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Differences in glucose metabolic activity in liver metastasis separates two groups of metastatic uveal melanoma patients with different prognosis
(John Wiley & Sons, 2023-07-01) Del Carpio Huerta, Luis Paul; Algarra, Maria Asuncion; Sabaté Llobera, Aida; Rodriguez-Vida, Alejo; Rossi-Seoane, Susana; Ruiz Osuna, Sandra; Leiva Pedraza, David; Ramos Rubio, Emilio; Lladó Garriga, Laura; Lorenzo Parra, Daniel; Gutiérrez Miguélez, Cristina; Cortes Romera, Montserrat; Caminal Mitjana, Jose Maria; Piulats Rodríguez, Josep María
Background: Uveal melanoma metastasizes to the liver. We aimed to explore the metabolic activity of liver metastases (LM) as a biomarker for survival.Methods: We analyzed newly diagnosed patients with metastatic UM (MUM) with LM detected by liver-directed imaging and had undergone a PET/CT at diagnosis.Findings: 51 patients were identified between 2004 and 2019. Median age was 62 years, 41% male and 22% ECOG =1. LDH, ALP, and GGT were elevated in 49%, 37%, and 57% of patients. Median LM SUVmax was 8.5 (3-42.2). Same size lesions presented a wide range of metabolic activity. Median OS was 17.3 m (95% CI:10.6-23.9). Patients with SUVmax = 8.5 had an OS of 9.4 m (95% CI:6.4-12.3), whereas patients with SUVmax <8.5 had an OS of 38.4 m (95% CI:21.4-55.5; p < 0.0001, HR = 2.9). We observed similar results when studying M1a disease separately. Multivariate analysis showed SUVmax as an independent prognostic factor for the whole population and those with M1a disease.Interpretation:Increased metabolic activity of LM seems to be an independent predictor of survival. MUM is a heterogeneous disease and metabolic activity probably reflects a different intrinsic behavior.
Consistent Metabolomic and Genetic Evidence Supports Acisoga as a Key Contributor to Colorectal Neoplasia Progression
(AMER ASSOC CANCER RESEARCH, 2026-08-03) Rius Sansalvador, Blanca; Chatziioannou, Anastasia Chrysovalantou; Keski-Rahkonen, Pekka; Robinot, Nivonirina Ranoroarivony; Moratalla Navarro, Ferran; Moragas Garcia, Nuria; Guino Domenech, Elisabet; Jenab, Mazda; Moron Duran, Francisco David; Atencia Rojas, Carmen Rosa; Ibañez Sanz, Gemma; Rodríguez Alonso, Lorena; Mata, Alfredo; García Rodríguez, Ana; Noh, Hwayoung; Fryer, Ella; Zamora Ros, Raul; Mokoroa, Olatz; Delfrade, Iosu; Caini, Saverio; Huerta, Jose Maria; Truong, Therese; Severi, Gianluca; Asgari, Yazdan; Tumino, Rosario; Panico, Salvatore; Tjonneland, Anne; Rostgaard-Hansen, Agnetha Linn; Sanchez, Maria-Jose; Pala, Valeria; Ricceri, Fulvio; Gunter, Marc J.; Moreno Aguado, Victor Raul; Obon Santacana, Mireia
Background: Colorectal cancer is a leading cause of cancer incidence and mortality worldwide. Early detection and accurate risk stratification of precursor lesions remain critical challenges. Integrating metabolomics with genetic analysis may improve the understanding of colorectal cancer development and identify disease determinants.Methods: Untargeted serum metabolomics was performed in 513 individuals: 185 controls; 74 with low-, 98 with intermediate-, and 100 with high-risk lesions; and 56 colorectal cancer cases. Overall, 1,562 metabolic features were analyzed using linear trend models with multiple testing correction. Significant metabolites were further investigated through metabolite-level genome-wide association studies (GWAS). Findings were externally validated in 1,121 colon cancer-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and in colorectal cancer GWAS meta-analysis.Results: The polyamine N-(3-acetamidopropyl)pyrrolidine)-2-one (Acisoga) showed statistically significant increasing trends across colorectal cancer progression (P = 2.8 & times; 10-5). The association was independently validated in EPIC [odds ratio (OR) = 1.23; 95% confidence interval, 1.01-1.50). Metabolite-level GWAS identified genome-wide significant loci, including OPCML, EWSAT1, CTBP2, and CMKLR1. Genetically predicted Acisoga levels were positively associated with colorectal cancer risk (P = 0.003), with consistent results in sensitivity analyses using previously reported Acisoga-associated variants.Conclusions: We show a reproducible association between Acisoga and colorectal cancer progression and risk, supported by metabolomic, genetic, and external data. This integrative approach advances the understanding of metabolic processes involved in colorectal cancer and supports further evaluation of Acisoga in risk research.Impact: This work supports Acisoga as a potential circulating biomarker for colorectal cancer risk, with implications for early detection and prevention in screening populations.
Predictors of Developing Positive Attitudes and Increasing Perceptions of Training in Tobacco Control Among Catalan Nursing Students: A Follow-Up Study
(Lippincott, Williams & Wilkins. Wolters Kluwer Health, 2025-09-19) Laroussy El Tayea, Kenza; Fernández Muñoz, Esteve; Castellano, Yolanda; Fu Balboa, Marcela; Feliu, Ariadna; Tigova, Olena; Puig Llobet, Montserrat; Galimany Masclans, Jordi; Moreno Arroyo, M. Carmen; Martínez Martínez, Cristina
Background: The knowledge and attitudes toward tobacco control among nurses are important factors in ensuring appropriate management of the tobacco dependence. Therefore, we aimed to evaluate the predictors of developing positive attitudes toward tobacco control and increasing perceptions of tobacco-related training received during the nursing degree, among a cohort of Catalan nursing students.Methods: Observational prospective study of 1,097 Catalan nursing students. Participants completed a paper-and-pencil questionnaire at baseline (2015–2016) and an online survey at follow-up (2018–2019). We examined predictors of developing positive attitudes and increasing perceptions of training using Poisson regression models to compute the adjusted prevalence ratios (aPRs).Results: Students in their last years of studies at baseline were less likely than those in the first years to develop a positive attitude towards the exemplary role of nursing students in tobacco control at follow-up (aPR = 0.74). Former smokers were more likely than current smokers to develop positive attitudes towards the exemplary role of health care professionals (aPR = 1.55) and, together with never smokers, to come to recognize the importance of nursing students setting a good example (aPR = 2.23 and aPR = 2.32, respectively). Last year’s students were also less likely than those in the first years to increase their perceptions of tobacco-related training received (all aPR < 0.71). Never smokers were less likely than current smokers to increase their perception of training in pharmacological treatments other than nicotine replacement therapy (aPR = 0.81) and to consider themselves capable of helping smokers quit (aPR = 0.78).Conclusions: The year of school and smoking status were strong predictors of developing positive attitudes and increasing perceptions of training in tobacco control.
Satisfaction of patients with amyotrophic lateral sclerosis with an oral appliance for managing oral self-biting injuries and alterations in their masticatory system: A case series study
(Elsevier, 2019-04-01) Riera-Punet, Nina; Martínez Gomis, Jordi; Zamora Olave, Carla; Willaert Jiménez-Pajarero, Eva; Peraire Ardèvol, Maria
Statement of problem: About 10% of patients with amyotrophic lateral sclerosis (ALS) are candidates for oral treatment specifically because of traumatic injuries in the lips, cheeks, or tongue due to self-biting. However, patients with ALS have a prevalence of temporomandibular disorder (TMD) similar to that in the general population. Purpose: The purpose of this case-series study was to determine the degree of satisfaction of patients with ALS with an oral appliance for managing oral self-biting lesions or symptoms related to TMDs. This study also assessed the degree of improvement of the chief complaint and the compliance with and adverse effects of this treatment. Material and methods: Eleven patients with ALS who sought oral treatment because of oral self-biting or TMD-related symptoms were included. A custom complete-coverage acrylic resin device was fabricated and fitted to each participant. A follow-up visit was planned for 3 months after the placement of the oral appliance, at which point the patients would rate the degree of improvement or worsening of the chief complaint and their degree of satisfaction with the treatment. A 1-sample t test was used to assess whether the degree of improvement of the chief complaint was significant. Results: Participants reported a mean of 61% (95% confidence interval [CI] 38% to 84%) improvement of the chief complaint and a mean of 84% (95% CI 72% to 97%) satisfaction with the treatment. The mean rate of compliance was 62% (95% CI 40% to 84%) of the recommended time, and only a few adverse effects were reported. Conclusions: Participants with ALS were highly satisfied with the use of an oral appliance to manage oral self-biting or TMD-related symptoms. Adherence to this treatment was high, and no major adverse effects were observed.
Cost-effectiveness of short implants (6–8.5 mm) compared to regular length implants (> 10 mm) with bone regeneration in posterior atrophic mandible: a 8-year microsimulation model
(BioMed Central, 2026-07-10) Sáenz-Ravello, Gustavo; Baeza, Mauricio; Fan, Shengchi; Rosa Gay, María Cristina de la; Valmaseda Castellón, Eduardo; Mattheos, Nikos
Background: To evaluate the cost-effectiveness of short implants (6–8.5 mm) placed without guided bone regeneration (GBR) vs. regular length implants (> 10 mm) placed with vertical GBR for the rehabilitation of the posterior atrophic mandible (Seibert type II defects). Methods: A discrete-time state-transition microsimulation model was developed to compare two strategies over an 8-year horizon from a private-payer perspective. Clinical inputs were extracted from a recent meta-analysis of randomized trials, while unit costs were obtained from publicly available Chilean fee schedules and converted to 2025 USD using purchasing power parity. Outcomes included implant survival, biological and prosthetic complications, summarized as implant-years (IY) and complication-free IY (CFIY) as a stricter secondary measure. Incremental cost-effectiveness ratios (ICERs) were calculated. Uncertainty was addressed through one-way deterministic sensitivity analysis (OWSA), and probabilistic sensitivity analysis (PSA, 2,000 iterations). Results: Over an 8-year horizon, short implants were associated with lower mean costs (USD 3,662 vs. 6,030) and modestly greater effectiveness (6.77 vs. 6.49 IY; 6.71 vs. 6.27 CFIY) compared with regular-length implants with GBR, yielding incremental savings of USD 2,367 and incremental gains of 0.28 IY and 0.44 CFIY. OWSA identified initial implant costs as the most influential parameters. PSA across 2,000 iterations corroborated these findings, with the great majority of simulations falling in the south-east quadrant of the cost-effectiveness plane. Conclusions: Within the Chilean private-payer setting and over an 8-year horizon, single-tooth short implants (6–8.5 mm) placed without GBR were cost-saving and at least non-inferior in effectiveness compared with regular-length implants with vertical GBR for the posterior atrophic mandible. This cost advantage remained consistent across deterministic, probabilistic, and scenario analyses, although transferability to other settings requires re-estimation using local cost structures.
Associations between dietary intake of flavonoids and adiposity: cross-sectional findings from the Fenland Study, the United Kingdom
(SPRINGERNATURE, 2026-05-01) Gil Lespinard, Mercedes; Forouhi, Nita G.; Imamura, Fumiaki; Zamora Ros, Raul
BackgroundProspective and experimental evidence supports beneficial effects of flavonoids on weight management and metabolic health, but their impact on specific adiposity parameters remains unclear. We aimed to investigate associations of total and subclasses of dietary flavonoids with adiposity markers, several of which have been linked to metabolic risk.MethodsWe evaluated cross-sectional data from 11,568 adults recruited to the Fenland Study between 2005 and 2015 in Cambridgeshire, the United Kingdom. Habitual diets were evaluated using food frequency questionnaires. Flavonoid intakes were calculated mainly using the United States Department of Agriculture food composition databases. We examined associations using robust regression adjusted for relevant confounders and corrected for false discovery rate (FDR) for multiple flavonoids and adiposity parameters: body fat (BF) (dual-energy X-ray absorptiometry), visceral fat (VAT), subcutaneous fat (SCAT), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), VAT:SCAT ratio, and a body shape index (ABSI).ResultsMedian flavonoid intake was 428 mg/d (interquartile range 258.5-568.6). Doubling in total flavonoid intake was inversely associated with BF [betalog2 -0.54% (95% CI -0.70; -0.40)]; VAT [-0.13 cm (-0.17; -0.08)]; SCAT [-0.05 cm (-0.08; -0.02)]; BMI [-0.33 kg/m2 (-0.44; -0.22)]; WC [-0.84 cm (-1.13; -0.55)]; and WHR [-0.004 (-0.006; -0.002)]. Most of flavonoid subclasses showed similar results, except isoflavones that were positively associated with BF, VAT and WC. Intakes of proanthocyanidins and anthocyanidins showed the strongest negative associations independently of BMI. Subgroup analyses resulted in stronger negative associations in women, older adults, and non-smokers.ConclusionFlavonoids may influence adiposity, a potential pathway for the relationship between flavonoid-rich foods and metabolic risk. Proanthocyanidins and anthocyanidins may affect site-specific fat distribution, particularly visceral adiposity. Further investigation in prospective, interventional, and mechanistic studies is warranted to understand the link between flavonoids and adiposity.
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.
Toward standardized iPSC testing: Insights from a multi-year international Quality Assessment Round
(Elsevier, 2026-04-14) Hägg, Alice; Wood, Rachel; Mochizuki, Ayako L.; Abberton, Keren; Abranches, Elsa; Álvarez Palomo, Ana Belén; Baptista, Ricardo; Quintanilha Barbosa, Raiana Andrade; Barry, Jacqueline; Carvalho, Adriana Bastos; Bennaceur Griscelli, Annelise; Campos de Carvalho, Antonio Carlos; Chaker, Diana; Chang, Hong; Choi, Hye Young; Codinach, Margarita; Aran Corbella, Begoña; Cowan, Scott; Dickerson, Sarah Jane; Elwood, Ngaire; Fan, Xueling; Feyeux, Maxime; Forrester, Maddy; Gaffney, Andrew; Guilbert, Solenn M.; Ha, Hye-Yeong; Hirst, Adam J.; Hunter, Arwen L.; Jamieson, Leanne G.; Judson, Robert N.; Kanemura, Yonehiro; Kasai-Brunswick, Tais Hanae; Kim, Jun H.; Kim, Howard; Kintali, Manisha; Krishnan, Siddharth; Kuebler, Bernd; Lau, Chui Yu; Li, Wilson; Mack, Amanda; MacLeod, Michael R.; Madrid, Marinna; Mamiya, Hiroaki; Manache-Alberici, Lucie; Mărginean, Dragoş; Mentre, Olivier; Morgan, Stefanie L.; Mountford, Joanne; Munir, Humayun; Ng, Siemon H.S.; Ogawa, Haruna; Oh, Steve; Ohara, Hidetaka; Oono, Keiko; Park, Niall; Pereira, Lygia V.; Pereira da Silva Bezerra, Izabella; Podovei, Alexandru Robert; Querol, Sergio; Raje, Jainy; Raya Chamorro, Ángel; Sakamoto, Satoko; Sarafian, Raquel; Schmit, Kathleen; Selvitella, Silvia; Singh, Gurbind; Smart, Matthew J.K.; Song, Jiwhan; Stacey, Glyn N.; Sullivan, Stephen; Sumida, Miho; Terrenoire, Cecile; Tian, Pei; Uhlin, Elin; Vaquero, José M.A.; Veiga, Anna; Vicky Wang, Jar Wei; Warre-Cornish, Katherine; Wood, Jamie; Yamamoto, Atsuyo; Zhang, Gaojun; Hikichi, Takafusa; Turner, Marc; Falk, Anna
Despite rapid clinical translation, induced pluripotent stem cell (iPSC)-derived therapies face limited global adoption. Harmonized quality control (QC) remains absent, with even fundamental parameters evaluated inconsistently across laboratories. To address this, we conducted two international Quality Assessment Rounds (QARs): QAR 2019 (18 sites, 11 countries) and QAR 2023 (23 sites, 12 countries), evaluating flow cytometry-based assessment of the undifferentiated state and qPCR-based genomic integrity testing. QAR 2019 showed high consistency in genomic integrity testing, while uncovering substantial variability in flow cytometry, prompting QAR 2023 to introduce standardized workflows. These improvements enabled systematic, cross-site evaluation of marker performance across cell states, identifying OCT3/4, TRA-1-60, and SSEA5 as consistently robust pluripotency-associated markers. This global benchmarking effort provides the first empirical multi-site evidence for reproducible iPSC QC and marker-level reliability. Together, these findings establish a foundation for harmonized QC supporting interoperable iPSC banks, regulatory alignment, and scalable manufacturing of globally accessible regenerative therapies.
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.
Characterizing Aeromonas spp. as a Potential Sentinel Organism for Antimicrobial Resistance Dissemination in Wastewater and Drinking Water Treatment Systems: A Case Study in the Barcelona Metropolitan Area, Spain
(MDPI, 2026-03-01) Mondéjar, Laura; Gabasa, Yaiza; Castellsagués, Laura; Vilaró, Carles; Galofre, Belén; González-Díaz, Aida; Martí Martí, Sara; Sanz, Sergi; Soto González, Sara M.; Ballén, Victoria; Pinar-Méndez, Anna
Background: Wastewater treatment plants (WWTPs) are hotspots of antimicrobial resistance (AMR) due to inputs from diverse anthropogenic sources. Aeromonas spp., ubiquitous in aquatic environments, often carry clinically relevant antibiotic resistance genes (ARGs) and can persist beyond fecal contamination indicators, making them promising sentinel organisms for AMR dissemination. The aim of this study was to assess the suitability of Aeromonas spp. in this role by characterizing resistance profiles, associated virulence factor genes (VFGs), genetic mobility, and persistence across wastewater and drinking water treatment processes in the Barcelona metropolitan area, Spain. Methods: Isolates were phenotypically characterized and screened for ARGs, VFGs, integrons, and heavy metal tolerance genes, followed by whole-genome sequencing (WGS). Biofilm formation was assessed in vitro. Conjugation assays with Escherichia coli evaluated horizontal gene transfer (HGT) potential. Results: A total of 428 antibiotic-resistant Aeromonas spp., the most abundant antibiotic-resistant bacteria isolated during the 2023 sampling campaigns from two WWTPs and one drinking water treatment plant (DWTP), were characterized. Trimethoprim/sulfamethoxazole (SXT) non-susceptibility was most frequent (72%), followed by cefoxitin resistance (65.4%). The sul1 (57.5%) and blaMOX (78.6%) genes predominated among SXT- and β-lactam-resistant isolates. The merA gene was detected in 23.6%; 97.9% harbored at least one VFG (aerA, act, fla, alt, or hlyA), and 70.3% carried intI1. Half formed biofilm. Conjugation confirmed bi-directional HGT, and WGS revealed persistent ST3458 clones across treatment stages. Conclusions: WWTPs and DWTPs act as reservoirs of antibiotic-resistant Aeromonas spp., demonstrating persistence and HGT potential. Findings support their use as sentinel organisms for AMR surveillance in aquatic environments and for assessing treatment efficacy, highlighting variability across treatment types and locations, and reinforcing their relevance for urban water reclamation monitoring. Keywords: Aeromonas spp.; antimicrobial resistance; antibiotic resistance genes; wastewater treatment plants; drinking water treatment; horizontal gene transfer; biofilms; environmental surveillance
Rapid identification of a Serratia marcescens outbreak in a neonatal intensive care unit by third-generation long-read nanopore sequencing
(BioMed Central, 2025-06-04) Henares, Desiree; Cubero, Meritxell; Martínez de Albéniz, Irene; Arranz Betegón, Ángela; Rocafort, Mercedes; Brotons, Pedro; Perez-Argüello Amaresh; Troyano Maria José; Gené, Amadeu; Lluansí, Aleix; Iriondo Sanz, Martín; Jordán García, Iolanda; Fortuny, Clàudia; Urrea, Mireia; Muñoz Almagro, Carmen
Background Serratia marcescens is a frequent cause of outbreaks in high-risk hospital settings such as neonatal intensive care units (NICU). This study investigated a potential S. marcescens outbreak in the NICU of a reference children’s hospital using Whole Genome Sequencing (WGS). Additionally, it assessed the performance of third-generation sequencing for the rapid and accurate identification and characterization of the outbreak’s clonal strain. Methods A prospective study was conducted from September 8th to November 12th 2021, following a sharp increase in invasive S. marcescens infections in the NICU of University Children’s Hospital Sant Joan de Déu (Barcelona, Spain). This study included all patients admitted to NICU and other hospital wards from whom S. marcescens was isolated in any sample type. Nanopore sequencing was performed on S. marcescens isolates. Genomic characterization included phylogenetic analyses and detection of antimicrobial resistance genes. Results Twenty-nine patients (16 NICU and 13 non-NICU patients) infected/colonized by S. marcescens were detected during the study period, accounting for a total of 61 isolates. The genomic characterization was performed on 24 isolates from 14 NICU-patients and 10 isolates from eight non-NICU patients. Phylogenetic analyses evidenced three clusters of closely related strains; cluster I (n = 22), II (n = 2) and III (n = 5). The remaining isolates (n = 5) did not cluster. Cluster I contained most isolates from NICU patients (20/24), and most isolates from NICU-patients with confirmed invasive disease (7/8). Cluster II contained two isolates from two NICU-patients, one presenting with invasive disease. The resistance gene blaSRT was found in 97% of S. marcescens isolates (33/34). All isolates exhibited the amikacin-tobramycin aac(6’) resistance gene and three multi-drug efflux pumps genes; sdeY, sdeB and smfY. The tetracycline tet(41) resistance gene was found in non-clustered isolates (4/34). The first results were available less than one month after the outbreak’s alarm, and complete genomic study after two months. Conclusion Two clonal strains were co-circulating in the NICU setting, with one being the major strain responsible for the outbreak. Rapid molecular characterization with nanopore sequencing confirmed the outbreak. It revealed the phylogenetic relationships among isolates and their antimicrobial potential. This approach enabled effective contextualization of the outbreak and allowed for monitoring its progression.
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.
Impaired expression of ecto-nucleotidases in human endometrial pathologies
(Sercrisma International, 2019-09-09) Martín Satué, Mireia; Matias-Guiu, Xavier, 1958-; Rodríguez-Martínez, Aitor; Trapero Candela, Carla; Vidal, August; Gómez de Aranda, Immaculada; Fernandez-Montolí, M.A.; Piulats, Josep M.; Coroleu, Buenaventura; Barri, Pere; Tresserra, Francesc; Ponce Sebastià, Jordi
The levels of extracellular ATP and its derivatives such as adenosine are impaired in the tissue microenvironment during tissue stress conditions such as hypoxia, infection, metabolic stress, tumor transformation and inflammation. Ecto-nucleotidases are the main regulators of extracellular ATP and adenosine levels. The aim of the present work is to upgrade our understanding of the role and location of ecto-nucleotidases in the context of two endometrial pathologies: cancer and endometriosis, as well as to investigate new diagnostic and treatment modalities based on the inhibition of ecto-nucleotidases' activities. We have analyzed by means of immunolabeling and in situ enzyme histochemistry human endometrial samples from: 1) endometrial tumors, and, 2) eutopic endometria as well as ectòpic endometriotic lesions from women with endometriosis. We have also studied endometrial cell cultures to evaluate the consequences of the overexpression of ecto-nucleotidases in their proliferative and invasive phenotypes. Ecto-nucleotidases showed impaired expression in pathological conditions when compared with non-pathological endometria. This altered pattern includes changes in expression levels and changes in protein localization, mainly a switch between epithelium and stroma. Overexpression of ecto-nucleotidases in endometrial cell cultures lead to changes in the proliferation and invasion rates. Impaired ecto-nucleotidases activities in endometrium might contribute to the pathogenesis and maintenance of endometrial pathologies with an inflammatory component such as cancer and endometriosis.
New method to simultaneously characterize the expression and in situ activity of ecto-nucleotidase in human tissues
(Sercrisma International, 2017) Villamonte-Román, María; Torrejón-Escribano, Benjamín; Vidal-Bel, August; Ponce Sebastià, Jordi; Matias-Guiu, Xavier, 1958-; Martín Satué, Mireia
Introduction: Extracellular nucleotides, such as ATP, and nucleosides, such as adenosine, act as autocrine and paracrine molecules that have multiple roles in virtually all organs and tissues, including female reproductive organs. Extracellular ATP and adenosine levels are regulated by the action of ecto-nucleotidases that hydrolyse ATP to adenosine. The aim of the present study was to set up a new method to simultaneously localize the cellular distribution and in situ activity of ecto-nucleotidases in tissue sections. We used this method to characterize the expression of ecto-nucleotidases in human oviducts. Material and Methods: Cryosections of non-pathological human oviducts were obtained from salpingectomy at the Service of Gynecology of Bellvitge Hospital. Samples were incubated with the following primary antibodies against human enzymes: anti-nucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39), anti-NTPDase2, and anti-placental alkaline phosphatase (PLAP). In situ activity reactions were performed on the same slides using the Wachstein/Meisel lead phosphate method with ATP or ADP as substrate. For alkaline phosphatase activity, the BCIP/NBT revealing reagent was used. The sections were then incubated with the appropriate Alexa Fluor-conjugated secondary antibodies and mounted with Prolong Gold antifade with DAPI medium. Results: NTPDase1 was expressed in the smooth muscle and endothelial cells, coinciding with localization of ADPase activity. NTPDase2 was largely expressed and active (ATPase activity) in ciliated cells and in connective tissue. PLAP was immunodetected and active in luminal epithelium. Conclusions: We found that this new method is specific, sensitive, and useful with diferent tissues. Our results show that ecto-nucleotidases are abundantly present in human oviducts where these enzymes work in concert to metabolize extracellular ATP to adenosine. This study contributes to knowledge of purinergic signaling by ecto-nucleotidases in the female reproductive system.
Ecto-nucleotidase expression and activity in endometrioid-type endometrial carcinoma cell lines
(Sercrisma International, 2017-09-08) Rodríguez-Martínez, Aitor; Matias-Guiu, Xavier, 1958-; Martín Satué, Mireia
Introduction: ATP and adenosine are known for their role in promoting an immunosuppressive environment at the tumor site. It is known that some ecto-nucleotidases, proteins that handle the hydrolysis of tri-, di- and monophosphate nucleotides, are overexpressed in endometrial tumor tissues although the mechanisms underlying these processes remain controversial. In the present study we characterized, with cytochemistry and i mmunofluorescence, the ecto-nucleotidase profiles in endometrioid-type endometrial carcinoma cell lines. Furthermore, we have developed a new approach capable of simultaneously detecting both alkaline phosphatase expression and activity. Materials and methods: Cell lines: 3 endometrioid endometrial carcinoma cell lines (Ishikawa, HEC-1B and ECC-1) were used for cytochemistry and immunofluorescence experiments. In situ ecto-nucleotidase enzyme activities: ATPase, ADPase, and AMPase activity experiments were performed in all cell lines, based on the Wachstein/Meisel technique. Immunofluorescence experiments: cell immunolabeling was performed using primary antibodies against different members of the ecto-nucleotidases: anti-ectonucleoside triphosphate diphosphohydrolase 2 (E-NTPDase2), anti-E-NTPDase3, anti-CD73, and anti-placental-like alkaline phosphatase (PLAP). Alkaline phosphatase immunoactivity assay: for the detection of both activity and al kaline phosphatase expression we developed a combinatorial assay in which enzyme activity can be co-visualized with protein expression. Immunofluorescence followed by an activity assay was performed on AP-expressing cells. Results: Cytochemistry enzyme assays showed moderate ATPase activity in both Ishikawa and ECC-1 cell lines. Moderate ADPase activity was found in ECC-1 cells and high AMPase activity was detected in HEC-1B cells. In immunolabeling experiments we found NTPDase2 protein expression in all three cell lines, with NTPDase3 expression restricted to ECC-1 cells. CD73 was detected in all three cell lines. Moderate alkaline phosphatase activity and protein expression were found in Ishikawa and ECC-1 cells. A wide differential range of activities and ecto-nucleotidase expression among the studied cell lines was observed. NTPDase2 and NTPDase3 expression correlated with ATPase activity. CD73 protein expression coincided with the high AMPase activity shown with HEC-1B. Conclusions: Ishikawa, HEC-1B, and ECC-1 cell lines represent a useful cell model for the study of ecto-nucleotidases in the context of endometrioid-type endometrial carcinoma.
Editorial: Purinergic pharmacology, Volume II
(Frontiers Media, 2023-05-16) Ciruela Alférez, Francisco; Jacobson, Kenneth A.
Extracellular purine nucleotides and nucleosides serve as crucial signalling molecules, acting as neurotransmitters and neuromodulators. Tightly regulated extracellular levels of adenosine 5′-triphosphate (ATP) and adenosine, which are controlled by various enzymes and transporters, activate a variety of purinergic receptors. These receptors, which appear early in evolution, are among the most abundant receptors in living organisms and regulate numerous physiological processes, making them attractive therapeutic targets for a wide range of diseases. While P1 (adenosine) receptors are selective for adenosine, the breakdown product of ATP, P2 receptors respond to purine and pyrimidine nucleotides. Importantly, purinergic receptors, including both G protein-coupled receptors (ARs and P2YRs) and ligand-gated ion channel receptors (P2XRs), are involved in a multitude of neuronal and non-neuronal mechanisms, such as pain, immune responses, exocrine and endocrine secretion, platelet aggregation, endothelium-mediated vasodilatation, and inflammation. However, since purinergic receptors are widely distributed throughout the body, it is challenging to develop drugs that selectively target specific receptor subtypes without causing unwanted side effects. Additionally, extracellular levels of purines and pyrimidines can also vary greatly, leading to the simultaneous activation of different purinergic receptors in response to oscillating concentrations of endogenous purines. Consequently, through these different subtypes of P1 and P2 receptors, cells integrate extracellular purine responses, harmonising short- and long-term purinergic signalling. Therefore, the selectivity of drugs is a crucial goal in the field of purinergic pharmacology. For decades, medicinal chemists have been developing potent and selective synthetic agonists and antagonists for purinergic receptors, as well as allosteric modulators that allow for event-responsive and temporally specific manipulation of the endogenous purinergic system. Additionally, modulation of the metabolism and uptake of extracellular purine nucleotides and nucleosides can also regulate purinergic processes. Overall, the field of purinergic pharmacology is rapidly expanding and presents exciting opportunities for pharmacotherapeutic development.
Effect of different wavelengths and powers of laser on surface topography and biofilm removal from titanium implants: an in vitro study
(BioMed Central, 2025-12-04) Sedrak, Paul Ashraf; Abdelhakim, Ahmed Adel; Arnabat Domínguez, Josep; Rady, Nermeen Abd Elsalam
Background: This in vitro study aimed to evaluate the effect of using different wavelengths and powers of laser on the surface topography of titanium implants, and to investigate their efficacy in removal of the biofilm complex from the implant surface. Methods: Ten titanium implants, consisting of five new and five failed implants, were randomized and divided into five separate test groups; (Group 1) Erbium Chromium: Yttrium Scandium Gallium Garnet (Er, Cr: YSGG) 2780 nm, (Group 2) Erbium-doped: Yttrium Aluminum Garnet (Er: YAG) 2940 nm, (Group 3) Neodymium-doped: Yttrium Aluminum Garnet (Nd: YAG) 1064 nm, (Group 4) Diode 940 nm, and (Group 5) Diode 445 nm. Each test group consisted of two implants; one new and one failed implant. A total of 160 implant sites were irradiated. Each area was scanned using Scanning Electron Microscope (SEM) prior to and following laser irradiations. A descriptive analysis was conducted by summarizing the data in terms of frequencies and percentages. Pearson Chi Square test and Fisher’s Exact test were used for comparison between different laser type and laser power intensities. The significance level was set at P < .05. Results: Within the parameters under investigation, both Er, Cr: YSGG and Er: YAG lasers displayed no to minimal alterations in surface topography across the different power intensities. Nd: YAG and Diode lasers showed more evident alterations at high power intensities; with Nd: YAG resulting the most prominent damage to the implant surface. Regarding efficacy in removal of biofilm, Er, Cr: YSGG and Er: YAG lasers consistently exhibited positive results across all different power intensities under investigation. In comparison, Nd: YAG and Diode lasers showed inferior efficacy in biofilm removal at low power intensities with significant power-dependent improvements. Conclusions: Er, Cr: YSGG and Er: YAG lasers present superior implant decontamination potential without causing notable implant surface alterations. Diode (940 nm) laser can be used at low power intensities without causing detrimental effects. Nd: YAG and Diode (445 nm) lasers are able to disrupt the biofilm complex but can induce more evident implant surface damage.

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