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Infective endocarditis: it takes a team
Get PDFInfective endocarditis; Multidisciplinary; TeamEndocarditis infecciosa; Multidisciplinari; EquipEndocarditis infecciosa; Multidisciplinario; EquipoInfective endocarditis (IE) is a relatively rare but life-threatening systemic infection, which remains associated with high morbidity and mortality. The epidemiology of IE has shifted to involve an increasing numbers of older patients with both cardiovascular and other types of prosthetic devices, multiple comorbid conditions often requiring invasive procedures, increasingly virulent pathogens, in particular Staphylococcus aureus, or that can harbour anti-microbial resistance, and an escalation of injection drug use in many areas of the world. In parallel, advancements in diagnostic and therapeutic options have led to complex strategies in patients’ management. Despite these epidemiologic shifts, clinical trials have been rare and most of the evidence guiding IE management derives from expert consensus or analysis of large registries. Because of this, a multi-disciplinary IE team-based approach has been recommended as the standard of care. The aim of this review is to explore the rationale for a multi-disciplinary team-based approach to the management of IE. This approach has proved to be potentially beneficial based on multiple investigations that have evaluated patient outcomes. In addition, implementation strategies, feasibility and options of the team approach have also been highlighted
Pentoxifylline use in alcohol-associated hepatitis with acute kidney injury does not improve survival: a global study
Get PDFAcute kidney injury; Liver diseases, alcoholic; PentoxifyllineLesión renal aguda; Enfermedades hepáticas alcohólicas; PentoxifilinaLesió renal aguda; Malalties hepàtiques alcohòliques; Pentoxifil·linaBackground Severe alcohol-associated hepatitis (sAH) is a life-threatening condition with high mortality, where corticosteroid use is the only treatment that has shown short-term benefits. Pentoxifylline, an anti-tumour necrosis factor-alpha agent, has been proposed for its potential to improve outcomes, especially in patients with acute kidney injury (AKI). We aimed to evaluate the impact of pentoxifylline on mortality in patients with sAH and AKI in a well-characterised global cohort.
Methods We conducted a retrospective, registry-based study including patients meeting the National Institute on Alcohol Abuse and Alcoholism clinical criteria for sAH and AKI. Mortality was the primary endpoint, with liver transplantation as a competing risk. Statistical analysis included Cox regression and Kaplan-Meier survival estimates.
Results We included 525 patients from 20 centres across eight countries. The median age was 48 years, with 26.1% females, and 76.9% had a history of cirrhosis. Multivariable Cox regression models showed that pentoxifylline use was not associated with survival (HR 1.20, 95% CI 0.85 to 1.69, p=0.291). Factors associated with mortality included age (HR 1.23, 95% CI 1.10 to 1.36, p<0.001), Model for End-Stage Liver Disease score at admission (HR 1.06, 95% CI 1.04 to 1.08, p<0.001) and renal replacement therapy use (HR 1.39, 95% CI 1.05 to 1.84, p=0.019). The main causes of death were multiple organ failure (42%), infections (10%), oesophageal varices bleeding (7%) and renal failure (6%).
Conclusion Pentoxifylline showed no significant benefit on mortality in patients with sAH and AKI. Further studies are needed to refine treatment strategies for this high-risk group.MA receives support from the Chilean government through the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT 1241450)
Prosthetic Joint Infections due to Candida Species: A Multicenter International Study
Get PDFCandida spp; Echinocandins; Prosthetic joint infectionCandida spp; Equinocandines; Infecció de pròtesi articularCandida spp; Equinocandinas; Infección de prótesis articularBackground
Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI.
Methods
This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up.
Results
A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0–79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5–181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079–3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157–3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305–.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777).
Conclusions
Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration
Mitigating catastrophic forgetting in Multiple sclerosis lesion segmentation using elastic weight consolidation
Get PDFCatastrophic forgetting; Lesion segmentation; Multiple sclerosisOlvido catastrófico; Segmentación de lesiones; Esclerosis múltipleOblit catastròfic; Segmentació de lesions; Esclerosi múltipleMultiple sclerosis (MS) lesion segmentation is crucial for monitoring disease progression. Deep learning methods have shown promising results but suffer from domain shift problems when evaluated in data from different protocols or scanners. Transfer learning (TL) achieves successful domain adaptation, but can lead to catastrophic forgetting, resulting in a significant performance drop on the source domain. Continuous learning aims to address this issue by retaining knowledge from previous domains while adapting to new ones. This work applies Elastic Weight Consolidation (EWC) for the first time in the context of domain-incremental learning for MS lesion segmentation. The approach was evaluated using a 3D U-Net trained on public datasets (WMH2017 and Shifts) and fine-tuned on an in-house dataset using both TL and EWC, in both full training and few-shot scenarios. Results show that with only 3 training images from the target domain, EWC leads to a 10% improvement in F-score, while using 5 images achieves similar results to using all available training images. Catastrophic forgetting was reduced by 8%–19% compared to standard TL, where performance drops ranged from 20 to 37%. This work demonstrates that EWC enables models to adapt to new domains while preserving previous knowledge, with minimal data requirements, advancing towards more generalizable deep learning models for clinical MS applications.This work has been supported by DPI2020-114769RB-I00 and PID2023-146187OB-I00 from the Ministerio de Ciencia, Innovación y Universidades, Spain and also by the ICREA Academia program . This work was carried out in collaboration with The Observatoire Français de la Sclérose en Plaques (OFSEP), who is supported by a grant provided by the French State and handled by the “Agence Nationale de la Recherche”, within the framework of the “Investments for the Future” program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation
Evaluación de las pruebas genéticas relacionadas con la hipoacusia y su rol en el cribado poblacional neonatal
Get PDFHipoacúsia; Proves genètiques; Cribratge neonatalHipoacusia; Pruebas genéticas; Cribado neonatalHearing loss; Genetic testing; Newborn screeningL’objectiu general d’aquest informe d’avaluació de tecnologies sanitàries (ATS, en espanyol ETS) és l’avaluació de les proves genètiques per al diagnòstic etiològic de la hipoacúsia en nounats i la determinació del seu rol en el programa de cribratge poblacional de la hipoacúsia neonatal vigent en nounats amb una prova de cribratge auditiu positiva o alterada (proves OEA o PEATC-A).El objetivo general de este informe de evaluación de tecnologías sanitarias (ETS) es la evaluación de las pruebas genéticas para el diagnóstico etiológico de la hipoacusia en recién nacidos y la determinación de su rol en el programa de cribado poblacional de la hipoacusia neonatal vigente en recién nacidos con una prueba de cribado auditivo positiva o alterada (pruebas OEA o PEATC-A).The general objective of this health technology assessment (HTA) report is to evaluate genetic tests for the aetiological diagnosis of hearing loss in newborns and to determine their role in the current population screening programme for neonatal hearing loss in newborns with a positive or abnormal hearing screening test (OAE or AABR tests)
Cambio climático y seguridad alimentaria microbiológica
Get PDFCanvi climàtic; Seguretat alimentària microbiològica; Riscos biològicsCambio climático; Seguridad alimentaria microbiológicaClimate change; Microbiological food safetyAquest informe, aprovat pel Comitè Científic Assessor de Seguretat Alimentària el març del 2025, aborda la influència del canvi climàtic en la seguretat alimentària microbiològica. Explica com els canvis en els patrons meteorològics afavoreixen la proliferació de perills biològics (bacteris, virus, fongs i paràsits) al llarg de tota la cadena alimentària, cosa que espera que augmenti les malalties d'origen alimentari. El document destaca la importància de factors ambientals clau com la temperatura i les precipitacions en la presència de patògens i la necessitat d'adoptar un enfocament “Una Salut” per abordar aquests riscos de manera integral. Finalment, subratlla la importància d'adaptar els sistemes de control, desenvolupar models de risc i millorar la recopilació de dades per fer front a aquest escenari canviant.El cambio climático constituye un desafío transversal que afecta a todos los eslabones de la cadena alimentaria, desde la producción hasta la distribución y el consumo. El incremento de las temperaturas globales y la variabilidad de los patrones meteorológicos influyen directamente en la proliferación y distribución de peligros biológicos, lo que puede traducirse en un aumento de enfermedades de origen alimentario.
Factores como la temperatura, las precipitaciones, el pH, la salinidad y la intensidad de la luz ejercen una influencia crucial en la contaminación y la seguridad de los alimentos. Los cambios en estos parámetros pueden modificar tanto la presencia de patógenos como la calidad de los cultivos y productos alimentarios, afectando la disponibilidad de agua potable e incrementando el riesgo de contaminación en diferentes etapas del procesamiento.
Dado el complejo escenario que se plantea, resulta imprescindible adoptar medidas con un enfoque global que integren la salud humana y animal en el medio ambiente. Esto debe traducirse en la revisión y adaptación de los sistemas de control, en el desarrollo de marcos de modelización del riesgo y en la implementación de medidas preventivas adecuadas a la evolución detectada. La recogida sistemática de datos epidemiológicos, el desarrollo de nuevas tecnologías para el monitoreo y la detección de peligros, así como la colaboración entre autoridades, industria y comunidad científica serán claves para adaptarse a los nuevos escenarios que se deriven.Climate change constitutes a crosscutting challenge affecting every stage of the food supply chain, from production to distribution and consumption. The increase in global temperatures and the variability of meteorological patterns directly influence the proliferation and distribution of biological hazards, which may lead to a rise in foodborne illnesses.
Factors such as temperature, precipitation, pH, salinity, and light intensity play a crucial role in food contamination and safety. Changes in these parameters can affect both the presence of pathogens and the quality of crops and food products, thus bearing on the availability of drinking water and increasing the risk of contamination at various stages of processing.
Given the complex climate change scenario, a global focus that integrates human and animal health with environmental changes is imperative. This approach should be manifest in the revision and adaptation of control systems, the development of risk modelling frameworks and the implementation of preventive measures based on the detected changes. The systematic collection of epidemiological data, the development of new technologies for hazard detection and monitoring, and enhanced collaboration between authorities, industry, and the scientific community will be key to adapting to the new scenarios arising from climate change
Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry
Get PDFN-acetylglutamate synthase; Arginase 1; Urea cycle disordersN-acetilglutamat sintasa; Arginasa 1; Trastorns del cicle de la ureaN-acetilglutamato sintasa; Arginasa 1; Trastornos del ciclo de la ureaBackground/Objectives: The present study updates the Spanish registry of patients with urea cycle disorders (UCD), originally established in 2013, to provide comprehensive epidemiological data and evaluate the impact of therapeutic strategies and newborn screening (NBS) on clinical outcomes. Methods: This retrospective, multicenter study focuses on 255 Spanish UCD patients. It includes all living and deceased cases up to February 2024, analyzing demographic, clinical, and biochemical variables. Results: The incidence of UCD in Spain over the past decade was 1:36,063 births. The most common defects were ornithine transcarbamylase deficiency (OTCD) and argininosuccinate synthetase deficiency. Early-onset (EO) cases comprised 32.7%, and 10.6% were diagnosed through NBS. Global mortality was 14.9%, higher in carbamoylphosphate synthetase 1 deficiency (36.8%) and male OTCD patients (32.1%) compared to other defects (p = 0.013). EO cases presented a higher mortality rate (35.8%) than late-onset (LO) cases (7.1%) (p < 0.0001). The median ammonia level in deceased patients was higher at 1058 µmol/L (IQR 410–1793) than in survivors at 294 µmol/L (IQR 71–494) (p < 0.0001). Diagnosis through NBS improved survival and reduced neurological impairment compared to symptomatic diagnosis. Neurological impairment occurred in 44% of patients, with worse neurological outcomes observed in patients with argininosuccinate lyase deficiency, arginase 1 deficiency, hyperornithinemia-hyperammonemia-homocitrullinuria, EO presentations, pre-2014 diagnosis, and patients with higher levels of ammonia at diagnosis. Among transplanted patients (20.6%), survival was 95.2%, with no significant neurological differences compared to non-transplanted patients. Conclusions: This updated analysis highlights the positive impact of NBS and advanced treatments on mortality and neurologic outcomes. Persistent neurological challenges underscore the need for further therapeutic strategies.This research was partially funded by Lucane SL and Immedica Pharma Spain. Medical writing support was funded by Immedica Pharma Spain
STELLAR-304: a phase III study of zanzalintinib (XL092) plus nivolumab in advanced non-clear cell renal cell carcinoma
Get PDFImmune checkpoint inhibitor; Non-clear cell renal cell carcinoma; Tyrosine kinase inhibitorInhibidor del punt de control immunitari; Carcinoma renal de cèl·lules no clares; Inhibidor de la tirosina cinasaInhibidor del punto de control inmunitario; Carcinoma renal de células no claras; Inhibidor de la tirosina quinasaManagement of advanced non-clear cell renal cell carcinoma (nccRCC) is challenging due to disease rarity and heterogeneity. The combination of multi-targeted tyrosine kinase inhibitor (TKI) with immune checkpoint inhibitor (ICI) has emerged as an effective treatment strategy, but well-designed, phase III randomized clinical trials are needed to demonstrate superiority over current treatment options. Zanzalintinib is a novel, multi-targeted TKI that has demonstrated promising preclinical anti-tumor activity in combination with ICIs. STELLAR-304 is a phase III trial evaluating first-line zanzalintinib plus nivolumab versus sunitinib in advanced nccRCC. Primary endpoints are progression-free survival and objective response rate. Secondary endpoint is overall survival. To our knowledge, STELLAR-304 is the first phase III study assessing a TKI-ICI combination in nccRCC patients across multiple subtypes.STELLAR-304 is sponsored by Exelixis, Inc. (Alameda, CA, USA)
Drug dosing in obese critically ill patients, a literature review
Get PDFDosificación de fármacos; Paciente obeso; Unidad de cuidados intensivosDrug dosing; Obese patient; Intensive care unitDosificació de fàrmacs; Pacient obès; Unitat de cures intensivesIntroducción
la obesidad constituye un problema de salud pública global y el conocimiento sobre la dosificación de fármacos en pacientes obesos es limitado. Los ensayos clínicos en pacientes críticos raramente incluyen individuos obesos, lo que resulta en la falta de información específica sobre la dosificación en las fichas técnicas de los productos. El objetivo de esta revisión bibliográfica es proporcionar a los clínicos pautas eficientes y seguras para este grupo de pacientes.
Método
se constituyó un grupo multidisciplinar compuesto por farmacéuticos especialistas en farmacia hospitalaria y médicos especialistas en medicina intensiva. Se identificaron y revisaron los grupos terapéuticos y, en profundidad, los principios activos más utilizados en la unidad de cuidados intensivos. La revisión bibliográfica se realizó utilizando términos como: «obese», «overweight», «critical illness», «drug dosification», y «therapeutic dose monitoring». Toda la información fue evaluada por el grupo de trabajo, que consensuó recomendaciones de dosificación para cada fármaco en pacientes obesos críticos.
Resultados
se identificaron 83 fármacos pertenecientes a los siguientes grupos terapéuticos: antivirales, antibacterianos, antifúngicos, inmunosupresores, antiepilépticos, vasopresores, anticoagulantes, bloqueadores neuromusculares y sedantes. Se elaboró una tabla con la recomendación consensuada de dosificación para cada uno de ellos tras su revisión.
Conclusiones
la dosificación de medicamentos en pacientes obesos, tanto en entornos críticos como no críticos, sigue siendo un área con importantes incertidumbres. Esta revisión proporciona información actualizada y exhaustiva sobre la dosificación de los principales grupos terapéuticos en pacientes obesos críticos, siendo una herramienta útil tanto para médicos en unidades de cuidados críticos como para farmacéuticos clínicos en su práctica asistencial en dicho entorno.Introduction
The prevalence of obesity represents a significant global public health challenge, and the available evidence concerning the appropriate dosing of pharmaceutical in patients with obesity is limited. It is uncommon for clinical trials in critically ill patients to include obese individuals, which results in a lack of specific dosing information in product data sheets. The objective of this literature review is to provide clinicians with efficacious and secure guidelines for this cohort of patients.
Methods
A multidisciplinary team comprising pharmacists specialized in hospital pharmacy and physicians with expertise in intensive care medicine was established. The therapeutic groups and, in particular, the most commonly used active ingredients within the Intensive Care Unit were identified and subjected to detailed analysis. The following terms were included in the search: “obese”, “overweight”, “critical illness”, “drug dosification”, and “therapeutic dose monitoring”. All the information was then evaluated by the working group, which reached a consensus on the dosing recommendations for each drug in obese critically ill patients.
Results
A total of 83 drugs belonging to the following therapeutic groups were identified: antivirals, antibacterials, antifungals, immunosuppressants, antiepileptics, vasopressors, anticoagulants, neuromuscular blocking agents and sedatives. A table was produced containing the consensus dosing recommendations for each of the aforementioned drugs following a review of the available evidence.
Conclusions
Drug dosing in obese patients, both in critical and noncritical settings, remains an area with significant uncertainty. This review provides comprehensive and up-to-date information on the dosing of the main therapeutic groups in obese critically ill patients, offering a valuable resource physicians in critical care units and clinical pharmacists in their practice in this setting
Impacto medioambiental de las terapias inhaladas en una unidad de fibrosis quística: Estrategias de sostenibilidad
Get PDFInhaler; Environmental impact; Cystic fibrosisInhalador; Impacto medioambiental; Fibrosis quísticaInhalador; Impacte mediambiental; Fibrosi quísticaObjective: Inhaled therapy is essential in cystic fibrosis; however, inhalers have a significant environmental impact due to the greenhouse gases (GHGs) emitted. The environmental impact of a product is estimated by its carbon footprint (CF). Pressurized metered-dose inhalers (pMDIs) have a higher CF than dry powder inhalers (DPIs) and soft mist inhalers (SMIs) due to the incorporation of GHGs. The objectives are to analyze the consumption of inhalers (β2-adrenergic agonist bronchodilators, anticholinergics, and/or corticosteroids) in a cystic fibrosis unit and estimate the generated CF.
Method: Retrospective determination (January 2018-December 2023) of consumption and CF (tCO2eq) by type of inhaler was conducted. Consumption and CF trends were evaluated using linear regression.
Results: Annually, 1.529 (1.279-1.613) pMDIs, 1.055 (855-1.333) DPIs, and 28 (20-42) SMIs were dispensed, representing 55.97%, 42.33%, and 1.70%, respectively. A statistically significant positive trend in the consumption of SMIs was observed. The median annual CF was: pMDIs 38.3 (31.2-40.3) tCO2eq, DPIs 0.8 (0.6-0.9) tCO2eq, and SMIs 0.02 (0.02-0.03) tCO2eq, representing 97.86%, 2.04%, and 0.10%, respectively.
Conclusions: pMDIs were the inhalers with the highest consumption and CF, although their consumption appears to be decreasing, with an increase in the consumption of SMIs.Objetivo
La terapia inhalada es esencial en fibrosis quística; sin embargo, los inhaladores presentan un impacto medioambiental significativo derivado de los gases de efecto invernadero (GEI) emitidos. El impacto medioambiental de un producto se estima mediante su huella de carbono (HC). Los inhaladores de cartucho presurizado (pMDIs) presentan mayor HC que los inhaladores de polvo seco (DPIs) y de nube de vapor suave (SMIs) al incorporar GEI.
Los objetivos son analizar el consumo de inhaladores (broncodilatadores agonistas β2-adrenérgicos, anticolinérgicos y/o corticoides) en una unidad de fibrosis quística y estimar la HC generada.
Método
Se determinó retrospectivamente (enero 2018-diciembre 2023) el consumo y la HC (tCO2eq) por tipo de inhalador. Se evaluó la tendencia de consumo y HC mediante regresión lineal.
Resultados
Se dispensaron anualmente 1.529 (1.279–1.613) pMDIs, 1.055 (855–1.333) DPIs y 28 (20–42) SMIs, representando el 55,97%; 42,33%; y 1,70%, respectivamente. Se observó una tendencia positiva estadísticamente significativa del consumo de SMIs. La HC mediana anual fue: pMDIs 38,3 (31,2–40,3) tCO2eq, DPIs 0,8 (0,6–0,9) tCO2eq y SMIs 0,02 (0,02–0,03) tCO2eq, representando, respectivamente, el 97,86%, 2,04% y 0,10%.
Conclusiones
Los pMDIs fueron los inhaladores con mayor consumo y HC, aunque parece que su consumo tiende a disminuir, incrementándose el de SMIs