Scientia, Dipòsit d’Informació Digital del Departament de Salut
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Adjuvant Nivolumab for Localized Renal Cell Carcinoma at High Risk of Recurrence After Nephrectomy: Part B of the Randomized, Placebo-Controlled, Phase III CheckMate 914 Trial
Get PDFAdjuvant nivolumab; Localized renal cell carcinoma; NephrectomyNivolumab adjuvant; Carcinoma de cèl·lules renals localitzat; NefrectomiaNivolumab adyuvante; Carcinoma de células renales localizado; NefrectomíaPurpose: CheckMate 914 is a two-part, randomized phase III trial evaluating adjuvant nivolumab plus ipilimumab (part A) or adjuvant nivolumab monotherapy (part B) versus placebo in mutually exclusive populations of patients with localized renal cell carcinoma (RCC) at high risk of postnephrectomy recurrence. Part A showed no disease-free survival (DFS) benefit for adjuvant nivolumab plus ipilimumab versus placebo. We report results from part B.
Methods: Patients were randomly assigned (2:1:1) to nivolumab (240 mg once every 2 weeks for up to 12 doses), placebo, or nivolumab (240 mg once every 2 weeks for up to 12 doses) plus ipilimumab (1 mg/kg once every 6 weeks for up to four doses). The planned treatment duration was 24 weeks (approximately 5.5 months). The primary end point was DFS per blinded independent central review (BICR) for nivolumab versus placebo; safety was a secondary end point.
Results: Overall, 825 patients were randomly assigned to nivolumab (n = 411), placebo (n = 208), or nivolumab plus ipilimumab (n = 206). With a median follow-up of 27.0 months (range, 18.0-42.4), the primary end point of improved DFS per BICR with nivolumab versus placebo was not met (hazard ratio [HR], 0.87 [95% CI, 0.62 to 1.21]; P = .40); the median DFS was not reached in either arm, and 18-month DFS rates were 78.4% versus 75.4%. The HR for DFS per investigator was 0.80 (95% CI, 0.58 to 1.12; P = .19). Grade 3-4 all-cause adverse events (AEs) occurred in 17.2%, 15.0%, and 28.9% of patients with nivolumab, placebo, and nivolumab plus ipilimumab, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6%, 1.0%, and 28.4%, respectively.
Conclusion: Part B of CheckMate 914 did not meet the primary end point of improved DFS for nivolumab versus placebo in patients with localized RCC at high risk of postnephrectomy recurrence.
Trial registration: ClinicalTrials.gov NCT03138512
Novel Approaches to Treatment of Immune-Mediated Chronic Intestinal Pseudo-Obstruction
Get PDFTreatment; Chronic intestinal pseudo-obstructionTractament; Pseudo-obstrucció intestinal crònicaTratamiento; Pseudo-obstrucción intestinal crónicaBackground and Objectives
The optimal immunosuppressive treatment for autoimmune chronic intestinal pseudo-obstruction (CIPO) is unknown due to lack of clinical trials. Even less data exist on treatment recommendations for patients who do not respond to first-line immunotherapy.
Methods
We describe 4 patients with autoimmune CIPO treated with vedolizumab (3/4), a monoclonal antibody that interferes the lymphocyte trafficking to the gastrointestinal tract, or rituximab (1/4) who did not respond to steroids or IV immunoglobulins. We made a systematic review of previously published cases of CIPO treated with these biological agents.
Results
Vedolizumab was effective in 2 of 3 patients but failed in a child with nonparaneoplastic anti-Hu–associated CIPO, who had generalized dysautonomia. The 2 patients who responded to vedolizumab had an isolated CIPO, and they did not present neuronal antibodies. Rituximab was prescribed in a case of anti-Hu–associated, nonparaneoplastic CIPO, who showed a complete clinical response after this treatment. Our review of the literature retrieved 4 previous cases of autoimmune CIPO treated with rituximab but none treated with vedolizumab. All patients treated with rituximab had Hu antibodies. Two patients showed a clinical response to the treatment with rituximab.
Discussion
Our findings underscore the potential efficacy of rituximab and vedolizumab in the management of autoimmune CIPO refractory to first-line treatments
Execució de proves de rendiment sobre sistemes d’informació de Salut
Get PDFMonitoratge; Proves de rendiment; Sistemes d'informació; Arquitectura tecnològicaMonitorización; Pruebas de rendimiento; Sistemas de información; Arquitectura tecnológicaMonitoring; Performance testing; Information systems; Technology architectureEl propòsit d'aquest document és ressaltar la importància de les proves de rendiment dins el cicle de vida dels sistemes informàtics, i explicar les característiques essencials i tipus de proves requerides al Departament de Salut.
Està dirigit tant als proveïdors d'aplicacions (encarregats de la construcció del sistema segons les característiques d’arquitectura demanades), com als gestors d’aquestes solucions (que han de garantir-ne la implantació amb èxit a producció). Les proves s’han de fer sobre escenaris definits per l’equip de desenvolupament, i validats i aprovats per l’equip funcional o responsables de solució, que són els que millor coneixen les necessitats d’aquesta.The purpose of this document is to highlight the importance of performance testing within the life cycle of IT systems, and explain the essential characteristics and types of tests required in the Department of Health. It is aimed at both application providers (responsible for building the system according to the requested architectural characteristics), and managers of these solutions (who must guarantee their successful implementation in production). The tests must be carried out on scenarios defined by the development team, and validated and approved by the functional team or solution managers, who are the ones who best know the needs of the solution.El propósito de este documento es resaltar la importancia de las pruebas de rendimiento dentro del ciclo de vida de los sistemas informáticos, explicando las características esenciales y tipos de pruebas requeridas en el Departamento de Salud. Está dirigido tanto a los proveedores de aplicaciones (encargados de la construcción del sistema según las características de arquitectura solicitadas), como a los gestores de estas soluciones (que deben garantizar su implantación con éxito a producción). Las pruebas deben realizarse sobre escenarios definidos por el equipo de desarrollo, y validados y aprobados por el equipo funcional o responsables de solución, que son los que mejor conocen las necesidades de esta
Cardiac Tamponade Complicating Type A Acute Aortic Dissection: Insights From 25 Years of Registry Research
Get PDFMalaltia aòrtica; Tamponament cardíac; Dissecció aòrtica aguda tipus aEnfermedad aórtica; Taponamiento cardíaco; Disección aórtica aguda tipo aAortic disease; Cardiac tamponade; Type a acute aortic dissectionBackground
Cardiac tamponade (TMP) is a catastrophic complication of type A acute aortic dissection (TAAAD), increasing the risk of morbidity and mortality.
Objectives
The present study aimed to assess the characteristics, management, and outcomes of TAAAD patients with preoperative TMP enrolled in the International Registry of Acute Aortic Dissection database from 1996 to 2022.
Methods
Data from 63 aortic centers were analyzed and TAAAD patients with and without preoperative TMP were compared. Multivariable modeling to assess factors associated with the presence of preoperative cardiac TMP and survival curves were performed. Overall median follow-up was 35.8 months (Q1-Q3: 11.6-59.4 months).
Results
Of the 6,014 patients with TAAAD in the International Registry of Acute Aortic Dissection during the 25-year study period, 865 individuals (14.4%) developed TMP. Patients with TMP were older (age 64.9 vs 60.8 years; P < 0.0001) and less often male (61.8% vs 66.8%; P = 0.005). No differences were seen in time to presentation or diagnosis. Prior cardiac surgery was less common in patients with TMP (7.6% vs 12.8%; P < 0.0001). Syncope (37.4% vs 13.4%; P < 0.0001) and coma or altered consciousness (28% vs 8%; P < 0.0001) on presentation were more frequent in the TMP group. The majority of the cohort were managed surgically, rates of which were similar between groups (87.5% vs 87.7%; P = 0.911). In-hospital mortality was higher in patients with TMP (38.4% vs 15.4%; P < 0.001) but 4-year survival was similar (log-rank P = 0.767).
Conclusions
TMP is an important prognosticator of in-hospital mortality. It is associated with increased mortality of TAAAD and prompt surgery is required. Those who survive the hospital course, go on to share the same postdischarge course as those who did not have TMP
NK cell depletion in bispecific antibody therapy is associated with lack of HIV control after ART interruption
Get PDFNK cell; Bispecific antibody therapy; HIVCèl·lules NK; Teràpia d'anticossos biespecífics; VIHCélulas NK; Terapia d'anticuerpos biespecíficos; VIH:esHIV infection remains incurable as the virus persists within a latent reservoir of CD4+T cells. Novel approaches to enhance immune responses against HIV are essential for effective control and potential cure of the infection. In this study, we designed a novel tetravalent bispecific antibody (Bi-Ab32/16) to simultaneously target the gp120 viral protein on infected cells, and the CD16a receptor on NK cells. In vitro, Bi-Ab32/16 triggered a potent, specific, and polyfunctional NK-dependent response against HIV-infected cells. Moreover, addition of the Bi-Ab32/16 significantly reduced the latent HIV reservoir after viral reactivation and mediated the clearance of cells harboring intact proviruses in samples from people with HIV (PWH). However, the in vivo preclinical evaluation of Bi-Ab32/16 in humanized mice expressing IL-15 (NSG-Hu-IL-15) revealed a significant decline of NK cells associated with poor virological control after ART interruption. Our study underscores the need to carefully evaluating strategies for sustained NK cell stimulation during ART withdrawal.This study was supported by the Spanish Secretariat of Science and Innovation, FEDER funds (RTI2018-101082-B-I00, PID2021-123321OB-I00, PDC2022.133836-100), two Gilead fellowships (GLD21/00049, GLD22/00152) as well as partially funded by the PI20/00160 grant from the Spanish Health Institute Carlos III, co-funded by ERDF/ESF, “A way to make Europe”/“Investing in your future”, the CNS2022-135549 grant, funded by MCIN/AEI/10.13039/501100011033 and by the European Union «Next Generation EU»/PRTR. M.B. is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179 and CPII22/00005). N.S-G is supported by the Spanish Secretariat of Science and Innovation Ph.D. fellowship (PRE2019-087393). We would like to thank Dr. Julia G. Prado from IrsiCaixa Institute for AIDS Research for generating the viral stock R5-BaL and Jorge Díaz from the Comparative Medicine and Bioimage Centre of Catalonia (CMCIB) for its excellent technical assistance with in vivo animal studies. The funders had no role in study design, data collection, and analysis, the decision to publish, or preparation of the manuscript
Topical miRNA Delivery via Elastic Liposomal Formulation: A Promising Genetic Therapy for Cutaneous Lupus Erythematosus (CLE)
Get PDFGene therapy; Lupus cutaneous; Topical drug deliveryTerapia génica; Lupus cutáneo; Administración tópica de fármacosTeràpia gènica; Lupus cutani; Administració tòpica de fàrmacsCutaneous lupus erythematosus (CLE) is a chronic autoimmune skin disorder with limited therapeutic options, particularly for refractory discoid lupus (DLE), which often results in scarring and atrophy. Recent studies have identified miR-31, miR-485-3p, and miR-885-5p as key regulators of inflammation, apoptosis, and fibrosis in CLE skin lesions. This research investigates a novel topical miRNA therapy using DDC642 elastic liposomes to target these pathways in CLE. DDC642 liposomes were complexed with miRNAs (anti-miR-31, anti-miR-485-3p, pre-miR-885-5p) and characterized through dynamic light scattering and Cryo-TEM. Cytotoxicity, cellular penetration, and therapeutic efficacy were evaluated in primary keratinocytes, PBMCs, and immune 3D-skin organoids. miRNA lipoplexes were successfully synthesized with optimized particle size, surface charge, and encapsulation efficiency. These lipoplexes exhibited effective cellular penetration and low cytotoxicity. Anti-miR-31 lipoplexes reduced miR-31 and NF-κB levels while increasing STK40 and PPP6C expression. Pre-miR-885-5p lipoplexes elevated miR-885-5p levels and downregulated PSMB5 and NF-κB in keratinocytes. While anti-miR-485-3p lipoplexes reduced T-cell activation markers. Anti-miR-31 and pre-miR-885-5p lipoplexes successfully modulated inflammatory pathways in 3D-skin CLE models. miRNA lipoplexes represent promising candidates for pioneering topical genetic therapies for CLE. Further studies, including animal models, are necessary to validate and optimize these findings.This research was funded by the Instituto de Salud Carlos III (ISCIII), grant number PI21/01869
Revisión panorámica sobre paneles diagnósticos de proteómica urinaria para el diagnóstico precoz del deterioro cognitivo leve y la enfermedad de Alzheimer
Get PDFPanells diagnòstics; Proteòmica urinària; Deteriorament cognitiu lleu; Malaltia d'AlzheimerPaneles diagnósticos; Proteómica urinaria; Deterioro cognitivo leve; Enfermedad de AlzheimerDiagnostic panels; Urinary proteomics; Mild cognitive impairment; Alzheimer’s diseaseL'objectiu d'aquest informe és avaluar, en una fase primerenca, l'impacte en la qualitat de vida dels pacients i en el sistema de salut dels panells diagnòstics basats en proteòmica urinària per al diagnòstic precoç del deteriorament cognitiu lleu i la malaltia de Parkinson, els quals es troben en una fase inicial de recerca i encara no han estat desenvolupats ni comercialitzats per cap empresa.El objetivo de este informe es evaluar, en una fase temprana, el impacto en la calidad de vida de los pacientes y en el sistema de salud de los paneles diagnósticos basados en proteómica urinaria para el diagnóstico precoz del deterioro cognitivo leve y la enfermedad de Parkinson, los cuales se encuentran en una fase inicial de investigación y aún no han sido desarrollados ni comercializados por ninguna empresa.The aim of this report is to assess, at an early stage, the impact on patients' quality of life and on the healthcare system of diagnostic panels based on urinary proteomics for the early diagnosis of mild cognitive impairment and Parkinson’s disease. These panels are currently in an early research phase and have not yet been developed or commercialized by any company
La hipertensió arterial: què n'he de saber? [cartell]
No full textHipertensió arterial; Tractament no farmacològic; MedicamentsHipertensión arterial; Tratamiento no farmacológico; MedicamentosArterial hypertension; Non-pharmacological treatment; MedicationsInfografia sobre la hipertensió arterial, es detallen les recomanacions de tractament per aquesta malaltia crònica. Consells tant farmacològic, com tractament no farmacològic, dins de la campanya "Pastilles, només les necessàries".En este documento sobre la hipertensión arterial, se detallan las recomendaciones de tratamiento para esta enfermedad crónica. Consejos tanto farmacológicos como no farmacológicos, dentro de la campaña " Pastilles, només les necessàries ".In this document about high blood pressure, detailing treatment recommendations for this chronic condition. Includes both pharmacological and non-pharmacological advice, as part of the campaign " Pastilles, només les necessàries"
Eficacia del pesario cervical en la prolongación del embarazo tras un episodio detenido de trabajo de parto pretérmino: revisión sistemática y metaanálisis con datos individuales de pacientes
No full textCervical pessary; Pessary; Preterm birthPesario cervical; Pesario; Parto prematuroPessari cervical; Pessari; Part prematurBackground
Randomized controlled Trials (RCTs) show conflicting results on the effectiveness of a cervical pessary after an arrested episode of preterm labor (PTL) aiming to prolong pregnancy.
Objective
To assess the effectiveness of a cervical pessary in prolongation of pregnancy after an arrested episode of PTL by utilizing individual participant data (IPD) meta-analysis.
Data sources
Databases Central, Embase, Medline, and clinical trial databases (ClinicalTrials.gov, ISRCTN, EU-CTR) were searched from inception until January 2024.
Study Eligibility Criteria
Randomized controlled trials investigating individuals between 24+0 and 34+0 weeks of gestation with an arrested episode of PTL and who were subsequently randomized to cervical pessary or no intervention.
Study Appraisal and Synthesis Methods
Studies were assessed for data integrity and risk of bias. Main outcomes were prolongation of pregnancy >7 days, interval between randomization and delivery, and a composite of adverse neonatal outcome. A one-step meta-analysis approach was employed, and the intention-to-treat principle was applied.
Results
Four RCTs had IPD available. In singleton pregnancies (total N=546; 275 individuals in the pessary group, 271 individuals in the control group), pessary placement did not decrease delivery risk within 7 days (relative risks [RR] 0.87; 95% confidence intervals [CI] 0.40–1.9), prolong pregnancy (mean differences 4.5 days; 95% CI –0.08 to 9.0), nor reduce the risk of adverse neonatal outcomes (RR 0.95; 95% CI 0.53–1.7). The incidence of readmissions for a new episode of PTL was significantly less frequent in the cervical pessary group (RR 0.66, 95% CI 0.50–0.85). Two studies investigating multiple pregnancies (N=167, 84 individuals in the pessary group, 83 individuals in the control group) were identified, showing contradictory results that could not be explained by study differences. Therefore, merging IPD and pooling of was uninformative.
Conclusion
In individuals with a singleton pregnancy with an episode of PTL between 24 and 34 weeks of gestational age, pessary placement does not prevent delivery within 7 days, preterm birth, or neonatal outcomes. A pessary might reduce the probability of readmissions for PTL.ANTECEDENTES
Los ensayos clínicos aleatorizados (ECA) han mostrado resultados contradictorios sobre la eficacia del pesario cervical para
prolongar el embarazo tras un episodio detenido de trabajo de parto pretérmino (TPP).
OBJETIVO
Evaluar la efectividad del pesario cervical en la prolongación del embarazo después de un episodio detenido de TPP, utilizando
un metaanálisis con datos individuales de participantes (IPD, por sus siglas en inglés).
FUENTES DE DATOS
Se realizaron búsquedas desde el inicio hasta enero de 2024 en las bases de datos CENTRAL, Embase, Medline y registros de
ensayos clínicos (ClinicalTrials.gov, ISRCTN, EU-CTR).
CRITERIOS DE ELEGIBILIDAD DEL ESTUDIO
Ensayos clínicos aleatorizados que incluyeran personas embarazadas entre las 24+0 y 34+0 semanas de gestación con un episodio detenido de TPP, posteriormente aleatorizadas a pesario cervical o sin intervención.
EVALUACIÓN DEL ESTUDIO Y MÉTODOS DE SÍNTESIS
Se evaluó la integridad de los datos y el riesgo de sesgo. Los desenlaces principales fueron la prolongación del embarazo >7
días, el intervalo entre la aleatorización y el parto, y un desenlace neonatal adverso compuesto. Se utilizó un enfoque de metaanálisis en un solo paso, aplicando el principio de intención de tratar.
RESULTADOS
Se contó con datos individuales de cuatro ECA. En embarazos únicos (N=546; 275 en el grupo con pesario, 271 en el grupo
control), el uso del pesario no redujo el riesgo de parto dentro de los 7 días (riesgo relativo [RR]: 0.87; IC 95%: 0.40−1.9), no
prolongó significativamente la gestación (diferencia media: 4.5 días; IC 95%: −0.08 a 9.0), ni disminuyó el riesgo de desenlaces
neonatales adversos (RR: 0.95; IC 95%: 0.53−1.7). Sin embargo, la tasa de reingresos hospitalarios por un nuevo episodio de
TPP fue significativamente menor en el grupo del pesario cervical (RR: 0.66; IC 95%: 0.50−0.85).
Se identificaron dos estudios sobre embarazos múltiples (N=167; 84 en el grupo con pesario, 83 en el grupo control), cuyos
resultados fueron contradictorios y no explicables por diferencias metodológicas, por lo que el agrupamiento de IPD fue poco
informativo.
CONCLUSIÓN
En personas con embarazo único y un episodio de TPP entre las 24 y 34 semanas de gestación, el uso de pesario cervical no
reduce el riesgo de parto en los 7 días posteriores, ni mejora la prolongación del embarazo o los desenlaces neonatales. No
obstante, puede disminuir la probabilidad de reingresos por nuevos episodios de TPP
Recomanacions per a l’atenció a la fragilitat en els dispositius d’urgències
Get PDFPersones grans fràgils; Urgències; HospitalitzacióFrail elderly people; Emergencies; HospitalizationPersonas mayores frágiles; Urgencias; HospitalizaciónAquest document té com a objectiu principal proporcionar les bases conceptuals per a la identificació i l’atenció de les persones grans fràgils en els dispositius d’atenció urgent, per oferir la millor resposta possible a les seves necessitats. Vol ser un punt de partida per afrontar una realitat respecte a l’increment d’aquest perfil de persones que consulten a urgències. L’abordatge del contingut es basa en tres premisses: L’atenció a les persones fràgils als serveis d’urgències ─en un context d’increment de la longevitat de la població─ és un dels reptes principals que haurà d’afrontar Catalunya al llarg dels anys vinents. Cal dissenyar propostes operatives específiques i flexibles que es puguin adaptar a la realitat de cada centre o dispositiu d’atenció urgent. Parteix d’una evidència científica sòlida i el consens multidisciplinari en l’àmbit de coneixement de la fragilitat