Plasmonic Copper Sulfide Nanoparticles Enable Dark Contrast in Optical Coherence Tomography

This is the peer reviewed version of the following article: Marin, R., Lifante, J., Besteiro, L. V., Wang, Z., Govorov, A. O., Rivero, F., ... & Jaque, D. (2020). Plasmonic Copper Sulfide Nanoparticles Enable Dark Contrast in Optical Coherence Tomography. Advanced Healthcare Materials 2020 9.5 (2020): 1901627, which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.201901627. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsOptical coherence tomography (OCT) is an imaging technique affording noninvasive optical biopsies. Like for other imaging techniques, the use of dedicated contrast agents helps better discerning biological features of interest during the clinical practice. Although bright OCT contrast agents have been developed, no dark counterpart has been proposed yet. Herein, plasmonic copper sulfide nanoparticles as the first OCT dark contrast agents working in the second optical transparency window are reported. These nanoparticles virtually possess no light scattering capabilities at the OCT working wavelength (≈1300 nm); thus, they exclusively absorb the probing light, which in turn results in dark contrast. The small size of the nanoparticles and the absence of apparent cytotoxicity support the amenability of this system to biomedical applications. Importantly, in the pursuit of systems apt to yield OCT dark contrast, a library of copper sulfide nanoparticles featuring plasmonic resonances spanning the three optical transparency windows is prepared, thus highlighting the versatility and potential of these systems in light-controlled biomedical applicationsThis project was partially funded by the European Commission through the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant agreement No. 797945 “LANTERNS”. This work was partially supported by the Ministerio de Economía y Competitividad de España (MAT2016-75362-C3-1-R) and (MAT2017-83111R), by the Instituto de Salud Carlos III (PI16/00812), by the Comunidad Autónoma de Madrid (B2017/BMD-3867RENIMCM), and co-financed by the European Structural and investment fund. Additional funding was provided by the European Commission Horizon 2020 project NanoTBTech. L.V.B was supported by the Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China and China Postdoctoral Science Foundation (2017M622992 and 2019T120820). Z.W. was supported by the National Basic Research Program of China (Project 2013CB933301) and the National Natural Science Foundation of China (Project 51272038). A.G. was funded via the 1000-talent Award of Sichuan and by the Volkswagen Foundation. Prof. Jorge Rubio-Retama is gratefully acknowledged for granting access to the dynamic light scattering instrument and for the fruitful discussio

Ecocardiografía en la valoración de un fibroelastoma papilar múltiple

Fibroelastoma is the second most common primary benign cardiac tumor. It can be multiple; the aortic valve is the most frequently affected location and the most important complication is systemic embolism. We present the case of a 67-year-old woman who attended the emergency room due to heart failure. In the study, the echocardiogram showed a nodular small mass in the left coronary leaflet of the aortic valve suggestive of fibroelastoma. The transesophageal echocardiogram confirmed the finding and found a second mass in the non-coronary leaflet, for which to the final diagnosis of multiple papillary fibroelastoma.El fibroelastoma es el segundo tumor benigno cardiaco primario más frecuente. Puede ser múltiple, la válvula aórtica es la localización más frecuentemente más afectada y la complicación más importante es el embolismo sistémico. Presentamos el caso de una mujer de 67 años que acudió a Urgencias por insuficiencia cardiaca. En el estudio se realizó un ecocardiograma en el que se apreció una imagen nodular en el velo coronariano izquierdo de la válvula aórtica sugestiva de fibroelastoma, El ecocardiograma transesofágico confirmó el hallazgo y encontró una segunda masa en el velo no coronariano, por lo que se llegó al diagnóstico final de fibroelastoma papilar múltiple

Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si lo hubiere, y los autores pertenecientes a la UAMSome patients with COVID-19 pneumonia develop an associated cytokine storm syndrome that aggravates the pulmonary disease. These patients may benefit of anti-inflammatory treatment. The role of colchicine in hospitalized patients with COVID-19 pneumonia and established hyperinflammation remains unexplored. In a prospective, randomized controlled, observer-blinded endpoint, investigator-initiated trial, 240 hospitalized patients with COVID-19 pneumonia and established hyperinflammation were randomly allocated to receive oral colchicine or not. The primary efficacy outcome measure was a composite of non-invasive mechanical ventilation (CPAP or BiPAP), admission to the intensive care unit, invasive mechanical ventilation requirement or death. The composite primary outcome occurred in 19.3% of the total study population. The composite primary outcome was similar in the two arms (17% in colchicine group vs. 20.8% in the control group; p = 0.533) and the same applied to each of its individual components. Most patients received steroids (98%) and heparin (99%), with similar doses in both groups. In this trial, including adult patients with COVID-19 pneumonia and associated hyperinflammation, no clinical benefit was observed with short-course colchicine treatment beyond standard care regarding the combined outcome measurement of CPAP/BiPAP use, ICU admission, invasive mechanical ventilation or deat

Molecular imaging of infarcted heart by biofunctionalized gold nanoshells

"This is the peer reviewed version of the following article: Advanced Healthcare Materials 10.10 (2021): 2002186 which has been published in final form at https://doi.org/10.1002/adhm.202002186. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions"Algunos investigadores de la UAM pertenecen al Nanomaterials for Bioimaging GroupThe unique combination of physical and optical properties of silica (core)/gold (shell) nanoparticles (gold nanoshells) makes them especially suitable for biomedicine. Gold nanoshells are used from high-resolution in vivo imaging to in vivo photothermal tumor treatment. Furthermore, their large scattering cross-section in the second biological window (1000–1700 nm) makes them also especially adequate for molecular optical coherence tomography (OCT). In this work, it is demonstrated that, after suitable functionalization, gold nanoshells in combination with clinical OCT systems are capable of imaging damage in the myocardium following an infarct. Since both inflammation and apoptosis are two of the main mechanisms underlying myocardial damage after ischemia, such damage imaging is achieved by endowing gold nanoshells with selective affinity for the inflammatory marker intercellular adhesion molecule 1 (ICAM-1), and the apoptotic marker phosphatidylserine. The results here presented constitute a first step toward a fast, safe, and accurate diagnosis of damaged tissue within infarcted hearts at the molecular level by means of the highly sensitive OCT interferometric techniqueThis work was partially supported by the Ministerio de Economía y Competitividad de España (MAT2016-75362-C3-1-R) and (MAT2017-83111R), by the Ministerio de Ciencia e Innovación de España (PID2019-106211RBI00), by the Instituto de Salud Carlos III (PI16/00812) and (PI19/00565), by the Comunidad Autónoma de Madrid (B2017/BMD-3867RENIMCM), and co-financed by the European Structural and investment fund. Additionally, the research was financed by the European Commission Horizon 2020 project NanoTBTech, the Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP18_38 (2018/0265), and also by COST action CA1740. D.H.O. is grateful to the Instituto de Salud Carlos III for a Sara Borrell scholarship (CD17/00210

Major bleeding predictors in patients with left atrial appendage closure: The iberian registry II

Introduction and objective: Major bleeding events in patients undergoing left atrial appendage closure (LAAC) range from 2.2 to 10.3 per 100 patient-years in di erent series. This study aimed to clarify the bleeding predictive factors that could influence these di erences. Methods: LAAC was performed in 598 patients from the Iberian Registry II (1093 patient-years; median, 75.4 years). We conducted a multivariate analysis to identify predictive risk factors for major bleeding events. The occurrence of thromboembolic and bleeding events was compared to rates expected from CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, stroke history, vascular disease, sex) and HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, drugs or alcohol) scores. Results: Cox regression analysis revealed that age 75 years (HR: 2.5; 95% CI: 1.3 to 4.8; p = 0.004) and a history of gastrointestinal bleeding (GIB) (HR: 2.1; 95% CI: 1.1 to 3.9; p = 0.020) were two factors independently associated with major bleeding during follow-up. Patients aged <75 or 75 years had median CHA2DS2-VASc scores of 4 (IQR: 2) and 5 (IQR: 2), respectively (p < 0.001) and HAS-BLED scores were 3 (IQR: 1) and 3 (IQR: 1) for each group (p = 0.007). Events presented as follow-up adjusted rates according to age groups were stroke (1.2% vs. 2.9%; HR: 2.4, p = 0.12) and major bleeding (3.7 vs. 9.0 per 100 patient-years; HR: 2.4, p = 0.002). Expected major bleedings according to HAS-BLED scores were 6.2% vs. 6.6%, respectively. In patients with GIB history, major bleeding events were 6.1% patient-years (HAS-BLED score was 3.8 1.1) compared to 2.7% patients-year in patients with no previous GIB history (HAS-BLED score was 3.4 1.2; p = 0.029). Conclusions: In this high-risk population, GIB history and age 75 years are the main predictors of major bleeding events after LAAC, especially during the first year. Age seems to have a greater influence on major bleeding events than on thromboembolic risk in these patient

Validating the predictive ability of the 2MACE score for major adverse cardiovascular events in patients with atrial fibrillation:results from phase II/III of the GLORIA-AF registry

The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1–3) and 1 (IQR 0–2), respectively (p &lt; 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of ≥ 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21–2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641–0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration: http://www.clinicaltrials.gov . Unique identifiers: NCT01468701, NCT01671007 and NCT01937377

Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation:a post-hoc analysis from the GLORIA-AF Registry

Background: Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods: From the GLORIA-AF Registry Phase II–III (November 2011–December 2014 for Phase II, and January 2014–December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377. Findings: 34,421 patients were included (70.0 ± 10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n = 6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n = 15,449, 56.1%) and North America (n = 8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22–0.25] and 0.66 [0.61–0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67–1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76–0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding. Interpretation: Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis. Funding: The GLORIA-AF Registry was funded by Boehringer Ingelheim GmbH.</p

Anticoagulant selection in relation to the SAMe-TT₂R₂ score in patients with atrial fibrillation:The GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores &gt;2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores &gt;2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score &gt;2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores &gt;2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores &gt;2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.</p

Bariatric surgery: evidence-based practical recommendations

[Resumen] La obesidad mórbida es, habitualmente, refractaria a los tratamientos convencionales, por lo que la modificación de hábitos dietéticos y de actividad física y/o el uso de fármacos consiguen pérdidas de peso parciales con habitual recuperación posterior. La cirugía bariátrica constituye una opción terapéutica para los casos de obesidad con elevado índice de masa corporal (IMC) asociada a comorbilidades, con buenos resultados a corto y largo plazo. El Grupo de Trabajo sobre Obesidad de la Sociedad Española de Endocrinología y Nutrición (GOSEEN) ha elaborado un documento con recomendaciones prácticas basadas en la evidencia para el tratamiento quirúrgico de la obesidad. La revisión se estructura en 3 partes. En la primera se definen los conceptos de obesidad y comorbilidades asociadas, los tratamientos médicos y sus resultados, las indicaciones y contraindicaciones para el tratamiento quirúrgico con los criterios de selección de los pacientes, el manejo pre y perioperatorio y la valoración de grupos especiales, como adolescentes y personas de edad avanzada. En la segunda parte se describen las distintas técnicas quirúrgicas, las vías de acceso y los resultados comparativos, las complicaciones tanto a corto como a largo plazo, la repercusión de la pérdida ponderal sobre las comorbilidades y los criterios para evaluar la efectividad de la cirugía. En la tercera parte se desarrolla el seguimiento postoperatorio, el control dietético en fases tempranas y más tardías tras la cirugía, y el calendario de control médico y analítico con la suplementación de los distintos macro y micronutrientes en función de la técnica quirúrgica empleada. Se incluye un apartado final sobre gestación y cirugía bariátrica, así como tablas y gráficos complementarios al texto desarrollado. La cirugía bariátrica sigue siendo un tratamiento discutido para la obesidad, pero los resultados en la corrección del exceso ponderal con mejoría en las patologías asociadas y en la calidad de vida confirman que puede ser el tratamiento de elección en pacientes seleccionados, con la técnica quirúrgica apropiada y con un correcto control pre y postoperatorio.[Abstract] Morbid obesity is usually refractory to conventional treatments. Consequently, weight that is lost by modifying diet and exercise and/or the use of drugs is usually later regained. Bariatric surgery constitutes a therapeutic option in obese patients with a high body mass index associated with comorbidities and achieves good results in both the short and the long term. The Obesity Working Group of the Spanish Society of Endocrinology and Nutrition has produced a document with practical, evidencebased recommendations for the surgical treatment of obesity. The review is structured in three parts. The first part defines the concepts of obesity and associated comorbidities, medical treatments, their results, and the indications and contraindications for surgical treatment, as well as the criteria for patient selection, pre- and perisurgical management, and assessment of special groups such as adolescents and the elderly. The second part discusses the different surgical techniques, approaches and comparative results, short- and long-term complications, the repercussions of weight loss on comorbidities, and the criteria for assessing the effectiveness of surgery. The third part discusses postsurgical follow-up, dietary control in the early and subsequent stages after surgery and the schedule for medical and laboratory follow-up, together with the different macro- and micronutrient supplements that should be used depending on the surgical technique employed. A final section is included on pregnancy and bariatric surgery, as well as tables and figures that complement the text. Although bariatric surgery continues to be a questionable treatment for obesity, the results correcting excess weight, with improvements in associated comorbidities and in quality of life, confirm that this option could be the treatment of choice in selected patients when the appropriate surgical technique and correct preand postoperative follow-up are employed

Optical detection of atherosclerosis at molecular level by optical coherence tomography: an in vitro study

There is an urgent need for contrast agents to detect the first inflammation stage of atherosclerosis by cardiovascular optical coherence tomography (CV-OCT), the imaging technique with the highest spatial resolution and sensitivity of those used during coronary interventions. Gold nanoshells (GNSs) provide the strongest signal by CV-OCT. GNSs are functionalized with the cLABL peptide that binds specifically to the ICAM-1 molecule upregulated in the first stage of atherosclerosis. Dark field microscopy and CV-OCT are used to evaluate the specific adhesion of these functionalized GNSs to activated endothelial cells. This adhesion is investigated under static and dynamic conditions, for shear stresses comparable to those of physiological conditions. An increase in the scattering signal given by the functionalized GNSs attached to activated cells is observed compared to non-activated cells. Thus, cLABL-functionalized GNSs behave as excellent contrast agents for CV-OCT and promise a novel strategy for clinical molecular imaging of atherosclerosisMinisterio de Ciencia e Innovación (PID2019-106211RB-I00); Instituto de Salud Carlos III (PI16/00812) and (PI19/00565); Comunidad Autónoma de Madrid (S2017/BMD-3867 RENIM-CM) co-financed by the European Structural and Investment Fund; Horizon 2020 FET Open grant agreement no. 801305 (NanoTBTech project); Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal project IMP18_38 (2018/0265); COST action CA1740; Chinese Academy of Sciences Pioneer “Hundred Talents Program” Young talents (Class C) (JH