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OAS1 and OAS3 genetic variants enhance inflammatory responses to SARS-CoV-2
(Elsevier BV, 2025-11-13) L. Dediego, Marta; López-fernández-sobrino, Raúl; Pedragosa, Jordi; López-garcía, Darío; Nogales, Aitor; Durbán, Jordi; Cardona, Fernando; Llucià-carol, Laia; Rivero, Vanessa; Vazquez-utrilla, Paula; Palomo Sanchez-grande, Laura; Cobo, Miriam; Lloret, Lara; Márquez-kisinousky, Leonardo; Ruiz-jaén, Francisca; Lozano, Francisco; Sibila, Oriol; Faner, Rosa; Castro, Pedro; Domingo, Carlos; Robles, Verónica; L. Bedini, Josep; Rico, Verónica; Aguero, Daiana; Soriano, Alex; Martín Nalda, Andrea; Parra Martínez, Alba; Colobran, Roger; Soler-palacín, Pere; Serra-llovich, Alexandre; Dietl, Beatriz; Jesús Arranz, M.; Dalmau, David; Signes-costa, Jaime; Gil-carbonell, Joan; Todolí, José; Martínez, Jacobo; Rojo, Silvia; Fiz-lópez, Aida; Arribas, Elisa; Cal-sabater, Paloma; Bernado, David; Vogel, Marina; Wiemann, Stefan; Abolhassani, Hassan; Pan-hammarström, Qiang; Pujol, Aurora; C. Su, Helen; Lee, Danyel; Zhang, Shen-ying; Casanova, Jean-laurent; Fernández-cadenas, Israel; Pérez-tur, Jordi; M. Planas, Anna
Recessive deficiency in 2',5' -oligoadenylate synthetase (OAS) or RNase L can cause systemic inflammation in children with SARS-CoV-2 infection, but its role in adult respiratory disease is unclear. We analyzed rare OAS1/OAS3 variants and the common OAS1 rs10774671 polymorphism in 342 COVID-19 patients, assessing enzymatic activity, RNase L activation, viral replication, and inflammation in cell systems and Oas3-deficient mice. Rare heterozygous variants showed impaired RNase L activation but were not enriched in pneumonia cases. In contrast, the rs10774671 A/A genotype (OAS1-p42 isoform) was associated with severe disease (OR = 2.28; 95% CI = 1.13-4.58; p = 0.0107) and reduced viral control despite intact RNase L activation. OAS3 and OAS1-p46 isoform limited viral replication and inflammatory responses, whereas Oas3-deficient mice showed increased cytokines. These findings suggest that common OAS1 variation influences COVID-19 severity, while rare OAS variants may affect inflammation regulation rather than respiratory pathology.
Development of a blood-based lipidomic fat quality score for the risk of ischemic stroke
(Oxford University Press (OUP), 2026-01-01) Lázaro, Iolanda; Luján-barroso, Leila; Soldevila-domenech, Natalia; J Amor, Antonio; Ortega, Emilio; Ros, Emilio; Sánchez, Maria-josé; Rodríguez-barranco, Miguel; Guevara, Marcela; Moreno-iribas, Conchi; Schröder, Helmut; Fitó, Montserrat; L Tintle, Nathan; Ryder, Nathan; S Harris, William; Agudo, Antonio; Sala-vila, Aleix
Introduction: Poor-quality diets promote ischemic stroke. Red blood cell fatty acids (RBC-FAs) are objective, longterm biomarkers of diet. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain, we developed a blood-based lipidomic fat quality (LFQ) score considering pre-defined RBC-FA diet-related biomarkers, and examined whether LFQ score relates to the risk of ischemic stroke. Patients and methods: We determined the RBC-FAs (n = 438 cases of incident ischemic stroke, n= 438 matched controls). For each participant, we scored 1 for each beneficial metric (C15:0+C17:0; C18:2n-6; C18:3n-3; C20:5n-3; C22:6n-3) >= the median of the control group; and 1 for each detrimental metric (C16:0; C16:1n-7; C18:0) < the median of the control group. LFQ score resulted from the 8-component sum (range = 0-8; higher values, higher fat quality). We explored the validity of findings in a different background (n = 2468 participants from the Framingham Offspring Study without ischemic stroke at baseline, 12-year median follow-up, n= 121 cases). Results: In a fully adjusted model, the Odds Ratio (OR) for ischemic stroke was 0.86 (95% confidence interval [CI] = 0.77-0.95) for each 1-unit increase of the LFQ score. Compared to individuals at the lowest category of LFQ score (0-3 points), those at the top category (5-8 points) had lower odds (OR = 0.64, 95% CI = 0.44-0.94). The findings were similar in the Framingham Offspring Study (Hazard Ratio [HR] for each 1-unit increase = 0.83; 95% CI = 0.70-0.99; HR for those at top category = 0.49; 95% CI = 0.29-0.84, compared to those at the lowest category). Conclusion: Low blood-based LFQ scores relate to a high risk of ischemic stroke.
Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: impact on axillary morbidity and survival—a propensity score cohort study
(Springer Verlag, 2024-04-18) Fernandez Gonzalez, Sergi; Falo, Catalina; Pla Farnos, Maria Jesus; Campos Delgado, Míriam; Ortega-Exposito, Carlos; Ortega, Raul; Vicente, Maria; Petit, Anna; Bosch Schips, Jan; Bajén Lázaro, Ma. Teresa; Reyes, Gabriel; Martínez. Evelyn; González Viguera, Javier; Stradella, Agostina; Pernas, Sònia; Ponce, Jordi; Peñafiel, Judith; García Tejedor, María Amparo
Purpose In patients with clinically lymph node-negative (cN0) breast cancer, performing sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) has been preferentially embraced in comparison to before NACT. However, survival outcomes associated with both strategies remain understudied. We aimed to compare the axillary lymphadenectomy (ALND) rate, disease-free survival (DFS), and overall survival (OS), between two strategies. Methods We included 310 patients in a retrospective observational study. SNLB was performed before NACT from December 2006 to April 2014 (107 cases) and after NACT from May 2014 to May 2020 (203 patients). An inverse probability of treatment weighting (IPTW) method was applied to homogenize both groups. Hazard ratios (HR) and odd ratios (OR) are reported with 95% confidence intervals (95%CI). Results The lymphadenectomy rate was 29.9% before NACT and 7.4% after NACT (p<0.001), with an OR of 5.35 95%CI (2.7–10.4); p=.002. After 4 years of follow-up, SLNB after NACT was associated with lower risk for DFS, HR 0.42 95%CI (0.17–1.06); p=0.066 and better OS, HR 0.21 CI 95% (0.07–0.67); p=0.009 than SLNB before NACT. After multivariate analysis, independent adverse prognostic factors for OS included SLNB before NACT, HR 3.095 95%CI (2.323–4.123), clinical nonresponse to NACT, HR 1.702 95% CI (1.012–2.861), and small tumors (cT1) with high proliferation index, HR 1.889 95% (1.195–2.985). Conclusion Performing SLNB before NACT results in more ALND and has no benefit for patient survival. These findings support discontinuing the practice of SLNB before NACT in patients with cN0 breast cancer.
Dual-energy computed tomography (CT) versus cone-beam computed tomography (CT) in chronic thromboembolic pulmonary hypertension: diagnostic accuracy compared with digital subtraction angiography
(Elsevier, 2026-01-01) Páez Carpio, Alfredo; Serrano, Elena; Domenech Ximenos, Blanca; Cornellas Escayola, Llúria; Barberà i Mir, Joan Albert; Vollmer Torrubiano, Ivan; Blanco Vich, Isabel; Gomez, F. M.
AIM The aim of this study was to compare the diagnostic accuracy and interobserver agreement of dual-energy computed tomography pulmonary angiography (DECT-PA) and cone-beam computed tomography pulmonary angiography (CBCT-PA) for the evaluation of chronic thromboembolic pulmonary hypertension (CTEPH), using digital subtraction angiography pulmonary angiography (DSA-PA) as the reference standard. MATERIALS AND METHODS This retrospective study included 109 patients with confirmed CTEPH who underwent DECT-PA, CBCT-PA, and DSA-PA within a three-month interval between January 2017 and June 2022. Pulmonary arteries were evaluated at main, lobar, segmental, and subsegmental levels. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. Interobserver agreement was assessed using Cohen's kappa (κ). RESULTS Overall diagnostic accuracy was comparable between DECT-PA (89.5%) and CBCT-PA (89.3%). DECT-PA demonstrated higher overall sensitivity (65.0% vs 53.5%, P = 0.019) but CBCT-PA achieved greater interobserver agreement (κ = 0.76 vs 0.74). Sensitivity declined in distal segments for both modalities, with CBCT-PA outperforming DECT-PA at the subsegmental level (51.9% vs 43.6%). Specificity remained high across modalities (>89%). The CBCT-PA showed superior agreement for lesion subtype classification, particularly for occlusions (κ = 0.839). CONCLUSION DECT-PA and CBCT-PA offer complementary strengths for the evaluation of CTEPH. DECT-PA provides high specificity for central and segmental lesions, supporting its role in initial assessment. CBCT-PA improves sensitivity and reproducibility in distal arteries, reinforcing its value for procedural planning and detailed vascular assessment. These findings support the use of DECT-PA as a first-line diagnostic tool and highlight the role of CBCT-PA as an adjunct in patients with distal or morphologically complex disease, potentially influencing diagnostic pathways and procedural planning in CTEPH.
Unravelling the Link between Polyphenol Intake and the Risk of Digestive System Cancer: An Umbrella Review Using Meta-Analyses and Systematic Reviews
(Cambridge University Press (CUP), 2026-01-01) Amjadi, Arezo; Abbasi, Hamid; Tahavorgar, Atefeh; Esfahanian, Mohammadreza; Torkaman, Mahdie; Shahrokhi Sardoo, Adel; Erfanimanesh, Ali; Shamsi-goushki, Ali; Esmail Akbari, Mohammad; Alhouei, Barbod; Gholamalizadeh, Maryam; Doaei, Saeid
Background Digestive system cancers (DSCs) constitute a significant number of cancer cases and are closely associated with modifiable risk factors.Objective This umbrella review synthesizes evidence from meta-analyses on the association between dietary polyphenol consumption and the risk of DSCs, addressing limitations in the literature and identifying optimal polyphenol types and doses.Methods Following Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across PubMed, Scopus and Web of Science until April 2025, using specific keywords related to polyphenols and DSCs. Eligible studies included meta-analyses that examined polyphenol intake and DSC risk. The quality was assessed via the AMSTAR 2 and GRADE framework. Statistical analyses were performed using RStudio, employing random-effects models based on the heterogeneity metrics.Results Data from six meta-analyses, encompassing 27 effect sizes, revealed a statistically significant 11% reduction in the risk of DSCs associated with polyphenol consumption (RR: 0.89; 95% CI: 0.85-0.93; I2: 63%). Subgroup analysis revealed significant risk reductions for specific polyphenol classes: flavonols (22%), quercetin (22%), anthocyanidins (16%), flavan-3-ols (12%) and isoflavones (9%). Publication bias was evident, but adjustments using the trim-and-fill method still indicated a 13% overall reduction in risk (RR: 0.87; 95% CI: 0.83-0.92; I2: 64%).Conclusions Our findings support the protective role of dietary polyphenols against DSCs, particularly flavonols and quercetin, suggesting that further investigations into the optimal intake levels and mechanisms of action are needed. These findings underscore the potential of dietary modification as a strategy for DSC prevention.
DSC-PWI presurgical differentiation of grade 4 astrocytoma and glioblastoma in young adults: rCBV percentile analysis across enhancing and non-enhancing regions
(Springer Verlag, 2024-08-01) Pons Escoda, Albert; Naval Baudin, Pablo; Viveros, Mildred; Flores-Casaperalta, Susanie; Martínez Zalacaín, Ignacio; Plans, Gerard; Vidal Sarró, Noemí; Cos Domingo, Mònica; Majós Torró, Carlos
Purpose The presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding in prognostic assessment, guiding molecular diagnostics and surgical planning, and identifying candidates for IDH-targeted trials. Despite its potential, the full capabilities of DSC-PWI remain underexplored. This research evaluates the differentiation ability of relative-cerebral-blood-volume (rCBV) percentile values for the enhancing and non-enhancing tumor regions compared to the more commonly used mean or maximum preselected rCBV values. Methods This retrospective study, spanning 2016–2023, included patients under 55 years (age threshold based on World Health Organization recommendations) with grade 4 astrocytic tumors and known IDH status, who underwent presurgical MR with DSC-PWI. Enhancing and non-enhancing regions were 3D-segmented to calculate voxel-level rCBV, deriving mean, maximum, and percentile values. Statistical analyses were conducted using the Mann-Whitney U test and AUC-ROC. Results The cohort consisted of 59 patients (mean age 46; 34 male): 11 astrocytoma-4 and 48 glioblastoma. While glioblastoma showed higher rCBV in enhancing regions, the differences were not significant. However, non-enhancing astrocytoma-4 regions displayed notably higher rCBV, particularly in lower percentiles. The 30th rCBV percentile for non-enhancing regions was 0.705 in astrocytoma-4, compared to 0.458 in glioblastoma (p = 0.001, AUC-ROC = 0.811), outperforming standard mean and maximum values. Conclusion Employing an automated percentile-based approach for rCBV selection enhances differentiation capabilities, with non-enhancing regions providing more insightful data. Elevated rCBV in lower percentiles of non-enhancing astrocytoma-4 is the most distinguishable characteristic and may indicate lowly vascularized infiltrated edema, contrasting with glioblastoma’s pure edema.
Prevalence of Mandibular Third Molar Impaction, Associated Pathologies, and Correlation With Temporomandibular Joint Morphology in a Hospital-Based Spanish Cohort: A Panoramic Radiography Study
(Hindawi, 2026-12-01) Assiri, Hassan; Estrugo Devesa, Albert; Egido-Moreno, Sonia; Roselló Llabrés, Xavier; Hameed, Mohammed; Alqarni, Abdullah; López López, José, 1958-
Background Mandibular third molar is the most frequent impacted tooth in the oral cavity. Its presence can be associated with complications including the temporomandibular joint (TMJ) symptoms. Therefore, the present study aimed to assess the prevalence of impacted mandibular third molar (IMTM), associated pathologies, and its correlation with TMJ morphology in a hospital-based Spanish cohort. Methods We retrospectively reviewed existing orthopantomographs (OPGs) records, panoramic images of patients aged ≥18 with at least one IMTM who attended the Dental Hospital of the University of Barcelona (HOUB) between September 2021 and May 2023. The OPGs were assessed and interpreted by an experienced oral and maxillofacial radiologist for the type of impaction according to Winter’s classification system, associated pathologies, and shape of mandibular condyle. Results Out of 80 OPGs, 60% (95% confidence interval [CI]: 48.4%−70.7%) were females, and the majority 53.8% (95% CI: 42.3–64.9) were between 18 and 28 years of age. The prevalence rate of IMTM was 86.88%, with the left side commonly involved. On both sides, oval-shaped condyle and vertical IMTM were the most common, with dental caries and bone loss being the frequently observed pathologies. Sclerotic changes were depicted in 15% (95% CI: 8.2%−24.7%) of the cases on both sides of TMJ. On the other hand, no statistically significant associations were noticed between the pathologies and condyle shape (p > 0.05, Cramér’s V < 0.25). Vertical and mesioangular, followed by horizontally IMTMs, were the most prevalent types of impactions, indicating nonsignificant association with condylar shape (p > 0.05, Cramér’s V = 0.21–0.23). Conclusion In this hospital-based cohort, vertical IMTM and oval condylar morphology were predominant; however, condylar shape did not correlate with impaction type on panoramic radiographs. The findings are preliminary and require validation in sufficiently powered cone beam computed tomography (CBCT)-based studies with clinical TMJ assessment.
Clinical governance in radiation oncology
(VM Media Group sp. z o.o, 2025-12-16) Malicki, Julian; Guedea, Ferran; Krengli, Marco
Clinical governance (CG) is an emerging framework that ensures accountability for delivering safe, effective, and continuously improving healthcare services. Originally introduced in the United Kingdom in the late 1990s as part of reforms in the National Health Service, CG draws upon principles of corporate governance to establish system-wide oversight of clinical quality, safety, and accountability. CG provides an overarching organisational framework encompassing leadership structures, clinical effectiveness, risk management, audits, professional development, and patient engagement. In radiation oncology, CG plays a critical role in enhancing treatment safety and quality by standardising protocols, conducting regular audits and peer reviews, implementing risk management strategies, and supporting continuous education for multidisciplinary teams. It also ensures accountability through transparent reporting to regulators, collaboration with patient groups, and commitment to evidence-based practice. Ethical principles - beneficence, non-maleficence, autonomy, and justice - are central to CG and provide the foundation for maintaining professional standards of care. Despite the increasing use of the term clinical governance, it is often only poorly understood. In the present review, we define the concept of clinical governance and discuss its role in healthcare, with a particular focus on the field of radiation oncology.
From Evidence to Action: Advancing Timely Implementation of Triple Therapy in Type 2 Diabetes Mellitus and CKD
(Elsevier BV, 2025-10-04) Fernandez-fernandez, Beatriz; Luis Gorriz, Jose; Cebrian-cuenca, Ana; Fácila, Lorenzo; Maria Fernandez Rodriguez, Jose; Perez Maraver, Manuel; Ortiz, Alberto
Amid rapid advances in treating chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) and evolving guidelines, implementation remains a major bottleneck. Suboptimal implementation of guidelines, from lack of albuminuria testing for early CKD detection to delayed initiation of triple therapy with renin-angiotensin system inhibitors (RASi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and nonsteroidal mineralocorticoid receptor antagonists (nsMRA), may deny patients kidney and cardiovascular benefits. We emphasize the residual risk despite RASi-SGLT2i therapy and the added value of nsMRA, and address real-world implementation challenges. The addition of a nsMRA may delay the need for kidney replacement therapy (KRT) by up to a decade. Based on epidemiological data, > 90% of patients eligible for therapy may be diagnosed and managed in the primary care setting, identifying the owners of the process, in close collaboration with nephrology, endocrinology, cardiology, and internal medicine, as needed. In addition, primary care provides the optimal setting, given the easy and repeated contact, for ensuring lifestyle measures essential to nephroprotection, as well as maximizing the use of RASi and SGLT2 inhibitors when not contraindicated, together with the rapid initiation of triple therapy, facilitated by its safety profile. In this regard, the CONFIDENCE trial supports the safety and efficacy (in terms of albuminuria reduction) of prescribing simultaneously, nsMRA plus SGLT2i combination therapy on a prior RASi background. In conclusion, widespread uptake of albuminuria assessment in primary care will prevent patients with CKD and T2DM from missing out on the diagnosis or the rapid implementation of optimal guideline-directed therapy.
Patient-reported outcomes in patients with hematologic malignancies treated with CAR T-cell therapy in Europe
(American Society of Hematology, 2025-09-24) R. A. Pennings, Elise; M. Spanjaart, Anne; W. Thielen, Frederick; Oerlemans, Simone; Fleischer, Anna; Sanges, Carmen; Gomes Da Silva, Maria; Cabrerizo, Yolanda; Lecot, Pacôme; Roux-opstaele, Lutgart; Dreuillet, Caroline; Gonzalez-marcano, Eglys; Millán, Olga; Jaeger, Ulrich; Delgado, Julio; Luu, Maik; Huber, Barbara; Lorrain, Margot; Pina, Mariana; Kremer, Andreas; Bolaños, Natacha; Clavreul, Solène; Nier, Samantha; D. K. Liu, Roberto; I. Lissenberg-witte, Birgit; Anguille, Sébastien; Robin, Marie; C. Morris, Emma; Sureda, Anna; Préau, Marie; Pannard, Myriam; H. De Bock, Geertruida; S. Wagers, Scott; Negre, Hélène; Maucort-boulch, Delphine; Hudecek, Michael; A. Uyl-de Groot, Carin; José Kersten, Marie
Patient-reported outcomes (PROs) give direct insights into the treatment's impact on patient's life and complement clinical outcomes. However, since the advent of chimeric antigen receptor T-cell therapy (CAR-T), PROs have been underreported. Particularly, little is known about long-term health-related quality of life (HRQoL) and dimensions such as mental- and social well-being, working life, and financial burden. Therefore, we evaluated multidimensional PROs in a cross-sectional study among European patients who received CAR-T for hematologic malignancies. Patients completed validated questionnaires (EQ-5D-5L/EORTC-QLQ-C30/PCL-5/modified-iPCQ) and ad hoc items on treatment experiences, unmet care needs, and HRQoL. The survey was available online (January-October 2023) in 7 languages. Outcomes were compared with the European general population, a matched CAR-T-naive cohort with hematologic malignancies and across subgroups, using established thresholds for clinically important differences/problems and regression models. From 10 European countries, 389 patients participated (>1 year post-CAR-T: 56%). Mean EQ-VAS was 73.1 (standard deviation, 18.5). HRQoL was similar or better than reference cohorts, except for role-, social-, and cognitive-functioning. Physical-functioning problems were most frequently reported (41%), particularly by women, older individuals, and those who experienced neurotoxicity. The latter subgroup also reported more cognitive- and social-functioning problems. Anxiety regarding disease recurrence (76%), infections (66%) and long-term side effects (59%) was common. Among working-age patients, 72% could continue paid work after CAR-T. Younger patients (32%) reported more financial difficulties than older patients (9%). This study shows favorable general HRQoL after CAR-T compared with reference cohorts. However, a notable proportion of patients experienced problems in physical-, mental- and social well-being. We identified high-risk subgroups and care needs that should be addressed during follow-up.
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.
Efficacy of Stromal Vascular Fraction Treatment for Knee Osteoarthritis: A Single-Arm Experimental Trial
(MDPI AG, 2025-11-28) Boada-pladellorens, Anna; Avellanet, Merce; Veiga, Anna; Pages-bolibar, Esther
Background/Objectives: Knee osteoarthritis (KOA) is a common pathology characterized by impaired joint cartilage. Mesenchymal stromal cell (MSC)-based treatments, such as stromal vascular fraction (SVF), are increasingly being used for their potential cartilage-generating capabilities; however, there is still insufficient evidence to confirm their effectiveness. The aim of the study was to assess the efficacy of SVF treatment in KOA in terms of pain relief. Methods: An experimental clinical trial was performed. We included adults with symptomatic KOA who attended Celular Clinic (Andorra). A laboratory-manufactured and standardized SVF product (Celstem (R)) was applied to selected patients. Clinical, functional, and radiological assessments using the visual analog scale, KOOS (Knee Injury and Osteoarthritis Outcome Score), SF-36 scale, and MOCART classification (Magnetic Resonance Observation of Cartilage Repair Tissue) were performed. Variables were compared before treatment and at one, six, and twelve months after treatment. Adverse effects were reported. Results: In total, 184 patients were included in the clinical trial, 78 of whom were finally analyzed. There were statistically significant differences in both resting and activity-related pain and in all KOOS subscales after SVF treatment (p < 0.001). The quality of life also showed significant changes (p = 0.021). No significant changes were observed in MOCART values. However, a positive association was found between MOCART and cell yield. Few adverse effects were reported. Conclusions: Our nonrandomized uncontrolled clinical trial showed that SVF treatment has promise to reduce pain in patients with KOA. Improvements in functionality and quality of life were also observed. Future randomized controlled trials regarding SVF versus placebo therapies will further clarify this potential.
Long-term liver stiffness dynamics after sustained virological response in patients with HIV/HCV co-infection and advanced fibrosis
(Ovid Technologies (Wolters Kluwer Health), 2025-09-23) Martín-carmona, Jesica; Corona-mata, Diana; Téllez, Francisco; Navarrete Lorite, Miguel Nicolás; Barroso, Isabel; Carlos Alados, Juan; Palacios Muñoz, Rosario; De Los Santos, Ignacio; Vera-méndez, Francisco Jesús; Imaz, Arkaitz; Raffo Márquez, Miguel; Morano Vázquez, Aitana Carla; José Galindo, María; Belinchón, Olga; Serrano Fuentes, Miriam; López Zúñiga, Miguel Ángel; Galera Peñaranda, Carlos; Reus-bañuls, Sergio Javier; A. Pineda, Juan; Macías, Juan; Corma-gómez, Anaïs; Gehep-011 Study Group, The
Objective: This study analyses liver stiffness (LS) dynamics in people with HIV (PWH) and advanced liver fibrosis who achieved sustained virological response (SVR) and assess factors associated with LS normalization or progression, after long-term follow-up.Design:Prospective multicenter cohort study. Methods: This study included individuals with HIV/HCV co-infection from the Spanish GEHEP-011 cohort, fulfilling: pretreatment LS >= 9.5 kPa; sustained virological response (SVR) with direct-acting antiviral regimen; available measurement of LS at SVR. Factors associated with LS normalization (achieving <= 7.2 kPa in two consecutive measurement) and progression (increase of >20% LS at the last measurement available) were analyzed. Results: A total of 678 patients were included. The median follow-up was 40 (17-71) months. The repeated measures ANOVA revealed a significant main effect of time on LS. Overall, 221 (32.6%) achieved normalization. Lower probability of normalization was associated with advanced liver disease [baseline LS: sHR = 0.26 (95% CI, 0.19-0.37), P < 0.001; liver decompensation before SVR: sHR = 0.22 (0.05-0.97), P < 0.001; baseline MELD score: sHR = 0.81 (0.69-0.94), P = 0.006]. LS progression occurred in 50 (7.4%). Progression was associated with higher baseline LS [sHR = 1.04 (1.01-1.07), P = 0.007], controlled attenuation parameter (CAP) [CAP >= 280 dB/m: sHR = 2.94 (1.16-7.44)] and older age [sHR 1.06 (1.00-1.13), per year, P = 0.04]. Conclusions: In PWH, LS significantly decreases after HCV cure in the long-term, achieving values of <= 7.2 kPa. In a substantial proportion of patients, LS remain stable or even increases. Older age and concomitant steatotic liver disease are associated with LS progression.
Complications of Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide—A Prospective Study on Behalf of the EBMT Transplant Complications Working Party
(MDPI AG, 2025-12-18) Tomaszewska, Agnieszka; W. Basak, Grzegorz; Peczynski, Christophe; Polge, Emmanuelle; Ambron, Pascale; Boreland, William; Sica, Simona; Arat, Mutlu; Passweg, Jakob; Luis Lopez Lorenzo, Jose; Salmenniemi, Urpu; Jindra, Pavel; Kulagin, Alexander; Martino Bufarull, Rodrigo; Eder, Matthias; Bekadja, Mohamed-amine; Mussetti, Alberto; E. Graham, Charlotte; Schoemans, Hélène; Penack, Olaf; Moiseev, Ivan; Perić, Zinaida
Background: Haploidentical hematopoietic cell transplantations (haplo-HCTs) with post-transplant cyclophosphamide (PT-Cy) are standard practice, but complications causing morbidity and mortality are not well described. Methods: The aim of this prospective non-interventional multicenter study was to document frequency of potential non-infectious and infection-related complications and main transplant outcomes after the first unmanipulated haplo-HCT with PT-Cy between 2017 and 2019 in 129 adult patients with hematological malignancies. The median follow-up was 37.3 months [95% CI: 34.3-39.7]. Results: The cumulative incidence (CI) of acute graft versus host disease (aGvHD) at day +100 was 22.4% grade II-IV [95% CI: 15.5-30.1] and 8.8% grade III-IV [95% CI: 4.6-14.6], respectively. The cumulative incidence of chronic GvHD (cGvHD) at 24 months was 25.8% [95% CI: 18.5-33.6]; extensive cGvHD was 10.9% [95% CI: 6.3-17.1], respectively. The most frequent non-infectious complications for the whole study population were mucositis-37.5% (n = 48); renal insufficiency-18% (n = 23); and cardiovascular complications-10.9% (n = 14). The following infection-related complications were diagnosed: bacterial in 84 (65.1%), viral in 66 (51.6%), and fungal in 24 (18.6%) recipients. Two-year OS was 58.1% [95% CI: 50.2-67.3]; NRM-27.1% [95% CI: 19.7-35]; PFS-50.4% [95% CI: 42.5-59.8]; and GRFS-38.8% [95% CI: 31.2-48.1]. About 50% of all deaths were directly caused by infection or infection-related conditions. Conclusions: Disease remission status at transplant significantly affected PFS, chronic GvHD, and GRFS. Although clinical applications of haplo-HCT with PTCy are widespread, the study confirms the need to reduce infection-related mortality after this type of GvHD prophylaxis.
Use of Cefiderocol for Carbapenem-Resistant Gram-Negative Infections in Hospital at Home: Multicentric Real-World Experience
(MDPI AG, 2025-12-03) Parra-plaza, Andrea; Ugarte, Ainoa; Benavent, Eva; García-poutón, Nicole; Mujal, Abel; Rosa Oltra, María; Parra-rojas, Andrés; Rico, Verónica; Del Río, Manuel; Nicolás, David
Background: Cefiderocol (CFD) is a novel cephalosporin targeting multidrug-resistant Gram-negative bacterial (GNB) infections. It mimics siderophores to enter into GNB through iron transport receptors. However, evidence on its use in Hospital at Home (HaH) and outpatient parenteral antibiotic therapy (OPAT) programs remains scarce. Objectives: The primary objective was to evaluate feasibility and efficacy of CFD in HaH setting. The secondary objective was to assess its safety. Methods: A retrospective, observational study was conducted across six Spanish centers between January 2023 and December 2024. Adult patients with documented GNB infections treated with CFD in HaH units were included. Demographic, clinical and microbiological data, treatment characteristics, and outcomes were collected. Statistical analysis was descriptive; no inferential or correlation tests were performed. Results: 27 patients were included; 70.4% were male, with a median age of 69 years. Most infections were nosocomial (65.4%), particularly skin and soft tissue (37%). Septic shock occurred in 14.8% of patients. Pseudomonas aeruginosa (66.7%) and Klebsiella pneumoniae (14.8%) were the most frequent pathogens involved, with Verona Integron-encoded metallo-B-lactamase (VIM, 50%) being the predominant resistance mechanism. CFD was used as a first-line therapy in 63% of cases and in combination with other antibiotics in 40.7%. Median treatment duration was 21.7 days. Administration was mainly via peripherally inserted central catheters (PICC, 33.3%) and electronic pumps (52%). Adverse effects occurred in 7.4% of patients, leading to discontinuation in one case. A total of 88.8% of patients achieved clinical success, with 7.7% recurrence within a month. Escalation of care occurred in 7.7% and 19.2% were readmitted within a month after HaH discharge. No infection-related deaths were reported. Conclusions: CFD is a feasible, safe, and effective treatment for difficult-to-treat GNB infections in HaH settings.
Association Between Dietary Fatty Acid Intake With Cardiovascular Disease Risk and Serum Lipid Levels
(Wiley, 2025-12-21) Hassanpour Ardekanizadeh, Naeemeh; Abbasi Mobarakeh, Khadijeh; Nami, Sheyda; Shojaei, Maryam; Fazel Nasimi, Seyed; Moradi, Saba; Tejareh, Faezeh; Shekari, Yeganeh; Bahmani, Parsa; Gholamalizadeh, Maryam; Ajami, Marjan; Kooshki, Akram; Doaei, Saeid
Background Despite early interest in the effects of dietary fats on cardiovascular diseases (CVDs), substantial controversy remains regarding the evidence linking different types of fatty acids to CVDs. This study aimed to examine the association between dietary fat intake, CVD risk, and serum lipid biomarkers.Methods This cross-sectional study included data from 4200 adult participants (1218 patients with CVDs and 2982 healthy participants) from the Persian Cohort Study. Data on heart disease (hypertension, myocardial infarction, and ischemic heart disease) were collected. Dietary intake was assessed using a validated food frequency questionnaire (FFQ), and the intake of different fatty acids was evaluated using Nutritionist-IV software. Serum lipid profiles were analysed using enzymatic and chromatographic methods.Results Higher monounsaturated fatty acids (MUFA) intake showed an inverse association with CVDs (OR = 0.931, 95% CI: 0.867-0.998, p = 0.045). Adjustments for age, gender, smoking, alcohol consumption, physical activity, BMI, and caloric intake did not alter this association. No significant associations were observed for other dietary fats.Conclusion The findings suggest an inverse association between MUFA intake and CVD risk. Further longitudinal studies are warranted to confirm these results.
Efficacy and Safety of Glofitamab Plus Polatuzumab Vedotin in Relapsed/Refractory Large B-Cell Lymphoma Including High-Grade B-Cell Lymphoma: Results From a Phase Ib/II Trial
(American Society of Clinical Oncology (ASCO), 2025-10-20) Hutchings, Martin; Sureda, Anna; Bosch, Francesc; Stauffer Larsen, Thomas; Corradini, Paolo; Avigdor, Abraham; José Terol, María; Rueda Dominguez, Antonio; Pinto, Antonio; Skarbnik, Alan; Cordoba, Raul; Meszaros Jørgensen, Judit; Luigi Zinzani, Pier; Leung, Wilfred; Bottos, Alessia; Li, Donghang; Relf, James; Tandon, Maneesh; Sellam, Gila; Gritti, Giuseppe
PURPOSEAn unmet need remains for more effective therapies for relapsed/refractory (R/R) large B-cell lymphoma (LBCL), especially high-grade B-cell lymphoma (HGBCL). We present the primary analysis of a phase Ib/II study (ClinicalTrials.gov identifier: NCT03533283) investigating efficacy and safety of glofitamab plus polatuzumab vedotin (Glofit-Pola) in patients with R/R LBCL, including HGBCL and those who received previous chimeric antigen receptor (CAR) T-cell therapy.METHODSPatients received 1,000 mg obinutuzumab on Cycle (C)1 Day (D)1 (once daily). Polatuzumab vedotin (1.8 mg/kg) was given on C1D2 and D1 of C2-6 (21-day cycles; once daily). Glofitamab was given as step-up doses in C1 (D8, 2.5 mg; D15, 10 mg) followed by 30 mg on D1 of C2-12 (21-day cycles; once daily). Polatuzumab vedotin was given for six fixed-duration cycles, and glofitamab for 12.RESULTSAs of September 2, 2024, 129 patients with LBCL (HGBCL; n = 44, 34.1%), received >= 1 dose of study treatment. The median age was 67 years (range, 23-84), and 63.6% were male. Patients had received a median of 2 (range, 1-7) previous lines of treatment (previous CAR T-cell therapy, n = 28, 21.7%). The independent review committee-assessed overall response rate was 78.3% (complete response rate, 59.7%). The median progression-free survival and overall survival (OS) were 12.3 and 33.8 months, respectively (median OS follow-up time, 32.7 months). The most common adverse event (AE) was cytokine release syndrome (43.4%; grade 1-2: 41.9%; one grade 5 event). Grade 3-4 AEs occurred in 58.9% of patients; 9.3% had grade 5 AEs, and 14.7% discontinued treatment because of AEs.CONCLUSIONGlofit-Pola demonstrated high efficacy and durable responses, with manageable safety, in heavily pretreated patients with R/R LBCL, including patients with HGBCL and previous CAR T-cell therapy failure.
Expanding the spectrum of NUS1-related progressive myoclonic epilepsy: a novel variant and exploratory use of metformin
(Frontiers Media SA, 2025-12-17) Sau, Cristina; López-rodríguez, Sergi; Falip, Mercè; Esteve-garcia, Anna; Sala-padró, Jacint; Aguilera, Cinthia; Navarro-romero, Alba; Lasa-aranzasti, Amaia; Rodríguez-bel, Laura; Hernández-pérez, Guillermo
Introduction Progressive myoclonic epilepsies (PME) are rare genetic disorders typically presenting with myoclonus, seizures, and cognitive decline. While several genes are associated with PME, the NUS1 gene has recently emerged as a potential cause. We report the case of a 41-year-old woman who presented with tics, myoclonus, and language difficulties followed by gait instability, tremor, absence seizures, and psychotic symptoms including persistent hallucinations and delusional misidentification.Methods Neurology and psychiatry specialists reviewed clinical data. Brain MRI, scalp video-EEG monitoring, and [18F]-FDG-PET/MRI were performed following standardized protocols. Whole exome sequencing (WES) guided by human phenotype ontology (HPO) terms was performed, and variants were interpreted according to American College of Medical Genetics and Genomics (ACMG) guidelines. Additionally, we conducted a review of previously reported cases of NUS1 pathogenic/likely pathogenic variants associated with PME to better characterize the clinical and paraclinical features and to explore potential management strategies.Results A novel heterozygous frameshift likely pathogenic variant in the NUS1 gene, c.248del, p. (His83Profs*22), was identified in the patient. This finding led to the introduction of a targeted therapeutic strategy, including the initiation of metformin and a thorough revision of the patient's existing psychiatric treatment. The patient showed an improvement in her psychiatric manifestations. However, neurological examination revealed either stable or slightly worsened signs, and she did not achieve seizure freedom.Discussion This is the first review of NUS1 from a PME perspective and the first report describing the exploratory use of metformin as a potential therapeutic intervention. In our case, metformin was introduced simultaneously with a change in antipsychotic treatment, so its specific clinical impact cannot be determined. Additional studies are needed to improve understanding of the benefits of using metformin and other therapeutic strategies in NUS1-related disorders. Further studies are essential to clarify the full phenotypic spectrum associated with NUS1 variants and to improve our understanding of how specific variant types and locations contribute to clinical presentation.
Endoresection in Choroidal Melanoma: Outcomes of Intentional Incomplete Tumor Removal
(MDPI, 2025-12-04) Anduaga Beramendi, Alexander; Caminal Caramés, Marta; Lorenzo Parra, Daniel; Cobos Martín, Estefanía; Mateos Olivares, Milagros; García Bru, Pere; Morwani, Rahul; Santamaría Álvarez, Juan Francisco; Garcia Garcia, Olga; Arias Barquet, Lluís; Caminal Mitjana, Josep Maria
To assess the outcomes of a modified surgical approach for the treatment of uveal melanoma involving endoresection with intentional residual tumor at the margins, combined with adjuvant ruthenium-106 brachytherapy. This technique aims to reduce surgical morbidity, while preserving visual function and maintaining effective local tumor control and survival. We conducted a retrospective observational study including 33 patients with choroidal melanoma treated between January 2017 and August 2024 at a single tertiary ocular oncology center in Spain. Patients underwent pars plana vitrectomy and endoresection leaving residual tumor followed by ruthenium-106 brachytherapy. Clinical, functional, and oncological outcomes were analyzed, including tumor recurrence, metastasis, visual acuity, complications, and cytogenetic findings. Kaplan-Meier analysis was used to estimate survival and recurrence rates. After a mean follow-up of 41.7 months, local tumor recurrence occurred in 2 patients (6.06%) and enucleation was performed in 1 patient (3.03%). Two patients (6.06%) developed metastases, with one disease-specific death, resulting in a 5-year survival rate of 97%. Visual acuity of 20/200 or better was preserved in 60.61% of patients. The most frequent complications were retinal detachment (36.36%) and macular edema (45.45%). Cytogenetic analysis showed a significant association between chromosome 1p loss and both recurrence and metastasis (p = 0.032). No cases of phthisis bulbi or severe hypotony were observed. This modified endoresection technique with intentional tumor residuals and adjuvant ruthenium-106 brachytherapy offers a safe and function-preserving option for selected patients with choroidal melanoma. It achieves good tumor control and visual outcomes, with a low rate of enucleation and metastasis. Further studies are required to validate its long-term efficacy.
TROPION-Lung15: a randomized phase III study of osimertinib combined with datopotamab deruxtecan (Dato-DXd) or Dato-DXd alone versus platinum-doublet chemotherapy in patients with EGFR -mutated advanced non-small cell lung cancer and whose disease has progressed on prior osimertinib
(SAGE Publications, 2025-12-01) Shao-weng Tan, Daniel; Nadal, Ernest; Cheema, Parneet; Wu, Yi-long; Ahn, Myung-ju; Tanizaki, Junko; Grainger, Ellie; Nizialek, Emily; Forcina, Alessandra; Van Der Gronde, Toon; A. Yu, Helena
Background: Osimertinib is the preferred treatment for patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) in several settings; however, disease progression is common, and treatment options after progression are limited. Datopotamab deruxtecan (Dato-DXd), an antibody-drug conjugate comprising a humanized anti-trophoblast cell-surface antigen 2 (TROP 2) monoclonal antibody conjugated to a potent topoisomerase I inhibitor via a plasma-stable linker, has demonstrated efficacy in advanced NSCLC, including previously treated EGFR-mutated advanced NSCLC. Combining osimertinib and Dato-DXd may overcome heterogeneous osimertinib resistance mechanisms and limit tumor progression.Objectives: TROPION-Lung15 is an ongoing, phase III, open-label, sponsor-blind, multicenter, randomized trial evaluating Dato-DXd +/- osimertinib versus chemotherapy in patients with EGFR-mutated advanced NSCLC and disease progression on prior osimertinib.Methods and design: Approximately 630 patients with histologically/cytologically confirmed non-squamous NSCLC, documented epidermal growth factor receptor tyrosine kinase inhibitor-sensitive mutations, and radiologic progression on prior osimertinib monotherapy will be enrolled. Patients will be randomized 1:1:1 to Dato-DXd (6 mg/kg intravenously every 3 weeks), osimertinib (80 mg orally once daily) plus Dato-DXd, or platinum-doublet chemotherapy, stratified by the history/presence of brain metastases (yes vs no), prior osimertinib therapy (adjuvant vs post-chemoradiotherapy/first-line vs second-line), and race. Treatment will continue until radiological progression (per Response Evaluation Criteria in Solid Tumors version 1.1), unacceptable toxicity, or another discontinuation criterion is met. The dual primary endpoints are progression-free survival (PFS) by blinded independent central review (BICR) for osimertinib + Dato-DXd and PFS by BICR for Dato-DXd alone versus chemotherapy. Secondary endpoints include overall survival, central nervous system PFS by BICR, and safety/tolerability.Ethics: The study is approved by independent ethics committees/institutional review boards at each center. Patients will provide written informed consent.Discussion: TROPION-Lung15 will assess Dato-DXd +/- osimertinib in patients with EGFR-mutated advanced NSCLC and disease progression on prior osimertinib. Data from this study could lead to a new treatment option in this setting.Trial registration: ClinicalTrials.gov identifier: NCT06417814 (date of registration: May 13, 2024).

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