https://hdl.handle.net/2072/378092 Mon, 06 Apr 2026 14:46:19 GMT 2026-04-06T14:46:19Z https://hdl.handle.net/11351/14422 Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed Martínez-Castelao, Alberto; Gorriz, Jose Luis; FERNANDEZ-FERNANDEZ, BEATRIZ; Soler, María José; Navarro-González, Juan F. Chronic kidney disease; Diabetes mellitus; Diabetic kidney disease; Malaltia renal crònica; Diabetis mellitus; Malaltia renal diabètica; Enfermedad renal crónica; Diabetes mellitus; Enfermedad renal diabética; Diabetes mellitus (DM) continues to be a global world health problem. Despite medical advances, both DM and chronic kidney disease (CKD) remain global health issues with high mortality and limited options to prevent end-stage renal failure. Current therapies encompass five classes of drugs: (1) angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin II receptor blockers (AIIRB); (2) sodium-glucose-transporter 2 (SGLT2) inhibitors; (3) glucagon-like peptide-1 receptor agonists (GLP-1 RA); and (4) an antagonist of type 1 endothelin receptor (ET1R) with proven efficacy to reduce albuminuria and proteinuria. (5) The mineralocorticoid receptor antagonist (MRA) finerenone has been tested in RCTs as a kidney protective agent. In our review, we summarize many of the principal trials that have generated evidence in this regard. Many novel agents—many of them proven not only for DM management but also for the treatment of obesity with or without DM or heart failure (HF)—are now in development and may be added to the five classical pillars: other non-steroidal MRA (balcinrenone); aldosterone synthase inhibitors (baxdrostat and vicadrostat); other GLP-1 RA (tirzepatide, survodutide, retatrutide, and cagrilintide); ET1 R antagonists, (zibotentan); and soluble guanylate cyclase activators (avenciguat). These new agents aim to slow disease progression further and reduce cardiovascular risk. Future strategies rely on integrated, patient-centered approaches and personalized therapy to curb renal disease and its related complications. Wed, 01 Apr 2026 12:48:25 GMT https://hdl.handle.net/11351/14422 2026-04-01T12:48:25Z https://hdl.handle.net/11351/14423 Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis Langtry, Alberto; Rabadan, Raul; Alonso, Lola; Filip, Ioan; Sabroso-Lasa, Sergio; Moreno-Oya, Ane; Molero, Xavier; Balsells Valls, Joaquim Prognosis; Pancreatic cancer; Pronòstic; Càncer de pàncrees; Pronóstico; Cáncer de páncreas; Pancreatic ductal adenocarcinoma (PDAC) genetic susceptibility is partially identified. The complement system (CS) influences carcinogenesis and participates in immunological defense and homeostasis; however, its role in PDAC genetic susceptibility and prognosis is underexplored. The association of SNPs within 111 CS-related genes with PDAC risk is assessed in the PanGenEU study and validated in the UKBiobank. We investigate the association between the CS-related gene variation and PDAC risk, followed by an in-depth functional in silico study using TCGA and ICGC data. We assess whether CS-related genes are associated with prognosis at the germline and somatic levels. We investigate the immune infiltration of PDAC tumors according to their transcriptomic profile. Genetic variation in FCN1 and PLAT is significantly associated with PDAC risk. PDAC patients with elevated expression of IGHG3, IGKC, IGHM, F2R, F2RL2, CFI, A2M, or C4A display improved survival and higher infiltration of CD8+, B cells, and Th1 cells. Individuals with high expression levels of either FGA, SERPINE1, FGG, or F3 exhibit poorer survival, higher infiltration of Tregs, and lower infiltration of CD8+ cells. Results from this study suggest that CS-related genes play a role in PDAC genetic susceptibility and survival through specific immune cell infiltration.; The work was partially supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain (#PI061614, #PI11/01542, #PI0902102, #PI12/01635, #PI12/00815, #PI15/01573, #PI18/01347, #PI21/00495); Ministerio de Ciencia, Innovación y Universidades, Madrid, Spain (#RTI2018-101071-B-I00 and #PID2021-128125OB-I00); Red Temática de Investigación Cooperativa en Cáncer, Spain (#RD12/0036/0034, #RD12/0036/0050, #RD12/0036/0073); Fundación Científica de la AECC, Spain; European Cooperation in Science and Technology - COST Action #BM1204: EUPancreas. EU-6FP Integrated Project (#018771-MOLDIAG-PACA), EU-FP7-HEALTH (#259737-CANCERALIA, #256974-EPC-TM-Net); Associazione Italiana Ricerca sul Cancro (#12182); Cancer Focus Northern Ireland and Department for Employment and Learning; and ALF (#SLL20130022), Sweden; Pancreatic Cancer Collective (PCC): Lustgarten Foundation & Stand-Up to Cancer, USA (SU2C #6179). Wed, 01 Apr 2026 12:49:44 GMT https://hdl.handle.net/11351/14423 2026-04-01T12:49:44Z https://hdl.handle.net/11351/14424 Mepolizumab for hypereosinophilic syndrome: effectiveness and safety from real-world evidence Lemes Castellano, Angelina; Velasco, Beatriz; Hernandez Rivas, Jesus Maria; Mora, Elvira; Fox, Maria Laura Antibodies; Hypereosinophilic syndrome; Interleukin-5; Anticuerpos; Síndrome hipereosinofílico; Interleucina-5; Anticossos; Síndrome hipereosinofílica; Interleucina-5; Hypereosinophilic syndrome (HES) is a rare condition characterized by elevated eosinophil levels and related symptoms of eosinophil-mediated organ damage. We reviewed the effectiveness and safety of mepolizumab for the treatment of HES. A scoping review was conducted following the PRISMA Scoping Reviews Checklist to identify real-world evidence of mepolizumab use in HES. In total, 36 references were identified as relevant and selected for review. Overall, 105 patients previously treated with glucocorticoids received mepolizumab at different dosages (range: 100–750 mg), routes of administration (subcutaneous/intravenous), and schedules (every 2–12 weeks). Remission rates were 57.1–76.0%. Most studies reported a range of 71.4–99.1% reduction in mean blood eosinophil counts with mepolizumab treatment. In addition, a glucocorticoid-sparing effect was observed; 85.7% of patients discontinued glucocorticoids after 12 months of mepolizumab administration. Mepolizumab was considered safe and well-tolerated and severe adverse events were rare. Mepolizumab provided clinically significant benefits in patients with HES in a real-world setting.; The author(s) declare financial support was received for the research and/or publication of this article. This research was funded by GSK. Wed, 01 Apr 2026 12:56:03 GMT https://hdl.handle.net/11351/14424 2026-04-01T12:56:03Z https://hdl.handle.net/11351/14388 The combination of avutometinib and defactinib in treating recurrent low-grade serous ovarian cancer: a plain language summary of the Phase II clinical trial ENGOT-OV60/GOG-3052/RAMP 201 Banerjee, Susana; Clamp, Andrew; Van Nieuwenhuysen, Els; Aghajanian, Carol; D'Hondt, Veronique; Monk, Bradley; OAKNIN, ANA Avutometinib; Defactinib; Plain language summary; Avutometinib; Defactinib; Resumen en lenguaje sencillo; Avutometinib; Defactinib; Resum en llenguatge senzill; What is this summary about?This plain language summary describes the results of the ENGOT-OV60/ GOG-3052/RAMP 201 clinical study, which were published in 2025. The Phase II study evaluated treatments for patients with a rare type of ovarian cancer, low-grade serous ovarian cancer (LGSOC). The study specifically involved those whose cancer came back or persisted, despite already having surgery and previous chemotherapy. Researchers investigated the effect of avutometinib on its own and in combination with defactinib to see which treatment would be more effective and to determine if both treatments were safe. They also investigated the combination of a lower dose of avutometinib with defactinib. All trial participants were tested for a specific KRAS genetic mutation (non-hereditary, also called somatic). The main goal of the study was to determine the confirmed objective response rate of each treatment. This is the percentage of patients whose cancer shrinks by at least 30% after treatment and maintains this shrinkage for at least 2 months. The study also closely monitored for any adverse events associated with each treatment and looked at other measures of treatment effectiveness.What were the results?The percentage of patients with an objective response was 31% in the combination treatment group and 17% in the avutometinib-only group. Amongst patients receiving the combination, the objective response rate was 44% in the group of participants with a KRAS mutation and 17% in the group without a KRAS mutation. The lower dose of avutometinib used in combination with defactinib was not as effective as the standard dose.In the standard dose combination treatment group, most adverse events were not severe (categorized as grade 1 or 2 on a scale of 0 to 5) and were managed with dose holds or dose reductions. The most frequent adverse events reported were nausea, increased creatine phosphokinase (CPK), diarrhea, peripheral edema, and rash. A total of 10% of participants discontinued treatment due to adverse events.What do the results mean?The results of the study support using the combination of avutometinib and defactinib as a treatment option for women with recurrent LGSOC.Clinical trial number: NCT06072781. Wed, 25 Mar 2026 08:52:17 GMT https://hdl.handle.net/11351/14388 2026-03-25T08:52:17Z