Scientia, Dipòsit d’Informació Digital del Departament de Salut
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Longitudinal Genomic Analysis to Fine-tune Targeted Therapy: Results of the Phase II LOGIC 2 Trial in Patients with BRAFV600-Mutant Metastatic Melanoma
Get PDFTargeted therapy; Metastatic melanoma; BRAFV600-mutantTeràpia dirigida; Melanoma metastàtic; Mutació BRAFV600Terapia dirigida; Melanoma metastásico; Mutación BRAFV600Purpose:
LOGIC 2 (NCT02159066), a multicenter, open-label, two-part, phase II study, assessed encorafenib plus binimetinib combined with a third targeted agent after tumor progression on encorafenib plus binimetinib in patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma.
Patients and Methods:
Adults with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma who were BRAF inhibitor/MEK inhibitor (BRAFi/MEKi) treatment–naïve or pretreated received encorafenib plus binimetinib (part I/run-in). Based on the genomic testing at disease progression following encorafenib plus binimetinib, patients were assigned to one of four treatment arms to receive encorafenib plus binimetinib with an appropriate molecularly targeted agent (ribociclib, infigratinib, capmatinib, or buparlisib; part II). The primary endpoint was best overall response; safety, biomarkers, pharmacokinetics, and other efficacy endpoints were also assessed.
Results:
In part I/run-in, 75 BRAFi/MEKi-naïve patients and 83 BRAFi/MEKi-pretreated patients were treated; in part II, 58 patients were treated (ribociclib, n = 38; infigratinib, n = 1; capmatinib, n = 13; buparlisib, n = 6). The overall confirmed response rate was 73.3% [95% confidence interval (CI), 61.9–82.9] in BRAFi/MEKi-naïve patients, 25.3% (95% CI, 16.4–36.0) in pretreated patients, 2.6% (95% CI, 0.1–13.8) in the ribociclib arm, and 0% in the other three arms. Adverse events were manageable and consistent with the known safety profile of each drug.
Conclusions:
LOGIC 2 supports the use of encorafenib plus binimetinib for treatment-naïve and previously treated, locally advanced, unresectable or metastatic BRAFV600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance
Dolor crònic: què n'has de saber? [fullet]
No full textDolor crònic; Tractament no farmacològic; MedicamentsDolor crónico; Tratamiento no farmacológico; MedicamentosChronic pain; Non-pharmacological treatment; MedicationsInfografia sobre el dolor crònic amb punts clau de la informació a pacients d’edat avançada i
situació de fragilitat sobre el tractament del dolor crònic
no oncològic osteomuscularInfografía sobre el dolor crónico con puntos clave de la información a pacientes de edad avanzada y
situación de fragilidad sobre el tratamiento del dolor crónico
no oncológico osteomuscularInfographic on chronic pain with key points of information for elderly patients and frailty situations regarding the treatment of chronic non-oncological musculoskeletal pai
Tractament farmacològic de la malaltia d’Alzheimer: informe del Registre de Tractament Farmacològic de la Malaltia d’Alzheimer a l’any 2024
No full textAlzheimer; Registre del tractament farmacològic; Població atesaAlzheimer; Registro del tratamiento farmacológico; Población atendidaAlzheimer's; Registration of pharmacological treatment; Population servedLa malaltia d’Alzheimer (MA) és un trastorn neurodegeneratiu progressiu i irreversible normalment de desenvolupament lent però sostingut en el temps. La MA és la causa més freqüent de demència (69%). La seva prevalença és d’un 5,1% i augmenta exponencialment amb l’edat, amb els valors més elevats al voltant dels 90 anys. El tractament actual de la MA és simptomàtic. Es disposa de dos grups farmacològics: els inhibidors de l’enzimacetilcolinesterasa (IACE), donepezil, rivastigmina i galantamina, i un antagonista no competitiu dels receptors d’Nmetil D-aspartat (NMDA), la memantina.La enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo progresivo e irreversible, normalmente de desarrollo lento pero sostenido en el tiempo. La EA es la causa más frecuente de demencia (69%). Su prevalencia es del 5,1% y aumenta exponencialmente con la edad, alcanzando los valores más elevados alrededor de los 90 años. El tratamiento actual de la EA es sintomático. Se dispone de dos grupos farmacológicos: los inhibidores de la enzima acetilcolinesterasa (IACE), donepezilo, rivastigmina y galantamina, y un antagonista no competitivo de los receptores de N-metil D-aspartato (NMDA), la memantina.Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder, usually with a slow but sustained course over time. AD is the most common cause of dementia (69%). Its prevalence is 5.1% and increases exponentially with age, reaching the highest values around 90 years of age. The current treatment for AD is symptomatic. Two pharmacological groups are available: acetylcholinesterase inhibitors (AChEIs)—donepezil, rivastigmine, and galantamine—and a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, memantine
Genetic evolution and relapse-associated mutations in adult T-cell acute lymphoblastic leukemia patients treated in PETHEMA trials
Get PDFMutations; Relapse; T-cell acute lymphoblastic leukemiaMutacions; Recaiguda; Leucèmia limfoblàstica aguda de cèl·lules TMutaciones; Recaída; Leucemia linfoblástica aguda de células TRelapse is the main cause of treatment failure in T-cell acute lymphoblastic leukemia (T-ALL). Despite this, data from adult T-ALL patients treated with specific chemotherapeutic regimens that examine predictive markers and describe relapse mechanisms are scarce. In this study, we studied 74 paired diagnosis-relapse samples from 37 patients homogeneously treated with three consecutive measurable residual disease-oriented trials to identify genetic determinants involved in relapse in adult T-ALL. Analysis of single-nucleotide variants and copy number alterations consistently found N/KRAS mutations (20% relapsed cases) at diagnosis and at relapse (resistance profile). N/KRAS mut patients frequently relapse early during consolidation treatment. Relapse-specific mutations in NT5C2, NR3C1, SMARCA4, and TP53 (40% relapse cases) were not detected at diagnosis by conventional molecular techniques (relapse profile). However, single-cell-based analysis revealed a very minor clone containing the NT5C2(p.R367Q) variant at diagnosis. Patients with the NT5C2(p.R367Q) variant mostly relapse later during maintenance treatment. Tracking the NT5C2 variant by digital PCR confirm the expansion of the NT5C2 clone at maintenance treatment. Overall, our exploratory analysis suggests a role for these genetic events, most of which have already been described in pediatric cases, driving resistance associated to specific chemotherapeutic agents, contributing to the relapse of a high proportion of adult T-ALL patients (60%).This project was supported by the AECC (GC16173697BIGA), ISCIII (PI19/01828, PI19/01183, and PI22/01880), co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future,” and CERCA/Generalitat de Catalunya SGR 2021 (ref 00560). Thaysa Lopes was supported by the Leukemia Stiftung (DJCLS 08R/2022)
Anatomical study of ultrasound vs landmark guidance for needle placement in the obliquus capitis inferior
Get PDFCadaver; Needling; Obliquus capitis inferiorOblic capitis inferior; Ecografia; PalpacióOblicuo capitis inferior; Ecografía; PalpaciónNeedling of obliquus capitis inferior (OCI) muscle could be an important intervention for individuals with upper cervical pain; however, precision is important due to its sensitive location. The aim was to assess the accuracy, safety and performance of needling OCI using palpation versus ultrasound-guidance in a cadaveric model. A cross-sectional anatomical study was conducted. Five therapists each performed a series of 20 needle insertion tasks (n = 100) on 10 anatomical samples. Distance from the needle tip to the target, if the OCI muscle belly was reached (accuracy), surrounding sensitive structures targeted (safety), time needed, number of needles passes, and the length of the needle remaining outside the skin were assessed. The ultrasound-guided procedure was associated with significantly greater accuracy and safety (p < 0.001). The ultrasound-guided procedure achieved 100% accuracy of reaching the OCI compared to 40% with the palpation-guided procedure, with a shorter distance from the needle tip to the target. In the palpation-guided procedure, potentially sensitive structures were pierced in 38% of cases compared to only 4% with the ultrasound-guided approach. However, the palpation-guided procedure required less time and fewer passes. Our findings suggest that ultrasound-guided procedure showed greater accuracy and safety than palpation-guided procedures for properly targeted the OCI muscle belly
Re-evaluating albumin use in traumatic brain injury
Get PDFAlbumin; Intracranial pressure; OutcomesAlbúmina; Presión intracraneal; ResultadosAlbúmina; Pressió intracranial; ResultatsTraumatic brain injury (TBI) affects approximately 69 million people annually, with the majority of cases being mild-to-moderate in severity. However, in severe TBI, early management is critical and includes fluid resuscitation to control intracranial pressure (ICP) and optimize cerebral perfusion pressure. The SAFE-TBI study linked hypotonic 4% albumin to higher mortality versus saline (33.2% vs. 20.4%; RR 1.63; P = 0.003), likely due to elevated ICP, prompting guidelines favoring saline. However, these recommendations are based on low-quality evidence and overlook hyperoncotic albumin. Preclinical data confirm that hypotonicity—not albumin—drives ICP elevation. Emerging data suggest that hyperoncotic albumin (20–25%) may reduce ICP and improve outcomes. This letter highlights evidence gaps and advocates re-evaluating albumin use in TBI, especially hyperoncotic formulations.This publication was supported by Grifols
Ixazomib decreases the risk of chronic graft-versus-host disease: identification of cGVHD biomarkers
Get PDFChronic graft-versus-host disease; BiomarkersEnfermedad crónica de injerto contra huésped; BiomarcadoresMalaltia crònica de empelt contra l'hoste; BiomarcadorsChronic graft-versus-host disease (cGVHD) is the leading cause of long-term morbidity and mortality after allogeneic hematopoietic stem cell transplantation. We hypothesize that it is possible to decrease its risk by manipulating the immune response in late phases of transplantation. We performed a prospective randomized trial including 73 patients. Patients in the treatment arm received 4 mg of ixazomib (IXZ) every 28 days from day +100. With a median follow-up of 24 months, the cumulative incidence of moderate/severe cGVHD in the IXZ vs control groups at 1 and 2 years were: 3.23% vs 30.2% (hazard ratio [HR], 0.089; P = .02) and 13% vs 43% (HR, 0.23; P = .01), respectively. Estimates for cGVHD and relapse-free survival at 2 years were 81% for IXZ and 49% for the control group (HR, 0.30). Increased STAT3 and p38 phosphorylation in T cells, and higher proportion of B cells that have undergone immunoglobulin isotype switching and circulating plasma cells on day +180 were associated with a significantly higher risk of developing moderate/severe cGVHD. The administration of IXZ decreases the risk of moderate/severe cGVHD. It is possible to identify biological patterns by flow cytometry to predict the risk of cGVHD. This trial was registered at www.clinicaltrials.gov as #NCT03225417.The authors also thank Takeda Company for providing funding to support the contract research organization and for the study drug (protocol number X16082)
The Spanish GIRO Guideline: A Paradigm Shift in the Management of Obesity in Adults
Get PDFAdipose tissue; Adults; ObesityTejido adiposo; Adultos; ObesidadTeixit adipós; Adults; ObesitatIntroduction: Current obesogenic environments, along with intrinsic factors, contribute to the obesity pandemic, which impacts the quality of life and healthcare for individuals with obesity. In addition, discrimination and stigma related to obesity remain widespread in our society. In this scenario, the Spanish Society for the Study of Obesity (SEEDO), in collaboration with 38 recognized scientific societies and 12 patients’ organization, has elaborated the Spanish guideline for obesity management in adults, referred to as the GIRO guideline. GIRO aims to drive a shift in obesity management and serve as a guide for healthcare professionals (HCPs) to address this chronic and multifactorial disease. Methods: A comprehensive systematic review was conducted and completed with experts’ contribution, with a particular focus on Spanish society. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Experts selected the recommendations and determined their strength through consensus. Results: A total of 121 recommendations were proposed, including 32 adopted from the Canadian Adult Obesity Clinical Practice Guidelines and 89 specific recommendations created for the Spanish context, and were distributed across five areas of application: (1) recognition of obesity as a chronic disease, (2) obesity assessment, (3) multidisciplinary approach to obesity treatment, (4) recommendations for obesity management in special populations, and (5) implementation of the GIRO guideline and future challenges. Conclusion: The GIRO recommendations are intended to serve as a useful and interactive tool for HCPs, policymakers, and other stakeholders to ensure access to and quality of healthcare for individuals living with obesity.The GIRO project (including the guideline elaboration and manuscript publication) has been promoted and driven by the SEEDO, through a non-conditional grant from Novo Nordisk Spain. The funder (Novo Nordisk Spain) had no role in the guideline nor the manuscript conception, planning, nor decision to publish
Evaluación del cumplimiento de la prescripción de soluciones de cloruro potásico
Get PDFErrors de medicació; Clorur Potassic; Prescripció electrònicaMedication errors; Potassium Chloride; Electronic prescriptionErrores de medicación; Cloruro Potassic; Prescripción electrónicaObjetivo: Analizar el cumplimiento de la prescripción de soluciones de potasio tras la implantación de un protocolo de uso seguro del potasio intravenoso en un hospital comarcal.
Método: Estudio descriptivo retrospectivo de octubre de 2024 a marzo de 2025. Se revisaron las prescripciones de pacientes que recibieron tratamiento con reposición de KCL en las plantas de hospitalización de agudos y urgencias en un hospital comarcal.
Resultados: Se recogieron un total de 319 pacientes que recibieron tratamiento endovenoso mediante sueroterapia con KCl. En el 77,12% (n=246) de los casos se cumplió la prescripción según la pauta normalizada de sueros.
Conclusiones: Tres cuartas partes de los profesionales se han adaptado a las presentaciones comercializadas incluidas en el protocolo del centro, valorándose positivamente el cumplimiento de prescripción
A Pooled Analysis of Datopotamab Deruxtecan in Patients With EGFR-Mutated NSCLC
Get PDFAntibody–drug conjugate; Datopotamab deruxtecan; EGFR mutationConjugado anticuerpo-fármaco; Datopotamab deruxtecan; Mutación EGFRConjugat anticossos-fàrmac; Datopotamab deruxtecan; Mutació de EGFRBackground: This exploratory analysis assessed datopotamab deruxtecan (Dato-DXd) in pretreated patients with advanced or metastatic NSCLC and EGFR mutations.
Methods: Data were pooled from the phase II TROPION-Lung05 (NCT04484142) and phase III TROPION-Lung01 (NCT04656652) trials. Patients with EGFR-mutated advanced or metastatic NSCLC, who had received previous targeted therapies and platinum-based chemotherapy, received Dato-DXd 6 mg/kg (TROPION-Lung05) or were randomized to Dato-DXd 6 mg/kg or docetaxel 75 mg/m2 (TROPION-Lung01) once every 3 weeks. End points included objective response rate, duration of response, and progression-free survival, all per blinded independent central review, overall survival, and safety.
Results: In total, 117 patients with EGFR mutations who received Dato-DXd were included in the pool. The population was heavily pretreated (median three lines of previous therapies; range, 1-5) and predominantly Asian (69%). The most common mutations were exon 19 deletion (51%), L858R (32%), and T790M (27%); more than one EGFR mutation could be present. The confirmed objective response rate was 43% (95% confidence interval [CI]: 34-52), including five complete responses (4%). Median duration of response was 7.0 months (95% CI: 4.2-9.8). Median progression-free survival and overall survival were 5.8 (95% CI: 5.4-8.2) and 15.6 months (95% CI: 13.1-19.0), respectively. The safety profile of Dato-DXd was consistent with the individual studies. No new safety signals were observed. Rates of grade greater than or equal to 3 treatment-related adverse events and serious adverse events were 23% and 6%, respectively.
Conclusion: Dato-DXd demonstrated meaningful clinical activity in patients with EGFR-mutated advanced or metastatic NSCLC who had progressed on EGFR-directed therapies and chemotherapy, with an acceptable safety profile.This work was supported by Daiichi Sankyo, Inc. (no grant number). In July 2020, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo, Inc., for Dato-DXd. The study was designed by the funder in collaboration with the study investigators