Scientia, Dipòsit d’Informació Digital del Departament de Salut
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Actuacions realitzades en el marc del Pla d’actuació per prevenir els efectes de la calor sobre la salut (POCS) 2023
Get PDFCalor elevada; Mesures de prevenció; ResultatsCalor elevado; Medidas de prevención; ResultadosHigh heat; Prevention measures; ResultsEl Pla d'actuació per prevenir els efectes de les onades de calor sobre la salut (POCS) a Catalunya és un pla estacional que s'activa anualment de l'1 de juny fins al 30 de setembre. Està coordinat per l'Agència de Salut Pública de Catalunya (ASPCAT) i el Servei Català de la Salut i compta amb la participació de més d'una quinzena d'entitats. L’informe presenta les actuacions realitzades i dels resultats obtinguts en relació al pla d’actuació per prevenir els efectes de les onades de calor sobre la salut (POCS) durant l'estiu de l'any 2023.The Action Plan to Prevent the Effects of Heat Waves on Health (POCS) in Catalonia is a seasonal plan that is activated annually from June 1 to September 30. It is coordinated by the Public Health Agency of Catalonia (ASPCAT) and the Catalan Health Service and has the participation of more than fifteen entities. The report presents the actions carried out and the results obtained in relation to the action plan to prevent the effects of heat waves on health (POCS) during the summer of 2023.El Plan de actuación para prevenir los efectos de las oleadas de calor sobre la salud (POCS) en Cataluña es un plan estacional que se activa anualmente del 1 de junio al 30 de septiembre. Está coordinado por la Agencia de Salud Pública de Cataluña (ASPCAT) y el Servicio Catalán de la Salud y cuenta con la participación de más de una quincena de entidades. El informe presenta las actuaciones realizadas y de los resultados obtenidos en relación con el plan de actuación para prevenir los efectos de las oleadas de calor sobre la salud (POCS) durante el verano del año 2023
Discordance between humoral and cellular immune responses to cytomegalovirus infection in CMV seropositive patients awaiting lung transplantation
Get PDFHumoral immune response; Immunocompromised; Infection riskRespuesta inmune humoral; Inmunocomprometido; Riesgo de infecciónResposta immune humoral; Immunocompromès; Risc d'infeccióIntroduction: Risk stratification for CMV infection in lung transplantation (LT) currently relies on determining donor and recipient CMV IgG before transplantation. However, it has been observed that some patients who test positive for CMV-specific humoral response before kidney transplantation (KT) exhibit a weak or absent CMV-specific cellular response. The significance of this observation in LT is still unknown.
Methods: This prospective, multicenter, observational study evaluated the agreement between CMV IgG serology and specific cell-mediated response (specific T cell Enzyme-Linked ImmunoSpot Assay, ELISPOT, against CMV pp65 and IE-1 antigens) in 121 patients on the waiting list for LT.
Results: One hundred and four (86%) patients were seropositive for CMV. Discordant humoral and cellular immunologic responses were observed, 29% of seropositive patients had a weak ELISPOT response to IE-1 and 39% to pp65. In 22% of seropositive patients, there was a weak or no response to both antigens. All seronegative patients did not respond to either antigen.
Conclusions: Therefore, over 20% of CMV seropositive LT candidates showed weak CMV-specific cellular immune responses despite detectable serological memory against CMV. This may be important in assessing the risk of developing a CMV infection after transplantation.This study was sponsored and funded by Merck Sharp & Dohme (MSD) Spain
Machine learning-based spatial characterization of tumor-immune microenvironment in the EORTC 10994/BIG 1-00 early breast cancer trial
Get PDFMachine learning; Tumor-immune microenvironment; Breast cancerAprendizaje automático; Microambiente inmunitario tumoral; Cáncer de mamaAprenentatge automàtic; Microambient immunitari tumoral; Càncer de mamaBreast cancer (BC) represents a heterogeneous ecosystem and elucidation of tumor microenvironment components remains essential. Our study aimed to depict the composition and prognostic correlates of immune infiltrate in early BC, at a multiplex and spatial resolution. Pretreatment tumor biopsies from patients enrolled in the EORTC 10994/BIG 1-00 randomized phase III neoadjuvant trial (NCT00017095) were used; the CNN11 classifier for H&E-based digital TILs (dTILs) quantification and multiplex immunofluorescence were applied, coupled with machine learning (ML)-based spatial features. dTILs were higher in the triple-negative (TN) subtype, and associated with pathological complete response (pCR) in the whole cohort. Total CD4+ and intra-tumoral CD8+ T-cells expression was associated with pCR. Higher immune-tumor cell colocalization was observed in TN tumors of patients achieving pCR. Immune cell subsets were enriched in TP53-mutated tumors. Our results indicate the feasibility of ML-based algorithms for immune infiltrate characterization and the prognostic implications of its abundance and tumor-host interactions.Open access funding provided by Karolinska Institute
Iatrogenic cerebral amyloid angiopathy and Alzheimer's disease co-pathology
Get PDFIatrogenic cerebral amyloid angiopathy; Alzheimer's diseaseAngiopatia amiloide cerebral iatrogènica; Malaltia d'AlzheimerAngiopatía amiloide cerebral iatrogénica; Enfermedad de AlzheimerIatrogenic cerebral amyloid angiopathy, a disease caused by contact with neurosurgical material or human growth hormone contaminated by beta-amyloid peptide (Aβ), has a prion-like transmission mechanism. We present a series of three patients under 55 years of age who underwent cranial surgery. All of them developed multiple cerebral hemorrhages, transient focal neurological deficits, and/or cognitive impairment after 3–4 decades. MRI was compatible with CAA, and Aβ deposition was confirmed. The third patient, who had a ventriculoperitoneal valve, also showed Aβ deposition in the peritoneum and diagnostic biomarkers of Alzheimer's disease. Co-pathology with Alzheimer disease and its iatrogenic transmission should be considered
Survey on the practice of skin-to-skin contact in Spanish neonatal units during the first days of life. Influence of the presence of umbilical catheters
Get PDFContacto piel con piel; Catéter umbilical; Cuidados intensivos neonatalesSkin-to-skin contact; Umbilical catheter; Neonatal intensive careContacte pell amb pell; Catèter umbilical; Cures intensives neonatalsIntroducción
El contacto piel con piel (CPP) en recién nacidos prematuros (RNPT) ofrece múltiples beneficios, pero su implementación puede retrasarse debido a la presencia de dispositivos, como los catéteres venosos umbilicales (CVU). El objetivo fue evaluar la práctica del CPP en RNPT en las unidades neonatales españolas y cómo el tipo de catéter afecta su inicio.
Métodos
Encuesta difundida a través de la Sociedad Española de Neonatología a las unidades neonatales españolas, analizando el momento de inicio del CPP y la influencia del tipo de dispositivos empleados.
Resultados
Se obtuvieron 74 respuestas de centros de las 17 comunidades autónomas, de los cuales el 67,6% atienden RNPT de cualquier edad gestacional o peso. El 39,2% de las unidades refiere iniciar el CPP en las primeras 24 h de vida (el 26% de las unidades que atienden a RNPT menores de 28 semanas o de 1.000 gramos).
En el 86,5% de los centros la canalización de CVU en RNPT es un procedimiento habitual y el 59,5% señala que el tipo de catéter canalizado influye en el momento de inicio del CPP. En el 37,8% de las unidades se realiza CPP con CVU, mientras que en el resto o no se emplea o se hace de forma excepcional.
Conclusión
Existe gran variabilidad en el inicio de la práctica del CPP en RNPT en España y se detecta el uso del CVU como una posible barrera para su implementación temprana. La existencia de guías clínicas o protocolos podría ayudar a mejorar la asistencia al RNPT y a homogeneizar las prácticas en las distintas unidades.Introduction
Skin-to-skin contact (SSC) offers multiple benefits in preterm newborns (PTNBs), but its implementation can be delayed due to the presence of some devices such as umbilical venous catheters (UVCs). Our objective was to evaluate the practice of SSC in PTNBs in Spanish neonatal units and how the type of catheter affects its initiation.
Methods
We distributed a survey through the Sociedad Española de Neonatología to Spanish neonatal units, analyzing the timing of SSC initiation and the influence on this practice of the types of devices being used.
Results
We obtained a total of 74 responses from centers across all 17 autonomous communities in Spain, of which 67.6% admitted PTNBs of any gestational age or birth weight. In 39.2% of the units, SSC was initiated within the first 24 hours of life (26% in the case of units that admitted PTNBs born before 28 weeks and/or weighing less than 1000 grams).
In 86.5% of the centers, UVC insertion in PTNBs was a routine procedure, and 59.5% reported that the type of inserted catheter affected the timing of SSC initiation. Skin-to-skin contact in infants carrying an UVC was performed in 37.8% of the units, but it was either not performed or rarely performed in the rest.
Conclusion
There is significant variability in the timing of SSC initiation in PTNBs in Spain, and the use of UVCs has been identified as a potential barrier to early implementation. The existence of clinical guidelines or protocols could help improve PTNB care and standardize practices across different units
Physical illness in schizophrenia and the role of tolerability in antipsychotic selection: an expert consensus with a focus on cariprazine
Get PDFAntipsychotics; Schizophrenia; Sexual dysfunctionsAntipsicòtics; Esquizofrènia; Disfuncions sexualsAntipsicóticos; Esquizofrenia; Disfunciones sexualesBackground
Schizophrenia is a highly heterogeneous disease, and a high percentage of patients are at high risk of developing somatic comorbidities, which must be taken into account in disease management and treatment selection.
Main body
Antipsychotics are often associated with side effects that worsen the somatic comorbidities. Among the different options, cariprazine is generally safe and usually well tolerated in both acute and long-term treatment and is often a good choice when balancing clinical benefits and side effects. Given the lack of consensus on the priority of symptoms to treat and the reasons for switching therapy based on the balance between side effects and symptom resolution, twelve psychiatrists met for an expert meeting to discuss the most common and worrisome antipsychotic side effects leading to switching, the most important somatic comorbidities, and the best way to address specific symptoms in both the acute and maintenance phases of treatment in schizophrenia. Special attention was given to metabolic comorbidities, sexual dysfunction, and cardiovascular disease. This paper aims to examine the relationship between schizophrenia and specific somatic comorbidities, to discuss how the balance between efficacy and tolerability influences treatment choice in the acute and maintenance treatment of schizophrenia, and how these two variables may have different priorities at different stages of treatment.
Conclusion
The choice of treatment is based primarily on efficacy and tolerability. Cariprazine is beneficial in patients with positive and negative symptoms, and it has a side-effect profile with low rates of metabolic side effects, sedation, and sexual dysfunction.This project was unconditionally supported by Recordati
Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial
Get PDFChemotherapy; Colorectal cancer; BRAF-mutantQuimioterapia; Cáncer colorrectal; Mutación BRAFQuimioteràpia; Càncer colorectal; Mutació BRAFEncorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC. The dual primary endpoint of progression-free survival is event driven; data were not mature at data cutoff. BREAKWATER met the other dual primary endpoint of objective response rate, demonstrating significant and clinically relevant improvement in objective response rate (EC+mFOLFOX6: 60.9%; SOC: 40.0%; odds ratio, 2.443; 95% confidence interval (CI): 1.403–4.253; 99.8% CI: 1.019–5.855; one-sided P = 0.0008). Median duration of response was 13.9 versus 11.1 months. At this first interim analysis of overall survival, the hazard ratio was 0.47 (95% CI: 0.318–0.691; repeated CI: 0.166–1.322). Serious adverse event rates were 37.7% versus 34.6%. The safety profiles were consistent with those known for each agent. BREAKWATER demonstrated a significantly improved response rate that was durable for first-line EC+mFOLFOX6 versus SOC in patients with BRAF V600E mCRC. ClinicalTrials.gov identifier: NCT04607421
TUXEDO-4: phase II study of trastuzumab-deruxtecan in HER2-low breast cancer with new or progressing brain metastases
Get PDFBreast; Metastasis; Novel therapyMama; Metástasis; Terapia novedosaMama; Metàstasi; Teràpia novaBreast cancer (BC) is the most common cause of leptomeningeal disease (LMD) and the second most common cause of brain metastases (BMs) among all solid malignancies. Both BMs and LMD are associated with high morbidity and mortality and treatment options are limited. Trastuzumab deruxtecan (T-DXd), an antibody drug conjugate combining a HER2-targeting antibody with a topoisomerase I inhibitor, has shown activity in HER2-positive (HER2[+]) and HER2-low tumors in both preclinical and clinical settings. Similarly, T-DXd has shown efficacy in HER2[+] BC patients with central nervous system (CNS) involvement. However, data on activity in HER2-low BC patients with BMs and/or LMD using T-DXd are limited. TUXEDO-4 is an international, multicenter, single-arm, two-stage optimal Simon’s design, phase II trial (NCT06048718) that will recruit a total of 27 adult patients (13 in the first stage, and 14 in second stage depending on responses in the first stage) to evaluate T-DXd in the HER2-low metastatic BC population presenting with newly diagnosed or progressing BM with or without type II LMD.
Clinical trial registration
NCT06048718 (clinicaltrials.gov); 2023 -506,702-39–00 (EudraCT number).The TUXEDO-4 trial has been funded by Daiichi Sankyo, who has been involved in the decision to publish, and the preparation of the manuscript
DPYD Genotyping, Fluoropyrimidine Dosage and Toxicity: An Umbrella Review of Systematic Reviews
Get PDFGenotipat del DPYD; Fluoropirimidines; ToxicitatDPYD genotyping; Fluoropyrimidines; ToxicityGenotipado de DPYD; Fluoropirimidinas; ToxicidadFluoropyrimidines are widely used chemotherapeutic agents in various solid tumors. Germline variants in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase (DPD), are known to impair drug metabolism and increase the risk of severe toxicity. This umbrella review aims to synthesize the current evidence from systematic reviews on the association between DPYD variants and fluoropyrimidine-induced toxicity. Methods: A comprehensive search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library from inception to 2023, including gray literature. Systematic reviews assessing fluoropyrimidine toxicity in oncologic patients with DPYD variants were included. Study quality was assessed using the AMSTAR-2 tool. Registration number in PROSPERO: CRD42023401226. Results: Two independent investigators performed the study selection, quality assessment, and data collection. Eight systematic reviews met the inclusion criteria. Methodological confidence was rated as critically low in six, low in one, and medium in another one. The reviews included 125 primary studies, most of them focused on four key DPYD variants (DPYD2*A, DPYD*13, c.2846A>T, and HapB3), all of which showed consistent associations with an increased risk of severe toxicity. Rare variants such as DPYD*4, *5, and *6 were also examined, though evidence remains limited. Pharmacogenetics-guided dosing of fluoropyrimidines significantly reduced toxicity rates in several studies. The integration of DPYD genotyping with phenotyping approaches faces limitations; these tests should complement rather than replace genotyping information. Conclusions: This umbrella review confirms the clinical relevance of DPYD genotyping to predict and mitigate fluoropyrimidine toxicity. Incorporating genotyping into clinical practice, potentially alongside phenotyping and therapeutic drug monitoring, may enhance patient safety and treatment efficacy
Cancer risks in people on dialysis and kidney transplant recipients: a Catalan cohort study, 2003-21
Get PDFCancer epidemiology; Dialysis; Kidney failure; Kidney transplantEpidemiología del cáncer; Diálisis; Insuficiencia renal; Trasplante de riñónEpidemiologia del càncer; Diàlisi; Insuficiència renal; Trasplantament de ronyóPeople with kidney failure have a higher risk of cancer compared with age- and sex-matched individuals in the general population, yet data from southern Europe are limited. This study explores cancer incidence in the kidney failure population in Catalonia.
We identified cancer cases through linkage of the Catalan Kidney Registry with Catalan cancer databases. Standardized incidence ratios (SIRs) were calculated for all-site and site-specific cancers in people on dialysis and kidney transplant recipients.
We described the epidemiology of cancer in 21 595 people on dialysis and 8037 kidney transplant recipients in Catalonia (2003-21). Cancer risk was more than two times higher in people on dialysis (SIR 2.11, 95% CI 2.02-2.19) and nearly four times higher in kidney transplant recipients (SIR 3.82, 95% CI 3.65-3.99) compared with the general population. Risks varied by cancer site, with a significantly higher incidence of kidney and thyroid cancers in the dialysis cohort, and skin cancer in the transplant cohort. The highest cancer risks were observed in the youngest, those with glomerular diseases, and those with the longest time since transplantation.
People with kidney failure face a high burden of cancer, particularly after kidney transplantation. Understanding the epidemiology of cancer in the kidney failure population is crucial for shaping health policies.This research was supported by a grant from the Spanish Government Instituto de Salud Carlos III (ISCIII) RICORS 2040 RD24/0004/0027 under the auspices of European Union— NextGenerationEU funds, Mecanismo para la Recuperación y la Resiliencia (MRR). L.O. was supported by a Río Hortega Fellowship, provided by the Carlos III Health Institute (ICSIII), Spain (CM23/00124)