Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules.

BACKGROUND: Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. RESULTS: We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism. CONCLUSIONS: This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.

The effect of age and sex on the diagnostic yield of the echocardiogram in patients with syncope. / Efecto de la edad y el sexo en el rendimiento diagnóstico del ecocardiograma en pacientes con síncope.

INTRODUCTION: Syncope is the motivation for numerous diagnostic tests, among them transthoracic echocardiography (TTE); however, previous evidence suggests there is little utility in this test. Our objective was to assess its diagnostic yield in syncope, analysing the effect of age and sex. MATERIAL AND METHODS: We conducted an observational study that included patients with syncope and who underwent TTE between 1990-2015. We defined diagnostic findings related to syncope and performed a descriptive analysis, assessing the diagnostic yield (overall and according to age and sex). RESULTS: The study included 3,302 patients and measured a diagnostic yield of 8.8%; the most common finding was ventricular dysfunction (4.5%). The probability of a diagnostic TTE significantly increased with age (p<.001) but was low for patients younger than 50 years (2.3%). The male sex was significantly related with a diagnostic TTE (p<.001), mostly due to the higher rate of ventricular dysfunction. CONCLUSIONS: The diagnostic yield of TTE in patients with syncope is moderate, low in patients younger than 50 years and lower in women than in men. These factors should be considered when conducting a diagnostic study of patients with syncope.

The effect of age and sex on the diagnostic yield of the echocardiogram in patients with syncope.

INTRODUCTION: Syncope is the motivation for numerous diagnostic tests, among them transthoracic echocardiography (TTE); however, previous evidence suggests there is little utility in this test. Our objective was to assess its diagnostic yield in syncope, analysing the effect of age and sex. MATERIAL AND METHODS: We conducted an observational study that included patients with syncope and who underwent TTE between 1990 and 2015. We defined diagnostic findings related to syncope and performed a descriptive analysis, assessing the diagnostic yield (overall and according to age and sex). RESULTS: The study included 3302 patients and measured a diagnostic yield of 8.8%; the most common finding was ventricular dysfunction (4.5%). The probability of a diagnostic TTE significantly increased with age (p<.001) but was low for patients younger than 50 years (2.3%). The male sex was significantly related with a diagnostic TTE (p<.001), mostly due to the higher rate of ventricular dysfunction. CONCLUSIONS: The diagnostic yield of TTE in patients with syncope is moderate, low in patients younger than 50 years and lower in women than in men. These factors should be considered when conducting a diagnostic study of patients with syncope.

An exaggerated increase in blood pressure with exercise does not predict mortality or severe cardiovascular events in women referred for exercise echocardiography for clinical reasons. / Un incremento exagerado de la presión arterial con el ejercicio no predice mortalidad ni eventos cardiovasculares graves en mujeres referidas a ecocardiografía de ejercicio por razones clínicas.

BACKGROUND AND OBJECTIVES: The association between an exaggerated systolic blood pressure increase with exercise (EBPIE) and the probability of cardiovascular events is controversial and poorly studied in the female population. Our aim was to determine the possible association between EBPIE on one hand and mortality and cardiovascular events on the other in women referred for exercise echocardiography due to known or suspected coronary artery disease. PATIENTS AND METHODS: A total of 3942 women with known or suspected coronary artery disease underwent exercise echocardiography. We defined EBPIE as a ≥70mm Hg increase in systolic blood pressure with exercise. The study endpoints were overall and cardiac mortality, acute myocardial infarction (MI), stroke and coronary revascularisation procedures. RESULTS: A total of 332 women developed EBPIE during the test. During the follow-up, 458 deaths (162 of cardiac origin), 212 MIs, 89 strokes and 345 coronary revascularisation procedures were recorded. The annual rates of overall and cardiac mortality were lower in the patient subgroup with EBPIE (0.15% vs. 2.3%, P=.02 and 0.01% vs. 0.2%, P=.015, respectively). There were no significant differences in the rates of MI, stroke and the need for coronary revascularisation procedures, which occurred in 1.1%, 0.43% and 2.24% of the patients with EBPIE, respectively, and occurred in 0.09%, 0.05% and 0.13% of the women without EBPIE (P=.66; P=.57; P=.19, respectively). After a multivariate adjustment, EBPIE was not a predictor of mortality or cardiovascular events. CONCLUSIONS: EBPIE is not associated with mortality or severe cardiovascular events in women with known or suspected coronary artery disease.

Adverse effects of mammalian target of rapamycin inhibitors during the postoperative period after cardiac transplantation.

INTRODUCTION: Safety of treatment with mammalian target of rapamycin inhibitors (mTORi) in the postoperative period after heart transplantation (HT) is controversial. METHODS: We evaluated the incidence of postoperative complications (pericardial, pleural, and surgical wound complications) among nine de novo heart transplant recipients treated with mTORi compared with 19 patients who did not receive them during the same period (control group). RESULTS: No significant differences were observed between the two groups regarding sex, age, body mass index, pretransplant diagnosis, history of diabetes mellitus, prior cardiac surgery, or baseline renal function. The main laboratory parameters at 1 month were also similar. During the first 2 months after HT, four patients (44%) in the mTORi group developed severe pericardial effusions requiring drainage, compared to 1 (5%) in the control group (P = .026). All patients presenting this complication in the mTORi group received everolimus. In addition, two cases of sternal dehiscence were observed in the mTORi group, compared to none in the control group (P = .09); one patient on everolimus required sternal reopening and debridement for clinically suspected mediastinitis. Duration of chest tube drainage, quantity of collected pleural fluid, and need for thoracentesis were similar in both groups. CONCLUSIONS: In our series, patients receiving mTORi-particularly everolimus-during the postoperative period after HT showed a higher incidence of severe pericardial effusion requiring drainage, as well as a trend toward a higher incidence of sternal dehiscence, as compared to a group not receiving mTORi. The use of mTORi during the early postcardiac transplant period should be individualized.

Exaggerated hypertensive response to exercise and myocardial ischaemia in patients with known or suspected coronary artery disease. / Respuesta hipertensiva exagerada al ejercicio e isquemia miocárdica en pacientes con enfermedad coronaria conocida o sospechada.

OBJECTIVES: The association between an exaggerated hypertensive response to exercise (EHRE) and the probability of ischaemia in stress tests is controversial. Our purpose was to determine the possible association between an EHRE and the development of chest pain and electrocardiographic or echocardiographic ischaemia with exercise. PATIENTS AND METHODS: A retrospective observational study was conducted of 10,047 patients with known or suspected coronary artery disease referred for exercise echocardiography. A logistic regression analysis assessed the effect of developing an EHRE (defined as a maximum systolic blood pressure with exercise ≥220mmHg) and the onset of chest pain and electrocardiographic and echocardiographic changes suggestive of ischaemia. RESULTS: A total of 402 patients developed an EHRE. The rates of angina, electrocardiographic ischaemia and echocardiographic ischaemia among the patients with an EHRE were 8.2, 16.2 and 22.6% versus 13.8, 14.7 and 27.5%, respectively, for patients without an EHRE (p=.001, p=.4, p=.032). After a multivariate fit, EHRE was associated with a lower probability of exercise-induced angina (OR, 0.44; 95% CI 0.30-0.65; p<.001) and echocardiographic ischaemia (OR, 0.63; 95% CI 0.48-0.83; p=.001) but not with the onset of electrocardiographic ischaemia. CONCLUSIONS: EHRE is associated with a lower prevalence of angina and echocardiographic ischaemia in patients with known or suspected coronary artery disease.