinusoidal vascular disease is a rare but life-shortening disease that affects mainly young people. Knowledge of the disrupted pathways involved in its development will help to identify novel therapeutic targets and new treatments. Using a systems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease.
Synthetic MRI in subarachnoid haemorrhage
(Elsevier, 2021-10-01) Montejo González, Carmen; Laredo Gregorio, Carlos; Llull Estrany, Laura; Martínez Heras, Eloy; López Rueda, Antonio; Torné, Ramón; Garrido, César; Bargalló Alabart, Núria; Llufriu Duran, Sara; Amaro Delgado, Sergio
Aim To evaluate the reliability of synthetic magnetic resonance imaging (SyMRI) for detecting complications associated with subarachnoid haemorrhage (SAH), such as ischaemic lesions, hydrocephalus, or bleeding complications. Materials and methods Twenty patients with SAH, who underwent a conventional brain MRI and a SyMRI on a 3 T MRI machine. Comparable conventional and synthetic T2-weighted fluid attenuated inversion recovery (FLAIR) images were acquired. The presence of ischaemic lesions, hydrocephalus, extra-axial blood collections as well as the volumes of grey matter (GMv), white matter (WMv), and cerebrospinal (CSFv) were compared. The acquisition times of both sequences was also analysed. Results The concordance between the two techniques was excellent for the detection of ischaemic lesions and extra-axial collections (kappa = 0.80 and 0.88 respectively) and good for the detection of hydrocephalus (kappa = 0.69). No significant differences were detected in the number of ischaemic lesions (p=0.31) or in the Evans index (p=0.11). The WMv and CSFv measures were also similar (p=0.18 and p=0.94, respectively), as well as the volume of ischaemic lesions (p=0.79). Compared to conventional MRI, the SyMRI acquisition time was shorter regardless of the number of sections (32% and 6% time reduction for 4 or 3 mm section thickness, respectively). Conclusions SyMRI allows the detection of potential complications of SAH in a similar way to conventional MRI with a shorter acquisition time.
Quality in diagnostic upper gastrointestinal endoscopy for the detection and surveillance of gastric cancer precursor lesions: Position paper of AEG, SEED and SEAP
(Elsevier, 2021-06) Pardo López, M.L.; Pérez Aisa, Á.; Sanz Anquela, J.M.; Fernández Esparrach, Glòria; Marín Gabriel, José Carlos; Díez Redondo, Pilar; Núñez, Héctor (Núñez López); Rodríguez de Santiago, Enrique; Rosón, Pedro; Calvet, Xavier; Cuatrecasas Freixas, Miriam; Cubiella, Joaquin; Moreira. Leticia; Asociación Española de Gastroenterología, la Sociedad Española de Endoscopia Digestiva y la Sociedad Española de Anatomía Patológica
This position paper, sponsored by the Asociación Española de Gastroenterología [Spanish Association of Gastroenterology], the Sociedad Española de Endoscopia Digestiva [Spanish Gastrointestinal Endoscopy Society] and the Sociedad Española de Anatomía Patológica [Spanish Anatomical Pathology Society], aims to establish recommendations for performing an high quality upper gastrointestinal endoscopy for the screening of gastric cancer precursor lesions (GCPL) in low-incidence populations, such as the Spanish population. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates different measures to improve the quality of upper gastrointestinal endoscopy in this setting and makes recommendations on how to evaluate and treat the identified lesions. We recommend that upper gastrointestinal endoscopy for surveillance of GCPL should be performed by endoscopists with adequate training, administering oral premedication and use of sedation. To improve the identification of GCPL, we recommend the use of high definition endoscopes and conventional or digital chromoendoscopy and, for biopsies, NBI should be used to target the most suspicious areas of intestinal metaplasia. Regarding the evaluation of visible lesions, the risk of submucosal invasion should be evaluated with magnifying endoscopes and endoscopic ultrasound should be reserved for those with suspected deep invasion. In lesions amenable to endoscopic resection, submucosal endoscopic dissection is considered the technique of choice.
Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases
(Wiley, 2021-09-19) Ginès i Gibert, Pere; Castera, Laurent; Lammert, Frank; Graupera, Isabel; Serra-Burriel, Miquel; Diaz Lorca, Maria Alba; Allen, Alina; Wong, Vincent W. S.; Hartmann, Phillipp; Roulot, Dominique; Thiele, Maja; Caballeria, Llorenç; Knegt Robert J. de; Grgurevic, Ivica; Augustin, Salvador; Tsochatzis, Emmanuel A.; Schattenberg, Jörn M.; Guha, Indra Neil; Martini, Andrea; Morillas, Rosa M.; Koning, Harry J. de; Garcia-Retortillo, Montserrat; Fabrellas i Padrès, Núria; Pich, Judit ; Ma, Ann T.; Díaz Lorca, Maria Alba; Roulot, Dominique; Newsome, Phillip N.; Manns, Michael; Kamath, Patrick S.; Krag, Aleksander; LiverScreen Consortium Investigators
Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.
Personality changes in patients with refractory epilepsy after surgical treatment: A systematic review
(Elsevier, 2021-02-01) Iurina, Elena; Bailles, Eva; Pintor Pérez, Luis
Purpose We aimed to conduct a systematic review to evaluate the personality changes in adult patients with drug-resistant epilepsy following surgical treatment. Methods A systematic review was conducted using the Preferred Reporting Items of Systematic Reviews and MetaAnalyses (PRISMA) statement. We searched PubMed, Medline databases, and the Cochrane Controlled Trials Register, with search terms ‘personality’, ‘epilepsy’, and ‘surgery’. Results Eleven studies were selected. In 7 out of 11 studies, personality changes were more adaptive, with patients experiencing decreased neuroticism, impulsivity, hypochondriasis, psychasthenia. One study showed increased emotional lability. The remainder of the studies showed no changes in personality dimensions. Changes in personality differed according to the localization of the epileptogenic area, depended on seizure status after treatment and duration of follow-up. Seizure freedom as an outcome of surgical treatment influenced the existence of personality changes, and their severity. Adaptive personality changes could be seen from early follow-up assessments even in patients who were not seizure-free, though further follow-ups showed that improvements after 1–2 years were specific to seizure-free patients.
Adjunctive Intra-Arterial Alteplase After Successful Thrombectomy for Acute Ischemic Stroke: The CHOICE-2 Randomized Clinical Trial
(American Medical Association (AMA), 2026-06-02) Renú, Arturo; Fernández Couto, Maria Dolores; Riva, Patricia de la; Delgado Mederos, Raquel; Herrera Isasi, Maria; Morales, Ana; Terceño, Mikel; López Hernández, Nicolás; Martínez Galdámez, Mario; Dorado, Laura; Vega, Pedro; Morales Caba, Lluis; González, Eva; Alonso, Maitane; Barredo Benítez, Pedro; Bermejo, Rebeca; Cabero Arnold, Andrea; Cabrera Maqueda, Jose Maria; Vargas, Martha; Calleja Bonilla, Ángel; Calleja, Sergio; Díaz Pérez, José; Rudilosso, Salvatore; Doncel Moriano, Antonio; Feal Painceiras, Maria J.; Gallego, José Ignacio; Hurtado, Paola; Laredo Gregorio, Carlos; Llull Estrany, Laura; Bartolomé Arenas, Inés; Martínez Calvo, Alberto; Ortega Sánchez, Álvaro; Rodríguez Vázquez, Alejandro; Rodríguez Caamaño, Isabel; Singla, Alba; Silva, Yolanda; Tarruella Hernández, Diana; Oleaga Zufiría, Laura; San Román, Luís; Serena, Joaquín; Freijo, Maria del Mar; Pérez de la Ossa, Natalia; Castellanos, Mar; Arenillas, Juan Francisco; Torres, Ferran; Leira, Enrique C.; Amaro Delgado, Sergio; Urra, Xabier; Chamorro, Ángel; CHOICE-2 Investigators
Importance Despite high recanalization rates with endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion, functional outcomes remain suboptimal. The benefit of adjunctive intra-arterial thrombolysis after successful thrombectomy is uncertain. Objective To assess whether adjunctive intra-arterial alteplase after successful thrombectomy improves functional outcomes and cerebral reperfusion. Design, Setting, and Participants Randomized, open-label trial with blinded outcome assessment conducted at 14 stroke centers in Spain from December 11, 2023, through November 26, 2025. A total of 440 patients with acute ischemic stroke due to large vessel occlusion treated with thrombectomy within 24 hours and achieving an expanded Treatment in Cerebral Ischemia score of 2b50 to 3 were randomized. Interventions Thrombectomy plus intra-arterial alteplase (0.225 mg/kg; maximum dose, 20 mg) infused over 15 minutes (n = 221) or thrombectomy alone (n = 219). Main Outcomes and Measures The primary outcome was an excellent functional outcome at 90 days, which was defined as a modified Rankin Scale score of 0 or 1. There were 6 secondary outcomes, including residual hypoperfusion on follow-up computed tomography perfusion. The safety outcomes included symptomatic intracranial hemorrhage and death. Results Of 3786 patients treated with thrombectomy, 2776 (73%) fulfilled angiographic criteria and 440 (12%) were randomized. There were 433 patients who were treated as randomized (median age, 76 [IQR, 75-78] years; 51% female). At 90 days, 57.5% of patients (123/214) in the thrombectomy plus intra-arterial alteplase group had a modified Rankin Scale score of 0 or 1 vs 42.5% of patients (93/219) in the thrombectomy alone group (adjusted risk difference, 15.0% [95% CI, 5.7% to 24.3%]; P = .002). Of 6 secondary outcomes, 4 showed no significant between-group differences. Residual hypoperfusion occurred in 28.6% (55/192) of patients in the thrombectomy plus intra-arterial alteplase group vs 50.5% (96/190) of patients in the thrombectomy alone group (adjusted risk difference, –22.0% [95% CI, −31.5% to −12.4%]; P < .001) and symptomatic intracranial hemorrhage occurred in 1.4% (3/214) vs 0.5% (1/219), respectively (adjusted odds ratio, 3.10 [95% CI, 0.32 to 30.0]; P = .33). Mortality at 90 days was 12.1% (26/214) in the thrombectomy plus intra-arterial alteplase group vs 6.4% (14/219) in the thrombectomy alone group (adjusted risk difference, 5.9% [95% CI, 0.5% to 11.3%]; P = .03). Conclusions and Relevance Among patients with acute ischemic stroke and successful thrombectomy, adjunctive intra-arterial alteplase increased the proportion achieving excellent functional outcome at 90 days without a significant increase in symptomatic intracranial hemorrhage. Higher mortality in the thrombectomy plus intra-arterial alteplase group warrants further study.
Seasonal longitudinal effects of winter birth on psychopathology, cognition, and functioning in schizophrenia-spectrum and affective disorders: Findings from the PsyCourse Study
(Elsevier B.V., 2026-09-01) Pérez Ramos, Anaid; Budde, Monika; Adorjan, Kristina; Amoretti Guadall, Silvia; Anghelescu, Ion-George; Arolt, Volker; Baune, Bernhard T.; Dannlowski, Udo; Dietrich, Detlef E.; Fallgatter, Andreas J.; Figge, Christian; Garriga, Marina; García Rizo, Clemente; Guasch Capella, Nora; Heilbronner, Maria; Lang, Fabian U.; Juckel, Georg; Kohshour, Mojtaba Oraki; Konrad, Carsten; Martínez-Arán, Anabel, 1971-; Mezquida Mateos, Gisela; Navarro Flores, Alba; Reich-Erkelenz, Daniela; Reimer, Jens; Reininghaus, Eva Z.; Senner, Fanny; Schmauß, Max; Schmitt, Andrea; Schulte, Eva C.; Spitzer, Carsten; Vieta i Pascual, Eduard, 1963-; Wiltfang, Jens; Falkai, Peter; Schulze, Thomas G.; Papiol, Sergi; Torrent Font, Carla; Heilbronner, Urs
Aims Winter birth (WB) is a replicated risk factor for mental health conditions, potentially due to third-trimester Vitamin D deficiency and maternal viral infections. Beyond diagnosis, WB is associated with psychopathology, cognition, and functionality as epiphenomena. We analysed these outcomes in psychosis and affective disorders, considering illness duration and sex-specific effects. Methods We included 535 individuals with schizophrenia-spectrum and 667 with affective disorders from the PsyCourse Study, evaluated at four time points over 18 months. Participants were stratified by the birth season: winter vs. other seasons and by duration of illness (</≥5 years). Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) for psychosis, Inventory of Depressive Symptomatology (IDS-C30) and Young Mania Rating Scale (YMRS) for affective disorders, functionality with the Global Assessment of Functioning Scale (GAF), and cognitive performance with Trail Making Tests A (TMT-A) and B (TMT-B), Verbal Digit Span, and Digit Symbol Test (DST). Linear mixed models adjusted for covariates were applied. Results No interaction effects between WB and diagnostic group or time remained significant after correction for multiple comparisons. In sex-stratified models, a significant WB × time interaction emerged for DST in females, with WB participants showing improvements over time in schizophrenia-spectrum disorders, and a crossover pattern in affective disorders. Conclusions WB has no robust effect on long-term outcomes on schizophrenia-spectrum or affective disorders. Subtle, sex-dependent effects on cognition were observed in females, with divergent longitudinal patterns between diagnostic groups, suggesting a possible early-life influence that attenuates over the course of illness.
Lymphocyte exhaustion in hepatocellular carcinoma: a dynamic evolution across disease stages
(Frontiers Media, 2025-06-06) Fuster, Carla; Corominas, Josep; Marsal García, Aida; Llarch, Neus; Iserte, Gemma; Sanduzzi Zamparelli, Marco; Forner González, Alejandro; Ferrer Fàbrega, Joana; Holguin Arce, Víctor Emilio; Morales, Albert; Saavedra Morales, Anny Carolina; Reig, María; Boix i Ferrero, Loreto; Marí, Montserrat; Diaz Lorca, Maria Alba
Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy. However, their efficacy in hepatocellular carcinoma (HCC) is limited, highlighting the need to further explore immune microenvironments and novel biomarkers. This study examined lymphocyte populations and immune checkpoint dynamics in early, advanced, and post-progression HCC to better understand immune dynamics in HCC and to help identify predictive biomarkers and immune modulation strategies.Methods: Tumoral and non-tumoral liver tissues were analyzed from HCC patients across early (n=25), advanced (n=22), and advanced-beyond-progression (n=15) stages. Lymphocyte profiling was performed using immunohistochemistry and flow cytometry, focusing on NK cells, T cells, and immune exhaustion markers. An exploratory analysis of this profile and its association with disease progression and recurrence was conducted.Results: Early HCC exhibited higher liver-resident NK (lrNK) cell densities in non-tumor regions, which diminished with advanced stages. Increased CD56+ cell infiltration in the tumor core was associated with recurrence. Tumor region showed elevated PD-1, NKG2A, and CD39 expression in CD4+ and CD8+ T cells, indicating progressive immune exhaustion. Advanced HCC stages demonstrated altered NK cell phenotypes, with reduced cytotoxic activation (CD16) and increased residency markers (CXCR6/CD69) in tumor-isolated lymphocytes.Conclusions: Progressive immune exhaustion and dysregulation of lrNK and T cells in HCC reflect the evolution of the immune microenvironment originating in the tumor and leaking into the non-tumoral liver, progressively diminishing the cytotoxic capacity of NK and T cells. CD56+ cell density and immune checkpoint profiles are potential biomarkers for therapeutic response and disease monitoring, underscoring the need for personalized immunotherapy strategies.
Testicular large B-cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL
(Wolters Kluwer, 2024-10-07) Karube, Kennosuke; Salaverria Frigola, Itziar; Enjuanes, Anna; Wiemann, Stefan; Heppner, Frank L.; Siebert, Reiner; Climent, Fina; Campo Güerri, Elias; Giné Soca, Eva; López Guillermo, Armando; Tapia, Gustavo; Beà Bobet, Sílvia M.; Luizaga Velasco, Luis; Bárcena, Cristina; Kelleher, Nicholas; Villamor i Casas, Neus; Baumann, Tycho; Muntañola, Ana; Sancho, Juan Manuel; García Sancho, Alejandro Martín; González Barca, Eva; Rivas Delgado, Alfredo; López González, Cristina; Clot Razquin, Guillem; Nadeu Prat, Ferran; Grau, Marta; Frigola G; Bosch Schips, Jan; Radke, Josefine; Ishaque, Naveed; Alcoceba, Miguel; Matutes, Estella; Brito, Jordi A.
Testicular large B-cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune-privileged site and has recently been recognized as a distinct entity from diffuse large B-cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B-cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next-generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations (p < 0.04) but more somatic variants (p < 0.02) than nodal DLBCL and had more frequent 18q21.32-q23 (BCL2) gains and 6q and 9p21.3 (CDKN2A/B) deletions. PIM1, MYD88L265P, CD79B, TBL1XR1, MEF2B, CIITA, EP300, and ETV6 mutations were more frequent in TLBCL, and BCL10 mutations in nodal DLBCL. There were no major genetic differences between TLBCL and PCNSL. Localized or disseminated TLBCL displayed similar genomic profiles. Using LymphGen, the majority of cases were classified as MCD. However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches.
Dynamic biomarkers in hormone receptor-positive/HER2-negative breast cancer trials: a new hope for precision oncology
(Springer Nature, 2026-01-28) Grazia, Giuseppe Di; Schettini, Francesco; Sánchez Bayona, Rodrigo; Casals Pascual, Climent; Pascual, Tomás; Generali, Daniele; Gennari, Alessandra; Vigneri, Paolo; Harbeck, Nadia; Cortés, Javier; Prat Aparicio, Aleix
Hormone receptor-positive/HER2-negative breast cancer evolves in response to therapy, demanding smarter, adaptive biomarker-based treatment strategies. We review emerging dynamic biomarkers to guide therapeutic decision-making, spanning tissue and liquid biopsies, metabolic imaging, and microbiome profiling, that capture tumor or host-related changes over time. By contrasting Academic and Industry approaches, we advocate for a cultural shift in clinical trial design and implementation, aiming to move from reactive to proactive Oncology.
Case Report: Personalized management of HER2-positive breast cancer with advanced nodal disease during pregnancy: a clinical case and review
(Frontiers Media, 2026-01-19) Gullotta, Gullotta; Walbaum, Benjamin; Seguí, Elia; López Rojano, Marta; Mension Coll, Eduard; Cebrecos, Isaac; Mollà, Meritxell; Oses, Gabriela; Bargallo, Xavier; Ganau, Sergi; Sanfeliu Torres, Esther ; Brasó-Maristany, Fara; Muñoz Mateu, Montserrat; Prat Aparicio, Aleix; Vidal Losada, Maria; Adamo, Barbara
Background: Pregnancy-associated breast cancer (PrBC) poses complex challenges in diagnosis and treatment, particularly when associated with biologically aggressive subtypes and extensive nodal involvement. Management must be individualized, integrating oncologic urgency, fetal safety, and limited validated evidence in this unique setting.Case Summary: We present the case of a 36-year-old woman diagnosed during the second trimester of pregnancy with HER2-positive (HER2+), node-positive (cT2[m]N3a) breast cancer (BC). After a multidisciplinary team discussion, patient initiated anthracycline- and taxane-based neoadjuvant chemotherapy during gestation. Given its contraindication during pregnancy, anti-HER2 therapy was added postpartum, and surgery included nipple-sparing mastectomy with targeted axillary dissection (TAD) of clipped nodes. Pathology revealed minimal residual invasive disease in the breast and a complete axillary response, allowing omission of axillary lymph node dissection (ALND). Genomic profiling with HER2DX supported high-risk disease and informed systemic therapy with delayed anti HER2 therapy, and conservative axillary management (TAD without ALND) in cT2N3 PrBC, without compromising fetal outcome. The patient subsequently received adjuvant chest wall and nodal region radiotherapy plus trastuzumab-emtansine (T-DM1).Conclusion: This case underscores the value of personalized, multidisciplinary management in PrBC, particularly in patients with high-risk biologic features and advanced nodal disease. Integrating clinical judgment, genomic tools, and adaptive strategies, while accounting for gestational limitations, can optimize oncologic outcomes without compromising fetal safety
Design and validation of a diagnostic suspicion checklist to differentiate epileptic from psychogenic nonepileptic seizures (PNES-DSC)
(Elsevier B.V., 2024-05-01) Sobregrau Sangrà, Pau; Bailles, Eva; Radua, Joaquim; Carreño, Mar; Donaire Pedraza, Antonio Jesús; Setoain Perego, Xavier; Bargalló Alabart, Núria; Rumià, Jordi; Sánchez-Vives, María Victoria; Pintor Pérez, Luis
Objective Psychogenic non-epileptic seizures (PNES) are complex clinical manifestations and misdiagnosis as status epilepticus remains high, entailing deleterious consequences for patients. Video-electroencephalography (vEEG) remains the gold-standard method for diagnosing PNES. However, time and economic constraints limit access to vEEG, and clinicians lack fast and reliable screening tools to assist in the differential diagnosis with epileptic seizures (ES). This study aimed to design and validate the PNES-DSC, a clinically based PNES diagnostic suspicion checklist with adequate sensitivity (Se) and specificity (Sp) to discriminate PNES from ES. Methods A cross-sectional study with 125 patients (n = 104 drug-resistant epilepsy; n = 21 PNES) admitted for a vEEG protocolised study of seizures. A preliminary PNES-DSC (16-item) was designed and used by expert raters blinded to the definitive diagnosis to evaluate the seizure video recordings for each patient. Cohen's kappa coefficient, leave-one-out cross-validation (LOOCV) and balance accuracy (BAC) comprised the main validation analysis. Results The final PNES-DSC is a 6-item checklist that requires only two to be present to confirm the suspicion of PNES. The LOOCV showed 71.4% BAC (Se = 45.2%; Sp = 97.6%) when the expert rater watched one seizure video recording and 83.4% BAC (Se = 69.6%; Sp = 97.2%) when the expert rater watched two seizure video recordings. Conclusion The PNES-DSC is a straightforward checklist with adequate psychometric properties. With an integrative approach and appropriate patient history, the PNES-DSC can assist clinicians in expediting the final diagnosis of PNES when vEEG is limited. The PNES-DSC can also be used in the absence of patients, allowing clinicians to assess seizure recordings from smartphones.
Whole-exome sequencing of vulvar squamous cell carcinomas reveals an impaired prognosis in patients with TP53 mutations and concurrent CCND1 gains
(Nature Publishing Group, 2024-10-01) Ordi, Oriol ; Saco, Adela; Peñuelas, Núria; Blanco Irazuegui, Odei; Pino Saladrigues, Marta del; Carreras Dieguez, Núria ; Marimon, Lorena; Rodrigo Calvo, María Teresa; Morató, Alba; Sisuashvili, Lia; Bustamante Pineda, Mariona; Cruells, Adrià; Darecka, Katarzyna; Vega, Naiara; Alos, Silvia; Trias Puigsureda, Isabel; Fusté, Pere; Parra, Genís; Gut, Marta; Munmany, Meritxell; Torné Bladé, Aureli; Jares Gerboles, Pedro; Rakislova, Natalia
Very little information is available on the mutational landscape of vulvar squamous cell carcinoma (VSCC), a disease that mainly affects older women. Studies focusing on the mutational patterns of the currently recognized etiopathogenic types of this tumor (human papillomavirus [HPV]-associated [HPV-A], HPV-independent [HPV-I] with TP53 mutation [HPV-I/TP53mut], and HPV-I with wild-type TP53 [HPV-I/TP53wt]) are particularly rare, and there is almost no information on the prognostic implications of these abnormalities.Whole-exome DNA sequencing of 60 VSCC and matched normal tissues from each patient was performed. HPV detection, immunohistochemistry (IHC) for p16, p53, and mismatch repair proteins were also performed. Ten tumors (16.7%) were classified as HPV-A, 37 (61.7%) as HPV-I/TP53mut, and 13 (21.6%) as HPV-I/TP53wt. TP53 was the most frequently mutated gene (66.7%), followed by FAT1 (28.3%), CDKN2A (25.0%), RNF213 (23.3%), NFE2L2 (20%) and PIK3CA (20%). All the 60 tumors (100%) were DNA mismatch repair proficient. Seventeen tumors (28.3%) showed CCND1 gain. Bivariate analysis, adjusted for International Federation of Gynecology and Obstetrics stage, revealed that TP53 mutation, CCND1 gain, and the combination of the 2 alterations were strongly associated with impaired recurrence-free survival (hazard ratio, 4.4; P < .001) and disease-specific survival (hazard ratio, 6.1; P = .002). Similar results were obtained when p53 IHC status was used instead of TP53 status and when considering only HPV-I VSCC. However, in the latter category, p53 IHC maintained its prognostic impact only in combination with CCND1 gains. All tumors carried at least one potentially actionable genomic alteration. In conclusion, VSCCs with CCND1 gain represent a prognostically adverse category among HPV-I/TP53mut tumors. All patients with VSCCs are potential candidates for targeted therapy.
Endocervical Brush Cytology After Cervical Conization as a Predictor of Treatment Failure: A Prospective Cohort Study
(Lippincott, Williams & Wilkins. Wolters Kluwer Health, 2025-01-01) Carreras Dieguez, Núria ; Torras, Ines; Martí Delgado, Cristina; Matas, Isabel; Glickman, Ariel; Fusté, Pere; Mula, Cristina; Alos, Silvia; Hoya, Sandra; Rakislova, Natalia; Saco, Adela; Marimon, Lorena; Ordi i Majà, Jaume; Torné Bladé, Aureli; Pino Saladrigues, Marta del
Objective Endocervical curettage (ECC) is the gold standard for predicting the persistence of high-grade squamous intraepithelial lesions (HSIL) after cervical conization. However, ECC has a high rate of unsatisfactory samples and may be uncomfortable for women. Endocervical sampling with brush (ECB) has been proposed as an alternative to ECC, which, in addition to the cytological evaluation, allows performing HPV testing using the same sample. The authors compared ECC and ECB performed immediately after conization to identify women with persistent HSIL. Materials and Methods This is a prospective single-center study, including 518 patients who underwent conization over a 10-year period (2012–2021). Immediately after treatment conization, the authors performed ECB sampling followed by ECC to all patients. They evaluated the accuracy of the 2 techniques for diagnosing persistent HSIL during follow-up. Results Persistent HSIL was identified in 8.9% of women. Eighteen percent of the ECC samples and only 7% of ECB cytology were unsatisfactory (p < .001). The accuracy of detecting persistent HSIL was similar for ECB and ECC (89.0%, 95% CI = 85.9–91.5 vs 90.8%, 95% CI = 87.7–93.2; p = .797). Adding HPV testing to ECB cytological evaluation increased the accuracy to 91.5% (95% CI = 88.8–93.6). Conclusions ECB can be reliably used to identify women with persistent HSIL after conization, as its accuracy is similar to ECC, with a lower rate of unsatisfactory results. The technique allows adding HPV testing to cytological evaluation, improving the accuracy of the test.
White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group.
(Nature Publishing Group, 2024-02-07) Kim, Bo-Gyeom; Kim, Gakyung; Abe, Yoshinari; Alonso Ortega, María del Pino; Ameis, Stephanie H.; Anticevic, Alan; Arnold, Paul D.; Balachander, Srinivas; Banaj, Nerisa; Bargalló Alabart, Núria; Batistuzzo, Marcelo C.; Benedetti, Francesco; Bertolín Triquell, Sara; Beucke, Jan C.; Bollettini, Irene; Brem, Silvia; Brennan, Brian P.; Buitelaar, Jan K.; Calvo Escalona, Rosa; Castelo-Branco, Miguel; Cheng, Yuqi; Chhatkuli, Ritu Bhusal; Ciullo, Valentina; Coelho, Anna; Couto, Beatriz; Dallaspezia, Sara; Ely, Benjamin A.; Ferreira, Sónia; Fontaine, Martine; Fouche, Jean Paul; Grazioplene, Rachael G.; Gruner, Patricia; Hagen, Kristen; Hansen, Bjarne; Hanna, Gregory L.; Hirano, Yoshiyuki; Höxter, Marcelo Q.; Hough, Morgan; Hu, Hao; Huyser, Chaim; Ikuta, Toshikazu; Jahanshad, Neda; James, Anthony; Jaspers-Fayer, Fern; Kasprzak, Selina; Kathmann, Norbert; Kaufmann, Christian; Kim, Minah; Koch, Katharina; Kvale, Gerd; Kwon, Jun Soo; Lázaro García, Luisa; Lee, Junhee; Lochner, Christine; Lu, Jin; Rodriguez Manrique, Daniela; Martínez Zalacaín, Ignacio; Masuda, Yoshitada; Matsumoto, Koji; Maziero, Maria Paula; Menchón Magriñá, José Manuel; Minuzzi, Luciano; Moreira, Pedro Silva; Morgado, Pedro; Narayanaswamy, Janardhanan C.; Narumoto, Jin; Ortiz García, Ana Encarnación; Ota, Junko; Pariente, Jose Carlos; Perriello, Chris; Picó Pérez, Maria; Pittenger, Christopher; Poletti, Sara; Real, Eva; Reddy, Y. C. Janardhan; Rooij, Daan van; Sakai, Yuki; Sato, João R; Segalàs Cosi, Cinto; Shavitt, Roseli G.; Shen, Zonglin; Shimizu, Eiji; Shivakumar, Venkataram; Soriano Mas, Carles; Sousa, Nuno; Sousa, Mafalda Machado de; Spalletta, Gianfranco; Stern, Emily R.; Stewart, S. Evelyn; Szeszko, Philip R.; Thomas, Rajat; Thomopoulos, Sophia I.; Vecchio, Daniela; Venkatasubramanian, Ganesan; Vriend, Chris; Walitza, Susanne; Wang, Zhen; Watanabe, Anri; Wolters, Lidewij H.; Xu, Jian; Yamada, Kei; Yun, Je-Yeon; Zarei, Mojtaba; Zhao, Qin; Zhu, Xi; ENIGMA-OCD working group; Thompson, Paul M.; Bruin, Willem B.; Wingen, Guido van; Piras, Federica; Piras, Fabrizio; Stein, Dan J., 1962-; Heuvel, Odile A. van den; Simpson, Helen Blair; Marsh, Rachel; Cha, Jiook
White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) “OCD vs. healthy controls” (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) “unmedicated OCD vs. healthy controls” (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) “medicated OCD vs. unmedicated OCD” (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6–79.1 in adults; 35.9–63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

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