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Effectiveness of training on vertigo/dizziness coding in primary care: a community-based cluster-randomized trial
(BioMed Central, 2026-06-09) Pérez Patiño, Jenniffer Elizabeth; Cunillera Puértolas, Oriol; Sanllorente Melenchon, Albert; Rando-Matos, Yolanda; Villar Balboa, Iván; Carrillo Muñoz, Ricard; Ballvé Moreno, José Luis; Peguero-Rodríguez, Eva
Background: Most patients with vertigo receive unspecific diagnoses, delaying treatment and causing unnecessary tests. Training primary care (PC) physicians is essential to improve accuracy. This study evaluates the effectiveness of an online training program with a face-to-face session on new specific diagnoses in PC. Methods: A multicenter, open-label, cluster-randomized controlled community trial (control group [CG]/ intervention group [IG]) in twenty PC centers in southern Barcelona province (10 per group) was conducted to evaluate the effectiveness of the intervention under real-world primary care conditions. IG professionals received 14 h of online training and one face-to-face session on vertigo management. The primary outcome was the description of new specific vertigo diagnoses. Secondary outcomes included the unspecific, and any vertigo/dizziness diagnoses, the description of individual specific diagnoses (benign paroxysmal positional vertigo [BPPV], Meniere’s disease, vestibular neuritis), unspecific diagnoses (dizziness and other peripheral vertigos) and sociodemographic characteristics obtained from the SIDIAP (Information System for the Development of Primary Care Research) database for 545,938 patients in 2019 and 513,638 in 2022. Results: In 2019, the mean age was 51.0 years; 51.3% were women, and 2.68% of patients received a new vertigo-related diagnosis (2.44% nonspecific, 0.28% specific). In 2022, after the intervention, this increased to 2.80% (2.59% nonspecific, 0.28% specific). The IG showed significantly greater use of specific diagnoses (0.30% vs. 0.25%, p = 0.003), particularly BPPV (0.27% vs. 0.23%, p = 0.005). Regression models confirmed higher odds of diagnosis in the IG for any vertigo code (OR = 1.061), specific diagnoses (OR = 2.280), especially BPPV (OR = 2.283). Conclusion: A structured training intervention significantly improved the diagnostic coding of vertigo in primary care, fostering more accurate and specific diagnoses.
Five-year quality of life in patients with high-risk localized prostate cancer treated with external beam radiotherapy alone versus external beam radiotherapy with high-dose-rate brachytherapy boost: a prospective multicenter study
(Polish Brachytherapy Society, 2021-02-18) Martinez, Evelyn; Garín, Olatz; Pardo, Yolanda; Fernández, Pablo, 1957-; Guix Melcior, Benjamín; Gutiérrez Miguélez, Cristina; Boladeras, Ana; Ferrer, Ferran; Hernández, Tania; Ayala Gil, Adriana; Egiguren, Mikel; Fernández, Gema; Muñoz, Víctor; Macías, Víctor; Pera Fàbregas, Joan; Pont, Angels; Ferrer García, Montserrat; Guedea Edo, Ferran
Purpose: Brachytherapy (BT) and external beam radiation therapy (EBRT) are effective treatments for high-risk prostate cancer (PCa). However, the impact of these treatments on health-related quality of life (HRQL) remains unclear. In this study, we compared EBRT alone with EBRT plus a boost with high-dose rate (HDR)-BT to determine the impact on HRQL in patients with high-risk PCa. Material and methods: Prospective, multicenter study comparing patients with high-risk PCa treated with EBRT alone or EBRT + HDR-BT from 2004 to 2006. HRQL was assessed at baseline (pre-treatment) and periodically over the 5-year follow-up, using the SF-36 (v.2), EPIC, and FACT-G and FACT-P questionnaires. Results: A total of 129 patients were included in the study, of these, 41 received EBRT alone and 88 EBRT + HDR-BT. All patients received hormonotherapy. Baseline clinical characteristics were similar, except for a slightly higher mean number of comorbidities in the EBRT group. During follow-up, the only significant between-group difference was a greater worsening on EPIC hormonal domain in the EBRT alone group (p = 0.028). There were no significant differences in time and interaction of treatment in SF-36, and FACT-G and FACT-P questionnaires or EPIC urinary incontinence, urinary irritative-obstructive, and bowel and sexual domains over the 5-year follow-up. Oncological outcomes were similar in both groups. Conclusions: After five years of follow-up, EBRT alone or combined with HDR-BT boost had a similar impact on HRQL in patients with high-risk localized PCa. However, patients in the EBRT alone group experienced greater wors ening of hormonal domain according to EPIC questionnaire.
Open-label, phase 2 study of blinatumomab after frontline R-chemotherapy in adults with newly diagnosed, high-risk DLBCL
(Harwood Academic Publishers, 2022-05-03) Katz, Deborah A.; Morris, Joan D.; Chu, Michael P.; David, Kevin A.; Thieblemont, Catherine; Morley, Nicholas J.; Khan, Sharif S.; Viardot, Andreas; Martín García-Sancho, Alejandro; Rodríguez García, Guillermo; Bastos Oreiro, Mariana; Lee, Seung-Tae; Kormany, William; Chen, Yuqi; Wong, Hansen L.; Anderson, Abraham A.; Katlinskaya, Yuliya; Avilion, Ariel A.; Dai, Tian; González Barca, Eva
This open-label, multicenter, single-arm, phase 2 study assessed the safety and efficacy of blinatumomab consolidation therapy in adult patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL; International Prognostic Index 3–5 and/or double-/triple-hit or double MYC/BCL-2 expressors) who achieved complete response (CR), partial response (PR), or stable disease (SD) following run-in with 6 cycles of R-chemotherapy (NCT03023878). Of the 47 patients enrolled, 28 received blinatumomab. Five patients (17.9%) experienced grade 4 treatment-emergent adverse events of interest (neutropenia, n = 4; infection, n = 1). Two deaths reported at the end of the study were unrelated to treatment with blinatumomab (disease progression, n = 1; infection, n = 1). 3/4 patients with PR and 4/4 patients with SD after R-chemotherapy achieved CR following blinatumomab. Consolidation with blinatumomab in patients with newly diagnosed, high-risk DLBCL who did not progress under R-chemotherapy was better tolerated than in previous studies where blinatumomab was used for treatment of patients with lymphoma.
Exploring glucocorticoid receptor signalling in lymphangioleiomyomatosis
(European Respiratory Society, 2026-06-29) Baiges, Alexandra; Ruiz Auladell, Lara; García, Irene; Rigo Bonnin, Raúl; Tang, Yan; Bou-Farhat, Elias J.; Espín, Roderic; Sanz, Rosario T.; Vicent, Guillermo Pablo; Donate-Castillo, Mercè; Shabbir, Arzoo; Adams Furmanski, Jonathan; Herranz Ors, Carmen; Laporta, Rosalía; Salas Antón, Clara; Ussetti, Piedad; Valenzuela-Pascual, Clàudia; Ancochea, Julio; Rodríguez-Portal, José Antonio; Molina Molina, María; Casanova, Álvaro; Revilla López, Eva; Gómez Carrera, Luis; Matias-Guiu, Xavier, 1958-; Pavón, Miquel Ángel; Jung, Dominik; Bachmann, Hagen S.; Lago Lestón, Ramón M.; Muinelo Romay, Laura; Farré, Xavier; Cid, Rafael de; Leung, Calvin S.; Zannas, Anthony S.; Esteller, Manel; Sellarés Torres, Jacobo; Błasińska, Katarzyna; Róży, Adriana; Skrońska, Paulina; Gómez, Antonio; Holz, Marina K.; Di Martino, Julie S.; Monk, David; Sefton, Charlotte; Walker, Leanne; White, Anne; Clements, Debbie; Miller, Suzanne; Johnson, Simon R.; Hunt, Hazel J.; Henske, Elizabeth P.; Kwiatkowski, David; Radzikowska, Elżbieta; Mateo González, Francesca; Pujana Genestar, M. Ángel
Background: Lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm that causes progressive cystic lung destruction and is often associated with renal angiomyolipomas (AMLs). Given evidence of pleiotropy linking LAM risk to pulmonary traits, we investigated whether glucocorticoid receptor (GR) signalling might influence LAM biology and clinical features. Methods: We combined cell-based studies, GR inhibition/activation assays, gene expression and single-cell RNA sequencing analyses, and hormone profiling in retrospective and prospective LAM cohorts. Cellular experiments employed murine Tsc2−/− embryonic fibroblasts and human TSC2−/− AML cells. Circulating steroid levels were measured in women with LAM and healthy controls, and associations with clinical variables were evaluated. Results: In LAM/AML models, GR activation by glucocorticoids elicited transcriptional responses, whereas GR inhibition reduced clonogenic potential. GR stimulation was associated with CDKN1C upregulation through enhancer binding, and single-cell profiling suggested a shift towards slower proliferation and differentiation-prone states enriched for a LAM cell signature. Clinically, our analyses suggest that women with LAM may show altered circulating hormone profiles, including elevated adrenocorticotropic hormone (ACTH) and cortisol levels, together with reduced 17-hydroxyprogesterone, compared with controls. In a prospective cohort, ACTH levels were suggestively associated with advanced radiological disease stage. AML cells showed elevated expression of POMC, which encodes the precursor of ACTH, and POMC peptide was detected in LAM lung tissue. Conclusions: Our findings suggest that GR signalling may contribute to aspects of LAM cell behaviour and disease status. Further investigation of this pathway could clarify its role as a disease modifier and potential therapeutic target.
Two-Stage Turnbull-Cutait Pull-Through Coloanal Anastomosis for Low Rectal Cancers-Reply.
(American Medical Association (AMA), 2021-02-01) Biondo, Sebastián; Trenti, Loris; Kreisler, Esther
We thank the authors for their comments on our article. We discuss the points highlighted in the letters. Regarding technique and homogeneity of the groups, we stress that only patients with rectal cancer who are candidates for ultralow anterior rectal resection with sphincter preservation and hand-sewn coloanal anastomosis (CAA) were considered for inclusion. Indicating an intersphincteric resection does not depend on the chosen anastomosis but on the lower distance of the tumor from the anal canal. This scenario was homogeneous between groups. Therefore, neither radiotherapy nor intersphincteric approach or characteristics of the rectal dissection were confounding issues. Vascular ligation, restricted to inferior mesenteric artery, splenic flexure mobilization, and mesorectum dissection did not differ depending on the type of anastomosis. Ischemia cannot be attributed to technical differences between anastomotic techniques. We no longer perform a pouch technique after the evidence of long-term scarce benefits.
The WID-EC test for the detection and risk prediction of endometrial cancer
(BioMed Central, 2023-05-01) Barrett, James E; Jones, Allison; Evans, Iona; Herzog, Chiara; Reisel, Daniel; Olaitan, Adeola; Mould, Tim; MacDonald, Nicola; Doufekas, Konstantinos; Newton, Claire; Crosbie, Emma J.; Bjørge, Line; Colombo, Nicoletta; Dostalek, Lukas; Costas, Laura; Peremiquel Trillas, Paula; Ponce Sebastià, Jordi; Matias-Guiu, Xavier, 1958-; Zikan, Michal; Cibula, David; Wang, Jiangrong; Sundström, Karin; Dillner, Joakim; Widschwendter, Martin
The incidence of endometrial cancer is rising. Measures to identify women at risk and to detect endometrial cancer earlier are required to reduce the morbidity triggered by the aggressive treatment required for advanced endometrial cancer. We developed the WID-EC (Women's cancer risk IDentification-Endometrial Cancer) test, which is based on DNA methylation at 500 CpG sites, in a discovery set of cervical liquid-based cytology samples from 1086 women with and without an endometrial cancer (217 cancer cases and 869 healthy controls) with a worse prognosis (grade 3 or ≥stage IB). We validated the WID-EC test in an independent external validation set of 64 endometrial cancer cases and 225 controls. We further validated the test in 150 healthy women (prospective set) who provided a cervical sample as part of the routine Swedish cervical screening programme, 54 of whom developed endometrial cancer within 3 years of sample collection. The WID-EC test identified women with endometrial cancer with a receiver operator characteristic area under the curve (AUC) of 0.92 (95% CI: 0.88-0.97) in the external set and of 0.82 (95% CI: 0.74-0.89) in the prospective validation set. Using an optimal cutoff, cancer cases were detected with a sensitivity of 86% and a specificity of 90% in the external validation set, and a sensitivity and specificity of 52% and 98% respectively in the prospective validation set. The WID-EC test can identify women with or at risk of endometrial cancer.
The Evolving Role of Taxanes in Combination With Cetuximab for the Treatment of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck: Evidence, Advantages, and Future Directions
(Frontiers Media, 2019-08-21) Guigay, Joël; Tahara, Makoto; Licitra, Lisa; Keilholz, Ulrich; Friesland, Signe; Witzler, Pauline; Mesía Nin, Ricard
The addition of cetuximab to platinum-based chemotherapy (cisplatin or carboplatin plus 5-fluorouracil [5-FU]), followed by maintenance cetuximab until disease progression (EXTREME), resulted in the first regimen to yield significantly improved survival outcomes in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in over 30 years. Currently, the EXTREME regimen is a guideline-recommended treatment in the first-line R/M setting, and, therefore, it is used as a control arm in all new first-line, phase 3 immunotherapy trials. More recently, new checkpoint inhibitor approaches have emerged and are changing the treatment landscape for PD-L1-positive patients with R/M SCCHN. Additionally, alternative chemotherapy backbones in R/M SCCHN are continually investigated. Replacing 5-FU with a taxane in the EXTREME regimen seeks to take advantage of the potential immunogenic and proapoptotic synergy between cetuximab and docetaxel or paclitaxel. These cetuximab-, platinum-, and taxane-based treatments have demonstrated promising survival results and cytoreductive properties in single-arm studies. Thus, these combination treatments may be of importance to patients with high tumor burden and dangerous site involvements (e.g., causing bleeding, suffocation, dysphagia, or ulceration), in whom symptom relief is a key treatment goal. TPExtreme is the first large, randomized trial comparing a cetuximab, platinum, and taxane combination regimen with EXTREME. Currently, the substitution of 5-FU with a taxane is a feasible and clinically beneficial option for patients with contraindications to 5-FU. The TPEx regimen appears to be a new option in first-line R/M SCCHN, with a shorter time on CT and significantly lower toxicity than the EXTREME regimen. For patients with R/M disease in whom further cisplatin- or carboplatin-based treatment is unsuitable, or whose disease has already progressed on first-line R/M therapy, treatment options such as cetuximab plus a taxane, which capitalize on the combinative ability of the 2 agents, can be considered. Notably, it is as of yet unknown what second-line treatments may be suitable to follow a checkpoint inhibitor-based first-line therapy. Keywords: B490; EXTREME; R/M SCCHN; TPEx; cetuximab; docetaxel; paclitaxel.
Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts
(Elsevier, 2021-06-02) Stacchiotti, Silvia; Miah, Aisha B.; Frezza, Anna Maria; Messiou, Christina; Morosi, Carlo; Caraceni, Augusto; Antonescu, Cristina R.; Bajpai, Jyoti; Baldini, Elisabeth H.; Bauer, S.; Biagini, Roberto; Bielack, Stefan S.; Blay, Jean-Yves; Bonvalot, S.; Boukovinas, I.; Bovée, Judith V. M. G.; Boye, Kjetil; Brodowicz, Thomas; Callegaro, Dario; Álava, Enrique de; Deoras-Sutliff, M.; Dufresne, Armelle; Eriksson, Mikael; Errani, Costantino; Fedenko, Alexander; Ferraresi, Virginia; Ferrari, Andrea; Fletcher, Christopher D. M.; García del Muro Solans, Xavier; Gelderblom, Hans; Gladdy, Rebecca A.; Gouin, François; Grignani, Giovanni; Gutkovich, J.; Haas, Rick; Hindi, Nadia; Hohenberger, Peter; Huang, Paul H.; Joensuu, Heikki; Jones, Robin L.; Jungels, Claude; Kasper, Bernd; Kawai, Akira; Le Cesne, Axel; Le Grange, Franel; Leithner, Andreas; Leonard, Hugh; López Pousa, Antonio; Martín Broto, Javier; Merimsky, Ofer; Merriam, Priscilla; Miceli, Rosalba; Mir, Olivier; Molinari, Michele; Montemurro, Michael; Oldani, Graziano; Palmerini, Emanuela; Pantaleo, Maria A.; Patel, Shreaskumar R; Piperno-Neumann, Sophie; Raut, Chandrajit P.; Ravi, Vinod; Razak, Albiruni Abdul; Reichardt, Peter; Rubin, Brian P.; Rutkowski, Piotr; Safwat, Akmal Ahmed; Sangalli, Claudia; Sapisochin, Gonzalo; Sbaraglia, Marta; Scheipl, Susanne; Schöffski, Patrick; Strauss, Dirk; Strauss, Sandra J.; Sundby Hall, Kirsten; Tap, William D.; Trama, Annalisa; Tweddle, Andrew; van der Graaf, Winette T. A.; Van De Sande, Michiel A. J.; Van Houdt, Winan J.; van Oortmerssen, Gerard; Wagner, Andrew J.; Wartenberg, Markus; Wood, J.; Zaffaroni, Nadia; Zimmermann, Camilla; Casali, Paolo G.; Dei Tos, A. Paolo; Gronchi, Alessandro
Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
Artificial intelligence in thoracic surgery consultations: evaluating the concordance between a large language model and expert clinical decisions
(Frontiers Media, 2025-11-17) Déniz Armengol, Carlos; Marcè, Judith; Macía, Ivan; Rivas Doyague, Francisco; Muñoz, Ana; Paradela, Marina; García, Sonia; Moreno, Camilo; Serratosa, Inés; García, Marta; Rodríguez-Martos, Tania; Ojanguren, Amaia
Background: Artificial intelligence (AI) and large language models (LLMs) are increasingly used in clinical workflows, but their real-world application in thoracic surgery decision-making remains underexplored. Methods: This retrospective observational study assessed the concordance between diagnostic and therapeutic recommendations generated by Scholar GPT (based on GPT-4) and decisions made by board-certified thoracic surgeons. All outpatient consultations over one week in a tertiary care hospital were included. Each case was evaluated using a 6-point concordance scale (0–5), developed to quantify agreement in diagnosis and treatment planning. This was a retrospective observational, single-centre analysis; two independent thoracic surgeons assigned the concordance score. We report descriptive statistics and used t-tests/ANOVA for continuous variables and chi-square tests for categorical variables. Given the exploratory design, no a priori sample-size calculation or power analysis was performed. Results: A total of 81 consultations were analysed. The mean concordance score was 3.67 ± 1.17. High concordance (scores 4–5) occurred in 56.8% of cases, particularly in oncological diagnoses such as mediastinal and pleural tumours. Lower concordance was observed in complex or functional conditions like metastatic lung disease and thoracic outlet syndrome. No significant differences were found between consultation modalities or visit types. Conclusion: Scholar GPT demonstrated promising alignment with surgeon decisions in structured oncologic cases but showed variability in complex scenarios. While AI may assist in streamlining outpatient workflows, its use should remain complementary to expert clinical judgment. These findings are exploratory and should be interpreted with caution given the small sample size and single-centre, one-week design.
Managing Enterococcus faecium bloodstream infection: a Delphi document on clinical recommendations and research agenda
(Elsevier, 2026-05-02) Rinaldi, Matteo; Bartoletti, Michele; Cojutti, Piergiorgio; Escolà Vergé, Laura; Fernández Hidalgo, Nuria; Hornuss, Daniel; Gatti, Milo; Gudiol González, Carlota; Gutiérrez-Gutiérrez, Belén; López Cortés, Luis E.; Kern, Winfried V.; Los-Arcos, Ibai; Muñoz, Patricia; Oliva, Alessandra; Papadimitriou-Olivgeris, Matthaios; Pai, Manjunath; Pea, Federico; Pericàs, Juan M.; Rieg, Siegbert; Russo, Alessandro; Soriano Viladomiu, Alex; Thursky, Karin; Udy, Andrew; Venditti, Mario; Yahav, Dafna; Mo, Yin; Viale, Pierluigi; Giannella, Maddalena
Background: Management of E faecium bloodstream infections (BSIs) remains debated, particularly the clinical impact of vancomycin resistance, the role of follow-up cultures, and optimal therapeutic regimens. This study aimed to reach expert consensus on these unresolved clinical domains and identify priorities for future research. Methods: We first conducted a systematic review and meta-analysis in January 20, 204 focusing on four predefined areas: mortality in E faecium BSIs compared with other BSIs, mortality in vancomycin-resistant enterococci (VRE)-BSIs compared with vancomycin-susceptible enterococci-BSIs, management of catheter-related E faecium BSIs, and 4) optimal antibiotic therapy for VRE-BSIs. These results informed a three-round Delphi process involving a panel of experts. An iterative approach was adopted: 16 initial questions developed from the systematic review (6-point Likert scale) were refined across rounds based on expert feedback. Consensus was defined as at least 80% agreement or disagreement. Findings: 13 statements were generated across three broader domains. Regarding clinical outcomes and diagnostics, experts agreed that mortality is heavily influenced by comorbidities; thus, therapeutic assessment should rely on clinical trends and inflammatory markers, with follow-up blood cultures used to confirm eradication. Catheter-related BSI should be managed with device removal and short-course (<7 days) antibiotics in selected uncomplicated cases. For therapeutic management, teicoplanin is preferred for vanB VRE-BSI. For vanA VRE-BSI, both linezolid and high-dose daptomycin (>9 mg/kg per day) are effective, reserving daptomycin-based combinations for challenging cases (deep-seated infections and/or high Minimum Inhibitory Concentrations). Finally, future trials evaluating the impact of antimicrobial therapy should use Desirability-of-Outcome-Ranking analysis; the in-vitro potential of oritavancin justifies targeted randomized trials to define its clinical efficacy in VRE-BSI. Interpretation: This paper delineates current evidence and expert consensus on management of E faecium BSI while identifying crucial knowledge gaps to guide future clinical research.
Genetic risk factors modulate the association between physical activity and colorectal cancer
(BioMed Central, 2026-03-09) Peoples, Anita R.; Obón Santacana, Mireia; Kim, Andre E.; Kawaguchi, Eric S.; Fu, Yubo; Qu, Conghui; Moratalla Navarro, Ferran; Morrison, John; Lin, Yi; Arndt, Volker; Berndt, Sonja I.; Bien, Stephanie A.; Bishop, D. Timothy; Bouras, Emmanouil; Brenner, Hermann; Buchanan, Daniel D; Campbell, Peter T.; Chan, Andrew T.; Chang-Claude, Jenny; Conti, David V.; Corley, Douglas A.; Devall, Matthew A.; Dimou, Niki; Drew, David A.; Gruber, Stephen B.; Gunter, Marc J.; Harlid, Sophia; Harrison, Tabitha A.; Hoffmeister, Michael; Hsu, Li; Huyghe, Jeroen R.; Keku, Temitope O.; Kundaje, Anshul; Lewinger, Juan Pablo; Li, Li; Lynch, Brigid M.; Le Marchand, Loïc; Martín, Vicente; Murphy, Neil; Newton, Christina C.; Ogino, Shuji; Hardikar, Sheetal; Ose, Jennifer; Pai, Rish K.; Palmer, Julie R.; Papadimitriou, Nikos; Pardamean, Bens; Pellatt, Andrew J.; Pinchev, Mila; Platz, Elizabeth A.; Potter, John D.; Rennert, Gad; Ruiz-Narvaez, Edward; Sakoda, Lori C.; Schoen, Robert E.; Shcherbina, Anna; Stern, Marianna C.; Su, Yu-Ru; Thomas, Claire E.; Tian, Yu; Tsilidis, Konstantinos K.; Um, Caroline; van Duijnhoven, Franzel J.B.; Van Guelpen, Bethany; Visvanathan, Kala; Wang, Junzhi; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Ulrich, Cornelia M.; Peters, Ulrike; Gauderman, W. James; Moreno Aguado, Víctor
Background: Physical activity is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene–physical activity interaction analysis. Methods: Using logistic regression (1-d.f), two-step screening and testing method (EDGE), and joint tests (3-d.f), we analyzed interactions between common genetic variants across the genome and physical activity in relation to CRC risk. Self-reported physical activity levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk; 39,992 participants) and as study- and sex-specific quartiles of activity (42,602 participants). Results: Physical activity was inversely associated with CRC risk overall (OR [active vs. inactive] = 0.85; 95% CI = 0.81–0.90). The two-step EDGE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and physical activity for CRC risk (p-interaction = 2.6 × 10−8). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95% CI = 0.75–0.85), but no significant physical activity–CRC associations among CT or TT carriers. When physical activity was modeled as quartiles, the 1-d.f. test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between physical activity and CRC (p-interaction = 3.5 × 10−8). Stratification at this locus showed that an increase in physical activity (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95% CI = 0.72–0.82). Conclusions: In summary, we identified two genetic variants that modified the association between physical activity and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be involved in the protective association between physical activity and colorectal carcinogenesis.
Inequities in Waiting Times for Major Elective Surgery Before and After the COVID-19 Pandemic: Socioeconomic and Sex Differences in the Southern Barcelona Metropolitan Area
(MDPI, 2026-03-01) Pericas Escale, Carles; Vilaplana Carnerero, Carles; Poltorak, Violeta; Redondo, Ana; Masuet Aumatell, Cristina; Tor Roca, Alba; Pagès Fernández, Constança; Grau, María
Background: Waiting times for elective surgery are widely used as indicators of health system performance, particularly following the disruption caused by COVID-19. The objective of this study is to compare the waiting times for major elective surgeries in the Southern Barcelona Metropolitan Area before (2018–2019) and after (2022–2023) the pandemic, examining differences according to sociodemographic characteristics. Methods: A retrospective comparative study was conducted using data from the Southern Barcelona Metropolitan Area between 2018 and 2023. Adults registered on the waiting list for major elective surgical procedures were included. All analyses were stratified by sex. A stratified pre–post pandemic analysis was conducted to examine differences in waiting times by Socioeconomic Index. Waiting times were modelled using generalized linear models with a Gamma distribution and log link, adjusting for age and Socioeconomic Index quartiles. Interaction between period and Socioeconomic Index was tested. Results: The analysis included 73,055 individuals (50.5% women). Median waiting time decreased after the COVID-19 pandemic for both sexes (women: 128 to 121 days; men: 99 to 94 days). This reduction showed an inverse socioeconomic gradient. Adjusted analyses showed longer waits in the lowest versus highest Socioeconomic Index quartile after the pandemic (women: RR = 1.23; men: RR = 1.30). Conclusions: Waiting times for major elective surgery decreased after COVID-19. An exclusive focus on waiting time indicators may conceal structural barriers to access and contribute to inequalities. Equity-sensitive monitoring of elective care is essential to ensure a fair recovery of surgical services.
Inpatient hospital admissions for people with obsessive-compulsive disorder (OCD). A position statement by the international college of obsessive-compulsive spectrum disorders
(Elsevier B.V., 2026-04) Brakoulias, Vlasios; Albert, Umberto; Chamberlain, Samuel R.; Dell'Osso, Bernardo; Ferretti, Casara J.; Girone, Nicolaja; Hollander, Eric, 1957-; Ioannidis, Konstantinos; Lochner, Christine; Menchón Magriñá, José Manuel; Mpavaenda, Davis; Pallanti, Stefano; Pampaloni, Ilenia; Pellegrini, Luca; Stein, Dan J., 1962-; Van Ameringen, Michael; Zohar, Joseph; Fineberg, Naomi A.
Background: The hospitalization of patients with obsessive-compulsive disorder (OCD) is less common in comparison to other mental disorders, and often a significant and distressing event. Objectives: This paper presents a position statement, developed by the International College of Obsessive-Compulsive Spectrum Disorders, on the indications for hospital admission for people with OCD, the treatment that is offered within hospital, the complications that may occur in this setting, and principles for best practice. Methods: Current literature was critically reviewed and narratively synthesized by a group of international experts in the field of OCD. Results; An inpatient hospital admission may be required for people with severe OCD who are unable to accept or tolerate pharmacological or psychological treatment as an outpatient or where there would be significant risks to the individual or those around them. Admissions have been associated with significant reductions in OCD severity. Inpatient treatment often involves psychoeducation of staff, patients and family members, pharmacotherapy, exposure and response prevention psychological work, addressing comorbidity as well as psychosocial issues such as family-relational issues, homelessness, grief or loss. Admissions can be distressing, and intensive inpatient-based therapy programs require the comprehensive assessment of risk. Conclusions: The inpatient treatment of people with OCD is an important management option that needs to be well considered and managed. Admissions often require close monitoring of risks, additional support to staff who may be unfamiliar with OCD, addressing comorbidity, pharmacotherapy and exposure and response prevention therapy.
Iron Matters: Comparative Impact of Beta-Adrenergic Stimulation and Iron Chelation on Cardiac Iron Metabolism and Mitochondrial Function
(MDPI, 2026-04-14) Francesch Manzano, Josep; Comín Colet, Josep; Tajes Orduña, Marta; Ramos Polo, Raúl; Enjuanes, Cristina; Ras Jiménez, Maria del Mar; Cosa, Andreea Eunice; Marinova, Katrin; Enrich Soria, Carla; Moliner, Pedro; Lorenzo Esteller, Laia; Jose Bazán, Núria
Iron deficiency (ID) is frequent in patients with heart failure (HF) and is correlated with adverse outcomes, yet its involvement in HF pathophysiology is not fully understood. Hyperactivity of the sympathetic nervous system (SNS) is the central feature of HF. We aimed to compare the effects of isoproterenol (ISO), a β-adrenergic agonist (SNS stimulation), with those of the iron chelator deferoxamine (DEF), to evaluate how β-adrenergic stimulation influences cardiac iron. In this study, H9c2 cardiac cells were challenged with ISO, DEF or both and several parameters related to iron metabolism were analyzed. In all cases, the cells decreased their intracellular iron levels. ISO induced alterations in key cardiac iron metabolism molecules that were, in most cases, comparable to those elicited by DEF, emphasizing the direct impact of β-adrenergic stimuli on iron metabolism and mitochondrial dysfunction. Nevertheless, unlike DEF, ISO triggered a shift in mitochondrial energy metabolism. These findings suggest that β-adrenergic stimulation, as a major component of neurohormonal activation, may contribute to the development of ID in cardiac cells, highlighting the importance of iron homeostasis and the need to further investigate iron dysregulation in this context.
Indocyanine green fluorescence for intraoperative detection of liver tumours in minimally invasive surgery: protocol for the LIVERGREEN phase IV multicentre clinical trial
(BMJ Publishing Group, 2026-04-16) Huerta, Martín; López Ben, Santiago; Lladó Garriga, Laura; Sánchez Cabús, Santiago; Mils, Kristel; Molina, Víctor; Dopazo, Cristina; Vidal, Laura; Dalmau, Mar; Caralt, Mireia; Rosón, Núria; Merino, Xavier; Armario, David; Salcedo Allende, María Teresa; Pellino, Gianluca; Sapisochin, Gonzalo; Gómez Gavara, Concepción; Pérez, Núria; Roig, Anna; Sanjuan, Anna; Pérez, Santiago; Sánchez Maroto, Olga; Delgado, Esther; Cabau, Claudia; Villasante, Sara; Galiana, Carmen; Herms, Daniel; Valencia, Sebastián; Cañete, Marta; García, Oliver; Barrios, Oriana; Vila, Marina; Leiva Ureña, David; Layreda, Karen
Introduction: Liver tumours are a leading cause of global morbidity and mortality. Current diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI) and intraoperative ultrasound (IOUS), have limitations in detecting liver neoplasms. Indocyanine green (ICG) has emerged as a promising tool for improving liver tumour detection. This study aims to assess the impact of preoperative ICG on intraoperative tumour detection in minimally invasive surgery and develop a machine-learning algorithm to enhance tumour detection using ICG fluorescence. Methods and analysis: This prospective, multicentre, phase IV clinical trial adheres to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Patients with liver tumours eligible for minimally invasive surgery and a preoperative imaging test will be included. ICG will be administered intravenously 24 hours before surgery. Intraoperative procedures will include IOUS, ICG mapping and photographic documentation. Patients will be followed for 90 days to assess tumour progression, morbidity and mortality. The photographic analysis will enable the development of an artificial intelligence algorithm using machine learning and neural networks to identify lesions based on ICG fluorescence. The estimated sample size is 173 patients and the trial is predicted to accrue in 3 years. Ethics and dissemination: The trial will be conducted in accordance with the Declaration of Helsinki and the Spanish Agency of Medicines and Medical Devices (AEMPS) guidelines. Approved by the local institutional Ethics Committee and the AEMPS, the results will be shared with the scientific community through publications and conferences.
Enhancing Type 1 Diabetes Polygenic Risk Prediction Through Neural Networks and Entropy-Derived Insights
(MDPI, 2026-03-25) Nadal Martínez, Antonio; Pérez Solero, Guillermo; Ferreiro López, Sandra; Blom Dahl, Jorge; Montanya Mias, Eduard; Alonso Bernáldez, Marta; Shabot, Moises; Binsch, Christian; Szczerbinski, Lukasz; Kretowski, Adam; Nevado, Julián; Lapunzina, Pablo; Wagner, Robert; Tenorio Castano, Jair
Type 1 diabetes (T1D) is an autoimmune disease with a strong genetic component (~70% heritability). Early identification of individuals at risk is crucial for early intervention or risk assessment. Although polygenic risk scores (PRS) have shown promise in risk assessment, most current approaches remain constrained by linear assumptions and limited generalizability. We aimed to develop a neural network-driven classifier using T1D-associated single nucleotide polymorphisms (SNPs). In addition, we explored the inclusion of an entropy-derived feature as a complementary variable, representing the degree of genetic variability within an individual’s genotype profile across the 67 T1D-associated SNPs, to evaluate its potential additive contribution to the model performance. We analyzed genotype data from 11,909 individuals in the UK BioBank (546 T1D cases and 11,363 controls). Sixty-seven well-known SNPs associated with T1D were utilized as inputs to the model, using two distinct allele-encoding strategies. A feed-forward neural network was evaluated under varying case–control ratios through five-fold cross-validation. Performance was assessed using the area under the receiver operating characteristic curve (AUC) on a held-out test set and on an external European cohort as a validation cohort. Across five-fold cross-validation, the best configuration achieved a median AUC of 0.903. On the held-out UK Biobank test set, the model generalized well, with an AUC of 0.8889 (95% CI: 0.8516–0.9262). A probability-based risk framework, constructed using five risk groups (“very low”, “low”, “intermediate”, “high”, and “very high” risk), yielded a negative predictive value (NPV) of 98.9% for the “very low” risk group and a Positive Predicted Value (PPV) of 61.9% with a specificity of 97.3% for the “very high” risk group, assuming a 10% T1D prevalence. External validation in the German Diabetes Study reproduced clear case–control separation; for individuals with recent onset diabetes and glutamic acid decarboxylase antibodies (GADA+) vs. controls, specificity reached 91.9% in the “high” risk group (PPV of 94.3%) and 97.6% in the “very high” risk group (PPV of 95.7%). The proposed neural network reliably predicts T1D genetic risk using a compact SNP panel of 67 SNPs and maintains accuracy in both internal and external European cohorts. Its probabilistic output enables clinically interpretable risk thresholds, while entropy features contributed modestly to performance. These results demonstrate that a neural network-based approach achieves discriminative performance that is comparable to established T1D genetic risk models, while offering flexible probability-based risk stratification and architectural extensibility for future integration of additional features.
Linear Accelerator Mask–Based Radiosurgery for Trigeminal Neuralgia: Prospective Evaluation of 50 Patients
(Elsevier, 2026-04) Rosselló Gómez, Aleix; Modolell Farré, Ignasi; Macià Garau, Miquel; Lucas Calduch, Anna; García Expósito, Nagore; Muñoz Vendrell, Albert; Campoy Diaz, Sergio; Huerta Villanueva, Mariano; Majós Torró, Carlos; Cos Domingo, Mònica; Cifre Serra, Pere Josep; Picón, Cristina; Gabarrós Canals, Andreu; Guedea Edo, Ferran
Background: Trigeminal neuralgia (TN) resistant to pharmacologic treatment can be treated with microvascular decompression, percutaneous procedures, or radiosurgery. Regarding radiosurgery, there is variability in target definition, dose selection, radiation delivery and positioning, and immobilization. Methods: This observational prospective study included patients with TN treated with 90 Gy prescribed to an anterior cisternal isocenter, delivered with a TrueBeam LINAC, under mask immobilization, Novalis couch positioning, and ExacTrac X-ray and infrared positioning and motion monitoring. Treatment response, intensity and frequency of pain, presence of recurrence, and adverse effects were analyzed. Results: A total of 91% of patients responded to treatment, with a median latency of 15 days (interquartile range [IQR], 41). Nine patients (22%) experienced minor recurrence at a median time of 7 months (IQR, 3), and 14 patients (34%) experienced a major recurrence at a median time of 12 months (IQR, 19). After recurrence, both frequency and intensity of episodes remained significantly lower than pretreatment. At last follow-up, response was maintained in 25 patients (60%). No radiosurgery-related severe morbidity or mortality was found. Conclusions: Mask-based immobilization combined with image-guided radiation delivered by rotating gantry-based LINAC system provides a safe and effective radiosurgical treatment for TN, which is indicated for drug-resistant idiopathic or secondary TN patients and for drug-resistant classical TN patients who are not candidates for microvascular decompression.
Pseudo-senescence induced by palbociclib does not sensitise pleural mesothelioma cells to combinations with senolytics
(Nature Publishing Group, 2026-04-10) Sreeram, Iswarya; Plans Marín, Sílvia; Cruz-Rodríguez, Mabel; Aliagas Marín, Elisabeth; Palau Gallinat, Didac; Muñoz Pinedo, Cristina; Nadal, Ernest
Pleural Mesothelioma (PM) is an aggressive neoplasm of the lung pleura with poor survival rates, highlighting the urgent need for novel therapeutic options. The CDK4/6 inhibitors abemaciclib and palbociclib have demonstrated promising results in patient-derived xenograft models of PM. In this study, we observed that palbociclib reduced proliferation, leading to increased cell size, enhanced SA-β-galactosidase activity, and elevated secretion of IL-6 and IL-8 (SASP), all of which are hallmarks of senescence. However, upon drug removal, the cells regrew. To enhance therapeutic efficacy, we attempted to induce cell death in palbociclib-pretreated PM cells with conventional senolytics, such as BH3 mimetics. While some cells showed sensitivity to Bcl-xL inhibitors, neither navitoclax nor the specific Bcl-xL inhibitor A-1331852, nor other BH3 mimetics targeting Bcl-2 (venetoclax) or Mcl-1 (S63845) increased cell death when combined with palbociclib. We explored the activity of signalling pathways after treatment with palbociclib and identified higher Src and STAT3 phosphorylation, as well as activation of the mTORC1 axis. Therefore, we employed inhibitors of these pathways, such as dasatinib, momelotinib or Torin-1, which did not synergise with palbociclib to kill the cells. In contrast, we found that the chemotherapeutic drug cisplatin induces permanent cell cycle arrest and complete senescence in PM cells. While both drugs increased the phosphorylation of γH2AX, the effects of cisplatin were stronger and more consistent across cell lines. The differential effects of palbociclib and cisplatin on permanent growth arrest were verified by sorting PM cells based on size and β-galactosidase activity. Our findings underscore the importance of understanding the nature of therapy-induced senescence when assessing the effectiveness of senolytics in different tumour models.
Evaluated Childhood Obesity Prevention and Management Programs in Europe, 2015–2024: A Structured Narrative Review of Behavioral and Anthropometric Outcomes
(MDPI, 2026-03-30) Wójcik, Małgorzata; Kozioł Kozakowska, Agnieszka; Iwańska, Anna; Cichocka Mroczek, Ewelina; Łuszczki, Edyta; Wyszyńska, Justyna; Baran, Ewa; González Ramos, Laura; Hartgring, Isa; Martínez, Lola; Parnarauskienė, Justė; Fernández Aranda, Fernando; Jankauskiene, Augustina; Drożdż, Dorota; Mazur, Artur; Álvarez Pitti, Julio
Background: This structured narrative review summarizes and critically appraises evaluated childhood obesity prevention programs implemented in European countries and published between 2015 and 2024. Methods: Systematic searches for PubMed, EBSCOhost, and Google Scholar, complemented by research registries, were conducted year-by-year and independently screened by two reviewers. Results: Five multinational/international programs were identified alongside multiple national initiatives delivered in family, school, community, healthcare, and digital settings. Overall, interventions consistently improved intermediate outcomes—such as selected dietary behaviors, physical activity participation, knowledge, and parental self-efficacy—more than anthropometric endpoints. Effects on BMI/BMI z-score or overweight/obesity prevalence were heterogeneous and frequently small or non-significant, especially for short-duration, single-setting educational interventions. More favorable anthropometric outcomes were commonly reported in long-term, population-scaled physical activity or community-based programs as well as in multidisciplinary healthcare-supported approaches; however, these strategies were typically resource-intensive and sometimes showed differential effectiveness across socioeconomic or cultural groups. Conclusions: The evidence indicates that single-setting or short-term interventions may improve selected behavioral outcomes but are generally insufficient to produce sustained effects on anthropometric measures without integration into broader, multi-level strategies. It is needed to integrate families, schools, communities, and health services with explicit attention to sustainability and equity. Technology-supported tools may strengthen reach and continuity when embedded within comprehensive prevention frameworks.
Common practice elements of cognitive behavioral therapy for gaming disorder: A systematic review and expert panel evaluation
(Elsevier Ltd., 2026-06) Radunz, Marcela; Stevens, Matthew W.R.; Behm, Sanni; Hameed, Muddsar; Bowden Jones, Henrietta; Delfabbro, Paul; Demetrovics, Zsolt; Higuchi, Susumu; Potenza, Marc N.; Wölfling, Klaus; Brandhorst, Isabel; Bore, Per; Claesdotter Knutsson, Emma; González Bueso, Ma. Vega; Herpertz, Stephan; Dieris-Hirche, Jan; Hofstedt, Annika; Gordh, Anna Söderpalm; Jimenez Murcia, Susana; Nielsen, Philip; Pallesen, Ståle; Paschke, Kerstin; Ratta-apha, Woraphat; Rigter, Henk; Santamaria, Juan José; Sugara, Gian Sugiana; King, Daniel L.
Gaming disorder (GD) is an addictive disorder with health and social impacts recognized by the World Health Organization. Although the GD treatment evidence base appear to favor cognitive behavioral therapy (CBT), knowledge of its common practice elements is limited. This systematic review critically evaluates CBT interventions for GD, encompassing individual, group, and mixed approaches, to identify and synthesize common practice elements. Employing a systematic review protocol following PRISMA guidelines and guided by an international expert panel, this review identified CBT studies and then critically reviewed their associated treatment manuals, guidelines, handouts, and related resources. A database search yielding 8479 results identified 28 studies from 12 countries reporting on 22 CBT interventions (n = 7 individual; n = 7 group; n = 8 mixed). Study authors were invited to share intervention materials, which were then independently coded and synthesized. Overall, 14 common practice elements were identified. The most frequent element was emotion regulation skills training (n = 21; 95.5%), followed by psychoeducation (n = 20; 90.9%) and cognitive restructuring (n = 19; 86.4%). Exposure techniques, and strength identification and self-compassion were the least frequent (n = 6; 27.3%). All individual CBT interventions used behavioral activation, psychoeducation, and relapse prevention, whereas emotion regulation skills training was the most frequently used element in group CBT. These findings reveal commonly reported CBT practice elements in the GD evidence base and provide expert summaries of established and less utilized therapeutic techniques. Improving the field's shared understanding of CBT is foundational to advancing GD clinical research and a model of best practice.

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