Representativeness in randomised clinical trials supporting acute coronary syndrome guidelines.

This project has received funding to cover the electronic case report form from the Balearic Society of Cardiology (Sociedad Balear Cardiología) through the ‘Bernat Nadal Ginard’ grant. Open access has been partly granted by the LIBERI PROGRAM 2023 of the Health Research Institute of the Balearic Islands (IdISBa).AIMS Clinical practice guidelines (CPGs) are published to guide the management of acute coronary syndrome (ACS). We aimed to critically appraise the representativeness and standard of care of randomised clinical trials (RCTs) supporting CPGs for ACS. METHODS AND RESULTS American and European CPGs for ST- and non-ST-elevation ACS were screened to extract all references (n = 2128) and recommendations (n = 600). Among the 407 primary publications of RCTs (19.1%), there were 52.6% and 73.2% recruiting patients in North America and Europe, respectively, whereas other regions were largely underrepresented (e.g., 25.3% RCTs recruited in Asia). There was 68.6% RCTs enrolling patient with ACS, whereas the remaining 31.4% did not enroll any patient with ACS. There was underrepresentation of some important subgroups, including elderly, female (29.9%) and non-white patients (<20%). The incidence and type of reperfusion reported in these RCTs were not reflective of current clinical practice (the percentage of patients who underwent percutaneous coronary intervention (PCI) among all RCTs was 42.7%; whereas for ST-Elevation Myocardial Infarction patients, the number of participants who underwent fibrinolysis was 3.3-fold higher than those who underwent primary PCI). All-cause mortality in these RCTs was 11.9% in RCTs with a follow-up ≤1 year. CONCLUSION RCTs supporting CPGs for ACS are not fully representative of the diversity of the ACS population and their current standard of care. While some of these issues with representativeness may be explained by how evidence has been accrued over time, efforts should be made by trialists to ensure that the evidence supporting CPGs is representative of the wider ACS population.S

Antifungal prophylaxis with nebulized amphotericin-B in solid-organ transplant recipients with severe COVID-19: a retrospective observational study

Aspergillosis; COVID-19; ProphylaxisAspergilosis; COVID-19; ProfilaxisAspergilosi; COVID 19; ProfilaxiCOVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a frequent complication in the intensive care unit (ICU). However, little is known about this life-threatening fungal superinfection in solid organ transplant recipients (SOTRs), including whether targeted anti-mold prophylaxis might be justified in this immunosuppressed population. We performed a multicentric observational retrospective study of all consecutive ICU-admitted COVID-19 SOTRs between August 1, 2020 and December 31, 2021. SOTRs receiving antifungal prophylaxis with nebulized amphotericin-B were compared with those without prophylaxis. CAPA was defined according the ECMM/ISHAM criteria. Sixty-four SOTRs were admitted to ICU for COVID-19 during the study period. One patient received antifungal prophylaxis with isavuconazole and was excluded from the analysis. Of the remaining 63 SOTRs, nineteen (30.2%) received anti-mold prophylaxis with nebulized amphotericin-B. Ten SOTRs who did not receive prophylaxis developed pulmonary mold infections (nine CAPA and one mucormycosis) compared with one who received nebulized amphotericin-B (22.7% vs 5.3%; risk ratio 0.23; 95%CI 0.032-1.68), but with no differences in survival. No severe adverse events related to nebulized amphotericin-B were recorded. SOTRs admitted to ICU with COVID-19 are at high risk for CAPA. However, nebulized amphotericin-B is safe and might reduce the incidence of CAPA in this high-risk population. A randomized clinical trial to confirm these findings is warranted.AR received a predoctoral research grant from the Instituto de Salud Carlos III, Spanish Ministry of Science, Innovation and Universities, (PFIS grant FI18/00183). This work was supported by the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain. We thank CERCA Programme/Generalitat de Catalunya for institutional support

Integration of solar energy systems for increased societal support

How can we integrate photovoltaic (PV) solar energy systems in the built environment and rural landscapes while increasing societal support and making effective use of space? This important research question is inspired by several grand societal challenges, namely humankind’s response to anthropogenic causes of climate change, the required sustainable energy transition and innovations in the design of systems, products, buildings and local infrastructures which enable an optimal use of solar energy. Consequently, new sustainable energy environments must be created which will meet the needs of users, will fit in a societal context, will have an excellent performance in energy production and which will be aesthetically appealing. For this purpose a new interdisciplinary Dutch research consortium has been established, which will evaluate so-called ‘Solar Integration’ from the perspectives of (1) public acceptance, law and governance, (2) biodiversity, ecosystems and spatial quality, (3) PV system configurations in rural and urban landscapes, (4) enabling technologies for integrated PV elements, and (5) design approaches. This research consortium will support Solar Integration by (a) design-driven research on innovations in PV solar energy, (b) the creation of a broad consortium of stakeholders with various backgrounds and interests, (c) execution of the project in both the Netherlands and internationally, and (d) involving adult and young citizens in knowledge utilization

Nanowire-Aperture Probe: Local Enhanced Fluorescence Detection for the Investigation of Live Cells at the Nanoscale

Fluorescence microscopy has tackled many of the burning questions in cellular biology. Probing low-affinity cellular interactions remains one of the major challenges in the field to better understand cellular signaling. We introduce a novel approach the nanowire-aperture probe (NAP) to resolve biological signatures with a nanoscale resolution and a boost in light detection. The NAP takes advantage of the photonic properties of semiconductor nanowires and provides a highly localized excitation volume close to the nanowire surface. The probing region extends less than 20 nm into the solution, which can be exploited as a local light probe in fluorescence microscopy. This confined detection volume is especially advantageous in the study of cellular signaling at the cell membrane, as it wraps tightly around the nanowire. The nanowire acts as a local nanoaperture, both focusing the incoming excitation light and guiding photons emitted by the fluorophore. We demonstrate a 20-fold boost in signal-to-background sensitivity for single fluorophores and membrane-localized proteins in live cells. This work opens a completely new avenue for next-generation studies of live cells

Deciphering multiple sclerosis disability with deep learning attention maps on clinical MRI

Deep learning; Disability; Structural MRIAprendizaje profundo; Discapacidad; Resonancia magnética estructuralAprenentatge profund; Discapacitat; Ressonància magnètica estructuralThe application of convolutional neural networks (CNNs) to MRI data has emerged as a promising approach to achieving unprecedented levels of accuracy when predicting the course of neurological conditions, including multiple sclerosis, by means of extracting image features not detectable through conventional methods. Additionally, the study of CNN-derived attention maps, which indicate the most relevant anatomical features for CNN-based decisions, has the potential to uncover key disease mechanisms leading to disability accumulation. From a cohort of patients prospectively followed up after a first demyelinating attack, we selected those with T1-weighted and T2-FLAIR brain MRI sequences available for image analysis and a clinical assessment performed within the following six months (N = 319). Patients were divided into two groups according to expanded disability status scale (EDSS) score: ≥3.0 and < 3.0. A 3D-CNN model predicted the class using whole-brain MRI scans as input. A comparison with a logistic regression (LR) model using volumetric measurements as explanatory variables and a validation of the CNN model on an independent dataset with similar characteristics (N = 440) were also performed. The layer-wise relevance propagation method was used to obtain individual attention maps. The CNN model achieved a mean accuracy of 79% and proved to be superior to the equivalent LR-model (77%). Additionally, the model was successfully validated in the independent external cohort without any re-training (accuracy = 71%). Attention-map analyses revealed the predominant role of frontotemporal cortex and cerebellum for CNN decisions, suggesting that the mechanisms leading to disability accrual exceed the mere presence of brain lesions or atrophy and probably involve how damage is distributed in the central nervous system.MS PATHS is funded by Biogen. This study has been possible thanks to a Junior Leader La Caixa Fellowship awarded to C. Tur (fellowship code is LCF/BQ/PI20/11760008) by “la Caixa” Foundation (ID 100010434). The salaries of C. Tur and Ll. Coll are covered by this award

Pancreatic ductal cells may have a negative effect on human islet transplantation.

AimTo evaluate the effect of pancreatic ductal cells on experimental human islet transplantation.Materials and methodsIsolated islets were additionally purified by handpicking. Ductal cells were purified by magnetic cell sorting and then clustered into ductal pancreatospheres (DPS). Islets, DPS, and islets + DPS (100 islets + 75 DPS, or 100 islets + 200 DPS) were cultured and glucose-stimulated insulin secretion, β-cell apoptosis, and gene expression was determined. Islets and islets + DPS preparations (800 islets + 600 DPS) were transplanted to streptozotocin-treated immunodeficient mice and glycemia, graft morphometry, and gene expression were determined.ResultsInsulin stimulation index was higher in islets than in islets co-cultured with DPS (5.59 ± 0.93 vs 4.02 ± 0.46; p0.05), and the ratio β-/endocrine non-β-cell mass was lower in islets + DPS grafts (islets: 2.05 ± 0.18, islets + DPS: 1.35 ± 0.15; pConclusionsIslet preparations enriched with ductal cells have a lower insulin stimulation index in vitro and achieved a worse metabolic outcome after transplantation. Inflammation may mediate the deleterious effects of ductal cells on islet cells

Renoportal Anastomosis during Liver Transplantation in Patients with Portal Vein Thrombosis

To evaluate the short- and long-term outcomes of renoportal anastomosis (RPA) in a large multicentric series. The current knowledge on RPA for portal reconstruction during liver transplantation (LT) in patients with diffuse portal vein thrombosis (PVT) and a large splenorenal shunt (SRS) is poor and limited to case reports and small case series