Scientia, Dipòsit d’Informació Digital del Departament de Salut
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Full informatiu del Sistema d’Informació per a la Vigilància d’Infeccions a Catalunya – 2025/12
Get PDFVigilància d'infeccions; Epidemiologia; Assistència sanitàriaInfection surveillance; Epidemiology; Health careVigilancia de infecciones; Epidemiología; Asistencia sanitariaL’objectiu de l’informe de la xarxa Sistema d’Informació per a la Vigilància d’Infeccions a Catalunya (SIVIC) és tenir un sistema de vigilància creat per seguir no només els casos més greus sinó també els casos comunitaris de diverses infeccions respiratòries, com són Covid-19, grip, virus sincitial respiratori i enterovirus, entre d’altres
Acsa brief - 2025, 05-novembre-desembre
No full textAliments; Riscos emergents; Seguretat alimentàriaAlimentos; Riesgos emergentes; Seguridad alimentariaFood; Food safety; Food risk assessmentEl fluorur en els aliments: usos i regulacióEl fluoruro en los alimentos: usos y regulació
Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN Expression
Get PDFPten; Androgen receptor signaling inhibitors; Hormone-sensitive prostate cancerPTEN; Inhibidors de la senyalització del receptor d'andrògens; Càncer de pròstata sensible a les hormonesPTEN; Inhibidores de la señalización del receptor de andrógenos; Cáncer de próstata sensible a las hormonasAlterations in the PTEN tumor suppressor gene are common in prostate cancer. They have been associated with a more aggressive disease and poor outcomes and potential benefit of targeted therapies. The purpose of this work is to study the clinical and transcriptional landscapes associated to low PTEN mRNA expression in metastatic hormone-sensitive prostate cancer (mHSPC) patients. A multicenter biomarker ambispective study was performed in mHSPC patients. PTEN mRNA expression was assessed by nCounter in formalin-fixed paraffin-embedded tumor samples. PTENlow status was defined by a previously validated cut-off and was correlated with castration-resistant prostate cancer (CRPC)-free survival (CRPC-FS) (primary endpoint) and overall survival (OS). RNA-Seq was performed to molecularly characterize PTENlow vs. PTENwt tumors. A total of 380 patients were included, 350 eligible. PTENlow was observed in 28.2% of patients and was independently associated with shorter CRPC-FS (HR 1.6, 95% CI 1.2-2.1, p = 0.002) and OS (HR 1.5, 95% CI 1.1-2, p = 0.014). PTENlow tumors showed overexpression of neuroendocrine, cell cycle, and DNA repair gene signatures, reduced expression of the androgen receptor pathway, and a distinct immune microenvironment. Using microarray data from the CHAARTED trial, we developed a PTEN-low related signature, independently associated with CRPC-FS (HR 1.5, 95% CI 1-2.3, p = 0.036) and OS (HR 1.9, C1 1.2-2.9, p = 0.005), and identified targets for potential therapies in PTEN-altered tumors. We conclude that PTENlow correlates with an aggressive clinical outcome in mHSPC patients and is associated with a unique transcriptional profile. These findings further support the investigation of novel therapeutic strategies for patients with PTEN alterations
Nivolumab plus ipilimumab with chemotherapy as first-line treatment of patients with metastatic non-small-cell lung cancer: final, 6-year outcomes from CheckMate 9LA
Get PDFChemotherapy; Nivolumab; Non-small-cell lung cancerQuimioteràpia; Nivolumab; Càncer de pulmó de cèl·lules no petitesQuimioterapia; Nivolumab; Cáncer de pulmón de células no pequeñasBackground
The phase III CheckMate 9LA study demonstrated durable overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy versus chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). Here, we report final, 6-year efficacy and safety outcomes.
Patients and methods
Treatment-naive adults with stage IV/recurrent NSCLC and no sensitizing EGFR/ALK alterations were randomized to nivolumab plus ipilimumab with chemotherapy (n = 361) or chemotherapy (n = 358). Assessments included OS, progression-free survival, objective response rate, and duration of response (DOR) in all randomized patients and subgroups, and OS by select somatic mutation status (KRAS, STK11, KEAP1, and TP53).
Results
With 68.6 months' minimum follow-up, nivolumab plus ipilimumab with chemotherapy demonstrated continued OS benefit versus chemotherapy (hazard ratio 0.74, 95% confidence interval 0.63-0.87, 6-year OS rates 16% versus 10%), regardless of tumor programmed death ligand 1 (PD-L1) expression (PD-L1 <1%, 20% versus 7%; PD-L1 ≥1%, 15% versus 10%) and histology (squamous, 14% versus 5%; non-squamous, 17% versus 12%). The 6-year DOR rate was 19% with nivolumab plus ipilimumab with chemotherapy; all patients in the chemotherapy arm were censored or stopped responding before this timepoint. Trends toward improved OS were observed with nivolumab plus ipilimumab with chemotherapy over chemotherapy regardless of KRAS, STK11, KEAP1, or TP53 mutation status. No new safety signals were observed.
Conclusions
These final analyses demonstrate the durable, long-term OS and response benefit with first-line nivolumab plus ipilimumab with chemotherapy over chemotherapy in patients with metastatic NSCLC, regardless of tumor PD-L1 expression, histology, or select somatic mutation status, further supporting this regimen as a standard-of-care treatment option.This work was supported by Bristol Myers Squibb, Princeton, NJ, USA (no grant number)
Safety overview and management of inavolisib alone and in combination therapies in PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer (GO39374)
Get PDFPI3K inhibitor; Breast cancer; Hormone receptor-positiveInhibidor de PI3K; Càncer de mama; Receptor hormonal positiuInhibidor de PI3K; Cáncer de mama; Receptor hormonal positivoBackground: Inavolisib is a potent and selective PI3Kα inhibitor that promotes degradation of mutated p110α. We report safety from a phase I/Ib dose-escalation/-expansion study (GO39374; NCT03006172) of inavolisib alone or in combination therapies in PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative advanced breast cancer.
Patients and methods: Patients received inavolisib [oral once daily (od)] alone, with letrozole (2.5 mg od) or fulvestrant (500 mg intramuscularly 4 weekly) ± palbociclib (125 mg od for 21/28 days); metformin was included in one arm.
Primary endpoint: safety and tolerability.
Results: At data cutoff (1 January 2024), 190 patients had been treated, of which 179 (94.2%) had discontinued study treatment, mainly due to progressive disease [146 (76.8%)]. Treatment-related any-grade and grade 3-5 adverse events (AEs) occurred in 181 (95.3%) and 107 (56.3%) patients, respectively. Inavolisib-related AEs led to inavolisib withdrawal in 5 (2.6%) and dose reductions/interruptions in 103 (54.2%) patients. Hyperglycemia, diarrhea, stomatitis (grouped terms), and rash (grouped terms) occurred in 129 (67.9%), 124 (65.3%), 93 (48.9%), and 47 (24.7%) patients, respectively. Hyperglycemia, diarrhea, and stomatitis mainly occurred early in treatment, and were manageable with supportive measures (including oral antihyperglycemic agents, common antidiarrheal medications, and dexamethasone mouthwash, respectively) and/or inavolisib dose modifications (dose interruptions with or without dose reductions). Hyperglycemia remained frequent in patients with risk factors, despite early metformin treatment. Rash was mostly grade 1 and required no treatment. Patients treated for ≥1 year [n = 65 (34.2%)] demonstrated encouraging long-term tolerability.
Conclusions: Inavolisib alone or in combination with HR-positive breast cancer therapies demonstrated a manageable safety and tolerability profile, which supports its ongoing development.This work was supported by Genentech, Inc., South San Francisco, CA; and the Memorial Sloan Kettering Cancer Center [support grant number P30 CA008748]
Recerca en salut mental: del finançament a l’impacte; anàlisi de l’impacte dels projectes finançats en el marc del PERIS 2016-2020 [resum]
No full textRecerca; Salut mental; Avaluació de l'impacteInvestigación; Salud mental; Evaluación del impactoResearch; Mental health; Impact assessmentAquest resum és una síntesi del document monogràfic: Recerca en salut mental: del finançament a l’impacte. Anàlisi de l’impacte dels projectes finançats en el marc del PERIS 2016-2020 que analitza elements del camí cap a l’impacte de les propostes finançades en el marc del PERIS 2016-2020. S’avalua la recerca finançada en la convocatòria de projectes en l’àmbit de salut mental on es van atorgar més de dos milions d’euros a 20 projectes de recerca amb un finançament triennal. Amb l’objectiu de retre comptes i identificar elements d’aprenentatge i millora, s’identifiquen adopcions dels resultats científics, s’analitza el perfil dels receptors i les interaccions que faciliten canvis en el sistema, partint d’una anàlisi de contextEste resumen es una síntesis del documento monográfico: Investigación en salud mental: de la financiación al impacto. Análisis del impacto de los proyectos financiados en el marco del PERIS 2016-2020, que examina los elementos del camino hacia el impacto de las propuestas financiadas en dicho programa.
Se evalúa la investigación financiada en la convocatoria de proyectos en el ámbito de la salud mental, en la que se otorgaron más de dos millones de euros a 20 proyectos de investigación con una financiación trienal.
Con el objetivo de rendir cuentas e identificar elementos de aprendizaje y mejora, se señalan las adopciones de los resultados científicos, se analiza el perfil de los receptores y las interacciones que facilitan cambios en el sistema, partiendo de un análisis de contexto.This summary is a synthesis of the monographic document: Mental health research: from funding to impact. Analysis of the impact of projects funded under PERIS 2016-2020, which examines the elements along the path to impact of the proposals financed within this program.
The evaluation focuses on research funded in the call for projects in the field of mental health, where more than two million euros were allocated to 20 research projects with three-year funding.
With the aim of ensuring accountability and identifying elements of learning and improvement, the study highlights the adoption of scientific results, analyzes the profile of the recipients, and explores the interactions that facilitate changes in the system, based on a context analysis
Ús dels fàrmacs opioides en dolor crònic no oncològic (DCNO) osteomuscular en pacients polimedicats fràgils [fullet]
Get PDFFàrmacs opioides; Dolor crònic no oncològic; Pacients polimedicatsOpioid drugs; Chronic non-oncological pain; Polymedicated patientsFármacos opioides; Dolor crónico no oncológico; Pacientes polimedicadosInfografia que pertany a la campanya "Pastilles, només les necessàries", detalla les indicacions sobre la determinació i tractament dels fàrmacs opioides en pacients polimedicats amb fragilitat.Infographic belonging to the "Pills, only those necessary" campaign, details the indications for the determination and treatment of opioid drugs in polymedicated patients with frailty.Infografía que pertenece a la campaña "Pastillas, sólo las necesarias", detalla las indicaciones sobre la determinación y tratamiento de los fármacos opioides en pacientes polimedicados con fragilidad
PIX
Get PDFPrograma d'intercanvi de xeringues; Consumidors de drogues injectades; Malalties infectocontagiosesNeedle exchange program; Injected drug users; Infectious diseasesPrograma de intercambio de jeringuillas; Consumidores de drogas inyectadas; Enfermedades infectocontagiosasEn aquest informe es presenten els principals resultats del Programa d’intercanvi de xeringues (PIX) de l’any 2024, amb l’objectiu que sigui un instrument de consulta per a professionals que col·laboren en el desenvolupament del Programa, persones que treballen en l’àmbit de les addiccions i altres destinataris que tinguin interès a conèixer l’evolució del PIX a Catalunya. Es presenten dades de l’evolutiu de la distribució general de xeringues, dels punts del PIX disponibles per tipus de dispositiu i per regió sanitària, així com indicadors relacionats amb la seva cobertura
Identification and characterization of short-chain dehydrogenase/reductase 3 (DHRS3) deficiency, a retinoic acid embryopathy of humans
Get PDFCraniosynostosis; Noncoding variant; Retinoic acidCraneosinostosis; Variante no codificante; Ácido retinoicoCraniosinostosi; Variant no codificant; Àcid retinoicPurpose: Signaling by the morphogen all-trans retinoic acid (RA) is critical for embryonic development, during which its tissue concentration must be tightly regulated. We investigated 8 sibships (12 individuals) segregating 5 different homozygous variants of dehydrogenase/reductase 3 ( DHRS3), which encodes an embryonically expressed enzyme (short-chain dehydrogenase/reductase 3; also termed SDR16C1) that catalyzes the reduction of retinaldehyde to retinol, limiting excessive RA synthesis.
Methods: We assessed variant pathogenicity using comparative phenotypic and bioinformatic analysis, quantification of DHRS3 expression, and measurement of plasma retinoid metabolites.
Results: Five homozygotes from 3 families (1 family segregating a deletion of the promoter and 5'-untranslated region of DHRS3, the other 2 a missense variant p.(Val171Met)), manifested a congruent phenotype, including coronal craniosynostosis, dysmorphic facial features, congenital heart disease (4/5 individuals), and scoliosis (5/5 individuals). Transcription of DHRS3 in whole blood cells from 2 homozygotes for the promoter/5'-untranslated region deletion was 90% to 98% reduced. Cells transfected with a DHRS3-Val171Met construct exhibited reduced retinaldehyde reduction capacity compared with wild-type, yielding reduced retinol and elevated RA; correspondingly, plasma from homozygous patients had significantly reduced retinol and elevated RA (exceeding the normal range), compared with controls and heterozygous relatives. Three additional homozygous missense variants of DHRS3 (p.(Val110Ile), p.(Gly115Asp), and p.(Glu244Gln)) were shown to reduce catalytic activity in vitro and/or in vivo but were associated with normal or different phenotypes that did not meet the threshold to assign likely pathogenicity.
Conclusion: We define a novel developmental syndrome associated with biallelic hypomorphic variants in DHRS3; a careful assessment of individual variants is required to establish a causal link to phenotype.This work was funded by the University of Oxford Goodger and Schorstein Research Scholarship in Medical Sciences (A.S.H.), a Doctoral Training Programme studentship funded jointly by the Radcliffe Department of Medicine, Exeter College (Oxford) Usher Cunningham Scholarship and the MRC (R.S.T.), the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (NIHR203308 to S.B.), the Wellcome Trust and Department of Health as part of the Health Innovation Challenge Fund scheme (R6-388/WT 100127 to J.C.T.), European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516) (D.W.), Wellcome Senior Investigator Award (102731/Z/13/Z to A.O.M.W.), MRC (Project Grant MR/T031670/1 to A.O.M.W.), the Oxford NIHR Biomedical Research Centre (J.C.T., S.R.F.T., A.O.M.W.), the University of Maryland School of Pharmacy Mass Spectrometry Center (SOP1841-IQB2014), and R01 HD077260 NICHD NIH HHS/United States (P.A.T., A.R.M., and M.A.K.). This research was made possible in part through access to data in the National Genomic Research Library, which is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The National Genomic Research Library holds data provided by patients and collected by the National Health Service (NHS) as part of their care and data collected as part of their participation in research. The National Genomic Research Library is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure
Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non–Small Cell Lung Cancer
Get PDFNeoadjuvant; Resectable; Non-small cell lung cancerNeoadyuvante; Resecable; Cáncer de pulmón de células no pequeñasNeoadjuvant; Resecable; Càncer de pulmó de cèl·lules no petitesPurpose: Adjuvant osimertinib is the standard of care for patients with resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes.
Methods: In this randomized, controlled, phase III study, patients with resectable, EGFR-mutated, stage II-IIIB NSCLC were randomly assigned (1:1:1) to receive neoadjuvant osimertinib (80 mg orally once daily for ≥9 weeks) plus platinum-based chemotherapy (once every 3 weeks for three cycles), osimertinib monotherapy (for ≥9 weeks), or placebo plus platinum-based chemotherapy (control), followed by surgical resection. Adjuvant osimertinib was offered to eligible patients after completion of surgery. The primary end point was major pathologic response (MPR) by blinded central pathology review. Event-free survival (EFS) was a secondary end point.
Results: Overall, 358 patients were randomly assigned to receive osimertinib plus chemotherapy (121 patients), osimertinib monotherapy (117 patients), or placebo plus chemotherapy (120 patients). Osimertinib plus chemotherapy (MPR rate 26%) and osimertinib monotherapy (25%) demonstrated statistically significant improvement in the MPR rate versus placebo plus chemotherapy (2%), with corresponding odds ratios of 19.82 (95.002% CI, 4.60 to 85.33; P < .0001) and 19.28 (99.9% CI, 1.71 to 217.39; P < .0001), respectively. With 15% data maturity, the EFS rates at 12 months were 93%, 95%, and 83% with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. In the neoadjuvant period, grade ≥3 adverse events of any cause occurred in 36%, 13%, and 33% of patients with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. No new safety concerns were identified.
Conclusion: Neoadjuvant osimertinib with or without chemotherapy demonstrated statistically significant improvement in the MPR rate over chemotherapy alone in patients with resectable, EGFR-mutated, stage II-IIIB NSCLC.
Trial registration: ClinicalTrials.gov NCT04351555.J.E.C. acknowledges the support of the National Institutes of Health (NIH) through the P30 grant (NCI Cancer Center Support Grant P30 CA008784 PI Vickers). The authors acknowledge Aaron Korpal, PhD, of Ashfield MedComms, an Inizio company, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP) guidelines (https://www.ismpp.org/gpp-2022). A complete list of the NeoADAURA trial investigators is provided in the Appendix (online only)