Confining Prepared Ultrasmall Nanozymes Loading ATO for Lung Cancer Catalytic Therapy/Immunotherapy.

Nanozymes with inherent enzyme-mimicking catalytic properties combat malignant tumor progression via catalytic therapy, while the therapeutic efficacy still needs to be improved. In this work, ultrasmall platinum nanozymes (nPt) in a confined domain of a wormlike pore channel in gold nanobipyramidal-mesoporous silica dioxide nanocomposites, producing nanozyme carriers AP-mSi with photoenhanced peroxidase ability, are innovatively synthesized. Afterward, based on the prepared AP-mSi, a lung-cancer nanozymes probe (AP-HAI) is ingeniously produced by removing the SiO2 template, modifying human serum albumin, and loading atovaquone molecules (ATO) as well as IR780. Under NIR light irradiation, inner AuP and IR780 collaborate for photothermal process, thus facilitating the peroxidase-like catalytic process of H2 O2 . Additionally, loaded ATO, a cell respiration inhibitor, can impair tumor respiration metabolism and cause oxygen retention, hence enhancing IR780's photodynamic therapy (PDT) effectiveness. As a result, IR780's PDT and nPt nanozymes' photoenhanced peroxidase-like ability endow probes a high ROS productivity, eliciting antitumor immune responses to destroy tumor tissue. Systematic studies reveal that the obvious reactive oxygen species (ROS) generation is obtained by the strategy of using nPt nanozymes and reducing oxygen consumption by ATO, which in turn enables lung-cancer synergetic catalytic therapy/immunogenic-cell-death-based immunotherapy. The results of this work would provide theoretical justification for the practical use of photoenhanced nanozyme probes.

Clinical Outcomes After Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study.

OBJECTIVE: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. BACKGROUND: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. METHODS: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cutoff values for annual volume of pancreatoduodenectomies (<60 vs ≥60).Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. RESULTS: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared <60 (4% vs 10%, P = 0.046). In multivariable analysis, annual volume <60 pancreatoduodenectomies (OR 3.78, 95% CI 1.18-12.16, P = 0.026), age (OR 1.07, 95% CI 1.01-1.14, P = 0.046), and estimated blood loss ≥2L (OR 11.89, 95% CI 2.64-53.61, P = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95% CI 1.56-5.26, P = 0.001) and estimated blood loss ≥2L (OR 3.52, 95% CI 1.25-9.90, P = 0.017) were associated with major complications. CONCLUSION: This pan-European prospective snapshot study found a 5% inhospital mortality after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.

Subclavian-Brachial Bypass for Chronic Limb Threatening Ischemia Associated with an Old Motorcycle Accident

Chronic limb-threatening ischemia is rarely associated with previous traumatic injury. We present a case of a 28-year-old male with progressive digit ulcers, a weak pulse, cyanosis, and a cold limb. Eight months prior, he had a motorcycle accident resulting in a right clavicle fracture and brachial plexus injury. Computed tomography angiography revealed occlusion of the right subclavian artery near a surgically implanted reduction plate. The patient underwent an open subclavianbrachial bypass with a reversed saphenous vein graft. His postoperative recovery was uneventful. After 3 months, he had a euthermic right hand with a palpable pulse and his ulcers had completely healed. This case reinforces the need for patients with a neurological deficit in the upper extremity caused by blunt trauma to undergo thorough vascular examination to identify potential arterial injury and compromised perfusion.

Altering model cell membranes by means of localized magnetic heating.

Isolated iron oxide magnetic nanoparticles (MNPs), 12 nm in diameter, coated with oleic acid molecules as capping agents have been deposited by the Langmuir-Blodgett (LB) method onto a model cell membrane incorporating 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and Cholesterol (Chol) in the 1:1 ratio, which was also fabricated by the LB technique. Atomic Force Microscopy (AFM) experiments showed that the application of an alternating magnetic field results in the embedding of the MNPs through the phospholipidic layer. These experimental results reveal that the heating of individual MNPs may induce a local increase in the fluidity of the film with a large control of the spatial and temporal specificity.

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams.

Benzo-fused γ-lactam rings such as isoindolin-2-ones and 2-oxindoles are part of the structure of many pharmaceutically active molecules. They can be often synthesized by means of multicomponent approaches and recent contributions in this field are summarized in this review. Clear advantages of these methods include the efficiency in saving raw materials and working time. However, there is still a need of new catalytic systems to allow the enantioselective preparation of these heterocycles by multicomponent reactions.

La degeneración real de la prótesis aórtica Mitroflow: análisis con riesgos competitivos / Real structural valve deterioration of the mitroflow aortic prosthesis: competing risk analysis

Introducción y objetivos: La prótesis aórtica Mitroflow es una válvula de pericardio bovino especialmente diseñada para aumentar el área valvular. Hay controversia en relación con su patrón de degeneración estructural valvular (DEV). El objetivo es conocer la incidencia acumulada de DEV, los factores que influyen en su aparición y su impacto sobre la mortalidad. Métodos: Se siguió a 1.028 pacientes clínica y ecocardiográficamente. Puesto que se trata de una población cardiópata y anciana, se realizó un análisis de riesgos competitivos. Resultados: El porcentaje de DEV a los 5 años fue 4,22% (IC95%, 2,96-5,81) y a los 8 años 15,77% (IC95%, 12,46-19,43). La incidencia fue superior para las válvulas de tamaños pequeños (19 y 21 mm). A los 5 años llegó al 6,43% (IC95%, 4,48-8,84) y a los 8 años al 20,06% (IC95%, 15,53-25,01). El desajuste paciente-prótesis (DPP) grave influyó en la incidencia de DEV (sHR = 3,53; IC95%, 2,20-5,66; p < 0,001). Sin embargo, el DPP moderado no tuvo ningún impacto. La presencia de DEV fue el mayor predictor de mortalidad (HR = 4,59; IC95%, 2,91-7,22; p < 0,001). Conclusiones: Utilizando una definición basada en el aumento del gradiente transprotésico, la incidencia de DEV de la prótesis Mitroflow es superior a la indicada por otras series, especialmente para las de tamaños pequeños (19 y 21 mm) o en pacientes con DPP grave. Aumenta exponencialmente a partir del quinto año y desde que se diagnostica aumenta por 4,5 el riesgo de muerte (AU)

Introduction and objectives: The Mitroflow aortic prosthesis is a bovine pericardial bioprosthesis specially designed to increase the valve area in relation to its size. There is controversy regarding the pattern of structural valve deterioration (SVD). Our aim was to determine the cumulative incidence of SVD, risk factors influencing its occurrence, and its impact on mortality. Methods: A total of 1028 patients were clinically and echocardiographically followed up. Because the study population was elderly and had heart disease, we used a competing risk analysis. Results: The percentage of patients with SVD at 5 years was 4.22% (95%CI, 2.96-5.81) and was 15.77% at 8 years (95%CI, 12.46-19.43). The incidence was higher for small valves (19 mm and 21 mm) reaching 6.43% at 5 years (95%CI, 4.48-8.84) and 20.06% at 8 years (95%CI, 15.53-25.01). Severe patient-prosthesis mismatch (PPM) influenced the incidence of SVD (sHR, 3.53; 95%CI, 2.20-5.66; P < .001) but moderate PPM had no impact. The most powerful predictor of mortality was the presence of SVD (HR, 4.59; 95%CI, 2.91-7.22; P < .001). Conclusions: This study used a definition based on the increase in the transprosthetic gradient and found a higher incidence of SVD of the Mitroflow prosthesis than that reported by other series, especially for sizes 19 mm and 21 mm and in patients with severe PPM. The incidence of SVD increased exponentially from the fifth year after implantation and its occurrence led to a 4.5-fold increase in the risk of death (AU)

Development of 100 Mo -containing scintillating bolometers for a high-sensitivity neutrinoless double-beta decay search.

This paper reports on the development of a technology involving 100 Mo -enriched scintillating bolometers, compatible with the goals of CUPID, a proposed next-generation bolometric experiment to search for neutrinoless double-beta decay. Large mass ( ∼ 1 kg ), high optical quality, radiopure 100 Mo -containing zinc and lithium molybdate crystals have been produced and used to develop high performance single detector modules based on 0.2-0.4 kg scintillating bolometers. In particular, the energy resolution of the lithium molybdate detectors near the Q-value of the double-beta transition of 100 Mo (3034 keV) is 4-6 keV FWHM. The rejection of the α -induced dominant background above 2.6 MeV is better than 8 σ . Less than 10 µ Bq/kg activity of 232 Th ( 228 Th ) and 226 Ra in the crystals is ensured by boule recrystallization. The potential of 100 Mo -enriched scintillating bolometers to perform high sensitivity double-beta decay searches has been demonstrated with only 10 kg × d exposure: the two neutrino double-beta decay half-life of 100 Mo has been measured with the up-to-date highest accuracy as T 1 / 2 = [6.90 ± 0.15(stat.) ± 0.37(syst.)] × 10 18 years . Both crystallization and detector technologies favor lithium molybdate, which has been selected for the ongoing construction of the CUPID-0/Mo demonstrator, containing several kg of 100 Mo .

Eficacia del tratamiento con 131I en la enfermedad de Graves pediátrica / Efficacy of treatment with I 131 in paediatric Graves disease

INTRODUCCIÓN: El tratamiento con radioyodo en la enfermedad de Graves (EG) es una opción terapéutica curativa cada vez más utilizada en niños por encima de 5 años. En Estados Unidos su uso está muy extendido, pero en Europa sigue existiendo controversia respecto a su indicación en la edad pediátrica. OBJETIVO: Presentar nuestra experiencia con la administración de I131 en la EG en edad pediátrica y analizar su eficacia y seguridad. PACIENTES Y MÉTODOS: Estudio retrospectivo descriptivo de los pacientes pediátricos (< 18 años) diagnosticados de EG en nuestro hospital desde 1982 hasta 2012. Al alcanzar la pubertad, se ofreció una opción curativa a aquellos pacientes que no habían respondido al tratamiento con fármacos antitiroideos (AT). Analizamos las características de los pacientes, niveles de hormona tirotropa, T3 y T4, y autoanticuerpos, respuesta a AT, frecuencia de la remisión de la enfermedad post-I131, aparición de hipotiroidismo y efectos secundarios del I131.ResultadosDesde 1982 hasta 2012 fueron diagnosticados de EG 50 pacientes. Todos recibieron como tratamiento inicial AT, con una duración media 35,3 ± 25,9 meses. Se consiguió remisión permanente en el 46%. Se realizó tiroidectomía a 5 pacientes y se administró I131 a 14 pacientes. La dosis de yodo administrada osciló entre 8,5 y 13 mCi (10,9 ± 1,09). Se obtuvo remisión en el 100%. La tasa de hipotiroidismo permanente fue del 90%. No se observaron progresión de la oftalmopatía ni efectos secundarios en ningún paciente tratado con I131. CONCLUSIONES: El tratamiento con 131I en la EG pediátrica es seguro, lleva a la remisión completa a costa de hipotiroidismo y no exacerba la oftalmopatía. Puede considerarse su utilización en mayores de 5 años cuando no existe respuesta a AT o ante efectos secundarios importantes con esta medicación

INTRODUCTION: Radioiodine is an important therapeutic option in young patients with Grave's disease (GD). In the United States it is a widespread therapy, but in Europe its use in paediatrics is still controversial. AIM: To report our experience in radioiodine therapy of paediatric GD patients and analyse its effectiveness and safety. PATIENTS AND METHODS: We retrospectively studied our paediatric population (<18 years of age) with GD, diagnosed from 1982 to 2012. A curative option was offered to patients who did not respond to anti-thyroid drug (AT) at puberty. We analysed, the patient characteristics, TSH, T4, T3 and thyroid antibodies levels, AT response, remission post I131, side effects, and hypothyroidism rates. RESULTS: A total of 50 patients were diagnosed with GD from 1982 to 2012. All patients received AT as initial treatment (mean duration: 35.3±25.9 months). Permanent remission was achieved in 46%. Thyroidectomy was performed in 5 patients, and 14 patients received I131 (mean dose: 10.9±1.09 mCi). Remission with I131 was obtained in 100%. The rate of permanent hypothyroidism was 90%. There was no progression of ophthalmopathy or side effects in any patientst reated with I131.CONCLUSION: Radioiodine treatment of paediatric GD patients is safe, leads to complete remission at the expense of hypothyroidism, and does not exacerbate ophthalmopathy. It can be considered in patients older than 5 years, who do no not respond to AT or with significant side effects with this medication

Importancia de la definición y la técnica en el diagnóstico de puentes intramiocárdicos por angiografía coronaria no invasiva / Importance of definition and technique when using noninvasive coronary angiography to diagnose myocardial bridging

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Grado de conocimiento sobre su enfermedad cardiaca entre los pacientes hospitalizados / Knowledge of cardiac disease among hospitalized patients

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Sobrecarga oral de glucosa como herramienta para la mejora tras intervencionismo coronario percutáneo / Oral glucose tolerance test as a tool for patient improvement after percutaneous coronary intervention

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Síndrome metabólico, diabetes y enfermedad coronaria: una relación muy frecuente / Metabolic syndrome, diabetes, and coronary artery disease: a very common association

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Rendimiento de la glucohemoglobina y un modelo de riesgo para la detecci¨®n de diabetes desconocida en pacientes coronarios / Performance of glycated hemoglobin and a risk model for detection of unknown diabetes in coronary patients

Introducción y objetivos: Clásicamente, la sobrecarga oral de glucosa ha diagnosticado la diabetes desconocida. Recientemente, la American Diabetes Association ha aceptado un valor de glucohemoglobina ≥ 6,5% como criterio de diabetes desconocida. Pretendemos conocer la rentabilidad que tiene la glucohemoglobina para la detección de diabetes desconocida y validar un modelo que permita ajustar la realización de la sobrecarga oral de glucosa en enfermos coronarios. Métodos: Se estudia el perfil glucémico de 338 enfermos coronarios sin diabetes conocida. Se usan los criterios de la American Diabetes Association de 2010 y, mediante regresión logística, se construye un modelo predictor de diabetes desconocida. Se valida el modelo en otra cohorte. Resultados: Se diagnosticó diabetes desconocida a 26 enfermos mediante glucohemoglobina y/o glucemia basal. Los demás presentaban, tras realizar sobrecarga oral de glucosa: diabetes desconocida, 53 (17%); prediabetes, 144 (46,2%), y normoglucemia, 115 (36,8%). Método diagnóstico de diabetes desconocida: glucemia basal, 25,3%; glucohemoglobina, 7,6%, y sobrecarga oral de glucosa, 67,1%. Un modelo que incluye glucemia basal, glucohemoglobina, fracción de eyección de ventrículo izquierdo, edad y enfermedad vascular no coronaria resultó eficaz como predictor de diabetes desconocida tras sobrecarga oral de glucos: área bajo la curva ROC, 0,8 (intervalo de confianza del 95%, 0,74-0,87). Realizando sobrecarga oral de glucosa sólo a la población con puntuación del modelo > 6 (el 31% del total), podemos localizar al 83% de los casos de diabetes desconocida reales (sensibilidad, 75%; especificidad, 73%; valor predictivo positivo, 40%; valor predictivo negativo, 93%). El modelo se validó correctamente en otra cohorte de 115 pacientes (área bajo la curva ROC, 0,84 [intervalo de confianza del 95%, 0,74-0,95]). Conclusiones: La glucohemoglobina diagnostica aisladamente pocos casos de diabetes desconocida. Sin embargo, su incorporación a un modelo de riesgo permite optimizar la indicación de la sobrecarga oral de glucosa, con un aprovechamiento óptimo (AU)

Introduction and objectives: Traditionally, the oral glucose tolerance test has been useful to diagnose unknown diabetes. Recently, the American Diabetes Association committee has accepted glycated hemoglobin ≥6.5% as a criterion for unknown diabetes. The aim was to determine the benefit of glycated hemoglobin for diagnosing unknown diabetes and also create a predictive model that adjusts the indication for oral glucose tolerance test in coronary patients. Methods: We examined the glycemic profile of 338 coronary patients without previous diagnosis of diabetes, applying 2010 American Diabetes Association criteria. A unknown diabetes risk predictive model was developed using logistic regression analysis, and then validated in another cohort. Results: Using the glycated hemoglobin criteria and/or fasting plasma glucose, unknown diabetes was diagnosed in 26 patients. The remaining patients were classified according to oral glucose tolerance test as follows: unknown diabetes 53 (17%), prediabetes 144 (46.2%), and normoglycemic 115 (36.8%). The diagnostic method for unknown diabetes was fasting plasma glucose in 25.3%, glycated hemoglobin in 7.6%, and oral glucose tolerance test in 67.1%. A risk model including fasting plasma glucose, glycated hemoglobin, left ventricular ejection fraction, age, and noncoronary vascular disease was shown to effectively predict unknown diabetes after oral glucose tolerance test: area under the ROC curve 0.8 (95% interval confidence: 0.74-0.87). When the oral glucose tolerance test is restricted to patients with a risk score >6 (31% of our sample) we properly identify 83% of unknown diabetes cases (sensitivity: 75%, specificity: 73%, positive predictive value: 40%, negative predictive value: 93%). The model was adequately validated in another cohort of 115 patients (area under the ROC curve 0.84 [95% interval confidence: 0.74-0.95]). Conclusions: In coronary patients, glycated hemoglobin alone failed to detect many cases of unknown diabetes. However, its inclusion in a risk prediction model leads to optimizing the usefulness of oral glucose tolerance test (AU)

Alteraciones de la homeostasia de la glucosa y síndrome coronario agudo / Impaired glucose homeostasis and acute coronary syndrome

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Test de sobrecarga oral de glucosa y síndrome coronario agudo / Oral glucose tolerance test and acute coronary syndrome

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Miopericarditis en paciente con colitis ulcerosa en tratamiento con mesalacina / Myopericarditis in a patient with ulcerative colitis treated with mesalazine

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